8 gi diseases modified - kerala

GOVERNMENT OF KERALA

STANDARD TREATMENT GUIDELINES

DEPARTMENT OF HEALTH AND FAMILY WELFARE

GI diseases

Committee for Development of Standard TreatmentGuidelines GI diseases

Convener

Dr D. Krishnadas Professor & HOD, Department of Medical

gastroenterology, Govt. MCH, Thiruvananthapuram

Members

1. Dr M. Narendranathan, Former Professor and HOD,

Department of Medical gastroenterology, MCH, Trivandrum

2. Dr T. M. Ramachandran, Associate Professor and HOD,

Kozhikode Medical College

3. Dr Sunil Kumar, Associate Professor, Kottayam Medical

College

4. Dr M. Narendranathan, Former Professor and HOD,

Department of Medical Gastroenterology, Govt. MCH,

Thiruvananthapuram

5. Dr Jayanthi V – Senior consultant & HOD, Sri Ramachandra

Medical College, Chennai

6. Dr Varghese Thomas- Senior consultant Gastroenterologist,

Malabar Medical College, Kozhikode; Former Prof & HOD,

Gastroenterology, Govt.MCH, Calicut

7. Dr T M Ramachandran- Additional Professor & HOD,

Gastroenterology, Govt.MCH, Calicut

8. Dr Premalatha N- Professor & HOD, Department of Medical

gastroenterology, Govt. MCH, Kottayam

9. Dr Prakash Zacharias- Senior consultant

Gastroenterologist, PVS Memorial Hospital, Kochi

10. Dr Roy J Mukkada- Senior consultant Gastroenterologist,

VPS Lakeshore Hospital

11. Dr Ismail Siyad K H- Senior consultant Gastroenterologist,

Aster Medicity, Kochi

12. Dr Shine Sadasivan- Clinical Professor, Department of

Gastroenterology and Hepatology, Amrita Institute of Medical

Sciences, Kochi

13. Dr Saji Sebastian- Department of Medical gastroenterology,

Govt. MCH, Thrissur

Additional Chief Secretary, Department of Health and Family Welfare, Government

of Kerala, the process of preparation of Standard Treatment Guidelines (STG) was

initiated by the Director of Medical Education Dr. Remla Beevi A. The process of

developing and finalizing the STG’s were coordinated by Dr. Sreekumari K. Joint

Director Medical education and Dr. Suma T K, Professor of Medicine and ably

supported by a dedicated team of experts, including external faculty”.

“Driven by the inspiration drawn from Shri. Rajeev Sadanandan IAS,

TABLE OF CONTENTS

Message by Chief Minister 11

Message by Health Minister 13

Foreword by Additional Chief Secretary 15

1. Spontaneous Bacterial Peritonitis 17

2. Upper Gi Bleed –variceal 25

Scope 19

Introduction 20

Definition 20

Indications for ascitic fluid study 20

Diagnosis 20

Other investigations 20

Management of spontaneous bacterial peritonitis 21

Treatment 21

1. Antibiotics 21

2. Intravenous albumin 23

References 24

Scope 27

Introduction 28

Investigations 28

Diagnosis 28

Treatment 28

1. General measures 28

2. Airway Protection 28

3. Obtaining an IV access 29

4. Restoring the circulation 29

5. Antibiotic prophylaxis 29

6. Vasoactive drugs 29

Management of gastric varices 30

Refractory bleeding 31

7. Endoscopy 30

8. Monitoring 30

Treatments for the Prevention of Recurrent

Esophageal Variceal Hemorrhage 31

Definition of HRS 46

Management of treatment failures 32

Management algorithm 33

References 33

Scope 37

Introduction 38

Classification 38

investigations 39

Management Algorithms 40

Treatment 40

1) Lactulose or Lactitol 40

2) Rifaximin 40

3) Oral Branched chain amino acids (BCAAs) 40

4) L-ornithine L-aspartate(LOLA) 40

Nutrition 40

Prevention 40

References 42

Scope 45

Definitions of kidney disease 46

Diagnostic criteria for HRS 46

Treatment strategies 47

Response to the treatment 48

Treatment of non responders 48

Prevention of HRS-AKI 49

References 49

Scope 53

Introduction 54

Diagnosis of ALF 54

3. Hepatic Encephalopathy 35

4. Hepato Renal Syndrome 43

5. Acute Liver Failure 51

Diagnosis and

Immediate measures at presentation of

patients with ALF to medical care. 54

Management 56

Clinical assessment at admission 56

Laboratory analysis at admission. 57

Diagnostic procedures, monitoring

and standard care at admission. 58

Suggested criteria for referral of cases of

ALF to specialist units 59

Organ specific management 59

Artificial and Bioartificial liver devices 61

Liver transplantation (Ltx) 61

Summary of medical management 62

References 62

Scope 65

Introduction 66

Diagnosis of HCC in a cirrhotic liver 66

Diagnosis of HCC in a non-cirrhotic liver 69

Surveillance 69

Diagnostic algorithm and recall policy in cirrhotic liver 71

Staging system and treatment allocation 71

Outcome prediction and treatment allocation 72

Modified BCLC staging system 72

Concept of treatment stage migration 75

Palliative and best supportive care 75

Antiviral therapies for hepatitis B virus-related

hepatocellular carcinoma 75

References 75

Scope 79

Introduction 80

Diagnostic criteria for acute cholangitis 80

6. Hepatocellular Carcinoma 63

7. Acute Cholangitis 77

Severity assessment criteria for acute cholangitis 81

Grade III (Severe) acute cholangitis 81

Grade II (moderate) acute cholangitis 81

Grade I (mild) acute cholangitis 81

Investigations 81

Management of acute cholangitis 82

Treatment 82

References 84

Scope 87

Introduction 88

Diagnosis of acute pancreatitis 88

Severity of acute pancreatitis 88

Definition of organ failure 89

Algorithm for the management of acute pancreatitis 90

Management - Initial management 91

ERCP in AP 91

Role of antibiotics in AP 91

Nutrition in AP 92

Role of surgery in AP 92

References 93

Scope 97

Initial assessment and risk stratification 98

Rockall Scoring System 98

Pre-endoscopic medical therapy

Medical therapy after endoscopy 101

8. Acute Pancreatitis 85

9. Peptic Ulcer Bleeding 95

. 98

Endoscopic 99

management of ulcer bleed 99

Endoscopic diagnosis of ulcer and stigmata

of recent hemorrhage 99

Forrest classification of peptic ulcer bleed 100

Clinical algorithm for the management of

peptic ulcer bleeding

Repeat endoscopy 101

Hospitalization for patients with UGIB 101

Long term prevention of recurrent bleeding ulcers 101

References 102

Introduction 106

Evaluation and risk stratification 106

Hemodynamic resuscitation 106

Management of coagulation defects 106

Colonoscopy 107

Non-colonoscopy interventions 108

Management algorithm 109

References 110

Scope 113

Introduction 114

Truelove and Witts classification of the severity of UC 114

Diagnosis of acute severe UC 114

Investigations 115

Treatment approach 115

Intravenous-steroid refractory Ulcerative colitis 116

Factors that predict the need for colectomy

in acute severe colitis 117

Second line therapy / Salvage therapy 117

Treatment according to site of disease

and disease activity 118

References 119

10. Acute Lower Gastrointestinal Bleeding 103

11. Severe Ulcerative Colitis 111

Scope 105

Message

The Government is taking many initiatives to ensure providing

quality health care to all. Out of the five missions launched by the

Government, the Aardram mission is primarily focussed to improve

Primary Health Care to provide standard health care facilities to people at

grassroots. This initiative is complemented by strategic investment for the

improvement of infrastructure in secondary and tertiary health care

institutions to provide quality health care services.

I am happy to note that the Department of Health is also taking

initiatives to bring standardization in treatment for various disciplines like

Cardiology, Critical care, Diabetes Mellitus, Cancer Care, etc. It is a

noteworthy initiative to improve the qualitative aspects of the health

service delivery. I appreciate the efforts taken by the experts from

Government sector and private sector from Kerala and also the subject

experts from outside the state. I am hopeful that the introduction of

standard guidelines for diagnosis and treatment will ensure better quality

and consistency in health care.

I wish all the success to this endeavour.

11

Pinarayi VijayanChief Minister

SecretariatThiruvananthapuram

Pinarayi VijayanChief Minister

Message

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Foreword

Patient care has moved away from management by an

individual based on personal knowledge and skill to an evidence

based, team managed operation. Decisions are reviewed more

rigorously post facto and their alignment verified with standard

practice. With the mode of payment for care moving from out of

pocket payments to third party payers there will be a demand for

rigorous documentation and evidence of having conformed to

standard practice. When analysis of big data and machine learning

becomes the norm it will require a standard set of procedures to act

as the baseline from which to measure deviations and differences in

impact.

To meet the requirement of these developments in the field

of medicine, it is necessary to have explicit, objectively verifiable set

of standard operating procedures. They have to be prepared based

on international guidelines with the highest acceptance, but have to

be modified to suit local knowledge and practice, so that there is

local ownership. Government of Kerala has been trying to get the

guidelines prepared for some time now. I would like to thank and

congratulate Dr. Sreekumari, Joint Director of Medical Education

and Dr. T.K.Suma, Professor of Medicine, T.D. Medical College,

Alappuzha who took on the task of preparing standard treatment

guidelines and completed it through a long, consultative process. I

also thank the conveners of the different thematic groups who

coordinated the work in their field as well as the innumerable

number of participants, in government and private sector, who

contributed their effort and knowledge to improve the guidelines.

Professional associations have also contributed in their fields. Their

efforts have resulted in a product they and Kerala can be proud of.

Treatment guidelines cannot be static if they are to remain

relevant. They must be updated based on new knowledge and the

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experience of treatment based on these guidelines. To do this the

group which prepared the guidelines has to remain active and have

a system for collecting data on the results of practice based on

these guidelines. I hope such an activity is institutionalised and

periodic revisions of the guidelines are prepared and published.

I wish that these guidelines contribute to raising the quality of

patient care in Kerala.

Rajeev Sadanandan IAS

Addl Chief Secretary

Health & Family Welfare

Department

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Section 1SPONTANEOUS BACTERIAL

PERITONITIS (SBP)

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STANDARD TREATMENT GUIDELINES - SEVERE TRAUMATIC BRAIN INJURY

STANDARD TREATMENT GUIDELINES - GI DISEASES

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Scope

Population

Key clinical issues covered:

Clinical issues not covered:

Health care setting:

Outcome:

Abbreviations

Adults more than 18 years of age; not applicable to paediatric

population

Diagnosis and management of spontaneous bacterial peritonitis

Detailed description of drugs and interventions

Secondary and tertiary health care, patient presenting in the

outpatient department or emergency department

Early diagnosis of spontaneous bacterial peritonitis with

appropriate management and reduction in mortality and morbidity.

SBP - spontaneous bacterial peritonitis

SAAG - serum-ascites albumin gradient

GI - Gastrointestinal

CRP - C-reactive protein

SIRS - systemic inflammatory response syndrome

AF - Ascitic fluid

MDRO - multidrug resistant organisms

MDR - multidrug resistant

SBE - spontaneous bacterial empyemaS

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Introduction

Definition

Indications For Ascitic Fluid Study

Spontaneous Bacterial Peritonitis (SBP) is the bacterial infection of

ascitic fluid without any intra-abdominal surgically treatable source

of infection. It is a frequent and serious complication of cirrhotic

patients with ascites (Low Protein, High SAAG). The prevalence of

SBP in cirrhotic hospitalized patients with ascites ranges between

10% and 30%, but in hospital mortality has now been reduced to

approximately 20% with early diagnosis and prompt treatment.

1. New onset ascites

2. A diagnostic paracentesis should be carried out in all patients

with cirrhosis and ascites without delay, at hospital admission

to rule out SBP.

3. A diagnostic paracentesis should also be performed in

cirrhotic patients with GI bleeding, shock, fever or other signs

of systemic inflammation, GI symptoms, as well as inpatients

with worsening liver and/or renal function, and hepatic

encephalopathy.

Suspect SBP in patients with cirrhosis and ascites presenting with fever, chills, abdominal pain ,GI bleeding or changes in mental status

Diagnosis

SBP is diagnosed based on neutrophil count in ascitic fluid of >250/mm3

Neutrophil count is determined by microscopy, but can be

substituted with a flow Cytometry based automated count. Although

ascitic fluid culture positivity is not a Prerequisite for the diagnosis of

SBP, culture should be performed in order to guide Antibiotic therapy.

Complete Blood Counts, ESR, CRP, Liver Function Test, Renal

Other Investigations

STANDARD TREATMENT GUIDELINES - GI DISEASESSe

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Function Test, Electrolytes, Urine Routine, Ascitic fluid Culture, and

Blood Culture before starting Antibiotics

Management Of Spontaneous Bacterial Peritonitis

Treatment

1. Antibiotics

Empirical I.V. antibiotics

Empirical I.V. antibiotics should be started immediately following

the diagnosis of SBP.

a) For community-acquired SBP - Third-generation

cephalosporins are


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recommended as first-line antibiotic in areas with low rates of

bacterial resistance.

In areas with high rates of bacterial resistance,

piperacillin/tazobactam or carbapenem should be

considered.

b) Healthcare associated and nosocomial SBP is more likely

to harbour resistance to antibiotics.

l Piperacillin/tazobactam should be given in areas with

low prevalence of multi-drug resistance while

carbapenem should be used in areas with high

prevalence of ESBL producing Enterobacteriaceae.

l Carbapenems should be combined with glycopeptides or

daptomycin or linezolid in areas with high prevalence of

gram positive MDR bacteria.

De-escalation according to bacterial susceptibility based on positive

cultures is recommended to minimize resistance.

The efficacy of antibiotic therapy should be checked with a second

paracentesis at 48 hr of starting treatment. Failure of first-line

antibiotic therapy should be suspected if there is worsening of

clinical signs and symptoms and/or increase or no marked reduction

in leucocyte count (at least 25%) in 48 h. This should raise the

suspicion of an infection caused by bacteria resistant to antibiotic

therapy, indicating the need for modification of antibiotic treatment

according to in vitro sensitivity

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The duration of treatment should be at least 5–7 days.

Bilirubin > 4 mg/dl or

Blood urea Nitrogen > 30 mg/dl or Creatinine > 1 mg/dl

IV albumin may be given on Day 1 and on Day 3

- Blood cultures should be performed in all patients

with suspected SBP before starting antibiotic treatment

l Patients with bacterascites (neutrophil count less than

250/mm3 but positive bacterial culture) exhibiting signs of

systemic inflammation or infection should be treated with

antibiotics. Otherwise, the patient should undergo a

second paracentesis.

l If the culture results come back positive again, regardless

of the neutrophil count, the patient should be treated for 5

days of IV antibiotic to which the organism is highly

susceptible empirically followed by more specific therapy

after susceptibility results are available.

l Secondary bacterial peritonitis should be suspected in

case of multiple organisms on ascitic culture, very

high ascitic neutrophil count and/or high ascitic protein

concentration, or in those patients with an inadequate

response to therapy. Patients with suspected secondary

bacterial peritonitis should undergo prompt CT scanning

and surgical consultation

a) Primary prophylaxis-Long Term with Norfloxacin (400

mg/day) in patients with Ascitic fluid protein lower than 1.5

g/dL along with:

2. Intravenous ALBUMIN

3. Monitor for Other complications like Acute kidney injury,

Hepatic Encephalopathy and manage accordingly .

Prophylaxis

Indications for Albumin

Intravenous albumin in patients with spontaneous bacterial

peritonitis

Kindly Note


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1. Child-Pugh score ≥9

2. Serum bilirubin level ≥3 mg/dl or

3. Impaired renal function Blood Urea Nitrogen > 25mg/dl,

Creatinine > 1.2 mg/dl or

4. Hyponatraemia Na <130

Short term prophylaxis for cirrhotic patients with GI bleed-

IV ceftriaxone 1g daily for 7 days or oral norfloxacin

400mg twice daily for 7 days.

Norfloxacin prophylaxis should be stopped in patients with

long-lasting improvement of their clinical condition and

disappearance of ascites

b) Secondary prophylaxis- The administration of prophylactic

Norfloxacin (400mg/day, orally) is recommended in

patients who recover from an episode of SBP.

Patients who recover from SBP have a poor long-term survival

and should be considered for liver transplantation.

1) The European Association for the Study of the Liver. EASL Clinical

Practice Guidelines for the management of patients with

d e c o m p e n s a t e d c i r r h o s i s . J H e p a t o l ( 2 0 1 8 ) ,

https://doi.org/10.1016/j.jhep.2018.03.024

2) EASL clinical practice guidelines on the management of ascites,

spontaneous bacterial peritonitis, and hepatorenal syndrome in

cirrhosis. J Hepatol 2010;53:397–417.

References

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Section 2UPPER GI BLEED –VARICEAL

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STANDARD TREATMENT GUIDELINES - SEVERE TRAUMATIC BRAIN INJURY

Scope


population

Diagnosis and management of acute variceal bleeding in cirrhosis




Diagnosis of acute variceal bleeding in cirrhosis with appropriate

management and reduction in mortality and morbidity.

VH - variceal hemorrhage

AVH - acute variceal hemorrhage

UGI - upper gastro intestinal

GOV - Gastro-oesophageal varices

IGV - Isolated gastric varices

OGD - Oesophagogastroduodenoscopy

EVL - Endoscopic variceal ligation

NSBB - Non selective beta blockers

CVP - central venous pressure

PTFE - polytetrafluoroethylene

TIPS - transjugular intrahepatic portosystemic shunt

BRTO - Balloon-occluded retrograde transvenous obliteration

EUS - Endoscopic ultrasound

Population




Outcome:

Abbreviations

Suspect variceal bleeding in any cirrhotic patient presenting

with hematemesis, melena,both or hematochezia


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Introduction

Investigations

Treatment

Variceal hemorrhage (VH) is the major cause of upper gastrointestinal

(UGI) bleeding in cirrhotic patients, accounting for 70% of cases. The

development of

one of the

major causes of mortality in cirrhotic patients. Mortality during the first

episode of variceal bleeding is estimated to 15–20%.

Complete Blood Counts, Liver Function Test, PT/INR, Renal Function

Test, Electrolytes, ECG, Oesophagogastroduodenoscopy (OGD)

Acute variceal hemorrhage (AVH) must be suspected in any cirrhotic

patient

presenting with upper acute GI bleeding (hematemesis/ melena or

both)and treatment should be started as soon as bleeding is clinically

confirmed, regardless of the lack of confirmation by upper endoscopy.

The gold standard for the diagnosis of variceal hemorrhage is

endoscopy. The diagnosis of VH is considered certain when active

bleeding from a varix is observed or when a sign of recent bleeding,

such as a “white nipple” is observed.

Initial resuscitation and management: follows the general ABC

(Airway, Breathing, Circulation) scheme and it is aimed at

maintaining an appropriate delivery of oxygen to the tissues.

l Place the patient on the side (left lateral decubitus).

l Extreme care of the airway should be maintained as the

patient is at high risk of bronchial aspiration of gastric

contents and blood.

l Endotracheal intubation is mandatory if there is any concern

about the safety of the airway.

l Pulse oximetry and oxygen administration are essential to

gastroesophageal varices(GEV) depends on the stage

of cirrhosis. In patients with compensated cirrhosis, GEV are present in

30%-40% of cases, whereas they can be present in up to 85% of patients

with decompensated cirrhosis. Acute variceal bleeding is

Diagnosis

1. General measures

2. Airway Protection

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maintain adequate blood oxygen saturation

To facilitate resuscitation at least two 16 guage cannulae should be

placed, large enough to allow rapid volume expansion.

l Volume expansion can usually be done with crystalloids. No

benefit has been demonstrated with the use of colloids

compared to crystalloids .

l Red blood cells are used to improve oxygen delivery to tissues in

case of severe anaemia.

l A restrictive transfusion strategy is adequate in most patients

with acute GI bleeding, with a hemoglobin threshold for

transfusion of 7 g/dl and a target range after transfusion of 7 to 9

g/dl. The threshold for transfusion may be higher in patients with

massive hemorrhage or in those with underlying conditions that

preclude an adequate physiological response to acute anemia

l Antibiotic prophylaxis is recommended in cirrhotic patients with

acute GI bleeding because it reduces the incidence of infections

and improves control of bleeding and survival.

l Treatment should be initiated on presentation of bleeding and

continued for up to 7 days.

l Ceftriaxone (1 g/24 h) is the first choice in patients with

decompensated cirrhosis, those already on quinolone

prophylaxis, and in hospital settings with high prevalence of

quinolone-resistant bacterial infections.

l Oral quinolones (Norfloxacin 400 mg b.i.d) should be used in the

remaining patients.

Terlipressin, somatostatin or octreotide should be initiated as soon

as AVH is suspected.

Starting vasoactive drugs before endoscopy decreases the

incidence of active bleeding during endoscopy and facilitates

endoscopic therapy, improving the control of bleeding and

potentially, survival. Terlipressin is the only agent shown to have

3. Obtain an IV access

4. Restore the circulation

5. Antibiotic prophylaxis

6.Vasoactive drugs


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survival benefit.

Vasoactive Agents Used in the Management of Acute Variceal

Hemorrhage

Drug Recommended Dose Duration

Initial 48 hours: 2mg IV every 4 hours until control of bleeding Maintenance: 1mg IV every 4 hours to prevent rebleeding

Terlipressin (VP

analogue) 2-5 days

Initial IV bolus of 50 micrograms (can be repeated in first hour if ongoing bleeding) Continuous IV infusion of 50 mcg/hr

Octreotide

(SMT analogue) 2-5 days

Initial IV bolus 250 mcg (can be repeated inthe first hour if ongoing bleeding) Continuous IV infusion of 250-500 mcg/h

2-5 days Somatostatin;

7.Endoscopy

8.Monitoring

Management of gastric varices

EGD should be performed as early as possible once the patient is

hemodynam ica l l y s t ab le . I f a va r i cea l sou rce i s

confirmed/suspected, EVL should be performed.

Endoscopic sclerotherapy can be done for patients with actively

bleeding varices, if EVL is not possible.

Ensure adequate intravascular volume by monitoring CVP and urine

output.

Urine output should be maintained at a minimum of 40 mL/h; an

output below 20 mL/h indicates poor renal function and impending

renal failure.

a) Endoscopic therapy with tissue adhesive (e.g. N-

butylcyanoacrylate) is recommended for acute bleeding from

isolated gastric varices (IGV) and gastroesophageal varices type

2 (GOV2). EUS guided combined coil and cyanoacrylate glue

injection appears to be highly effective for hemostasis.

b) Endoscopic variceal banding (EVL) or tissue adhesive can be

used in bleeding from gastroesophageal varices type 1 (GOV1).

c) TIPS or BRTO (Balloon Occluded Retrograde Transvenous

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Obliteration) is reserved for failures of endoscopic therapy.

a) Balloon tamponade due to high incidence of adverse events,

should only be used

in refractory esophageal variceal bleeding, as a temporary

''bridge'' (for a maximum of 24 hrs), until definitive treatment

can be instituted.

b) Use of self-expanding covered esophageal metal stents (SX-

ELLA Stent Danis) may be as efficacious and a safer option than

balloon tamponade in refractory esophageal variceal bleeding.

Refractory bleeding

Treatments for the Prevention of Recurrent Esophageal

Variceal Hemorrhage

Therapy Recommended Dose Therapy Goals Maintenance/Follow-up

l 20-40 mg orally

twice a day. l Adjust every 2-3

days until

treatment goal is

achieved. l Maximal daily

dose: 320

mg/day in patients

without ascites 160 mg/day in

patients with

ascites

l Start with 6.25 mg once a day

l After 3 days increase to 6.25 mg twice-daily

l Maximal dose: 12.5 mg/day (except in patients with persistent arterial hypertension)

l Resting heart

rate of 55-60

beats per minute l Systolic blood

pressure should

not decrease

<90 mm Hg

l Systolic arterial

blood pressure

should not

decrease <90

mm Hg

l At every

outpatient visit

make sure that

heart rate is on

target. l Continue

indefinitely

l Continue

indefinitely

Propranolol

Carvedilol


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Therapy Recommended Dose Therapy Goals Maintenance/Follow-up

l Every 1-4 weeks

until the

eradication of

varices

l Variceal

eradication (no

further ligation

possible)

l First EGD

performed 3-6

months after

eradication and

every 6-12

months thereafter

EVL

Management of treatment failures

Persistent bleeding despite combined pharmacological and endoscopic

therapy is best managed by PTFE-covered Transjugular intrahepatic

portosystemic shunt (TIPSS).

l Rebleeding during the first five days may be managed by a

second attempt at endoscopic therapy.

l The combination of either propranolol or carvedilol plus EVL is

recommended.

l First line therapy for all patients is the combination of Non

selective beta blocker (NSBB) + EVL.

l ·EVL should not be used as monotherapy unless there is

intolerance / contraindications to NSBB.

l NSBB should be used as monotherapy in patients with cirrhosis

who are unable or unwilling to be treated with EVL.

l NSBB should be started from day 6 of the index variceal bleed.

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Algorithm For The Management Of Upper Gi Bleeding In

Patients With Cirrhosis Due To Variceal Hemorrhage

References

1. de Franchis R; Baveno V Faculty. Expanding consensus in portal

hypertension. Report of the Baveno VI Consensus Workshop:

stratifying risk and individualizing care for portal hypertension. J

Hepatol 2015;63:743-752.

2. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal

hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and

management: 2016 practice guidance by the American Association

for the study of liver diseases. Hepatology. 2017;65(1):310–35.

https://doi. org/10.1002/hep.28906.


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Section 3HEPATIC ENCEPHALOPATHY(HE)

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of Hepatic encephalopathy in

cirrhosis




Early diagnosis of Hepatic encephalopathy with appropriate


HE - Hepatic encephalopathy

ALF - Acute liver failure

WHC - West Haven classification

MHE - Minimal Hepatic encephalopathy

OHE - Overt Hepatic encephalopathy

CHE - Covert Hepatic encephalopathy

BCAA - Branced chain amino acids

LOLA - L-ornitine L-aspartate

Suspect Hepatic encephalopathy in any cirrhotic patient

with altered mental status


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Introduction

Hepatic encephalopathy (HE) is a frequent and one of the most

debilitating manifestations of liver disease. HE is a brain dysfunction

caused by liver insufficiency and/or portosystemic shunting. It manifests

as a wide spectrum of neurological or psychiatric abnormalities ranging

from subclinical alterations to coma.

Hepatic encephalopathy should be classified according to all of the

following 4 factors

(1) According to the underlying disease, HE is subdivided into

Type A resulting from ALF

Type B resulting predominantly from portosystemic bypass

or shunting

Type C resulting from cirrhosis

(2) According to the severity of manifestations. The continuum

that is HE has been arbitrarily subdivided as in table(1)

(3) According to its time course, HE is subdivided into

a) Episodic HE

b) Recurrent HE denotes bouts of HE that occur within a

time interval of 6 months or less.

c) Persistent HE denotes a pattern of behavioral a

lterations that are always present and interspersed

with relapses of overt HE

(4) According to the existence of precipitating factors, HE is

subdivided into

a) Non precipitated

b) Precipitated, and the precipitating factors should be

specified. Precipitating factors can be identified in

nearly all bouts of episodic HE type C and should

beactively sought and treated when found

Classification

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Table 1

Diagnosis and Investigation

The diagnosis of Overt HE (OHE) is based on a clinical examination and

a

The diagnosis and grading of MHE and CHE can be made using several

neurophysiological and psychometric tests. Increased blood ammonia

alone does not add any diagnostic, staging, or prognostic value for

HE in patients with CLD. A normal value calls for diagnostic reevaluation.

clinical decision. Diagnosing cognitive dysfunction can be established

from clinical observation as well as neuropsychological or

neurophysiological tests. OHE still remains a diagnosis of exclusion

.Therefore, as clinically indicated, exclusion of other etiologies by

laboratory and radiological assessment for a patient with altered

mental status in HE is warranted.

Minimal hepatic encephalopathy and Covert HE (CHE) is defined as the

presence of test-dependent or clinical signs of brain dysfunction in

patients with CLD who are not disoriented or display asterixis.


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Management

Identification of precipitating factors and their correction.

Commencement of empirical HE treatment.

1. Lactulose or Lactitol is the first choice for treatment of

episodic OHE. Dosing initiated with 25 mL of

lactulose/lactitol syrup every 1-2 hrs until at least two soft

bowel movements per day are produced. Subsequently,

the dosing is titrated to maintain two to three bowel

movements per day.In patients who cannot take orally

(grade 3 or 4 OHE), lactulose should be given via

nasogastric (NG) tube or as enema.

2. Rifaximin is an effective add-on therapy to lactulose for

prevention of OHE

3. Oral Branched chain amino acids (BCAAs) can be used as

an additional agent to treat patients non responsive to

conventional therapy. Dose- 0.25g/Kg/Day

4. IV L-ornithine L-aspartate(LOLA) can be used as an

alternative or additional agent to treat patients

nonresponsive to conventional therapy. L -ornithine-L-

aspartate 20 g dissolved in 250 mL of 5% dextrose water and

infused intravenously for four hours a day for five consecutive

days .

Daily energy intakes should be 35-40 kcal/kg of ideal body

weight.

Daily protein intake should be 1.2-1.5 g/kg/day.

Small meals or liquid nutritional supplements evenly distributed

throughout the day and a late-night snack should be offered.

Lactulose is recommended for prevention of recurrent episodes

of HE after the initial episode.

Rifaximin as an add-on to lactulose is recommended for

Specific Approach to Overt hepatic encephalopathy

Treatment

Nutrition

Prevention

recurrence. Dose - 1200 mg/day in 2 or

3 divided doses

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prevention of recurrent episodes of HE after the second episode.


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Start lactulose NG tube or

enema

Improvement

Continue lactulose Add rifaximin for

maintenance

No improvement Reevaluate diagnosis and

precipitant

Ensure adequate stooling

Consider CT Head/EEG

Add Rifaximin

No improvement

evaluate for large portosystemic

shunt

Shunt+

Shunt embolization

Add LOLA

BCAA

Zinc

HE grade 3-4

Airway protection

Mechanical ventillation

Identify and treat precipitant

References

1. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice

Guideline by the European Association for the Study of the Liver and

the American Association for the Study of Liver Diseases. J Hepatol

(2014), http://dx.doi.org/10.1016/j.jhep.2014.05.042

2. Management of Hepatic Encephalopathy in the Hospital. Leise,

Michael D. et al.Mayo Clinic Proceedings , Volume 89 , Issue 2 , 241 –

253

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Section 4HEPATO RENAL SYNDROME(HRS)

IN CIRRHOSIS

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of Hepatorenal syndrome in cirrhosis




Early diagnosis of Hepatorenal syndrome with appropriate


AKI - Acute Kidney injury

AKD - Acute kidney disease

CKD - Chronic kidney disease

HRS - Hepatorenal syndrome

GFR - Glomerular filtration rate

ATN - Acute tubular necrosis

ICA - International club of ascites

NAKI - Non-AKI Kidney injury

ACE-I - Angiotensin converting enzyme inhibitors

ARB - Angiotensin receptor blockers

MAP - Mean arterial pressure

RRT - Renal replacement therapy


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Definitions of Kidney Disease

Definition of HRS

Diagnostic criteria for hrs in cirrhosis according to ICA- AKI

The concept that HRS is only a functional injury has been challenged

during the last decade and, thus the definition of HRS has to be

revised. In addition, as kidney biopsy is rarely performed in the setting

of AKI in clinical practice, the distinction between HRS-AKI and ATN is

difficult.In the recent revised ICA (international club of ascites)

classification, type 1 HRS now corresponds to HRS-AKI.

Consequently, type 2 HRS should now include renal impairment which

fulfills the criteria of HRS but not of AKI, namely non-AKI-HRS (NAKI).

1. Diagnosis of cirrhosis with ascites 2. Diagnosis of AKI according to ICA-AKI criteria. AKI is defined as the

increase of serum creatinine of at least 0.3mg/dl within 48hr and /or

≥50% from baseline which is known, or presumed, to have

occurred with in the prior 7 days. 3. No response after 2 consecutive days of diuretic withdrawal and

plasma volume expansion with adequate dose of albumin 4. Absence of shock 5. No current or recent use of nephrotoxic drugs (NSAIDS,

aminoglycosides, etc)6. No macroscopic signs of structural kidney injury , defined as

absence of proteinuria (> 500 mg/ day), absence of microhematuria

(> 50 RBCs /hpf) and normal findings on renal ultrasound.

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Treatment Strategies

1) Stop all nephrotoxic agents (ACEIs, ARBs, NSAIDs, diuretics)

2) Antibiotics for infections

3) IV albumin solution (20%) should be used at the dose 20–40 g/day.

Ideally, apart from routinely monitoring patients with HRS-AKI, the

serial measurement of CVP or other measures of assessing central

blood volume, can help to prevent circulatory overload by optimising

the fluid balance and helping to titrate the dose of albumin.

4) Vasoconstrictors and albumin are recommended in all patients

meeting the current definition of AKI-HRS stage should be

expeditiously treated with vasoconstrictors and albumin

Vasopressor therapy (in addition to albumin):

a) Terlipressin—start at 1 mg IV every 4-6 hr and increase

upto 2 mg IV every 4 hr if baseline serum creatinine level

HRS diagnosed

Start IV albumin+

Terlipressin/norepinephrine/midodrine+octreotide

Specific Treatment

Work for livertransplantation

up

Treatment S Cr within 0.3 mg/dl from

the baseline value

responded :final Treatment SCr >0.3 mg/dl from the

baseline value

not responded : final


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does not improve by 25% at day 2 of therapy

OR

b) Norepinephrine—0.1-0.7 μg/kg/min as an IV infusion.

Increase by 0.05 μg/kg/min every 4 hr and titrate to an MAP

increase of at least 10 mm Hg.Duration of vasopressor

treatment is generally a maximum of 2 weeks until reversal of

hepatorenal syndrome or liver transplantation

OR

c) Midodrine and octreotide—begin midodrine at 2.5-5 mg

orally 3 times daily and increase to a maximum dose of 15

mg 3 times daily. Titrate to an MAP increase of at least 15 mm

Hg; begin octreotide at 100 μg subcutaneously 3 times daily

and increase to a maximum dose of 200 μg subcutaneously 3

times daily, or begin octreotide at a 25-μg IV bolus and

continue at a rate of 25 μg/hr

Midodrine plus octreotide can be an option only when terlipressin or

noradrenaline are unavailable, but its efficacy is much lower than that of

terlipressin

For the duration of treatment, it is important to closely monitor the

patients. According to the type and severity of side effects, treatment

should be modified or discontinued

In cases of recurrence of HRS-AKI upon treatment cessation, a repeat

course of therapy should be given

According to the new definition of HRS-AKI, complete response to the

treatment should be defined by a final serum creatinine (SCr) within 0.3

mg/dl from the baseline value, while partial response should be defined

by the regression of AKI stage to a final serum creatinine SCr ≥0.3 mg/dl

from the baseline value.

There is insufficient data to advocate TIPS in HRS-AKI but it could be

suggested in selected patients with non-AKI- HRS

Liver transplantation is the best therapeutic option for patients with HRS

regardless of the response to drug therapy

The decision to initiate RRT should be based on the individual severity of

Response to the treatment

Treatment of non responders

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illness

The indication for liver-kidney transplantation remains controversial. This

procedure should be considered in patients with significant CKD or with

sustained AKI including HRS-AKI with no response to drug therapy

IV Albumin should be given in patients with SBP to prevent AKI

Norfloxacin (400mg/day) should be given as prophylaxis of SBP to

prevent HRS-AKI

1. The European Association for the Study of the Liver. EASL Clinical

Practice Guidelines for the management of patients with

d e c o m p e n s a t e d c i r r h o s i s . J H e p a t o l ( 2 0 1 8 ) ,

https://doi.org/10.1016/j.jhep.2018.03.024

2. EASL clinical practice guidelines on the management of ascites,

spontaneous bacterial peritonitis, and hepatorenal syndrome in

cirrhosis. J Hepatol 2010;53:397–417.

Prevention of HRS-AKI

References


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Section 5 ACUTE LIVER FAILURE

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of Acute liver failure




Early diagnosis of Acute liver failure with appropriate management

and reduction in mortality and morbidity.

ALF - Acute liver failure

ALI - Acute liver injury

Ltx - Liver transplantation

PEEP - Positive end-expiratory pressure

LDH - Lactate dehydrogenase

ANA - anti nuclear antibody

ASTHMA - Anti smooth muscle antibody

RRT - Renal replacement therapy

INR - International normalised ratio

PT - Prothrombin time


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Introduction

Acute liver failure (ALF) is a rare condition in which rapid deterioration of

liver function results in altered mentation and coagulopathy in individuals

without known preexisting liver disease. Acute liver failure often affects

young persons and carries a high morbidity and mortality

Evidence of coagulation abnormality, usually an International

Normalized Ratio (INR) >1.5, and any degree of mental alteration

(encephalopathy) in a patient without preexisting cirrhosis and with

an illness of <26 weeks duration.

Patients with Wilson disease, vertically-acquired hepatitis B virus

(HBV), or autoimmune hepatitis may be included in spite of the

possibility of cirrhosis if their disease has only been recognized

for <26 weeks.

1. In patients with severe ALI, screen intensively for any signs of

hepatic encephalopathy.

2. Exclude the presence of cirrhosis, alcohol induced liver injury

or malignant infiltration of the liver. Patients with extensive

malignant infiltration of the liver are not candidates for LTx.

3. Consider whether the pat ient does not have

contraindications for emergency LTx: the finding of

contraindications should not preclude transfer to a tertiary

unit.

4. Searching for an etiology allows treatment to be instituted

and facilitates prognostic stratification.

5. Transfer to a specialized unit early if the patient has an INR

>1.5 and onset of hepatic encephalopathy or other poor

prognostic features.

Diagnosis of ALF

Immediate measures at presentation of patients with ALF to

medical care.

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Summary of medical management strategy in patients with

acute liver failure

Patient's position

Prop-up 30 degree with neck in neutral position

Avoid: Sudden change in position

Head rotation

Head flexion

Heavy chest physiotherapy

Frequent endotracheal suctioning

N-acetylcysteine in patients with early

encephalopathy

Tenofovir/Entecavir/Lamivudine in case of HBV-

induced ALF. (Entecavir can cause lactic

acidosis)

Respiratory failure, advanced HE (grade ≥III)

and severe agitation

Prefer low tidal volume, low PEEP, higher

respiratory rates to maintain Pco2 between 34

and 41 mmHg

Avoid both hypoglycemia and hyperglycemia

Enteral route preferred

Feed should be dense ca lor ic and

isohyperosmolal Caloric goals 35–40

kcal/kg/day & Protein 1.2-1.5 g/kg/day

Avoid over- or underhydration. Correct

electrolyte imbalance, especially hyponatremia

Consider continuous RRT in the presence of

worsening renal dysfunction, academia and

fluid overload

Recommended for hypotension

Target mean arterial pressure: >60 mmHg

Norepinephrine is preferred over dopamine

Avoid adrenaline and vassopressin

Specific agents

Indications for endotracheal intubation

Mechanical ventilationstrategy

Blood sugarmanagement

Nutrition

Fluid and electrolyte balance

Renal replacement

therapy (RRT)

Vasopressors therapy


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Infection control/

treatment

Daily surveillance for infection and treat

a c c o r d i n g l y. C o n s i d e r p r o p h y l a c t i c

broadspectrum antibiotics in case of worsening

encephalopathy, hemodynamic instability or

systemic inflammatory response syndrome

I.V. mannitol or Hypertonic saline

In refractory cases: consider moderate

h y p o t h e r m i a , h y p e r v e n t i l a t i o n o r

phenobarbitone

Use propofol to reduce agitation and provide

antiseizure effect

Control pain with short-acting agent such as

fentanyl

Except for Vitamin K injection, prophylactic

c o r r e c t i o n c o a g u l o p a t h y a n d

thrombocytopenia is not required .

Corrections are required in the presence of

significant bleeding or before placement of

invasive devices

Fresh frozen plasma and platelet transfusion

should be used

Use cryoprecipitate in the presence of

hypofibrinogenemia

Use stress ulcer prophylaxis with proton pump

inhibitor

Management of

cerebral edema

Management of

coagulopathy

Management

I. Clinical assessment at admission

1) Search for an etiology:

a) Use of medication (ask specifically for paracetamol and

paracetamol containing compounds), herbal medicine

and food supplements <6 month, Rodenticide

poisoning

b) Substance abuse

c) History of suicidal attempt/depression

d) Gastrointestinal complaints after mushroom ingestion

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a) Pregnancy

b) Travelling in viral hepatitis endemic areas (HBV, HEV)

c) In receipt of immunosuppressive or chemotherapy

d) History of autoimmune disease

a) History of a chronic liver disease

b) Active and dependent alcohol or substance misuse

(individualised decision making)

c) History of cancer in recent past (specialist input

required)

d) Severe congestive heart disease or respiratory co-

morbidity

a) PT, INR and coagulation screen including fibrinogen

b) Liver blood tests including LDH and conjugated and

unconjugated bilirubin and creatinine kinase

c) Assessment of renal function: urine output: hourly.

d) Arterial blood gas and lactate

e) Arterial ammonia

a) Toxicology screen in urine and paracetamol serum level

b) Serological screen for virus infections

l HBsAg, anti-HBc IgM (HBV DNA), delta if positive for

HBV

l anti HAV IgM , anti-HEV IgM

l Serology for other rare viruses in appropriate clinical

situations

c) Autoimmune markers: ANA, ASMA, anti-soluble liver

antigen, globulin profile- in appropriate situations

d) Wilson's disease work up

Lipase or amylase

2) Conditions permissive for ALF:

3) Conditions that may impact upon decision in respect to

emergency LTx:

1) For assessing the severity of the disease:

2) For etiology:

3) For testing for complications:

II. Laboratory analysis at admission.


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III. Diagnostic procedures, monitoring and standard care at

admission.

1) Diagnostic tests:

2) Routine monitoring:

3) Standard care:

4) Preventative measures:

5) In case of hepatic encephalopathy:

l Cultures (respiratory, blood, urine)

l Chest X-ray/ECG/liver ultrasonography: axial imaging

of the abdomen and chest may also be required

l CT( Brain)- if clinically indicated

l Oxygen saturation, blood pressure, heart rate

respiratory rate, hourly urine output

l Clinical neurological status

l Glucose infusions (10–20%): glycemic target ± 140

mg/dl, Na 135–145 mmol/L

l Stress ulcer prophylaxis

l Restrict clotting factors unless active bleeding

l N-acetylcysteine in the early stage, even in non-

paracetamol cases

Dose- Paracetamol poisoning: 150mg/Kg IV in 200ml

5%Dextrose over 1 hr followed by 50mg/Kg in 500ml

5%Dextrose over 4 hrs, followed by 100mg/Kg in 1L

5%Dextrose over 16 hrs

Non-acetaminophen induced ALF-initial loading dose

of 150mg/kg over 1 hr followed by 12.5 mg/kg/hr for 4

hrs and continuous infusion of 6.25mg/kg/hr for

remaining 67 hrs

l Avoid sedatives

l Avoid hepatotoxic and nephrotoxic drugs

l Transfer to an appropriate level of care (ideally critical

care) at the first symptoms of mental alterations

l Keep the patient in quiet surrounding, with head of bed

>30 degree elevated, intubate, ventilate and sedate if

progression to > grade 3 coma.

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l Low threshold for starting empirical antibiotics if

hemodynamic deterioration and/or increasing

encephalopathy.

l In case of evolving HE, intubation and sedation prior to

the transfer

l Ensure volume repletion and normalize biochemical

variables (Na, Mg, PO4, K)

(any of the following)

l Most patients are volume depleted at presentation and

require crystalloid volume resuscitation

l Persistent hypotension requires critical care management,

with application of vasopressive agents guided by

appropriate monitoring techniques. Norepinephrine is the

vasopressor of choice. Volume overload should be avoided.

l Hypoxic hepatitis will require consideration of inotropic

agents.

l Standard sedation and lung protective ventilator techniques

should be utilised in patients with ALF.

l Avoid of excessive hyper or hypocarbia . CO2 target levels

between 4.5 and 5.5 kPa (34–41 mmHg)

l Regular chest physiotherapy should be carried out and

ventilator associated pneumonia avoided.

l Patients with ALF have increased resting energy

expenditure. Therefore, enteral or parenteral nutrition are

warranted.

IV. Suggested criteria for referral of cases of alf to specialist units

a) Cardiovascular management

b) Respiratory management

c) Gastrointestinal management

V. Organ specific Management


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l Avoid nasogastric feeding in those with progressive

encephalopathy.

l Monitor ammonia when instituting enteral nutrition.

l PPI administration should be balanced against the risk of

ventilator associated pneumonia and Clostridium difficile

infection.

l Consider stopping PPI when enteral feeding has been

established.

l Hypoglycemia is common in patients with ALF, is associated

with increased mortality and needs to be corrected avoiding

hyperglycemia. Avoid 5% Dextrose. 10% or 20% Dextrose

has to be used.

l Hyponatremia is detrimental to outcome and should be

corrected to maintain serum Na (140–150 mmol/L).

l Lactate elevation is related to increased production and

decreased clearance, and remains a poor prognostic

marker.

l RRT is indicated to correct acidosis and metabolic

disturbances.

l Early institution of extracorporeal support (RRT) should be

considered for persistent hyperammonaemia, control of

hyponatraemia and other metabolic abnormalities, fluid

balance and potentially temperature control.

l Continuous RRT should always be undertaken in the

critically ill patient with ALF as opposed to intermittent

haemodialysis.

l The routine use of fresh frozen plasma and other coagulation

factors is not supported, and should be limited to specific

situations, such as insertion of ICP monitors or active

bleeding.

l Haemoglobin target for transfusion is 7 g/dl.

l Venous thrombosis prophylaxis should be considered in the

d) Metabolic management

e) Acute kidney injury and renal replacement therapy

f) Coagulation: Monitoring and management

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daily review.

l Prophylactic antibiotics, non-absorbable antibiotics, and

antifungal have not been shown to improve survival in ALF.

l Regular periodic surveillance cultures should be performed

in all patients with ALF.

l Early anti-infection treatments according to local

antibiogram should be introduced upon appearance of

progression of hepatic encephalopathy, clinical signs of

infections, or elements of SIRS.

l Antifungal therapy in those with prolonged critical care

support for multiple organ failure may be considered

l Patients with low grade encephalopathy should be

frequently evaluated for signs of worsening encephalopathy.

l In patients with grade 3 or 4 encephalopathy, intubation

should be undertaken to provide a safe environment and

prevention of aspiration. Regular evaluation for signs of

intracranial hypertension should be performed.

l Mannitol or hypertonic saline should be administered for

surges of ICP with consideration for short-term

hyperventilation.

l Mild hypothermia and indomethacin may be considered in

uncontrolled ICH.

l Liver support systems (biological or adsorbent) should only

be used in the context of randomised controlled trials.

l Plasma exchange may be of greater benefit in patients who

are treated early (within first 3 days of admission) and who

will not ultimately undergo liver transplantation.

l Development of encephalopathy is of key prognostic

importance, with onset indicating critically impaired liver

function.

l Transplantation should be considered in those patients fulfilling

g) Sepsis, inflammation and anti-inflammatory management

h) Neurological management

VI. Artificial and bioartificial liver devices

VII. Liver transplantation (LTx)


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Kings College criteria.

1) Arterial pH <7.3 after resuscitation and >24 h since ingestion

2) Lactate >3 mmol/L or

3) All of The 3 following criteria:

I) Hepatic encephalopathy >grade 3

ii) Serum creatinine >3.4mg/dl

iii) INR >6.5

1) INR >6.5 or

2) 3 out of 5 following criteria:

i. Aetiology: indeterminate aetiology ,drug-induced hepatitis

ii. Age <10 years or >40 years

iii. Interval from jaundice to encephalopathy >7 days

iv. Bilirubin >17.5mg/dl

v. INR >3.5

l Assessment of patients with ALF for emergency LTx

requires input from a multidisciplinary team with

appropriate experience in this process.

l Patients with ALF, potential for deterioration and who

may be candidates for LTx, should be transferred to

specialist units before the onset of HE to facilitate

assessment.

l Patients with ALF listed for LTx should be afforded the

highest priority for donated organs.

l Irreversible brain injury is a contraindication to

proceeding with LTx .

l Patients transplanted for acute HBV infection need

ongoing therapy for suppression of viral replication

1. European Association for the Study of the Liver. EASL Clinical

Practical Guidelines on the management of acute (fulminant) liver

failure. J Hepatol 2017;66

2. Lee WM, Larson AM, Stravitz RT. AASLD position paper: The

Criteria for emergency liver transplantation King's College criteria

ALF due to paracetamol

ALF not due to paracetamol

References

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management of acute liver failure: Update 2011. Association for

the Study of Liver Diseases website.

http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFail

ureUpdate2011.pdf. Published 2011.

3. Nabi T, Nabi S, Rafiq N, Shah A: Role of N-acetylcysteine

treatment in nonacetaminophen-induced acute liver failure: A

prospective study. Saudi J Gastroenterol, 2017; 23(3): 169–75


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Section 6HEPATOCELLULAR CARCINOMA (HCC)

IN CIRRHOSIS

Scope


population

Diagnosis and management of Hepatocellular carcinoma in

Cirrhosis




Early diagnosis of Hepatocellular carcinoma in cirrhosis with

appropriate management

HCC - Hepatocellular carcinoma

APHE - Arterial phase hyperenhancement

LI-RADS - Liver imaging Reporting and data system

AFP - Alpha fetoprotein

DCP - Des-gamma carboxyprothrombin

SVR - Sustained Virological Response

BCLC - Barcelona clinic Liver cancer

ECOG - Eastern cooperative oncology group

RFA - Radiofrequency ablation

HVPG - Hepatic venous pressure gradient

TACE - Trans arterial chemo embolisation

TARE - Trans arterial radio embolisation

Population




Outcome:

Abbreviations


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Introduction

Diagnosis of HCC in a cirrhotic liver

Liver cancer is the fifth most common cancer and the second most

frequent cause of cancer-related death globally. Hepatocellular

carcinoma represents about 90% of primary liver cancers and

constitutes a major global health problem. Cirrhosis is an important risk

factor for HCC, and may be caused by chronic viral hepatitis, chronic

alcohol abuse, acquired and inherited metabolic diseases. All etiologic

forms of cirrhosis may be complicated by tumor formation, but the risk is

higher in patients with chronic viral hepatitis.

In cirrhotic patients, the diagnosis of HCC is often based on non-invasive

criteria as shown in the diagnostic algorithm (Fig. 1) and/or pathology.

Non-invasive criteria can only be applied to cirrhotic patients for

nodule(s) ≥ 1 cm and are based on imaging techniques obtained by

multiphasic CT, dynamic contrast-enhanced MRI. Diagnosis is based on

the identification of the typical radiological hallmarks of HCC,the

combination of arterial phase hyperenhancement [APHE] and washout

on portal venous and/or delayed phases on CT and MRI. CT and MR

exams should be performed, interpreted, and reported through its

CT/MRI Liver Imaging Reporting And Data System ( LI-RADS).

Biopsy of the lesion is indicated when the imaging based diagnosis

remains inconclusive, especially in lesions smaller than 2 cm in diameter

where the diagnostic performance of contrast-enhanced imaging is

lower. The diagnosis of liver cirrhosis might be difficult in some cases;

therefore in such cases, liver biopsy is recommended in the diagnostic

process for HCC as in non-cirrhotic patients.

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LI-RADS 5 Criteria

Size Criteria

≥ 20mm

APHE (nonrim) AND one or more of following: l “Washout” (nonperipheral) l Enhancing “capsule”

l Threshold growth- ≥ 50% in ≤ 6

months

APHE (nonrim) AND the following:

l “Washout” (nonperipheral)

l Enhancing “capsule”

l Threshold growth-≥ 50% in ≤ 6

months

APHE (nonrim)

AND “Washout” (nonperipheral)

APHE (nonrim)

AND threshold growth-≥ 50% in ≤ 6

months

10-19mm

Diagnosis of HCC in a non-cirrhotic liver

Surveillance

Imaging features of HCC developing in a non-cirrhotic liver are not

different from those in cirrhosis. HCC in non-cirrhotic livers tend to be

larger at diagnosis as patients are not enrolled in surveillance

programmes. Yet, the specificity of the imaging hallmarks (AHPE and

washout on portal venous and/or delayed phases) is lower than in

cirrhosis as alternative diagnoses are seen more commonly (e.g.

hepatocellular adenoma, and hypervascular metastases). Therefore, in

non-cirrhotic liver, imaging alone is not considered sufficient and

pathologic proof is required to establish the diagnosis of HCC.

Aim of surveillance is to obtain a reduction in HCC related mortality. This

is usually

achieved through a diagnosis of the disease at the early stage. Patients

at high risk of

developing HCC as in depicted(Table 1) should be entered into

surveillance programme. Surveillance should be performed using

abdominal ultrasound every six months. Tumour biomarkers (i.e.


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AFP or AFP-L3 or DCP) for accurate early HCC detection are

suboptimal, hence not used for routine surveillance.

Patients on the waiting list for liver transplantation should undergo

surveillance for HCC in order to detect and manage tumour occurrence

or tumour response, and to help define priority policies for

transplantation.

Surveillance should be offered to treated patients with chronic hepatitis

B who remain at risk of HCC development because of baseline factors,

or those with hepatitis C virus

(HCV)-induced advanced fibrosis or cirrhosis, even after achieving

SVR.

(Table 1)

Recommendations for HCC surveillance: Categories of adult

patients in whom surveillance is recommended.

Cirrhotic patients, Child-Pugh stage A and B.

Cirrhotic patients, Child-Pugh stage C awaiting liver transplantation.

Non-cirrhotic HBV patients at intermediate or high risk of *

HCC (according to PAGE-B classes for Caucasian subjects, respectively 10–17 and ≥18 score points).

*PAGE-B (Platelet, Age, Gender, hepatitis B) score

Non-cirrhotic F3 fibrosis patients, regardless of aetiology may be considered for surveillance based on an individual risk assessment

1

3

4

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Diagnostic algorithm and recall policy in cirrhotic liver

In patients at high risk of developing HCC, nodule(s) less than 1 cm in

diameter

detected by ultrasound should be followed at ≤ 4 month intervals in the

first year. If there is no increase in the size or number of nodules,

surveillance could be returned to the usual six-month interval thereafter.

Repeated biopsy sampling is recommended in cases of inconclusive

histological or discordant findings, or in cases of growth or change in

enhancement pattern identified during follow-up, but with imaging still

not diagnostic for HCC.

Cancer classification is intended to establish prognosis and enable the

selection of the adequate treatment for the best candidates.

Staging systems for clinical decision making in HCC should include

tumour burden, liver function and performance status.

The BCLC staging system (Fig. 3) has been repeatedly validated and

is recommended or prognostic prediction and treatment allocation.

Staging systems and treatment allocation


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Patients should be discussed in multidisciplinary teams to fully capture

and tailor individualised treatment options.

Fig 3 - Modified BCLC staging system and treatment strategy.

Outcome prediction and treatment allocation

Patients with HCC are classified into five stages (0, A, B, C and D)

according to pre-established prognostic variables, and therapies are

allocated according to treatment- related status. Prognosis prediction is

defined by variables related to tumour status (size,number, vascular

invasion, N1, M1), liver function (bilirubin, portal hypertension, liver

function preservation) and health status (ECOG).

is defined as the presence

of a

a).Single tumor <2 cm diameter

b). Without vascular invasion/satellites

c).Patients with good health status (ECOG-0) and

d). Well-preserved liver function (Child-Pugh A class).

Treatment options include either

1. radiofrequency ablation (RFA) /

2. hepatic resection.

Several cohort studies have reported five-year survival

beyond 70% after RFA in well - selected patients with very

Modified BCLC staging system

1. Very early HCC (BCLC stage 0):

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early HCC and resection and RFA are similar treatment

outcome. The only advantage of surgical resection would be

the opportunity to assess the risk of early recurrence by

pathology (microvascular invasion, poor differentiation or

presence of satellites). If a high risk of recurrence is detected

in the specimen, liver transplant might be indicated. If a

patient is not a candidate for liver transplant, RFA might

become the first-line option, leaving surgery for those

patients with nodules not suitable for RFA, or who fail

treatment.

:is defined in patients presenting

with

a).Single tumors >2cm or three nodules <3 cm in

diameter,

b).ECOG-0 and

c). Preserved liver function.

Median survival of patients with early HCC reaches 50% to

70% at five years after resection, liver transplantation or local

ablation in selected candidates.

Absence of clinically relevant portal hypertension (defined as

HVPG ≤10 mmHg) and normal bilirubin are key predictors

of survival in patients with single tumor undergoing

resection. Since liver transplantation may potentially cure

both the tumor and the underlying liver disease, variables

mostly related with HCC have been clearly established as

prognostic factors (single tumors ≤5 cm or three nodules ≤3 cm), defining the so-called Milan criteria.

include those patients

presenting with

a). Multinodular, unresectable tumor with

b). Preserved liver function and

c). ECOG-0.

Some of these proposals classify large solitary HCC beyond

5 cm with an expansive growth as intermediate-stage,

2. Early HCC (BCLC stage A)

3. Intermediate HCC (BCLC stage B):

TACE/TARE is considered the first-line treatment.


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although vascular invasion or tumor dissemination has to be

excluded with proper imaging evaluation. However, if

technically feasible they may

benefit from surgical resection, and these patients should be

classified as BCLC A. Child-Pugh A-B may include patients

with refractory ascites, and events such as spontaneous

bacterial peritonit is, hyponatremia or recurrent

encephalopathy, which predict poor outcome in the absence

of transplantation. In such instances, liver transplantation

should be considered and if HCC exceeds the accepted

criteria for the patient to be listed, then the patient must be

classified as BCLC D.

Patients with cancer-

related symptoms

a).Symptomatic tumors, ECOG 1-2),

b).Macrovascular invasion (either segmental or portal

invasion) or

c).Extrahepatic spread (lymph node involvement or

metastases)

They bear a poor prognosis, with expected median survival

times of 6–8 months.

Sorafenib – a multi- tyrosine kinase inhibitor is

considered the first-line treatment

in advanced HCC.

:

Patients with end-stage disease are characterized by very

poor

Performance status (Eastern Cooperative Oncology Group

3–4) that reflects a severe tumor-related disability. Their

median survival is 3–4 months or 11% at one year. Similarly,

Child-Pugh C patients with tumors beyond the

transplantation threshold also have a very poor prognosis.

They may be offered palliation.

4. Advanced HCC (BCLC stage C):

5. End-stage HCC

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Concept of treatment stage migration

Palliative and best supportive care

A proportion of patients in each stage do not fulfil all the criteria for

the treatment allocation. In these cases, the patient should be

offered the next most suitable option within the same stage or the

next prognostic stage.

Patients at BCLC D stage, who are not candidates for liver

transplantation should receive palliative support, including

management of pain, nutrition and psychological Support.

In HCC on cirrhosis, acetaminophen (paracetamol) up to 3 g/day can

be utilized for the management of pain of mild intensity.

Non-steroidal anti-inflammatory drugs should be avoided whenever

possible in patients with underlying cirrhosis.

Opioids can be utilised for the management of pain of intermediate or

severe intensity, paying attention to proactively avoid constipation.

Bone metastases causing pain or at significant risk of spontaneous

secondary fracture benefit from palliative radiotherapy.

Psycho-oncological support and adequate nutrition is

recommended according to patients condition.

Antiviral treatment is not only essential for preventing the incidence of

HCC in chronic hepatitis B patients, but also important for reducing HBV

reactivation, improving liver function, reducing or delaying HCC

recurrence, and prolonging overall survival of HBV-related HCC patients

after curative and palliative therapies. Hence antivirals has to be

continued even after HCC development in chronic hepatitis B patients.

1) European Association for the Study of the Liver. EASL Clinical

Practice Guidelines: Management of hepatocellular carcinoma. J

Hepatol 2018;69:182-236.

Antiviral therapies for hepatitis B virus-related hepatocellular

carcinoma

References


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Section 7ACUTE CHOLANGITIS

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of acute cholangitis




Diagnosis of acute cholangitis with appropriate management and

reduction in mortality and morbidity.

ULN - Upper limit of normal value

LLN - Lower limit of normal value

CBC - Complete blood counts


GGT - Gamma-glutamyl transpeptidase



APTT - Activated partial thromboplastin time

ABG - Arterial blood gas

MRCP - Magnetic resonance cholangiopancreatography

VRE - Vancomycin-resistant Enterococcus

TG - Tokyo guidelines


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Introduction

Diagnostic criteria for acute cholangitis

Acute cholangitis is a morbid condition with acute inflammation and

infection in the bile duct. It may cause a rapid deterioration in condition

due to sepsis, and prompt and appropriate treatment is therefore

required. Classical “Charcot triad” of Fever, abdominal pain and jaundice

may not be present in all setting.

A. Systemic inflammation

A-1. Fever and/or shaking chills

A-2. Laboratory data: evidence of inflammatory response

B. Cholestasis

B-1. Jaundice

B-2. Laboratory data: abnormal liver function tests

C. Imaging

C-1. Biliary dilatation

C-2. Evidence of the etiology on imaging (stricture, stone, stent

etc.)

Suspected diagnosis: One item in A + one item in either B or C

Definite diagnosis: One item in A, one item in B and one item in C

A-1 Body temp >38°C

A-2

or >10 Evidence of inflammatory response

WBC count (x 1000/μL) <4

CRP (mg/dL) ≥1

Fever

B-1 Jaundice Total Bili ≥2 (mg/dL)

B-2 Abnormal liver

function tests

ALP (IU) >1.5 x ULN

GGT (IU) >1.5 x ULN

AST (IU) >1.5 x ULN

ALT (IU) >1.5 x ULN

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Severity assessment criteria for acute cholangitis

The severity of acute cholangitis is classified as follows;

Grade III (severe): presence of organ dysfunction.

Grade II (moderate): risk of increased severity without early biliary

drainage.

Grade I (mild).

''Grade III'' acute cholangitis is defined as acute cholangitis

that is associated with the onset of dysfunction in at least one

of any of the following organs/systems:

1. Cardiovascular dysfunction Hypotension requiring

dopamine >5 mcg/kg per min,

or any dose of norepinephrine

2. Neuro log ica l dys funct ion Dis turbance o f

consciousness

3. Respiratory dysfunction PaO2/FiO2 ratio <300

4. Renal dysfunction Oliguria, serum creatinine >2.0

mg/dl

5. Hepatic dysfunction PT-INR >1.5

6. H e m a t o l o g i c a l d y s f u n c t i o n P l a t e l e t

count<100,000/mm 3

''Grade II'' acute cholangitis is associated with any two of the

following conditions:

1. Abnormal WBC count (>12,000/mm3,<4,000/mm 3)

2. High fever (>39 C )

3. Age (>75 years old )

4. Hyperbilirubinemia (total bilirubin >5 mg/dL )

5. Hypoalbuminemia (<LLN x 0.7)

''Grade I'' acute cholangitis does not meet the criteria of

''Grade III (severe)'' or

''Grade II (moderate)'' acute cholangitis at initial diagnosis.

CBC, ESR,CRP, Liver function test, GGT, PT/INR, APTT, Renal

Grade III (Severe) acute cholangitis

Grade II (moderate) acute cholangitis

Grade I (mild) acute cholangitis

Investigations


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Function test, Blood

Culture, ABG, Amylase , Lipase

Abdominal X-ray and abdominal US are carried out, followed by CT

scan,MRI, MRCP if required Blood culture and/or bile culture is

performed for Grade II (moderate) and III (severe) patients.

1) When acute cholangitis is suspected, diagnostic assessment is

made using diagnostic criteria every 6–12 h

2) Severity is repeatedly assessed using severity assessment criteria;

at diagnosis,within 24 h after diagnosis, and during the time zone of

24–48 h

3) As soon as a diagnosis has been made, the initial treatment is

provided.

The treatment is as follows:

1. Sufficient fluids replacement,

2. Electrolyte compensation, and

3. Intravenous administration of analgesics and

4. Antibiotics - Refer Table on Antimicrobial Therapy

Piperacillin/tazobactam- in all grades of community- acquired

acute cholangitis

Carbapenems- preferred in healthcare-associated acute biliary

infections

Anti-anaerobic therapy- Metronidazole or clindamycin, is

warranted if a biliary-enteric anastomosis is present.

Vancomycin is recommended to cover Enterococcus spp. for

grade III community acquired acute cholangitis and

healthcare-associated acute biliary infections.

Linezolid or daptomycin is recommended if Vancomycin-

resistant Enterococcus (VRE) is known to be colonizing the

patient or if previous treatment included vancomycin.

5 For patients with Grade I (mild), when no response to the initial

treatment is observed within 24 h, biliary tract drainage should be

carried out immediately

Management of acute cholangitis

Treatment

Biliary drainage

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6 For patients with Grade II (moderate), biliary tract drainage is

immediately performed along with the initial treatment. If early

drainage cannot be performed due to the lack of facilities or

skilled personnel, transfer of the patient is considered

7 For patients with Grade III (severe), urgent biliary tract

drainage is performed along with the initial treatment and

general supportive care. If urgent drainage cannot be performed

due to the lack of facilities or skilled personnel, transfer of the

patient to higher centre should be considered.

8 For patient with Grade III (severe), organ supports (non

invasive/invasive positive pressure ventilation, use of

vasopressors and antimicrobial agents, etc.) are immediately

performed

9 Treatment for etiology of acute cholangitis with endoscopic,

percutaneous, or operative intervention is considered once acute

illness has resolved. Cholecystectomy should be performed for

cholelithiasis after acute cholangitis has resolved.


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Antimicrobial Recommendations For Acute Biliary Infections

Community-acquired biliaryinfection

Grade I Cholangitis

Grade II Cholangitis

Grade III Cholangitis

Antimicrobial Agents

Piperacillin/tazobactam



Imipenem/cilastatin, meropenem, doripenem, ertapenem

Duration Of Antimicrobial Therapy

Community-acquired biliary infections

Healthcare-associated

biliary infections

Severity Grade 1/Grade II / Grade III Cholangitis

Duration of therapy

Once source of infection is controlled,duration of 4–7 days is recommended. If bacteremia with Gram-positive cocci such as Enterococcus spp.,Streptococcus spp. is present, minimum duration of 2 weeks is recommended

If bacteremia with Gram positive cocci such as Enterococcus spp., Streptococcus spp.is present, minimum duration of 2 weeks is recommended

Specific conditions

For extended

therapy

If residual stones or obstruction of the bile tract are present, treatment should be continued until these anatomical problems are resolved

References

1) Takada, T, Strasberg, SM, Solomkin, JS, Gomi, H, Yoshida,

M, Mayumi, T, et al. TG13: Updated Tokyo Guidelines for the

management of acute cholangitis and cholecystitis. J Hepatobiliary

Pancreat Sci. 2013; 20: 1– 7.

2) Kiriyama S, Kozaka K, Takada T, et al. Tokyo guidelines 2018:

diagnostic criteria and severity grading of acute cholangitis.

J Hepatobiliary Pancreat Sci 2018;25(1):17–30.

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Section 8ACUTE PANCREATITIS

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of acute pancreatitis




Diagnosis of acute pancreatitis with appropriate management and

reduction in mortality and morbidity.

AP - Acute pancreatitis

CECT - Contrast enhanced computerised tomography

MRI - Magnetic resonance tomography

MRCP - Magnetic resonance cholangiopancreatography

WON - Walled off necrosis

NJ - Nasojejunal

NG - Nasogastric

ERCP - Endoscopic retrograde cholangiopancreatography

TG - Triglycerides

FNA - Fine needle aspiration

CT-FNA - CT guided Fine needle aspiration

EUS - Endoscopic ultrasound


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Introduction

Diagnosis Of Acute Pancreatitis

Acute pancreatitis is best defined physiologically as an acute

inflammatory process of the pancreas with variable involvement of other

remote organ system

The diagnosis of acute pancreatitis requires two of the following three

features:

(1) Abdominal pain consistent with acute pancreatitis (acute onset

of a persistent, severe, epigastric pain often radiating to the

back)

(2) Serum lipase activity (or amylase activity) at least three times

greater than the upper limit of normal

(3) Characteristic findings of acute pancreatitis on contrast-

enhanced computed tomography (CECT) and less commonly

magnetic resonance imaging (MRI) or transabdominal

ultrasonography

Contrast-enhanced computed tomography (CECT) and / or magnetic

resonance imaging (MRI) of the pancreas should be reserved for

patients in whom the diagnosis is unclear or who fail to improve

clinically(e.g., persistent pain, fever, nausea, unable to begin oral

feeding), within the first 48 – 72 h after hospital admission or to evaluate

complications. MRCP has advantage of detecting small

choledocholithiasis.

1) Mild acute pancreatitis

No organ failure

No local or systemic complications

2) Moderately SAP

Transient organ failure (<48 hours) and/or

Local or systemic complicationsa without persistent organ failure

3) Severe acute pancreatitis

Persistent organ failure (>48 hours)––single organ or multiorgan

Severity of acute pancreatitis (2012 Atlanta classification revision of acute pancreatitis)

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Local complications are peripancreatic fluid collections, pancreatic

necrosis, and peripancreatic necrosis (sterile or infected), pseudocyst,

and WON (sterile or infected).

Three organ systems should be assessed to define organ failure:

respiratory, cardiovascular and renal. Organ failure is defined as a score

of 2 or more for one of these three organ systems using the modified

Marshall scoring system (table 1).

(Table 1)

Definition of organ failure


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Algorithm for the management of acute pancreatitis at various

stages in its course.

BUN, blood urea nitrogen; ICU, intensive care unit; NG,

nasogastric; NJ, nasojejunal; TG, triglycerides.

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Management

Initial Management

ERCP IN AP

The Role of Antibiotics in AP

1. Aggressive hydration, defined as 250 ml per hour of isotonic

crystalloid solution should be provided to all patients with acute

pancreatitis, unless cardiovascular, renal, or other related

comorbid factors exist. Early aggressive intravenous hydration

is most beneficial during the first 12 – 24 hr.

2. In a patient with severe volume depletion, more rapid repletion

as IV bolus may be needed.

3. Lactated Ringers solution may be the preferred isotonic

crystalloid replacement fluid .

4. Fluid requirements should be reassessed at frequent intervals

within 6 h of admission and for the next 24 – 48 h.

1. Patients with gallstone pancreatitis and concurrent acute

cholangitis or impacted stone should undergo ERCP within

24hrs of admission .

2. In the absence of cholangitis and / or jaundice, MRCP or EUS

rather than diagnostic ERCP should be used to screen for

choledocholithiasis .

3. Pancreatic duct stents and / or post-procedure rectal

nonsteroidal anti-infl ammatory drug (NSAID) suppositories

should be utilized to lower the risk of severe post-ERCP

pancreatitis in high-risk patients .

1. Antibiotics should be given for an extrapancreatic infection, such

as cholangitis, catheter-acquired infections, bacteremia, urinary

tract infections, pneumonia .

2. Routine use of prophylactic antibiotics in patients with severe AP

is not recommended.

3. The use of antibiotics in patients with sterile necrosis to prevent

the development of infected necrosis is not recommended.

4. Infected necrosis should be considered in patients with

pancreatic or extrapancreatic necrosis who deteriorate or fail to

improve after 7 – 10 days of hospitalization. In these patients,


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either (i) initial CT-guided fine-needle aspiration (FNA) for Gram

stain and culture to guide use of appropriate antibiotics or (ii)

empiric use of antibiotics after obtaining necessary cultures for

infectious agents, without CT FNA, should be given.

5. In patients with infected necrosis, antibiotics known to penetrate

pancreatic necrosis, such as carbapenems, quinolones, and

metronidazole, may be useful in delaying or sometimes totally

avoiding intervention, thus decreasing morbidity and mortality.

1. In mild AP, oral feedings can be started immediately if there is no

nausea and vomiting, and the abdominal pain has resolved.

2. In severe AP, enteral nutrition is recommended to prevent

infectious complications. Parenteral nutrition should be

avoided, unless the enteral route is not available, not tolerated,

or not meeting caloric requirements .

3. Nasogastric delivery and nasojejunal delivery of enteral feeding

appear equally efficacious .

1. In patients with mild AP, found to have gallstones in the

gallbladder, a cholecystectomy should be performed before

discharge to prevent a recurrence of AP.

2. In a patient with necrotizing biliary AP, in order to prevent

infection, cholecystectomy is to be deferred until active

inflammation subsides and fluid collections resolve or stabilize.

3. Asymptomatic pseudocysts and pancreatic and / or

extrapancreatic necrosis do not warrant intervention regardless

of size, location, and / or extension.

4. In stable patients with infected necrosis, surgical, radiologic, and

/ or endoscopic drainage should be delayed preferably for more

than 4 weeks to allow liquefication of the contents and the

development of a fibrous wall around the necrosis (walled-off

necrosis).

5. In symptomatic patients with infected necrosis, minimally

invasive methods of necrosectomy are preferred to open

necrosectomy.

Nutrition in AP

The role of surgery in AP

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References

1)

2)

3)

Banks PA, Bollen TL, Dervenis C et al. Classification of acute

pancreati tis—2012: revision of Atlanta classification and

definitions by international consensus. Gut 2013;62:102–11.

Tenner S, Baillie J, DeWitt J, Vege SS. American College of

Gastroenterology guideline: management of acute pancreatitis. Am

J Gastroenterol 2015; 108:1400–1415.

Sleisenger and Fordtran's gastrointestinal and liver disease

pathophysiology, diagnosis, management. 10th edition


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Section 9PEPTIC ULCER BLEEDING

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of peptic ulcer bleeding




Diagnosis of peptic ulcer bleeding with appropriate management


UGIB - Upper gastrointestinal bleed

PUD - Peptic ulcer bleed

NG - Nasogastric

PPI -

H RA -2

SRH - stigmata of recent hemorrhage

CV - Cardiovascular

COX - Cyclooxygenase

NSAID-

Proton pump inhibitor.

Histamine-2 receptor antagonist

non-steroidal anti-inflammatory drug

Suspect Peptic ulcer bleed in any patient,with previous history/

symptoms of PUD or frequent NSAID use, presenting with upper

GI bleeding


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1. Initial assessment and risk stratification

2. Pre-endoscopic medical therapy.

l Hemodynamic status should be assessed immediately upon

presentation and resuscitative measures begun as needed.

l Blood transfusions should target hemoglobin ≥ 7 g/ dl, with higher

hemoglobin targeted in patients with clinical evidence of

intravascular volume depletion or comorbidities such as coronary

artery disease .

l Risk assessment should be performed to stratify patients into higher

and lower risk categories.

l Pre-endoscopic intravenous proton pump inhibitor (e.g., 80 mg

bolus followed by 8 mg / h infusion) may be considered to

decrease the proportion of patients who have higher risk stigmata

of hemorrhage at endoscopy and who receive endoscopic

therapy.

l If endoscopy will be delayed or cannot be performed, intravenous

PPI is recommended to reduce further bleeding.

NG or orogastric lavage is not required in patients with UGIB for

diagnosis, prognosis, visualization, or therapeutic effect.

Patients with UGIB should generally undergo endoscopy as early

Rockall Scoring System for Upper GI Tract Bleeding

a) Proton pump inhibitor therapy

b) Gastric lavage

c) Timing of endoscopy

l

l

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as possible, following resuscitative efforts to optimize

hemodynamic parameters and other medical problems.

Clinical algorithm for the management of peptic ulcer bleeding

3. Endoscopic management of ulcer bleed

Endoscopic diagnosis of ulcer and stigmata of recent hemorrhage

Stigmata of recent hemorrhage (SRH) should be recorded as they

predict risk of further bleeding and guide management decisions.

The stigmata, in descending risk of further bleeding, are active

spurting, non-bleeding visible vessel, active oozing, adherent clot,

flat pigmented spot, and clean base .


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Forrest classification of peptic ulcer bleed

Forrest classification

Active spurting bleeding 1 A

Active oozing bleeding 1B

Non-bleeding visible vessel 11A

Adherent clot 11B

Flat pigmented spot 11C

Clean base 111

l Endoscopic therapy should be provided to patients with

active spurting or oozing bleeding or a non-bleeding visible

vessel. Endoscopic therapy may be considered for patients

with an adherent clot resistant to vigorous irrigation.

l Endoscopic therapy should not be provided to patients who

have an ulcer with a clean base or a flat pigmented spot.

l Epinephrine therapy should not be used alone. If used, it

should be combined with a second modality.

l Thermal therapy with bipolar electrocoagulation or heater

probe and injection of sclerosant are recommended because

they decrease further bleeding, need for surgery, and

mortality.

l Clips are recommended because they appear to decrease

further bleeding and need for surgery

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4. Medical therapy after endoscopy

5. Repeat endoscopy

6. Hospitalization for patients with UGIB

l After successful endoscopic hemostasis, intravenous PPI therapy

with 80 mg bolus followed by 8 mg / h continuous infusion for 72 hr.

should be given to patients who have an ulcer with active bleeding, a

non-bleeding visible vessel, or an adherent clot.

l Patients with ulcers that have flat pigmented spots or clean bases

can receive standard PPI therapy (e.g., oral PPI once-daily).

l Repeat endoscopy should be performed in patients with clinical

evidence of recurrent bleeding and hemostatic therapy should be

applied in those with high risk stigmata of hemorrhage.

l If further bleeding occurs after a second endoscopic therapeutic

session, surgery or interventional radiology with transcathether

arterial embolization is generally employed.

l Patients with high-risk stigmata (active bleeding, visible vessels,

clots) should generally be hospitalized for 3 days to monitor

rebleeding .

l Patients with clean-based ulcers may receive a regular diet and be

discharged after endoscopy once they are hemodynamically stable.

Long term prevention of recurrent bleeding ulcers

l Patients with H. pylori-associated bleeding ulcers should receive H.

pylori therapy. After documentation of eradication, maintenance ant

secretory therapy is not needed unless the patient also requires non-

steroidal anti-inflammatory drugs (NSAIDs) or antithrombotics .

l In patients with NSAID-associated bleeding ulcers, the need for


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NSAIDs should be carefully assessed and NSAIDs should not be

resumed if possible. In patients who must resume NSAIDs, a COX-

2-selective NSAID at the lowest effective dose plus daily PPI is

recommended.

l In patients with low-dose aspirin-associated bleeding ulcers, the

need for aspirin should be assessed. If given for secondary

prevention (i.e., established cardiovascular disease) then aspirin

should be resumed as soon as possible after bleeding ceases

ideally within 1–3 days and certainly within 7 days. Long-term daily

PPI therapy should also be provided. If given for primary prevention

(i.e., no established cardiovascular disease), antiplatelet

therapy likely should not be resumed in most patients.

Laine L, Jensen DM. Management of patients with ulcer bleeding.

Am J Gastroenterol 2012;107:345-60

References

1

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Section 10ACUTE LOWER GASTROINTESTINAL

BLEEDING

Scope

Population




Outcome:

Abbreviations


population

Diagnosis and management of acute lower GI bleed




Diagnosis of acute lower GI bleed with appropriate management


LGIB - Lower gastrointestinal bleeding

UGIB - Upper gastrointestinal bleeding

NGT - Nasogastric tube

PEG - Polyethylene glycol

DAPT - Dual antiplatelet therapy

CTA - Computerised tomographic angiography

EGD - Esophago-gastroduodenoscopy


Suspect in any patient presenting with maroon stools, bright

red blood per rectum or melena


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Introduction

Acute overt lower gastrointestinal bleeding (LGIB) accounts for 20% of all

cases of gastrointestinal (GI) bleeding usually leads to hospital

admission with invasive diagnostic evaluations, and consumes

significant medical resources

l Hematochezia associated with hemodynamic instability may be

indicative of an UGIB source, and an upper endoscopy should be

performed. A nasogastric aspirate/lavage may be used to assess

a possible upper GI source if suspicion of UGIB is moderate.

l Risk assessment and stratification should be performed to help

distinguish patients at high- and low-risk of adverse outcomes

and decide upon the timing of colonoscopy and the level of care.

l Patients with hemodynamic instability and/or suspected ongoing

bleeding should receive intravenous fluid resuscitation with the

goal of normalization of blood pressure and heart rate before

endoscopic evaluation.

l Packed red blood cells should be transfused to maintain the

hemoglobin above 7 g/dl. A threshold of 9 g/dl should be

considered in patients with massive bleeding, significant

comorbid illness or a possible delay in receiving therapeutic

interventions.

l Endoscopic hemostasis may be considered in patients with an

INR of 1.5–2.5 before or concomitant with the administration of

reversal agents. Reversal agents should be considered before

endoscopy in patients with an INR >2.5.

l Platelet transfusion should be considered to maintain a platelet

count of 50×10 9 /l in patients with severe bleeding and those

requiring endoscopic hemostasis.

l In patients on anticoagulant agents, a multidisciplinary approach

should be used to decide on whether to discontinue medications

or use reversal agents to balance the risk of ongoing bleeding

with the risk of thromboembolic events.

1. Evaluation and risk stratification

2. Hemodynamic resuscitation

3. Management of coagulation defects

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4. Colonoscopy

l Colonoscopy should be the initial diagnostic procedure for nearly

all patients presenting with acute LGIB.

l The colonic mucosa should be carefully inspected during both

colonoscope insertion and withdrawal, with aggressive attempts

made to wash residual stool and blood in order to identify the

bleeding site .The endoscopist should also intubate the terminal

ileum to rule out proximal blood suggestive of a small bowel

lesion.

l Once the patient is hemodynamically stable,

colonoscopy should be performed after adequate colon

cleansing. 2 to 4 liters of a polyethylene glycol-based

solution or the equivalent should be administered over

3–4 h until the rectal effluent is clear of blood and stool.

Unprepared colonoscopy/sigmoidoscopy is not

recommended.

l A nasogastric tube can be considered to facilitate colon

preparation in high-risk patients with ongoing bleeding

who are intolerant to oral intake and are at low risk of

aspiration.

l In patients with high-risk clinical features and signs or

symptoms of ongoing bleeding, a rapid bowel purge

should be initiated following hemodynamic resuscitation,

and a colonoscopy performed as early as possible after

adequate colon preparation to potentially improve

diagnostic and therapeutic yield.

l In patients without high-risk clinical features or serious

comorbid disease or those with high-risk clinical features

without signs or symptoms of ongoing bleeding,

colonoscopy should be performed after a colon purge.

l Endoscopic therapy should be provided to patients with

high-risk endoscopic stigmata of bleeding: active

a) Bowel preparation

b) Timing of colonoscopy

c) Endoscopic hemostasis therapy


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bleeding (spurting and oozing); non-bleeding visible

vessel; or adherent clot.

l Diverticular bleeding: through-the-scope endoscopic clips

are recommended as clips may be safer in the colon than

contact thermal therapy and are generally easier to

perform than band ligation particularly for right-sided

colon lesions. X

l Angioectasia bleeding: noncontact thermal therapy using

argon plasma coagulation is recommended.

l Post-polypectomy bleeding: mechanical (clip) or contact

thermal therapy, with or without the combined use of dilute

epinephrine injection, is recommended.

l Epinephrine injection therapy (1:10,000 or 1:20,000

dilution with saline) can be used to gain initial control of an

active bleeding lesion and improve visualization but

should be used in combination with a second hemostasis

modality including mechanical or contact thermal therapy

to achieve definitive hemostasis.

l Repeat colonoscopy, with endoscopic hemostasis if

indicated, should be considered for patients with evidence

of recurrent bleeding.

A surgical consultation should be requested in patients with high-risk

clinical features and ongoing bleeding. In general,surgery for acute

LGIB should be considered after other therapeutic options have

failed and should take into consideration the extent and success of

prior bleeding control measures, severity and source of bleeding,

and the level of comorbid disease. It is important to very carefully

localize the source of bleeding whenever possible before surgical

resection to avoid continued or recurrent bleeding from an

unresected culprit lesion. Radiographic interventions should be

considered in patients with high-risk clinical features and ongoing

bleeding who have a negative upper endoscopy and do not respond

adequately to hemodynamic resuscitation efforts and are therefore

unlikely to tolerate bowel preparation and urgent colonoscopy.

5. Non-colonoscopy interventions

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Management algorithm

Table 3- Risk factors for poor outcome in patients with LGIB

Age >60 years

Systolic blood pressure <100mmHg

Heart rate >100b.p.m.

Unstable comorbid illness

Altered mental status

Syncope

Non-tender abdomen

Bleeding in first 4h of hospitalization

Aspirin use

Initial hematocrit <35%

Gross blood on initial rectal exam

Creatinine > 150μMol/L or 1.7 mg/dL


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References

1. Strate LL, Gralnek IM. ACG Clinical Guideline: Management of

Patients With Acute Lower Gastrointestinal Bleeding. The American

Journal of Gastroenterology 2016.

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Section 11SEVERE ULCERATIVE COLITIS (UC)

Scope

Population


population

Diagnosis and management of acute severe ulcerative colitis




Diagnosis of severe ulcerative colitis with appropriate management


UC - Ulcerative colits

ESR - Erythrocyte sedimentation rate




CBC - Complete blood counts

CMV - Cytomegalovirus

PCR - Polymerase chain reaction

NSAIDs-




Outcome:

Abbreviations

non-steroidal anti-inflammatory drugs


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Introduction

UC is a chronic idiopathic inflammatory disease of the GI tract that affects

the large bowel and is a major disorder under the broad group of

conditions termed inflammatory bowel disease.

Truelove and Witts Classification of the Severity of UC

Mild

Moderate

Severe

<4 stools/day, without or with only small amounts of blood No fever No tachycardia Hb> 11.5 g/dL ESR < 30 mm/hr or CRP-Normal

4 or more stools/day with bloodTemperature ≤37.8°C Heart rate ≤ 90/min Hb level ≥10.5 g/dLESR ≤ 30 mm/hr orCRP ≤30 mg/L

≥ 6 stools/day with blood andFever > 37.8°C Heart rate > 90/min Hb level <10.5 g/dLESR > 30 mm/hr orCRP>30 mg/L

Diagnosis Of Acute Severe Uc

Patients with bloody diarrhoea ≥6/day and any signs of systemic

toxicity (tachycardia >90 bpm, fever >37.8 °C, Hb < 10.5 g/dL, or an

ESR > 30 mm/h) have severe colitis and should be admitted to hospital

for intensive treatment.

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Investigations

l CBC, CRP, Liver function Test, Renal Function , PT / INR, stool

testing for Clostridium difficle .

l Serum electrolytes

l Flexible sigmoidoscopy to assess the severity

l Colonic biopsy for CMV PCR to rule out CMV colitis

l IgM CMV

l X ray abdomen erect to r/o toxic megacolon

Treatment Approach

Acute severe UC- IV

Hydrocortisone 100mg every

6th hrly

Day 3Classify response

acccording to Oxford criteria

Incomplete responders: stool frequency 3-8/day and

CRP <45 mg/L

Non responders: stool frequency > 8/day or

3-8/day and CRP > 45 mg/L

Oral steroids; add AZA when steroid

dose < 20mg/day

Continue IV steroid till day 5-7, if no response consider medical

rescue therapy/colectomy

Medical rescue therapySurgical evaluation-colectomy

l All patients admitted with severe colitis require appropriate

investigations to confirm the diagnosis and exclude enteric infection.

l Intravenous corticosteroids remain the mainstay of conventional

therapy. It is essential to ensure that the therapeutic alternatives for

rescue of steroid-refractory disease (ciclosporin, tacrolimus, or

infliximab) are considered early (on or around day 3 of steroid

therapy) and that the decision making process is not delayed.

1) Corticosteroids are generally given intravenously using

methylprednisolone 60 mg/24 h or hydrocortisone 100 mg four

times daily. Higher doses are no more effective, but lower doses

are less effective. Bolus injection is as effective as continuous

infusion.Treatment should be given for a defined period as

extending therapy beyond 7 to 10 days carries no additional

benefit.

2) Monotherapy with ciclosporin (normally at 2 mg/kg/day) is a

useful option in those patients with severe colitis when steroids

Conventional therapy.

Complete responders: stool frequency <3/day


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are best avoided, such as those susceptible to steroid-

psychosis, patients with concomitant osteoporosis or those with

poorly controlled diabetes.

l Intravenous fluid and electrolyte replacement to correct and prevent

dehydration or electrolyte imbalance. Potassium supplementation

of at least 60 mmol/day is almost invariably necessary.

Hypokalaemia or hypomagnesaemia can promote toxic dilatation.

l Unprepared limited flexible sigmoidoscopy and biopsy to confirm the

diagnosis and exclude cytomegalovirus infection which is often

associated with a steroid refractory disease course and requires

appropriate treatment.

l Stool cultures and assay for co-existing Clostridium difficile, which is

becoming more prevalent in patients admitted with severe colitis and

is associated with increased morbidity, mortality. If detected

appropriate antibiotic therapy should be administered.

Consideration should be given to stopping immunosuppressive

therapy where possible, although this may not always be

appropriate.

l Subcutaneous prophylactic low molecular weight heparin to reduce

the risk of thromboembolism especially during a disease flare should

be considered.

l Nutritional support if the patient is malnourished. Enteral nutrition is

most appropriate and associated with significantly fewer

complications than parenteral nutrition in acute colitis. Bowel rest

through intravenous nutrition does not alter the outcome.

l Withdrawal of anticholinergic, antidiarrhoeal, NSAID and opioid

drugs, which may risk precipitating colonic dilatation.

l Topical therapy (corticosteroids or mesalamine) if tolerated and can

be retained.

l Antibiotics only if infection is considered or immediately prior to

surgery

l Blood transfusion to maintain a hemoglobin above 8– 10 g/dl.

l A multidisciplinary approach between the gastroenterologists and

Other measures that are considered appropriate in addition to

intravenous steroids include:

,

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colorectal surgeons looking after the patient is essential.

The response to intravenous steroids is best assessed objectively

around the third day. Treatment options including colectomy should

be discussed with patients with severely active UC not responding to

intravenous steroids. In addition to triggering a decision to

commence salvage therapy, meeting the criteria for steroid failure

with one of these predictive indices should mandate surgical

consultation

depend on measures such as stool frequency

or pyrexia. A stool frequency >12/day on day 2 of iv

corticosteroids was associated with rate of colectomy of 55%,

while a frequency >8/day or a stool frequency between three and

eight together with a CRP >45 mg/L on day 3 predicted

colectomy in 85% on that admission: the Oxford Criteria.

Similarly a stool frequency ×0.14 CRP being ≥ 8 on day 3

predicted colectomy in 75%: the Sweden Index.

An ESR >75 or a pyrexia >38 °C on

admission was associated with a 5–9-fold increase in the need

for colectomy .

include the presence of

colonic dilatation >5.5 cm (associated with a 75% need for

colectomy), or mucosal islands on a plain abdominal radiograph

(75% colectomy).

Ciclosporin, or infliximab or tacrolimus may be appropriate. If there is

no improvement within 4–7 days of salvage therapy, colectomy is

recommended.

2 mg/kg/day has become the standard dose used in current

clinical practice.

A median time to response is 4 days which allows timely

Intravenous-steroid refractory ulcerative colitis of any extent.

Factors that predict the need for colectomy in acute severe colitis

can broadly be divided into clinical, biochemical and radiological

markers.

Second line therapy / salvage therapy

a) Clinical markers

b) Biochemical markers-

c) Radiological/endoscopic criteria

a) Ciclosporin-


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colectomy in non-responders. Before treatment serum

magnesium and lipid profile has to be checked.

However ciclosporin has narrow therapeutic index and its

side-effect profile (including mortality rates of 3–4%) has

limited its acceptability. There is also concerns about its

ability to prevent colectomy in the longer term. Successful

transition to thiopurines therapy and being thiopurine-naïve

at baseline have been confirmed as factors that reduce the

risk of long term colectomy. Patients that have UC refractory

to adequate thiopurine therapy may be less suitable

candidates for ciclosporin rescue therapy

it is a Calcineurin inhibitor that acts via a

mechanism similar to

ciclosporin. have shown broadly. Results are similar to

ciclosporin after both intravenous (0.01 to 0.02 mg/kg) and

oral (0.1 to 0.2 mg/kg) administration)

single dose (5 mg/kg) has shown to be an

effective salvage therapy in

patients with severe UC refractory to iv steroids

Third line medical therapy(sequential use of Ciclosporin and

Infliximab) may be considered at a specialist centre. The

timing of colectomy for severe colitis remains one of the most

difficult decisions that a gastroenterologist has to make.

l A mesalamine 1 g suppository once daily is the preferred initial

treatment for mild or moderately active proctitis. Mesalamine

foam enemas are an alternative.

l Suppositories may deliver drug more effectively to the rectum

and are better tolerated than enemas.

l Combining topical mesalamine with oral mesalamine or topical

steroid is more effective than either alone and should be

considered for escalation of treatment.

l Oral mesalamine alone is less effective.

l Refractory proct i t is may requi re t reatment wi th

b) Tacrolimus-

c) Infliximab-

Proctitis

Treatment according to site of disease and disease activity

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immunosuppressants and/or biologics

l Left-sided active ulcerative colitis of mild–moderate severity

should initially be treated with an aminosalicylate enema 1 g/day

combined with oral mesalamine > 2 g/day.

l Topical therapy with steroids or aminosalicylates alone as well

as mono-therapy with oral aminosalicylates is less effective

than oral plus topical 5ASA therapy.

l Topical mesalamine is more effective than topical steroid. Once

daily dosing with 5ASA is as effective as divided doses.

l Systemic corticosteroids are appropriate if symptoms of active

colitis do not respond to mesalazine .

l Severe left-sided colitis is usually an indication for hospital

admission for intensive treatment with systemic therapy.

l Extensive ulcerative colitis of mild–moderate severity

should initially be treated with oral 5-ASA > 2 g/day, which should

be combined with topical mesalamine to increase remission

rates if tolerated.

l Once daily dosing with 5ASA is as effective as divided doses.

l Systemic corticosteroids are appropriate if symptoms of active

colitis do not respond to mesalamine.

l Severe extensive colitis is an indication for hospital admission for

intensive treatment.

1. Dignass A, Eliakim R, Magro F, et al. Second European evidence-

based consensus on the diagnosis and management of ulcerative

colitis part 1: definitions and diagnosis. J Crohns Colitis

2012;6:965–90.

2. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-

based consensus on the diagnosis and management of ulcerative

colitis part 2: current management. J Crohns Colitis

2012;6:991–1030.

3. Third European evidence-based consensus on diagnosis and

management of ulcerative colitis. Part 1: definitions, diagnosis,

Left sided colitis

Extensive ulcerative colitis

References


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extra-intestinal manifestations, pregnancy, cancer surveillance,

surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017

4. Harbord M, Eliakim R, Bettenworth D, et al. Third European

Evidence-based Consensus on Diagnosis and Management of

Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis

2017.

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Annexe II, Secretariat Thiruvananthapuram

Kerala-695001

Department Of Health And Fa ily WelfaremGovernment Of Kerala

Ke HEALTHrala

Feb

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021