Professor Richard

GearryUniversity of Otago

Consultant Gastroenterologist

Christchurch Hospital

8:30 - 9:25 WS #70: Gastroenterology - Basics and Beyond

9:35 - 10:30 WS #80: Gastroenterology - Basics and Beyond (Repeated)

Associate Professor

Catherine StedmanGastroenterologist

Clinical Pharmacologist

Christchurch Hospital

University of Otago

Dr Gary LimGastroenterologist

Christchurch Hospital

Clinical Lecturer

Christchurch Clinical School

Cirrhosis:

Diagnosis & Management tips

Catherine StedmanAssociate Professor of Medicine, University of Otago, ChristchurchGastroenterology Department, Christchurch Hospital

Cirrhosis

• Histological term - fibrosis and parenchymal nodules (Stage 4)

• Not disease specific

• Result of chronic persistent liver injury

Liver Biopsyvs

Fibroscan

Fibroscan• Advantages:

–Non-invasive, portable assessment of liver fibrosis

• Well validated in some diseases, e.g. active hepatitis C

–Not validated well in treated viral hepatitis

–Hepatitis C patients must be evaluated for liver fibrosis pre-treatment

• Inaccurate with:– significant oedema or liver inflammation (false positive)

– obesity, ascites

• Doesn’t give information on aetiology of liver disease

Compensated vs Decompensated Liver Disease

• Large hepatic reserve

• Advanced liver disease/cirrhosis may not be obvious

• “LFTs” may be only mildly abnormal or normal in cirrhosis

Tests for liver “function:”

–Bilirubin (↑)

–INR (↑)

–Albumin (↓)

–Platelets ( correlates with portal hypertension and splenomegaly)

INR and Albumin best

indicators of severity

Signs of chronic liver disease

1 point 2 points 3 points

Total bilirubin, μmol/L (mg/dL)

34 (<2) 34-50 (2-3) >50 (>3)

Serum albumin, g/dL >3.5 2.8-3.5 <2.8

International Normalised Ratio (INR)

<1.7 1.7-2.2 >2.2

Ascites None Mild, controlled Moderate to Severe

Hepatic encephalopathy NoneGrade I-II,controlled

Grade III-IV, refractory

Points Class 1 year survival

5-6 Child-Pugh A / compensated cirrhosis 100%

7-9 Child-Pugh B / decompensated cirrhosis/ moderate hepatic impairment

80%

10-15 Child-Pugh C / decompensated cirrhosis/ severe hepatic impairment

45%

How bad is it?Child’s Pugh Score Assessment of Patients with Cirrhosis

Complications of cirrhosis

1. Liver failure

2. Portal hypertension

3. Hepatocellular carcinoma

Liver: Synthetic & Storage Functions

Storage of….

• Vitamins: A, D, E, K, B12

• Fatty acids

• Glucose (as glycogen)

• Iron, copper

• Production of blood clotting factors, albumin

• Immune functions

In Liver Failure…..

• Vitamin Deficiencies

• Protein calorie malnutrition

• Hypo/hyperglycaemia

• Bleeding, bruising, oedema

• Infections

Nutrition

• Malnourished AND increased requirements

• Negative prognostic factor so important to look for and treat

Practical tips:

• High protein diet

• +/- no added salt (if ascites)

• Bedtime snacks preserve muscle mass– preferably protein

• Multivitamins; assume Folate and Thiamine deficiency in alcohol

• Nutritional support if needed

Liver Detoxification

In Health….

• Enzymes remove toxins from blood before it goes to body

–Alcohol

–Drugs

–Hormones

In Liver Failure…

• Jaundice

• Brain effects (encephalopathy)

• Sensitivity to drugs

• Infertility

• Feminization (men)

Hepatic encephalopathy

↑ serum ammonia

RifaxaminLaxatives

CNS active drugsBenzodiazepines,opiates

Accumulation of waste products due to poor hepatic clearance (function and shunting)Precipitants:

infection, bleeding, constipation, electrolyte imbalance (hypokalaemia), drugs (especially sedatives, opiates), shunts

Hepatic encephalopathy:assessment and management

• Clinical features:

– Sleep/wake reversal, confusion, asterixis(flap), apraxia, foetor

• Remove/treat precipitant

–e.g. stop benzodiazepines/reduce opiates

– Supportive care, fluids, electrolytes

• Reduce nitrogenous load

–Control bleeding

– Lactulose, Fleet enemas

–Antibiotics- rifaximin

• No driving- increased risk accidents

Complications of cirrhosis

1. Liver failure2. Portal hypertension3. Hepatocellular carcinoma

Portal Hypertension:Changes in Blood Flow

Ascites due to cirrhosis

• Most common complication of cirrhosis – 50% of compensated cirrhotics will develop ascites in 10 years

• Associated with poor prognosis:– Mortality 15% within 1yr, 44% in 5 years

• Pathophysiology:– Portal hypertension is a prerequisite (Pressure > 12mmHg)

– Splanchnic vasodilation – Na retention- renal vasoconstriction

– Dilutional hyponatraemia and hyperdynamic circulation

• Diagnosis: Albumin gradient > 11 g/l (transudate)

• Effects - discomfort, circulatory, respiratory function, infection, cosmetic

Ascites – tips for management• Daily weigh, fluid balance

• Restrict sodium (usually not water)

• Diuretics

– Spironolactone 100mg and frusemide 40mg, increase in this ratio

– If gynaecomastia a problem, try amiloride 10-40mg

–Mobilise ascites at 0.5-1.0 l/day

–Watch biochemistry, creatinine carefully

• Paracentesis with albumin cover if diuretic resistant and severe

• Spontaneous bacterial peritonitis:

– Suspect if pain, fever, encephalopathy, ↓ renal function

Infection

• Sepsis – high risk factor for mortality in cirrhotics

• Often absent typical signs and symptoms so think of it anyway!

• Most common urine > SBP > respiratory

• Prevent infections – flu vaccine

Spontaneous bacterial peritonitis (SBP):

–Suspect if pain, fever, encephalopathy, ↓ renal function

–Diagnosis: ascitic tap-WBC is > 250, +/- culture +ve

–Treat immediately: cefotaxime or ceftriaxone plus IV albumin

–Once had SBP should remain on long term prophylaxis:

• Ciprofloxacin, Norfloxacin or cotrimoxazole

Oesophageal Varices

Manage all upper GI bleeds in known cirrhoticsas presumed variceal haemorrhage

–Varices occur at porto-systemic anastomoses:

– Skin – Caput medusa

–Oesophageal & Gastric

–Rectal

– Stomal

–Mortality 20% in 6 weeks

–Medical emergency

Oesophageal varices• Primary prevention of bleeding (have not bled):

• Gastroscopy for cirrhotics

• If large varies:

• Non selective B blockers to reduce portal pressure – Nadolol /Propanolol / carvedilol

• If intolerant of B blocker, band large varices.

• Emergency control of bleeding• Vasopressors: IV Terlipressin or Octreotide to lower portal pressure

• Endoscopic banding

• Antibiotics (ceftriaxone or cefotaxime)

• Secondary Prevention (preventing re bleeding)• Banding and beta blockers (non-selective)

Complications of cirrhosis

1. Liver failure2. Portal hypertension3. Hepatocellular carcinoma

Hepatocellular carcinoma

• Usually occurs in cirrhotic livers

• Diagnosis:• imaging and alpha-fetoprotein (AFP)

• Survival poor if symptomatic • late presentation, liver disease and metachronous

tumours

• Better if diagnosed on screening USS (6 monthly)

• MRI used for definitive diagnosis

• Management options:• surgery, transplantation, local ablation, Chemo-

embolisation

All cirrhotics need 6 monthly USS

Drugs / AlcoholAlcohol• Alcohol cause of 25% of liver cirrhosis and contributes to another

25% of cases; also increases risk of hepatocellular cancer

• Abstinence is Goal

• Only considered for transplantation once abstinent for 6 months

• Cessation of alcohol can dramatically improve liver failure

Drugs to avoid • Drugs which promote Na retention ( NSAIDs) & nephrotoxins

• CNS depressants (morphine, benzodiazepines)

• Ace inhibitors and angiotensin receptor blockers in ascites

• B blockers often need to be discontinued in diuretic resistant ascites

Conclusions

• Liver failure is a multisystemic problem

• Liver fibrosis/cirrhosis can reverse with effective treatment

–e.g.antiviral therapy

• Liver failure can improve dramatically with excellent supportive care and removal/treatment of cause

• Hepatocellular cancer risk persists:

– USS screening 6 monthly