Ahmed Adel AbdelhakeemAssistant Lecturer ,

Internal Medicine Dept , GI & Hepatology UnitAsyut University Hospital

Preoperative Evaluation For Living Donor Liver

Transplantation

HISTORY

-Thomas Earl Starzl -The father of modern

transplantation -Performed the first

human liver transplant in 1963 , and The first successful human liver transplant in 1967 , both at the university of Colorado health center.

HISTORY

-Sir Roy Yorke Calne -Performed the first

liver transplantation operation in Europe in 1968

-Professor of Surgery at Cambridge between 1965 and 1998

-First who introduced cyclosporine as an immunosuppressive drug postoperative.

What is liver transplantation?

is the replacement of a diseased liver with some or all of a healthy liver from another person ( allograft ). The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original liver. Liver transplantation is a viable treatment option for end-stage liver disease and acute liver failure.

What is liver transplantation?

-One-year patient survival is 85-90-%

-Outcomes continue to improve

-The supply of liver allograft from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of living donor liver transplantation.

Living Donor Liver Transplantation

-In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the recipient’s diseased liver has been entirely removed.

-The concept of LDLT is based on (1) the remarkable regenerative capacities of the human liver and (2) the widespread shortage of cadaveric livers for patients awaiting transplant.

Living Donor Liver Transplantation

-The first report of successful LDLT was by Dr. Christoph Broelsch at the university of Chicago medical center in November 1989, when two-year-old Alyssa Smith received a portion of her mother's liver.

-Surgeons eventually realized that adult-to-adult LDLT was also possible, and now the practice is common

-It is considered more technically demanding than even standard, cadaveric donor liver transplantation

The first DDLT in the Arab World was performed in 1990 at Riyadh Military Hospital in Saudi Arabia .

The first LDLT was performed in 1991 at the National Liver Institute in Egypt.We have 27 liver transplant centers from 11 countries ( now 28 ).

80 % of cases are LDLT

The largest percentage of liver transplantation has been performed by 13 transplant centers in Egypt (56%), moreover 70% of LDLT in Egypt, while 90% of DDLT in KSA

Since 1991 , only 5 reported cases of donor death out of 3052 cases ( less than 0,2 % ) .

Status of liver transplantation in Arab Area and Egypt

Patient Evaluation

Who ?- Patient selection ( indications & contraindications ).

When ?- Timing of the operation.

- Is every patient with chronic liver disease a candidate for liver transplantation NOW ?

How ?- Patient preparation.- Patients on waiting list.

Liver transplantation :

1 – Assessment2 – Waiting3 – The operation4 – Immediate postoperative management5 – Long term management

WHO?

1 – ESLD ( LCF and other complications )

2 – Hepatocellular Carcinoma:

3 – Other less frequent indications :

- Autoimmune hepatitis

- Fulminant hepatic failure ( King’s college

criteria )

- Primary sclerosing cholangitis

- Metabolic liver diseases

- Budd-Chiari syndrome

Indications of LTX ( WHO )

Patients with child score above 9 ( Child C ) and MELD score above 15 are accepted candidates for liver transplantation. Numbers below this may be listed.

Exceptions of MELD are those with refractory ascitis , uncontrollable recurrent GI bleeding , repeated encephalopathy , port pulmonary hypertension , HPS , HCC and metabolic liver diseases.

Patients with MELD score less than 15 and Child B are listed and followed up until they become child C or develop HCC or any condition as a MELD exception.

Patients with high MELD ( above 30 ) score are risky with more postoperative morbidity and mortality , so , every case should be discussed separately.

End Stage Liver Disease

Patients with HCC are exceptions of the MELD score , and they receive a MELD of 20 once it is diagnosed even if the patient is child A.

The Milan criteria are currently the benchmark for the selection of HCC patients for liver transplantation , and the basis for comparison with other suggested criteria.

Milan Criteria : Single HCC less than 5 cm , or , 3 HCC the maximum size of each is/or less than 3 cm.Barcelona Expanded criteria : Single HCC ≤7cm

Multinodular HCC: 3 nodules ≤5cm, 5 nodules ≤3cm San Francisco criteria ( UCSF ) : one tumour ≤ 6·5 cm , three nodules at most with the largest ≤ 4·5 cm , and total tumour diameter ≤ 8 cm.

No malignant vascular invasion , no distant metastasis.

AFP is a valuable marker to predict tumour load and microvascular metastases ( omit if more than 400 ) but should be combined with imaging modalities.

Hepatocellular Carcinoma

Milan criteria and its modifications are not applicable to patients with HCC developing in a non-cirrhotic liver.

Such patients with non - resectable HCC and absence of macrovascular

invasion and extra hepatic spread may be considered as appropriate candidates for liver transplantation.

patients with HCC in a non-cirrhotic liver, who were treated by

resection and have intrahepatic recurrence of HCC and no evidence of macrovascular invasion or extrahepatic spread, may be considered for salvage transplantation.

Hepatocellular Carcinoma

1 -Advanced age ( > 70 yrs , biological age is important ).

2 – Uncontrolled active sepsis.

3 – Advanced cardiopulmonary disease.

4 – HIV infection.

5 – Hepatocellular carcinoma beyond acceptable criteria.

6 – Extensive occlusion of splanchnic venous flow ( non-

malignant , non-extensive PV thrombosis is not a

contraindication ).

7 – BMI > 30

8 – Previous upper abdominal surgery.

9 – Active ongoing Alcoholism.

10 – Extrahepatic malignancy

Contraindications

WHEN?

LT should be considered in any patient with liver disease in whom the procedure would extend life expectancy beyond what the natural history of under-lying liver disease would predict or in whom LT is likely to improve quality of life .

Patients should be selected if expected survival in the absence of transplantation is 1 year or less, or if the patient has an unacceptable quality of life because of liver disease.

Physicians have to determine which patients have liver disease that will endanger their lives before life-threatening systemic complications occur. This consideration is balanced by the risk of surgery and immunosuppressive treatment of LT if it is performed too early.

Timing

MELD score is an algorithm based on objective measures comprising creatinine , bilirubin and INR. The MELD was developed initially to determine the short-term prognosis for patients undergoing TIPS. It was considered to be highly accurate for predicting liver-related death .

patients with MELD scores ≤ 14 , the mortality rate with transplantation was found to be higher than that of patients with the same MELD score who had not undergone transplantation. Consequently, a MELD score higher than 15 is now considered a valid indication of LT in patients with ESLD.

Exceptions of MELD score ( mentioned previously )

MELD score

HOW?

Recipient Evaluation

History and physical examination. 1 – Indication ?? ( ESLD or HCC )

2 – MELD ? ( 15 – 30 ) , exceptions3 – Contraindication??

4 – Consider Age , BMI ( if > 30 >> should lose wt )

Blood profile : CBC , Bl. Group , PT , PC , INR , FACTOR V , PROTEIN C,S , ANTITHROMBIN III

Renal profile : UREA , Cr , URIC ACID , COMPLETE URINE ANALYSIS

Liver profile : AST , ALT , ALP , GGT , BILLIRUBIN , ALBUMIN , PROTEINS

Inection screen : ESR , CRP , ? PROCALCITONIN

Electrolytes : Na , K , Ca , Mg , Po4 , Iron , Copper

Lipid profile : complete lipogram , LDH , FBS , amylase

Immunology : ANA , schist. Ab

Drug Screen Tumor markers : AFP , PSA , CEA , CA19-9

LAB. INVESTIGATIONS

Virology:HCV : Ab , PCRHBV : sAg , sAb , eAg , eAb , cIgM , PCRHAV : Ab ( total and IgM )EBV , CMV , HSV , VZ : Ab ( IgG & IgM )Fungal serology : candida Ag , aspergillus Ag

LAB. INVESTIGATIONS

Abdominal U/S and dopplerTriphasic MSCTCT venography , portography & angiographyCarotid dopplerMammography for all womenIf HCC patient : CT brain , CT chest and bone scan.

IMAGING

CHEST : PFT , CXRCARDIOLOGY : ECG , ECHO , DOBUTAMINE ECHOPSYCHIATRYDENTALENTENDOSCOPY:

Upper as a routine , lower only if positive scist. Ab ( + rectal snip ).ANASTEHESIA CONSULTATION.

CONSULTATIONS

Management Of Patient s On Waiting List

1– Management of complications while patient with ESLD is on transplant waiting list:

-Acute upper GI bleeding

-Hepatic encephalopathy

-Hepatorenal syndrome

-SBP

-Refractory ascitis

2– Down staging for patients with HCC ( TACE – RFA )

3– Frequency of outpatient visits / update of MELD

Management of patient s on waiting list

-Primary prophylaxis : beta blockers with target 25% reduction in HR not less than 55 b/m , not so valuable in patients with child C.Endoscopic therapy : band ligation as a primary prophylaxis if risky on EGD.TIPS : risk of complications and malfunction.

Secondary prophylaxis :Beta blockers with endoscopic therapy.TIPS if failed combined medical and endoscopic therapy.

Acute bleeding : usual management of acute variceal bleeding .

Upper GI bleeding

-Most common complication of portal hypertension. -Patient is managed as usual : salt restriction and

diuretics with the conventional regimens. -Sodium restriction is mandatory in ensuring response.

-The most reliable method for assessing response is : urinary sodium excretion ( normally in afebrile cirrhotics is < 10 mmol / day ) , the goal is to achieve urinary sodium level of > 78 mmol/day.

-Hyponatremia in advanced cirrhosis is common and chronic and rarely problematic , take care not to correct it rapidly. Patients with serum Na < 120 are temporarily excluded until improvement (usually by fluid restriction)

-Nocturnal muscle cramps are a frequent complication and usually resolves with magnesium administration.

Ascitis

Ascitis not responsive to sodium restricted diet and full dose of diuretics in the absence of prostaglandin inhibitors.

Serial large volume paracentesis ( 5 liters at least ) with albumin replacement ( 5 – 8 g/L of fluid ) every 2 weeks ( or according ) is the therapy of choice in such cases.

Avoid frequent unnecessary tapping.

TIPS may be effective and superior to medical therapy in these patients but carries high risk of developing encephalopathy with higher mortality.

Refractory Ascitis

-Diagnosed by clinical and laboratory methods.

-Clinical : a patient with ascitis who develops diffuse abdominal

pain , tenderness , fever and vomiting is highly suggestive to have

SBP.

-Laboratory : leucocytosis + mild rise of renal chemistry +

diagnostic paracentesis ( more than 250 PMNL and/or positive

culture ).

-Sometimes the diagnosis is made by suspicion and diagnostic

tapping as the full picture may be absent.

-Once diagnosis is suspected , a 3rd generation cephalosporin or a

quinolones should be started ….. If no response tazobactam /

piperacillin OR imipenem / levofloxacin combination is a good

offer , but it is better to wait for culture results .

Spontaneous BP

Patients who Should receive short term oral quinilone

prophylaxis:

Low ascitic protein ( < 1 g/dl )

Variceal hemorrhage

Survived attack of SBP

Patients with previous attack of SBP should receive

long term prophylaxis .

Spontaneous BP

Admit and manage according to guidelines.

Such patients should be an exception of MELD score.

If no improvement:

Revise diagnosis ( alternative etiology )

Ensure sufficient therapy

Treat precipitating factors.

Hepatic encephalopathy

The hallmark of HRS is : reversible renal vasoconstriction + mild

systemic hypotension + normal structure of the kidney in a

patient with advanced cirrhosis and absent other etiology for

renal dysfunction.

It is crucial to diagnose the exact etiology of renal impairement :

Acute prerenal failure , contrast nephropathy , intrinsic renal

failure , drug toxicity or HRS.

Baseline renal function should be determined at first evaluation

of the recipient by : complete urine analysis , urea , creatinine ,

uric acid , 24 hr urine for proteins and clearance and renal

ultrasound.

Hepatorenal syndrome

The best management of HRS is liver transplantation ,

but still these patients have higher mortality and

morbidity than others.

Renal sparing regimen should be put in consideration

during the operation and postoperative (postpone CNIs

, give basiliximab D0,4)

Admit and treat with conventional therapy :

terlipressin , albumin and midodrine.

Hepatorenal syndrome

-Any transplant recipient who is hypoxic should be screened for

HPS.

-Clinically : chronic liver disease complicated by PHT that

develops cyanosis , clubbing , platypnea , orthodeoxea that is

relieved by recumbency.

-Investigations : ABG , Pulse oximetry while sitting if positive

( hypoxia ) then do contrast echo or MAA Scan to confirm

diagnosis.

-Usually HPS is a condition that improves with transplantation.

-High Preoperative risk for increased postoperative morbidity

and mortality are : PaO2 < 50 mmHg + MAA scan > 20.%

Hepatopulmonary syndrome

-Routine Echo is done for every recipient .

-One of the main parameters to be looked at is the

pulmonary pressure and RVSP.

-If RVSP is:

<45 :OK

45 – 55 :RISKY patient , careful decision should be made with therapy with sildenafil citrate.

>55 :excluded from the list.

Portopulmonary hypertension

-Malignant PV thrombosis is a contraindication to

surgery.

-Non malignant , non extensive PV thrombus is

permissible for transplantation.

Grades of PV thrombus:

G1 : partially thrombosed main PV < 50% of lumen.

G2 : > 50% occlusion of main PV + or – minimal extension

to SMV.

G3 : complete PV thrombosis + - proximal SMV extension.

G4 : complete PV thrombosis + proximal _ distal SMV

extension.

Portal Vein Thrombosis

-Preoperative therapy until HBV PCR negative ( Enticavir

0.5 – 1 mg/day )

-HBVIG is given as following:

4000 IU bolus dose intraoperative ,

2000 IU daily for 7 days

2000 IU every week for 1 month

2000 IU monthly for 1 year

-Serum HBsAb level should exceed 300

-Postoperative antiviral therapy for life.

-All recipients and donors should be vaccinated against

HBV .

Chronic HBV Patients

-Patients with HCC should be listed according to Milan

criteria.

-HCC patients are exceptions of MELD score.

-Dropout of HCC patients on the waiting list is common

because of cancer progression.

-Follow up is done for every patient every 3 months

( or one month after any bridge therapy to assess

response ).

-Follow up is done by Triphasic MSCT abdomen and

AFP.

HCC Patients On Waiting List

BRIDGE THERAPY:

- using loco regional therapy ( alcohol injection ,

radiofrequency ablation (RFA) , transarterial

chemoembolisation (TACE) , transarterial radioembolisation

(TARE), or liver resection ).

Aim:

(1 - )to decrease the tumour size and number in patients

initially

presenting with tumours that do not meet locally acceptable

criteria for liver transplantation.

(2 - )To keep the patient within Milan criteria if transplantation

is expected to be delayed more than 6 months.

HCC Patients On Waiting List

BRIDGE THERAPY:

-α-fetoprotein concentrations before and after downstaging

may add additional information.

-Based on existing evidence, no recommendation can be

made for preferring a specific locoregional therapy for

downstaging over others.

-No recommendation can be made on bridging therapy in

patients

With lesions ≤2 cm.

-Patients with progressive disease in whom locoregional

intervention is not considered appropriate, or is ineffective,

should be removed from the waiting list

HCC Patients On Waiting List

Donor Evaluation

Criteria of suitable donor1 –Age should be less than 45 yrs

2 – No chronic systemic medical diseases and good general condition ( mild controlled HTN is permitted ).

3 – Compatible blood group

4 – BMI less than 28

5 – No previous upper abdominal surgery (cholecystectomy is an exception)

6 – Relative ( recommended )

7 – Serologically negative

8 – Psychologically stable

9 – No drug abuse

10 – No pregnancy or hormonal therapy for 1 year postoperative.

Donor Evaluation

Donor Evaluation

Good News :

NO TISSUE TYPING IS NEEDED FOR LIVER TRANSPLANTATION

PHASE (1) EVALUATION :

Full history and examination

Basic lab. Investigations ( Liver , kidney , bleeding , lipid , electrolytes ).

Drug screen

Virology ( HAV , HBV , HCV , HIV )

HBV vaccination

Basic imaging : U/S , CXR , duplex abdomen , mammography

Donor Evaluation

PHASE (2) EVALUATION :

Extensive other viral markers ( HSV , VZ , EBV , CMV , PCR )

Tumour markers ( AFP , PSA , CEA . CA19-9 )

Consultations : Chest , cardiac , psychology.

Donor Evaluation

PHASE (3) EVALUATION :

Advanced Imaging :CT angiography , portography , venography

CT volumetry ( GRWR : 0.8 and remaining should be 35 % at least )

MRCP

Anesthesia and ICU consultation

Liver biopsy ( ?? Steatosis > 15 % … reject )

Donor Evaluation

The Procedure

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