Dr.Murat AKYILDIZ, MDAssociate Professor of Gastroenterology

Istanbul Bilim University, Department of Gastroenterology,Sisli Florence Nightingale Hospital, Organ Transplantation Center, Istanbul

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Recipient

Donor

Living Donor Liver Transplantation:Recipient and Donor Evaluation

Road map• Case presentation

• Recipient Evaluation– General information about

recipient evaluation– Cardiac– Pulmonary– Renal– Other spesific conditions

• Donor Evaluation

Case presantation-recipient

• 57 years-old woman,

• Referred to our center for liver transplantation since she had liver cirrhosis and chronic HCV infection

Medical History-1

• She had chronic HCV infection for 12 years • Regular interferon plus ribavirin treatment were given 12

months in 1999 and HCV RNA became negative after the tretment

• Three months later after the treatment, HCV RNA became positive and she was considered as recurrence of HCV infection

• Then she was followed up from hepatology outpatients clinic without antiviral treatment until 2002

• 2002– She had vomiting and fatigue – ALT 220– AST 200– T.BIL 1– HCV RNA 1.000.000 copy/ml– HCV genotype 1– USG: no mass, no splenomegaly, no ascites

Medical History-2

• PEG-INF+Ribavirin treatment were given for 2 years– HCV RNA was found 1000 copy/ml after 3 month of

the treatment– HCV RNA was negative 6-12 and 24 month of the

treatment– However, HCV RNA again became positive after 6

months of the treatment– Then she was followed up without any spesific

treatment from the outpatients clinic

Medical History-3

• 2010

– ascites developed and she was considered decompansated liver

cirrhosis

– furosemid 40 mgday and spironolactone 100 mg/day with salt

restriction were given.

– diuretics were increased up until furosemid 160 mg and

spironolactone 400 mg/day since she had tense ascites and

peripheral eodema.

– after ten months, diuretic therapies became unanswered and

therapeutic paracentesis were done.

Medical History-4

• Large volume paracenthesis was performed periodically (weekly/bimonthly),

• She had progressive dispne – No fever– physical examination with chest X-ray showed right hepatic hydrothorax.

• Thoracenthesis was performed – fluid was similar with ascites

• There was no tumor, infection and TBC lesion on thorax CT imaging.

• She begun to hospitalized with short time distances because of massive pleural effusion and respiratory distress and drainage with thorax tube.

Medical History-5

• Surgical History– 15 years ago gynecologic operation (exisional bx

from vulva)– No hepatobiliary operation

• Family History– No other liver disease– No genetic disease– Type 2 Diabetes Mellitus (older brother)

Medical History-6

• Habits: no alcohol and smoking and drug abuse

• Treatment– Furosemid 80 mg/day– Spironolactone 200 mg/day– Ursodeoxycolic acid 1000 mg/day– Norfloxacin 1x400 mg/day

Medical History-7

Physical Examination• Height 155 cm, Weight 59 kg, BMI 24.5• She was oriented, cooperation was normal,• She was subicteric and there was temporal muscle atrophy,

multiple spider angiomas, palmar erythema. • Blood pressure was 110/70 mmHg, heart rate 82/min/R, S1

and S2 were normal, no S3.• Respiratory sounds were decreased on the inferior and

middle zones of the right lung.• Abdomen: There was remarkable ascites around the 3 cm-

above umblical line, umblical hernia, Traube area was closed, 1 cm splenomegaly. There was (++) pretibial pitting edema

• No flapping tremor and other spesific findings

LaboratoryGlucose :88 mg/dlBUN :15 mg/dlCrea :0.5 mg/dlAST :79 IU/lALT :41 IU/lGGT :28 IU/lALP :101 IU/lT.Bil :2.9 mg/dlAlbumin : 2.9 g/dl

Na 131 mEq/dlK 4 mEq/dlCholesterol 107 mg/dlTryglycerid 45 mg/dlHbA1c 4AFP 2.1 ng/mlCa 19/9 84 ng/mlCEA 5.77 ng/ml

INR 1.52Hb 12 WBC 3300 PLT 88000 Blood type AB Rh(-)sT4 1.74TSH 2.15Ascites

SAAG>1.1WBC 100Culture was steril

HBs Ag (-)Anti-HBS (-)Anti-HBC IgG (+)AntiHAV IgG (+)HBV DNA (-)Anti-HCV (+)HCV-RNA:373.0000 Genotype: 1b

Laboratory

• Urinalysis: 2-3 wbc, no protein, no RBC

• Upper Endoscopy: no varices, portal hypertensive gastropathy

• Colonoscopy: internal hemoroid

Laboratory

Summary• 57 years old woman• Decompansated liver cirrhosis because of chronic HCV

infection• Refractory ascites • Hepatic hydrothorax• Child-Pugh B, score 9• MELD score 15• TX Indication:

– refractory ascites and hepatic hydrothorax– decompansated liver cirrhosis

Imaging• Thorax CT

– Bilateral pleural effusion– Atelectasia of the right lung– No active infltration or spesific lesion

• Abdomen CT+CT angiography– Liver cirrhosis– Portal hypertension– Ascites– No PVT

• Mamography– normal

Consultations• Cardiology

– Mild operational risk– EF: 63%– SPAP: 28 mmHg– Tal scannig: normal

• Infectious Disease– Rectal and urinary

cultures were normal.– No additional

recommendation

• Pulmonary – Moderate restrictive and

obstructive disease– Thoracentes fluid analysis

• similar with ascites– Albumin 0.3, LDH 61,

protein 0.6, WBC 200/mm3

• Transudative and culture was negative

• Gynecology– No spesific lesion and

smear was normal

Donor• 36 years-old, healthy woman, • Relationship: daughter of the recipient• Blood type AB Rh (+)• Height 160 cm• Weight 53 kg• BMI 21• Social status

– married, – has a 2 years old healthy child – she is house wife

Donor-2

• There was no pathology on phsysical examination

• No previous surgery• No habits• No drug using• No history of thrombosis• No previous systemic disease

Donor-3• BUN 11 mg/dl• Cr 0,4 mg/dl• Na 137 mEq/dl• K 4,4 mEq/dl• Gluc 93 mg/dl• HBA1C 4.6• HOMA-IR 2,17• Chol 185 mg/dl• Tg 82

• AST 15 IU/l• ALT 12 IU/l• ALP 83 IU/l• GGT 13 IU/l• T.Prot 8,2 g/dl• Albumin 5 g/dl• T. Bil 0,48 mg/dl• TSH 3.48• sT4 1.47• B-HCG <0.01

Donor-4• Hgb12,8• Hct 37,7• WBC 6680• PLT 256000• INR 0,96

• No Factor V leiden mut• No prothrombin gen

mut

• HBs Ag (-)• Anti-HBs (-)• AntiHBc IgG (-)• Anti-HAV IgG (+)• Anti-HCV (-)• Anti-HIV (-)• CMV IgG (+)• EBV IgG (+)

Donor-5

• Abdomen CT Imaging and Liver Volumetry– Total volume 1117 cc– Right lobe 712 cc– Left Lobe 405 cc (36%)

• MRCP

# of Cadaveric Donors pmp

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# of CD (pmp)

SpainBelgiumAustriaU.S.AFranceItalyEurotransplantGermanyHong KongTaiwanKoreaTurkey

When and Who Should be Transplanted ?

• Acute liver failure

• Decompansated liver cirrhosis– Ascites– Encephalopathy– Icter– Esophageal variceal bleeding

• Systemic Complications of Liver Cirrhosis– Hepatopulmonary syndrome– Hepatorenal syndrome

• HCC

PREOPERATİVE ASSESMENT

Transplantation team

Transplant Surgery

Hepatology

Radiology

Cardiology

Pulmonary Disease

Infectious Disease

Anestesiology and ICU

Internal Medicine

•Nephrology

•Hematology

•Endocrin•Onco

Psychiatry

LaboratoryPathology

Coordination•Nurses•Social support

Evaluation of the recipients• A careful history and physical examination;

• Liver cirrhosis is a systemic disease • Cardiopulmonary assessment,

– Cardiac echocardiography, – pulmonary function tests, – Dobutamine stress testing, – cardiac catheterization in selected patients;

• Laboratory studies to confirm the etiology and severity of liver disease

• Creatinine clearance

Laboratory Studies-1• Biochemical analysis

– LFT

– RFT

– Alb/protein

– Tumor markers (AFP, Ca 19/9,..)

– Urinalysis-• urinary tract infection, proteinuria, hematuria,

Laboratory Studies-2• Laboratory studies to determine the status of

– current or previous hepatitis B virus (HBV), – hepatitis C virus, – Epstein-Barr virus, – cytomegalovirus, – human immunodeficiency virus (HIV) infections

Radiology• Abdominal imaging to determine

– hepatic artery – portal vein anatomy – presence of collaterals and shunts– presence of hepatocellular carcinoma (HCC).

• Doppler USG and CT angiography

• MRI should be performed, If creatinin level is not normal or history of hepatorenal syndrome or suspicion of HCC

Cardiac Evaluation-1 – Attention should be paid

• Over 50 years old• Male• Family history of CAD• Pre-TX diabetes• Alcoholic liver disease• Smoking• hyperlipidemia

– Echocardiography– Dobutamine stress test/dipyrimadole MPS– Angiography

Cardiac Evaluation-2 – Echocardiography

• EF• LV diastolic function• SPAP <45 no problem• SPAP 45-59 moderate PHT and over 60 mmHg is high mortality

right cardiac cateterization should be performed– Patients who had severe PHT (SPAP>60 mmHg) is

contraindication for LT since high perioperative mortality – If the SPAP decreases after medical treatment with

vasodilatator therapy, liver transplantation can be considered.

– PHT resolves within 4-6 months after LT and can be stopped.

Cardiac Evaluation-3– Most centers perform provacative tests since the

patients are too debilitated for exercise testing • Dobutamine stress test• Dipyridamole MPS

• In high risk patients coronary angiography– Risk of bleeding and renal failure!!!

• There is poor correlation between the tests and angiographic findings

Cardiac Evaluation-4

• 772 LT candidates underwent MPS at one center– 710 were low risk– 36 intermediate– 17 high risk– 9 did not complete study

• Intermediate and high risk patients underwent coronary angiograpghy

and because of CAD 26 patients denied LT

• 291 patients underwent LT– 18 had pretranplant high risk MPS (6%)– 25 months follow-up

• 10 patients had 13 coronary events• 5 of them were low risk preoperative MPS

Bradley SM, et al. Am J Cardio 2010

Cardiac Evaluation-AASLD Practice Guidelines

Pulmonary Evaluation• Pulmonary Evaluation

– X-ray– Pulse oxygen monitorization– Pulmonary function test– Thorax CT

• HCC• Smoking and family history of lung cancer

• Hepatopulmonary syndrome-– clubbing and hypoxemia –arterial ortostatic

deoxygenataion • PPHT

Hepatopulmonary Sydrome (HPS)

Liver disease

hypoxemia (arterial oxygenation defect)

intrapulmonary vasodilatation

Prevalance 4-47 %

• Platipne • Orthodeoksi• hypoxemia during sleep• siyanosis• clubbing• spider nevi

Clinic features

HPS-Diagnosis

• No biochemical marker Ø• Arterial blood gas analysis• Pulse oxymetry• Orto-deoxygenation test• TT ECHO• Scintigraphy• Pulmonary angiography

Scintigraphy

Hepatopulmonary syndrome: Scintigraphy. Pulmonary perfusion images obtained with technetium 99m (99mTc) macroaggregated albumin show extrapulmonary

uptake in the kidneys. This indicates right-to-left shunting.

1. Medical treatment

2. TIPS?

coil for large AVM

3. Liver TX

pO2 < 50 high risk

100% O2 and no improvement------poor prognosis

HPS-Treatment

metilen blue

NOS inhibitors

Almitrine bimesylate

anti-TNF

Pulmonary angiography-CT

PPHT• There should not be any primary cardiac and pulmonary disease and

– SPAP <45 mmHg --no problem– SPAP 45-59 mmHg-- moderate PHT – SPAP over 60 mmHg-- has high mortality and right cardiac

cateterization should be performedor

mean PAP >25 mmHg, at resting or 30 mmHg during exercise, increased pulmonary vasculare resistance PVR>240 dynes/s/cm)pulmonary arterial wedge pressure <15 mmHg .

– Patients who had severe PHT (SPAP>60 mmHg) is contraindication for LT since high perioperative mortality

– If the SPAP decreases after medical treatment with vasodilatator therapy, liver transplantation can be considered.

– PHT resolves within 4-6 months after LT and can be stopped.

PPHT- medical treatment

PPHT- Liver TXmPAP 50 mm-Hg is independent factor for mortality and has 100% mortality

Renal Functions

• Elevated serum creatinine level is an independent factor for RF and decreased survival after LT

• Patients preexisting primary renal disease has diminished survival and increased risk for posttransplant hemodialysis requirement

• Patients with chronic RF and liver disease should be considered for combined liver-kidney transplantation

• Hepatorenal syndrome that result in acute RF usually improves after LT

Murray KF and Carithers RL. Hepatology 2005

Renal Functions• In the presence of hepatorenal sydrome

– Albumin (1 g/kg/day) plus terlipressin– Stop diuretics– Avoid nephotoxic drugs– Stop propanolol – LT is the treatment choice and should be given high priority– Combined liver-kidney transplantation does not provide overall

results and should not be recommended for HRS.

• Preexisting renal disease– Nephrology consultation should be performed– Proteinuria, CrCl, baseline Cr level are important for

posttransplant period and survival– Combined liver-kidney transplantation

Recipient-screening• Screening

–Mamography–Colonoscopy

• Age• Family history of colon cancer• Primary sclerosing cholangitis• Ulcerative colitis

–Urology and Gynecology colsultations

Osteoporosis• It is a common complication of cirrhosis

– Postmenuoposal women– PBC– PSC– Auotimmune hapatitis that were given prolonged

steroids– Alcoholic patients

• Vitamin D and calcium support for osteopenic patients

• Bisphosphonates should be given carefully because of varices !!!!

Recipient with HCC

• Patients with HCC– Abdomen CT/MRI and angiography

– Thorax CT

– Bone scannig

– PET-CT ?

– AFP (higher than 400 ng/ml has poor prognosis)

Specific issues• Age

– There is no spesific age limitation– Older patients have lower long-term survival

• Obesity– Morbid obesity should be considered a contrindication for LT– Patient with morbid obesity (BMI>40) and severe obesity

(BMI>35) has lower survival after LT– Bariatric surgery?

• Smoking– HAT is higher in chronic smokers– Increased malignancy and cardiac disease after LT

Disease Spesific Treatment-1• In patients with HBV

– Naïve patients• Entecavir• Tenofovir

– Under lamivudine therapy and DNA (-)• adding tenofovir at the posttransplant period

– Under LAM or entecavir and DNA (+) or viral breakthrough• Switch tenofovir or adding tenofovir on LAM or entecavir

• In decompansated HCV– If the patient has living donor, patient child B and well status

PEG-INF can be given with caution because of side effects and risk of progression of decompansation

– Child C patients, we do not give any spesific antiviral treatment

Recipient Evaluation-summary• Anamnesis and physical examination• Laboratory tests• Imaging• Preoperative treatment

– Renal functions, anti-viral treatment, diuretics, terlipressin plus albumin, lactulose, antibiotics, sildefanil, ….

• Consultations– Radiology: anotomy, mass, PVT, …– Cardiology– Pulmonary Evaluation– Infectious Disease– ICU and anestesiology– Gynecology/Urology– Psychiatric – Hematology/Nephrology/Endocrinology….

DONOR

EVALUATION

Living Donor-Step 1

• Age ->18, <50 years old

• Blood type and volunteering

• Interviewing for general information – should be lonely and without other relatives– psychiatric evaluation should be performed

• in the presence of suspicion of volunteering• suspicion of alcohol or drug abuse• psychiatric disease

• Anamnesis and physical examination– BMI– Systemic disease– Hepatobiliary disease– Thrombophila

Living Donor-Step-2

• Biochemical analysis– Liver FT– Renal FT– Fasting glucose– Lipid profiles– TSH– sT4– Protein electrophoresis– Seruloplasmin– Urinalysis– HOMA score– OGTT– HbA1c

• Hemogram• INR

• Serology– HBsAg– AntiHBC total– AntiHBs– AntiHAV IgG– Anti-HCV– Anti-HIV– VDRL

Living Donor-Step-2

• Hereditary tests for thrombosis– Factor V leiden mutation

– Protrombin gene mutation

• If the recipient has Wilson disease– 24 hour urinary copper– eye examination

• Autoimmune Tests– If the recipient disease is

autoimmune liver disease

• ANA• AMA• ASMA• LKM• SLA• HLA?

Living Donor-Step-3• Anotomical assessment

– Abdomen CT and CT angiography• GBWR should be 0.8 (lower limit 0.7, <0.7 SFSS)• Remnant volume should be 35%,

– sometimes could be 30% according to age and MHV satus • Steatosis should be <10%• PV anotomy• HV anotomy

– MRCP

Living Donor-Step-4• Liver Bx

– BMI>28– Hyperlipidemia– >10 steatosis on CT evaluation– antiHBC (+) donors– metabolic or autoimmune liver disease

diagnosis of the recipient and primary relationship

Living Donation and Steatosis• Most patients has insulin resistance and

overweight• Exercise and dietetian consultation• Metformin• Omega-3 fish oil• Hyperlipidemia should be corrected• Donor who should not weight loss in 4-8

weeks probably unwillingness !!!

Living Donor-Consultations

– Phsychiatry

– Pulmonary

– Cardiology-

Living Donor-Step-5

weekly meeting of liver transplantation unit

Transplantation team

Transplant Surgery

Hepatology

Radiology

Cardiology

Pulmonary Disease

Infectious Disease

Anestesiology and ICU

Internal Medicine

•Nephrology

•Hematology

•Endocrin•Onco

Psychiatry

LaboratoryPathology

Coordination•Nurses•Social support