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Living Donor Liver Transplantation: Recipient and Donor Evaluation. Dr.Murat AKYILDIZ, MD Associate Professor of Gastroenterology Istanbul Bilim University, Department of Gastroenterology, Sisli Florence Nightingale Hospital, Organ Transplantation Center, Istanbul /. Road map.
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Living Donor Liver Transplantation:Recipient and Donor Evaluation Dr.Murat AKYILDIZ, MD Associate Professor of Gastroenterology Istanbul Bilim University, Department of Gastroenterology, Sisli Florence Nightingale Hospital, Organ Transplantation Center, Istanbul /
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
Medical History-2 • 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-3 • 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-4 • 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-5 • 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-6 • Surgical History • 15 years ago gynecologic operation (exisionalbx from vulva) • No hepatobiliary operation • Family History • No other liver disease • No genetic disease • Type 2 DiabetesMellitus (olderbrother)
Medical History-7 • 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
Physical Examination • Height 155 cm, Weight 59 kg, BMI 24.5 • She was oriented, cooperation was normal, • She was subicteric and there was temporalmuscleatrophy, multiple spiderangiomas, palmarerythema. • Blood pressure was 110/70 mmHg, heart rate 82/min/R, S1 and S2 were normal, no S3. • Respiratorysoundsweredecreased on the inferior and middle zones of the right lung. • Abdomen: There was remarkable ascites around the 3 cm- aboveumblicalline, umblicalhernia, Traube area was closed, 1 cm splenomegaly. There was (++) pretibialpittingedema • No flapping tremor and other spesific findings
Laboratory Na 131 mEq/dl K 4 mEq/dl Cholesterol 107 mg/dl Tryglycerid 45 mg/dl HbA1c 4 AFP 2.1 ng/ml Ca 19/9 84 ng/ml CEA 5.77 ng/ml Glucose :88 mg/dl BUN :15 mg/dl Crea :0.5 mg/dl AST :79 IU/l ALT :41 IU/l GGT :28 IU/l ALP :101 IU/l T.Bil :2.9 mg/dl Albumin : 2.9 g/dl
Laboratory HBs Ag (-) Anti-HBS (-) Anti-HBC IgG (+) AntiHAVIgG (+) HBV DNA (-) Anti-HCV (+) HCV-RNA:373.0000 Genotype: 1b INR 1.52 Hb 12 WBC 3300 PLT 88000 Blood type AB Rh(-) sT4 1.74 TSH 2.15 Ascites SAAG>1.1 WBC 100 Culture was steril
Laboratory • Urinalysis: 2-3 wbc, no protein, no RBC • Upper Endoscopy: no varices, portal hypertensive gastropathy • Colonoscopy: internal hemoroid
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 • BUN11 mg/dl • Cr 0,4 mg/dl • Na137mEq/dl • K4,4mEq/dl • Gluc93 mg/dl • HBA1C 4.6 • HOMA-IR2,17 • Chol 185 mg/dl • Tg 82 • AST15 IU/l • ALT12 IU/l • ALP83 IU/l • GGT13 IU/l • T.Prot8,2 g/dl • Albumin 5 g/dl • T. Bil0,48 mg/dl • TSH 3.48 • sT4 1.47 • B-HCG <0.01
Donor-4 • Hgb12,8 • Hct37,7 • WBC6680 • PLT256000 • INR 0,96 • No Factor V leidenmut • No prothrombin gen mut • HBs Ag (-) • Anti-HBs (-) • AntiHBcIgG (-) • 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
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
Evaluation of the recipients • A carefulhistoryandphysicalexamination; • Liver cirrhosis is a systemic disease • Cardiopulmonaryassessment, • Cardiacechocardiography, • pulmonaryfunctiontests, • Dobutaminestresstesting, • cardiaccatheterization in selectedpatients; • Laboratorystudiestoconfirmtheetiologyandseverity of liverdisease • Creatinineclearance
Laboratory Studies-1 • Biochemical analysis • LFT • RFT • Alb/protein • Tumor markers (AFP, Ca 19/9,..) • Urinalysis- • urinary tract infection, proteinuria, hematuria,
Laboratory Studies-2 • Laboratorystudiestodeterminethestatus of • currentorprevioushepatitis B virus (HBV), • hepatitis C virus, • Epstein-Barrvirus, • cytomegalovirus, • human immunodeficiencyvirus (HIV) infections
Radiology • Abdominalimagingtodetermine • hepaticartery • portalveinanatomy • presence of collaterals and shunts • presence of hepatocellularcarcinoma (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 • Attentionshould be paid • Over 50 yearsold • Male • Familyhistory of CAD • Pre-TX diabetes • Alcoholicliverdisease • Smoking • hyperlipidemia • Echocardiography • Dobutaminestress 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 • Dobutaminestress 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
Pulmonary Evaluation • PulmonaryEvaluation • X-ray • Pulse oxygen monitorization • Pulmonaryfunction test • Thorax CT • HCC • Smokingandfamilyhistory of lungcancer • Hepatopulmonary syndrome- • clubbing and hypoxemia –arterial ortostaticdeoxygenataion • PPHT
HepatopulmonarySydrome (HPS) Liver disease hypoxemia (arterial oxygenation defect) intrapulmonaryvasodilatation Prevalance4-47 %
Clinic features • Platipne • Orthodeoksi • hypoxemia during sleep • siyanosis • clubbing • spider nevi
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.
HPS-Treatment 1. Medical treatment 2. TIPS? coil for large AVM 3. Liver TX pO2 < 50 high risk 100% O2 and no improvement------poor prognosis metilen blue NOS inhibitors Almitrinebimesylate anti-TNF
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 performed or mean PAP >25 mmHg, at resting or 30mmHgduring 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.