dr.murat akyildiz, md associate professor of gastroenterology
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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
0
5
10
15
20
25
30
35
# 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
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