Transcript Slide 1

Recipient
Donor
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
(weekly/bimonthly),
• She had progressive dispne
was
performed
periodically
– 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 (exisional bx
from vulva)
– No hepatobiliary operation
• Family History
– No other liver disease
– No genetic disease
– Type 2 Diabetes Mellitus (older brother)
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 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 cmabove umblical line, umblical hernia, Traube area was closed,
1 cm splenomegaly. There was (++) pretibial pitting edema
• No flapping tremor and other spesific findings
Laboratory
Glucose
BUN
Crea
AST
ALT
GGT
ALP
T.Bil
Albumin
:88 mg/dl
:15 mg/dl
:0.5 mg/dl
:79 IU/l
:41 IU/l
:28 IU/l
:101 IU/l
:2.9 mg/dl
: 2.9 g/dl
Na
K
Cholesterol
Tryglycerid
HbA1c 4
AFP
Ca 19/9
CEA
131 mEq/dl
4 mEq/dl
107 mg/dl
45 mg/dl
2.1 ng/ml
84 ng/ml
5.77 ng/ml
Laboratory
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
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
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
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Liver cirrhosis
Portal hypertension
Ascites
No PVT
• Mamography
– normal
Consultations
• Cardiology
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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
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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
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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
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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
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Hgb12,8
Hct 37,7
WBC 6680
PLT 256000
INR 0,96
• No Factor V leiden mut
• No prothrombin gen
mut
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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
35
30
25
20
15
10
5
0
# of CD (pmp)
Spain
Belgium
Austria
U.S.A
France
Italy
Eurotransplant
Germany
Hong Kong
Taiwan
Korea
Turkey
When and Who Should be Transplanted ?
• Acute liver failure
• Decompansated liver cirrhosis
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Ascites
Encephalopathy
Icter
Esophageal variceal bleeding
• Systemic Complications of Liver Cirrhosis
– Hepatopulmonary syndrome
– Hepatorenal syndrome
• HCC
PREOPERATİVE ASSESMENT
Transplant
Surgery
Coordination
•Nurses
•Social
support
Hepatology
Laboratory
Pathology
Radiology
Transplantation team
Psychiatry
Cardiology
Internal
Medicine
•Nephrology
•Hematology
•Endocrin
•Onco
Pulmonary
Disease
Anestesiology
and ICU
Infectious
Disease
Evaluation of the recipients
• A careful history and physical examination;
• Liver cirrhosis is a systemic disease
• Cardiopulmonary assessment,
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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
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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
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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
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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 EvaluationAASLD Practice Guidelines
Pulmonary Evaluation
• Pulmonary Evaluation
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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 %
Clinic features
• Platipne
• Orthodeoksi
• hypoxemia during sleep
• siyanosis
•clubbing
• spider nevi
HPS-Diagnosis
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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
metilen blue
NOS inhibitors
Almitrine bimesylate
anti-TNF
3. Liver TX
pO2 < 50 high risk
100% O2 and no improvement------poor prognosis
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 performed
or
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 TX
mPAP 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
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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
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Anamnesis and physical examination
Laboratory tests
Imaging
Preoperative treatment
– Renal functions, anti-viral treatment, diuretics,
terlipressin plus albumin, lactulose, antibiotics,
sildefanil, ….
• Consultations
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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
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Liver FT
Renal FT
Fasting glucose
Lipid profiles
TSH
sT4
Protein electrophoresis
Seruloplasmin
Urinalysis
HOMA score
OGTT
HbA1c
• Hemogram
• INR
• Serology
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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
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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
Transplant
Surgery
Coordination
•Nurses
•Social
support
Hepatology
Laboratory
Pathology
Radiology
Transplantation team
Psychiatry
Cardiology
Internal
Medicine
•Nephrology
•Hematology
•Endocrin
•Onco
Pulmonary
Disease
Anestesiology
and ICU
Infectious
Disease