timing and indications of liver transplantation

1. Whom to transplant?Whom to transplant?
And when?And when?
Dr. HarsHal rajekarDr. HarsHal rajekar

2. Chronic Liver disease : CirrhosisChronic Liver disease : Cirrhosis
 All patients with cirrhosis do not qualify for liverAll patients with cirrhosis do not qualify for liver
transplantation.transplantation.
 Transplantation is generally considered when aTransplantation is generally considered when a
patient has suffered from either a complication ofpatient has suffered from either a complication of
portal hypertension or decompensation.portal hypertension or decompensation.
 The onset of decompensation is associated withThe onset of decompensation is associated with
significantly impaired survival.significantly impaired survival.
 The development of hepatorenal syndrome is anThe development of hepatorenal syndrome is an
ominous marker that signals the need forominous marker that signals the need for
immediate transplant evaluation.immediate transplant evaluation.

3. Chronic Liver Disease — Signs ofChronic Liver Disease — Signs of
decompensationdecompensation
 AscitesAscites
 EncephalopathyEncephalopathy
 Portal Hypertensive BleedingPortal Hypertensive Bleeding
 Hepatocellular Carcinoma in the setting ofHepatocellular Carcinoma in the setting of
CirrhosisCirrhosis

4. Chronic Liver Disease—Indications forChronic Liver Disease—Indications for
TransplantationTransplantation
 AscitesAscites
 Ascites has a two-year mortality of 50%Ascites has a two-year mortality of 50%
 SBP has a two-year mortality of 80%SBP has a two-year mortality of 80%
 Hepato-Renal Syndrome :Hepato-Renal Syndrome :
-- 2 types, type 1 has very poor prognosis, >50%2 types, type 1 has very poor prognosis, >50%
mortality at 2 weeks, and type 2 has 50% mortalitymortality at 2 weeks, and type 2 has 50% mortality
at 1 year.at 1 year.
 Variceal bleed and hepatic encephalopathy:Variceal bleed and hepatic encephalopathy:
difficult to quantify the effect on mortality as theydifficult to quantify the effect on mortality as they
are a mechanical result of portal hypertensionare a mechanical result of portal hypertension

5. Liver TransplantationLiver Transplantation
Question for Transplant TeamQuestion for Transplant Team
•• When to list for liver transplantation?When to list for liver transplantation?
•• When to perform the liver transplant?When to perform the liver transplant?

6. When….?When….?
 Patients who are too well should not bePatients who are too well should not be
transplanted.transplanted.
 Likewise, transplantation of patients who are tooLikewise, transplantation of patients who are too
sick is associated with poor outcomes.sick is associated with poor outcomes.
 The goal of transplantation is to prolong survival.The goal of transplantation is to prolong survival.
 Thus, liver transplantation should be performed atThus, liver transplantation should be performed at
the time point when the patient is expected to havethe time point when the patient is expected to have
greater survival with a liver transplant than without.greater survival with a liver transplant than without.

7. When?When?
cirrhotics should be referred for evaluation whencirrhotics should be referred for evaluation when
eithereither
 the Child-Pugh score = B (>6 points) orthe Child-Pugh score = B (>6 points) or
 at the time they experience a first complication ofat the time they experience a first complication of
portal hypertension/ decompensation (ascites,portal hypertension/ decompensation (ascites,
portal hypertensive GI-bleeding, jaundice orportal hypertensive GI-bleeding, jaundice or
encephalopathy).encephalopathy).
 Less frequently, seriously impaired quality of lifeLess frequently, seriously impaired quality of life
attributable to chronic liver disease may by itselfattributable to chronic liver disease may by itself
represent an indication for OLT, irrespective ofrepresent an indication for OLT, irrespective of
liver function.liver function.

8. Other issues?Other issues?
Quality of life issuesQuality of life issues
–– Severe lethargySevere lethargy
–– Intractable itchingIntractable itching
–– Recurrent bile duct infectionsRecurrent bile duct infections
–– Intractable ascitesIntractable ascites
–– Severe bone thinningSevere bone thinning
–– PainPain

9. General PrognosisGeneral Prognosis
EVENTEVENT Survival (yrs)Survival (yrs)
Any decompensation 1.6
GI bleed d/t PHT 2 (dependent on CTP
score)
Ascites 2
SBP <1
HRS Weeks to months

10.  Acute Liver Failure (irrespective of etiology)Acute Liver Failure (irrespective of etiology)
 •• Contact transplant team when INR is >2.Contact transplant team when INR is >2.
 End-stage Chronic Liver Disease.End-stage Chronic Liver Disease.
 Refer to transplant team whenRefer to transplant team when
•• Child-Pugh score reaches >6 points.Child-Pugh score reaches >6 points.
OROR
•• At first decompensation with ascites, encephalopathy,At first decompensation with ascites, encephalopathy,
variceal bleeding or jaundicevariceal bleeding or jaundice
OROR
•• At diagnosis of HCC in cirrhosis, provided the MilanAt diagnosis of HCC in cirrhosis, provided the Milan criteriacriteria
are met.are met.
OROR
•• Impairment of quality of life due to liver disease becomesImpairment of quality of life due to liver disease becomes
intolerable (intractable pruritus, invalidating fatigueintolerable (intractable pruritus, invalidating fatigue
and/or performance status).and/or performance status).

11. PrognosticationPrognostication
 Survival of a patient with ‘‘Child’s C cirrhosis’’ isSurvival of a patient with ‘‘Child’s C cirrhosis’’ is
about 20–30% at 1 year and less than 5% at 5about 20–30% at 1 year and less than 5% at 5
years.years.
 In contrast, the survival rate after transplantation isIn contrast, the survival rate after transplantation is
85–90% at 1 year and over 70% at 5 years.85–90% at 1 year and over 70% at 5 years.
 By the time the patient has evidence of advancedBy the time the patient has evidence of advanced
clinical liver disease (Child’s C cirrhosis), theclinical liver disease (Child’s C cirrhosis), the
patient may not survive long enough to get apatient may not survive long enough to get a
transplant.transplant.

12. MELD scoreMELD score
•• MELD -- Model for End-Stage LiverMELD -- Model for End-Stage Liver DiseaseDisease
Scoring System – MELD ScoreScoring System – MELD Score
= 0.957 x Log= 0.957 x Logee(creatinine mg/dl)(creatinine mg/dl)
+ 0.378 x Log+ 0.378 x Logee(bilirubin mg/dl)(bilirubin mg/dl)
+ 1.120 x Log+ 1.120 x Logee(INR)(INR)
+ 0.643+ 0.643
MELD score depends upon kidney function,MELD score depends upon kidney function,
bilirubin level and clotting factor levelsbilirubin level and clotting factor levels

13. MELD scoreMELD score
 Introduced in Feb 2002.Introduced in Feb 2002.
 The MELD score originally was developed andThe MELD score originally was developed and
validated to assess the short-term prognosis ofvalidated to assess the short-term prognosis of
patients with cirrhosis undergoing TIPS.patients with cirrhosis undergoing TIPS.
 Developed by the Mayo Clinic.Developed by the Mayo Clinic.
 Using the MELD model, patients are assignedUsing the MELD model, patients are assigned
a score from 6 to 40.a score from 6 to 40.
 Estimated 3-month survival for a score of 6 isEstimated 3-month survival for a score of 6 is
90%, and for a score of 40 is 7%.90%, and for a score of 40 is 7%.

14. Requirements for TransplantationRequirements for Transplantation
 End stage liver diseaseEnd stage liver disease
 Physiologic ability to tolerate surgery: Cardiac,Physiologic ability to tolerate surgery: Cardiac,
pulmonary, renal, cerebral functionpulmonary, renal, cerebral function
 Anatomy – status of vessels (PV/HA/HV)Anatomy – status of vessels (PV/HA/HV)
 Social support/ psychological supportSocial support/ psychological support
 No extra-hepatic infection or malignancyNo extra-hepatic infection or malignancy
 Alcohol abstinence for 6 months/ no substanceAlcohol abstinence for 6 months/ no substance
abuseabuse

15. Contra-indicationsContra-indications
 Cardiopulmonary disease that cannot be corrected and is aCardiopulmonary disease that cannot be corrected and is a
prohibitive risk for surgery.prohibitive risk for surgery.
 Malignancy outside of the liver within five years ofMalignancy outside of the liver within five years of
evaluation (not including superficial skin cancers) or notevaluation (not including superficial skin cancers) or not
meeting oncologic criteria for cure.meeting oncologic criteria for cure.
 Active alcohol and drug use. Minimum period of abstinenceActive alcohol and drug use. Minimum period of abstinence
of at least six months (+/- participation in a structuredof at least six months (+/- participation in a structured
rehabilitation program) may be needed.rehabilitation program) may be needed.
 Advanced age and AIDS are examples ofAdvanced age and AIDS are examples of relativerelative
contraindications.contraindications.
 Liver transplantation can be performed in those older thanLiver transplantation can be performed in those older than
65 provided that there has been a comprehensive search65 provided that there has been a comprehensive search
made for co-morbiditiesmade for co-morbidities

16. Limitations of MELDLimitations of MELD
•• Patients with liver cancerPatients with liver cancer
•• Bile duct infectionsBile duct infections
•• ItchingItching
•• Disabling mental status changes (hepaticDisabling mental status changes (hepatic
encephalopathy)encephalopathy)
•• ? Criteria for living donors? Criteria for living donors
Other conditions like : HPS, metabolic diseases,Other conditions like : HPS, metabolic diseases,
congenital errors of metabolism, fulminant livercongenital errors of metabolism, fulminant liver
failure, graft non-function, etcfailure, graft non-function, etc

17. Special issuesSpecial issues
 HBV related: should ideally exhibit low levels ofHBV related: should ideally exhibit low levels of
HBV replication HBV DNA <10HBV replication HBV DNA <10^^
6 million copies/ml.6 million copies/ml.
 ALD: ≥ 6 months supervised communityALD: ≥ 6 months supervised community
abstinence is required prior to listing in mostabstinence is required prior to listing in most
transplant programs.transplant programs.
 PBC, PSC – usually the Mayo risk score is usedPBC, PSC – usually the Mayo risk score is used
for listing.for listing.
 Patients with non-resectable HCC are referred forPatients with non-resectable HCC are referred for
LTx, provided the Milan criteria are fulfilled: 1LTx, provided the Milan criteria are fulfilled: 1
nodule ≤ 5 cm OR ≤ 3 nodules each ≤ 3 cm ANDnodule ≤ 5 cm OR ≤ 3 nodules each ≤ 3 cm AND
no vascular invasion.no vascular invasion.

18. CASECASE
 A 52-year-old Mr. KG, k/c/o of cirrhosis secondaryA 52-year-old Mr. KG, k/c/o of cirrhosis secondary
to hepatitis C and alcohol, abstinent for 30 mths.to hepatitis C and alcohol, abstinent for 30 mths.
 His hepatitis C was treated in the past withHis hepatitis C was treated in the past with
pegylated interferon but he did not respond.pegylated interferon but he did not respond.
 He is well compensated without ascites orHe is well compensated without ascites or
encephalopathy, and had grade 1 varices onencephalopathy, and had grade 1 varices on
endoscopy.endoscopy.
 He has no past medical history and is only takingHe has no past medical history and is only taking
some herbal medication. He is not working andsome herbal medication. He is not working and
continues to smoke. He has a remote history ofcontinues to smoke. He has a remote history of
intravenous drug use.intravenous drug use.

19.  O/E:O/E:
Wt -78kg,Wt -78kg,
BP 110/70,BP 110/70,
HR - 65 and he is afebrile.HR - 65 and he is afebrile.
 He had no icterus.He had no icterus.
 Normal CVS andNormal CVS and
respiratory systems.respiratory systems.
 Abdominal examAbdominal exam
demonstrated a palpabledemonstrated a palpable
liver edge and a spleenliver edge and a spleen
tip, minimal ascites andtip, minimal ascites and
no ankle edema.no ankle edema.
 No asterixis.No asterixis.
 He reports some loss ofHe reports some loss of
weight (not quantified).weight (not quantified).
Laboratory StudiesLaboratory Studies
 Hb 12.5 g/dlHb 12.5 g/dl
 Platelets 84,000/μlPlatelets 84,000/μl
 INR 1.5INR 1.5
 Creatinine 1.2 mg/dlCreatinine 1.2 mg/dl
 Tbili 1.6 mg/dlTbili 1.6 mg/dl
 AST 47 iu/lAST 47 iu/l
 ALT 34 iu/lALT 34 iu/l
 ALP 112 iu/lALP 112 iu/l
 Albumin 3.1 g/dlAlbumin 3.1 g/dl
 AFP 12ng/mlAFP 12ng/ml
He underwent a CT scan.He underwent a CT scan.

20. CT imagesCT images

21. Answer:Answer: Multifocal Hepatocellular CarcinomaMultifocal Hepatocellular Carcinoma
 This patient has developed at least three lesions in theThis patient has developed at least three lesions in the
liver. The largest is hypervascular and is shown in theliver. The largest is hypervascular and is shown in the
first image. It measures 4 cm in diameter.first image. It measures 4 cm in diameter.
 Two smaller lesions are seen in the lower image andTwo smaller lesions are seen in the lower image and
appear not to enhance but still are suspicious forappear not to enhance but still are suspicious for
hepatocellular carcinoma (HCC).hepatocellular carcinoma (HCC).
 The liver has a nodular contour and the spleen isThe liver has a nodular contour and the spleen is
enlarged consistent with cirrhosis and portalenlarged consistent with cirrhosis and portal
hypertension.hypertension.
Any hypervascular lesion in a cirrhotic liver is consideredAny hypervascular lesion in a cirrhotic liver is considered
to be HCC until proven otherwise and biopsy runs theto be HCC until proven otherwise and biopsy runs the
risk of seeding the needle track with HCC cells.risk of seeding the needle track with HCC cells.
Biopsy/ FNAC is not required.Biopsy/ FNAC is not required.

22. LTx for HCCLTx for HCC
 Milan: single tumour ≤5 cm; two or three tumours,Milan: single tumour ≤5 cm; two or three tumours,
none >3 cm; no vascular invasionnone >3 cm; no vascular invasion
 UCSF: single tumour ≤6.5 cm; two or threeUCSF: single tumour ≤6.5 cm; two or three
tumours, none >4.5 cm; or total tumour diametertumours, none >4.5 cm; or total tumour diameter
≤8cm; no vascular invasion≤8cm; no vascular invasion
 Up to 7: in the absence of microvascular invasion,Up to 7: in the absence of microvascular invasion,
seven is the result of the sum of size in cm andseven is the result of the sum of size in cm and
number of tumours for any given HCC.number of tumours for any given HCC.
 Asan criteria: tumor diameter <or=5 cm, number ofAsan criteria: tumor diameter <or=5 cm, number of
lesions <or=6, no gross vascular invasionlesions <or=6, no gross vascular invasion

23. Donor liverDonor liver

24. Donor LiverDonor Liver
 CadavericCadaveric
donor liverdonor liver
after backafter back
tabletable
preparationpreparation

25. After reperfusion.After reperfusion.

26. Cirrhosis – HCV relatedCirrhosis – HCV related

27. Cirrhosis-Cirrhosis-
HemochromatosisHemochromatosis
 Cirrhosis – AlcoholCirrhosis – Alcohol
inducedinduced

28. THANK YOU!THANK YOU!