Whom to Whom to transplant?transplant?And when?And when?

Dr. Harshal RajekarDr. Harshal Rajekar

Chronic Liver disease : Chronic Liver disease : CirrhosisCirrhosis

All patients with cirrhosis do not qualify for All patients with cirrhosis do not qualify for liver transplantation.liver transplantation.

Transplantation is generally considered Transplantation is generally considered when a patient has suffered from either a when a patient has suffered from either a complication of portal hypertension or complication of portal hypertension or decompensation.decompensation.

The onset of decompensation is associated The onset of decompensation is associated with significantly impaired survival.with significantly impaired survival.

The development of hepatorenal syndrome The development of hepatorenal syndrome is an ominous marker that signals the need is an ominous marker that signals the need for immediate transplant evaluation.for immediate transplant evaluation.

Chronic Liver Disease — Signs of Chronic Liver Disease — Signs of decompensationdecompensation

AscitesAscites EncephalopathyEncephalopathy Portal Hypertensive BleedingPortal Hypertensive Bleeding Hepatocellular Carcinoma in the Hepatocellular Carcinoma in the

setting of Cirrhosissetting of Cirrhosis

Chronic Liver Disease—Indications Chronic Liver Disease—Indications for Transplantationfor Transplantation

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 2 types, type 1 has very poor prognosis, >50% mortality at 2 weeks, and prognosis, >50% mortality at 2 weeks, and type 2 has 50% mortality at 1 year.type 2 has 50% mortality at 1 year.

Variceal bleed and hepatic encephalopathy: Variceal bleed and hepatic encephalopathy: difficult to quantify the effect on mortality difficult to quantify the effect on mortality as they are a mechanical result of portal as they are a mechanical result of portal hypertensionhypertension

Liver TransplantationLiver TransplantationQuestion for Transplant TeamQuestion for Transplant Team

• • When to list for liver When to list for liver transplantation?transplantation?

• • When to perform the liver When to perform the liver transplant?transplant?

When….?When….?

Patients who are too well should not be Patients who are too well should not be transplanted. transplanted.

Likewise, transplantation of patients who are Likewise, transplantation of patients who are too sick is associated with poor outcomes. too sick is associated with poor outcomes.

The goal of transplantation is to prolong The goal of transplantation is to prolong survival. survival.

Thus, liver transplantation should be Thus, liver transplantation should be performed at the time point when the performed at the time point when the patient is expected to have greater survival patient is expected to have greater survival with a liver transplant than without.with a liver transplant than without.

When?When?

cirrhotics should be referred for evaluation cirrhotics should be referred for evaluation when either when either

the Child-Pugh score = B (>6 points) or the Child-Pugh score = B (>6 points) or at the time they experience a first at the time they experience a first

complication of portal hypertension/ complication of portal hypertension/ decompensation (ascites, portal decompensation (ascites, portal hypertensive GI-bleeding, jaundice or hypertensive GI-bleeding, jaundice or encephalopathy). encephalopathy).

Less frequently, seriously impaired quality Less frequently, seriously impaired quality of life attributable to chronic liver disease of life attributable to chronic liver disease may by itself represent an indication for may by itself represent an indication for OLT, irrespective of liver function. OLT, irrespective of liver function.

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

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

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 when Refer to transplant team when

• • Child-Pugh score reaches >6 points. Child-Pugh score reaches >6 points.

OR OR

• • At first decompensation with ascites, At first decompensation with ascites, encephalopathy, variceal bleeding or jaundice encephalopathy, variceal bleeding or jaundice

OR OR

• • At diagnosis of HCC in cirrhosis, provided the MilanAt diagnosis of HCC in cirrhosis, provided the Milan

criteria are met. criteria are met.

OR OR

• • Impairment of quality of life due to liver disease Impairment of quality of life due to liver disease becomes intolerable (intractable pruritus, becomes intolerable (intractable pruritus, invalidating fatigue and/or performance status).invalidating fatigue and/or performance status).

PrognosticationPrognostication

Survival of a patient with ‘‘Child’s C Survival of a patient with ‘‘Child’s C cirrhosis’’ is about 20–30% at 1 year and cirrhosis’’ is about 20–30% at 1 year and less than 5% at 5 years. less than 5% at 5 years.

In contrast, the survival rate after In contrast, the survival rate after transplantation is 85–90% at 1 year and transplantation is 85–90% at 1 year and over 70% at 5 years. over 70% at 5 years.

By the time the patient has evidence of By the time the patient has evidence of advanced clinical liver disease (Child’s C advanced clinical liver disease (Child’s C cirrhosis), the patient may not survive long cirrhosis), the patient may not survive long enough to get a transplant.enough to get a transplant.

MELD scoreMELD score

• • MELD -- Model for End-Stage Liver MELD -- Model for End-Stage Liver Disease Disease Scoring System – MELD Score Scoring 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

MELD scoreMELD score

Introduced in Feb 2002.Introduced in Feb 2002. The MELD score originally was The MELD score originally was

developed and validated to assess the developed and validated to assess the short-term prognosis of patients with short-term prognosis of patients with cirrhosis undergoing TIPS.cirrhosis undergoing TIPS.

Developed by the Mayo Clinic.Developed by the Mayo Clinic. Using the MELD model, patients are Using the MELD model, patients are

assigned a score from 6 to 40.assigned a score from 6 to 40. Estimated 3-month survival for a score Estimated 3-month survival for a score

of 6 is 90%, and for a score of 40 is 7%.of 6 is 90%, and for a score of 40 is 7%.

Requirements for TransplantationRequirements for Transplantation

End stage liver diseaseEnd stage liver disease Physiologic ability to tolerate surgery: Physiologic ability to tolerate surgery:

Cardiac, pulmonary, renal, cerebral functionCardiac, pulmonary, 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 Alcohol abstinence for 6 months/ no

substance abusesubstance abuse

Contra-indicationsContra-indications

Cardiopulmonary disease that cannot be corrected Cardiopulmonary disease that cannot be corrected and is a prohibitive risk for surgery.and is a prohibitive risk for surgery.

Malignancy outside of the liver within five years of Malignancy outside of the liver within five years of evaluation (not including superficial skin cancers) or evaluation (not including superficial skin cancers) or not meeting oncologic criteria for cure.not meeting oncologic criteria for cure.

Active alcohol and drug use. Minimum period of Active alcohol and drug use. Minimum period of abstinence of at least six months (+/- participation abstinence of at least six months (+/- participation in a structured rehabilitation program) may be in a structured rehabilitation program) may be needed.needed.

Advanced age and AIDS are examples of Advanced age and AIDS are examples of relative relative contraindications.contraindications.

Liver transplantation can be performed in those Liver transplantation can be performed in those older than 65 provided that there has been a older than 65 provided that there has been a comprehensive search made for co-morbiditiescomprehensive search made for co-morbidities

Limitations of MELDLimitations of MELD

• • Patients with liver cancerPatients with liver cancer

• • Bile duct infectionsBile duct infections

• • ItchingItching

• • Disabling mental status changes (hepatic Disabling mental status changes (hepatic encephalopathy)encephalopathy)

• • ? Criteria for living donors? Criteria for living donors

Other conditions like : HPS, metabolic Other conditions like : HPS, metabolic diseases, congenital errors of diseases, congenital errors of metabolism, fulminant liver failure, graft metabolism, fulminant liver failure, graft non-function, etcnon-function, etc

Special issuesSpecial issues

HBV related: should ideally exhibit low levels HBV related: should ideally exhibit low levels of HBV replication HBV DNA <10of HBV replication HBV DNA <10^̂6 million 6 million copies/ml.copies/ml.

ALD: ≥ 6 months supervised community ALD: ≥ 6 months supervised community abstinence is required prior to listing in most abstinence is required prior to listing in most transplant programs.transplant programs.

PBC, PSC – usually the Mayo risk score is PBC, PSC – usually the Mayo risk score is used for listing.used for listing.

Patients with non-resectable HCC are Patients with non-resectable HCC are referred for LTx, provided the Milan criteria referred for LTx, provided the Milan criteria are fulfilled: 1 nodule ≤ 5 cm OR ≤ 3 nodules are fulfilled: 1 nodule ≤ 5 cm OR ≤ 3 nodules each ≤ 3 cm AND no vascular invasion.each ≤ 3 cm AND no vascular invasion.

CASECASE

A 52-year-old Mr. KG, k/c/o of cirrhosis A 52-year-old Mr. KG, k/c/o of cirrhosis secondary to hepatitis C and alcohol, secondary to hepatitis C and alcohol, abstinent for 30 mths. abstinent for 30 mths.

His hepatitis C was treated in the past with His 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 or He is well compensated without ascites or encephalopathy, and had grade 1 varices on encephalopathy, and had grade 1 varices on endoscopy. endoscopy.

He has no past medical history and is only He has no past medical history and is only taking some herbal medication. He is not taking some herbal medication. He is not working and continues to smoke. He has a working and continues to smoke. He has a remote history of intravenous drug use. remote history of intravenous drug use.

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 and Normal CVS and

respiratory systems.respiratory systems. Abdominal exam Abdominal exam

demonstrated a demonstrated a palpable liver edge and palpable liver edge and a spleen tip, minimal a spleen tip, minimal ascites and no ankle ascites and no ankle edema. edema.

No asterixis.No asterixis. He reports some loss of He 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 He underwent a CT scan.scan.

CT imagesCT images

Answer:Answer: Multifocal Hepatocellular Carcinoma Multifocal Hepatocellular Carcinoma

This patient has developed at least three lesions This patient has developed at least three lesions in the liver. The largest is hypervascular and is in the liver. The largest is hypervascular and is shown in the first image. It measures 4 cm in shown in the first image. It measures 4 cm in diameter. diameter.

Two smaller lesions are seen in the lower image Two smaller lesions are seen in the lower image and appear not to enhance but still are suspicious and appear not to enhance but still are suspicious for hepatocellular carcinoma (HCC). for hepatocellular carcinoma (HCC).

The liver has a nodular contour and the spleen is The liver has a nodular contour and the spleen is enlarged consistent with cirrhosis and portal enlarged consistent with cirrhosis and portal hypertension. hypertension.

Any hypervascular lesion in a cirrhotic liver is Any hypervascular lesion in a cirrhotic liver is considered to be HCC until proven otherwise and considered to be HCC until proven otherwise and biopsy runs the risk of seeding the needle track biopsy runs the risk of seeding the needle track

with HCC cells. with HCC cells. Biopsy/ FNAC is not required.Biopsy/ FNAC is not required.

LTx for HCCLTx for HCC

Milan: single tumour ≤5 cm; two or three Milan: single tumour ≤5 cm; two or three tumours, none >3 cm; no vascular invasiontumours, none >3 cm; no vascular invasion

UCSF: single tumour ≤6.5 cm; two or three UCSF: single tumour ≤6.5 cm; two or three tumours, none >4.5 cm; or total tumour tumours, none >4.5 cm; or total tumour diameter ≤8cm; no vascular invasiondiameter ≤8cm; no vascular invasion

Up to 7: in the absence of microvascular Up to 7: in the absence of microvascular invasion, seven is the result of the sum of invasion, seven is the result of the sum of size in cm and number of tumours for any size in cm and number of tumours for any given HCC.given HCC.

Asan criteria: tumor diameter <or=5 cm, Asan criteria: tumor diameter <or=5 cm, number of lesions <or=6, no gross vascular number of lesions <or=6, no gross vascular invasioninvasion

Donor liverDonor liver

Donor LiverDonor Liver

Cadaveric Cadaveric donor liver donor liver after back after back table table preparationpreparation

After reperfusion.After reperfusion.

Cirrhosis – HCV relatedCirrhosis – HCV related

Cirrhosis- Cirrhosis- HemochromatosisHemochromatosis

Cirrhosis – Alcohol Cirrhosis – Alcohol inducedinduced

THANK YOU!THANK YOU!