Indications for Liver Transplantation Dr.K.PANDURANGA RAO

The Liver The largest single organ in the human body. In an adult, it weighs about 1.5 Kg and is roughly the size of a football. Located in the upper right-hand part of the abdomen, behind the lower ribs.

Gross Anatomy The liver is divided) into four lobes: the right (the largest lobe), left, quadrate and caudate lobes. Supplied with blood via the protal vein and hepatic artery. Blood carried away by the hepatic vein. It is connected to the diaphragm and abdomainal walls by five ligaments. Gall Bladder Muscular bag for the storage, concentration, acidification and delivery of bile to small intestine The liver is the only human organ that has the remarkable property of self-regeneration. If a part of the liver is removed, the remaining parts can grow back to its original size and shape.

Microscopic Anatomy

What does the liver do? Multi-function, blood-processing “factory” Temporary nutrient storage (glucose-glycogen) Remove toxins from blood Remove old/damaged RBC’s Regulate nutrient or metabolite levels in blood—keep constant supply of sugars, fats, amino acids, nucleotides (including cholesterol) Secrete bile via bile ducts and gall bladder into small intestines.

LIVER FUNCTION TESTS ALT AST (SGOT) ALKALINE PHOSPHATASE BILIRUBIN PROTHROMBIN TIME/INR ALBUMIN

Acute and Chronic Liver Disease

Acute Liver Disease Infections Drugs – MANY – HERBALS/OTC Alcohol Viral Hepatitis A, B, C, D, E, EBV, CMV, HSV, Others – Leptospirosis, Toxoplasma, Drugs – MANY – HERBALS/OTC Alcohol Toxins Vascular obstruction (eg. Budd-Chiari)

Acute Liver failure(ALF) ALF is defined as hepatic encephalopathy occurring within 24 weeks of the onset of symptoms in patients with out preexisting liver disease.

Hyperacute Liver Failure 7 days or less Categorization of FHF Based on the time interval between onset of jaundice and encephalopathy Hyperacute Liver Failure 7 days or less Acute Liver Failure 8 to 28 days Subacute Liver Failure 5-24 weeks O’Grady et al.

Aetiology of FHF in india Acharaya et al Jaiswal et al (1999) (1996) No of Pt 458 95 HAV 4% 4.2% HBV 10.5% 27.3% HCV 4.4% 2.1% HDV 0% 5.2% HEV 23% 41% Mixed 6.3% 4.1% Non A, Non B 47% 15% Drugs 5% 0%

Chronic Liver Disease Alcohol Viral hepatitis: B & C Autoimmune – autoimmmune hepatitis, PBC (Primary Biliary cirrhosis), PSC (Primary Sclerosing Cholangitis) Non-alcoholic fatty liver disease (NAFLD) Drugs (MTX, amiodarone) Haemochromatosis Cystic fibrosis, a1antitryptin deficiency, Wilsons disease, Vascular problems (Portal hypertension + liver disease) Cryptogenic Others: sarcoidosis, amyloid, schistosomiasis

What is Cirrhosis?

Cirrhosis Definition: Hepatic necrosis and degeneration combined with hepatic regeneration and fibrosis leading to Nodular formation

Cirrhosis Of Liver

Complications of cirrhosis Variceal haemorrhage

Complications of cirrhosis Ascites

Hepato Renal Syndrome

Complications of cirrhosis Hepatic Encephalopathy

Liver Transplantation Liver transplantation (LT) is now established as the only definitive treatment for end stage liver disease (ESLD) Starzl et al carried out 1st human liver transplant in 1963 Survival following liver transplant 1 year survival: 87 – 93% 3 year survival: > 75% .....(http://www.ustransplant.org The 2009 Annual Report of the OPTN and SRTR: Transplant Data 1999-2008).

Liver Transplantation Issues Whether patient needs LT? When to refer or consider for LT? Is patient suitable for LT?

Scoring systems CHILD-TURCOTTE - PUGH SCORE CTP score:   Scoring systems CHILD-TURCOTTE - PUGH SCORE Measure 1 point 2 points 3 points Total Bilirubin  (mg/dl) < 2 2-3 >3 Serum albumin (g/dl) >3.5 2.8-3.5 <2.8 INR <1.7 1.71-2.3 > 2.3 Ascites None Slight/Suppressed with medication Moderate despite diuretics/Refractory Hepatic encephalopathy Grade I-II Grade III-IV CTP score: - Disease severity for pts with ESLD - Used to predict peri-operative mortality in patients with liver disease.

Perioperative mortality 5-6 A 15-20 years 10% 7-9 B Points Class Life expectancy Perioperative mortality 5-6 A 15-20 years 10% 7-9 B Candidate for transplant 30% 10-15 C 1-3 months 82% Shortcomings of CTP scores Subjective nature of the assessment of ascites & encephalopathy Limited discrimination into only three disease severity categories

Model for End-Stage Liver Disease (MELD) MELD score = 0.957 x Loge (creatinine mg/dl) + 0.378 x Loge (bilirubin mg/dl) + 1.12 x Loge (INR) + 0.643 Multiply the score by 10 and round to the nearest whole number Established in Feb 2002 Numerical scale, from 6 (less ill) to 40 (gravely ill) This ‘score’ tells us how urgently LT is required within next 3 months Most patients on LT waiting list have MELD score between 11 and 20

Upper limit of MELD.Estimated Survival A retrospective longitudinal cohort study in 232 patients The estimated survival for patients with MELD score > 25 was lower at 12 months (68.86% vs 39.13%). Ilka Fatima Ferreira Santana Boin et al, Arq Gastroenterol. 2008 Oct- ec;45(4):275-83

Indications for Liver Transplantation Proportion of liver transplants for specific etiologies, 1992–2007 O’Leary et al Gastroenterology 2008

Indications for Liver Transplantation

Main indications for LTx: complications of ESLD GE variceal bleed- each episode of bleeding carries a 20% mortaliity rate. LT is the best way to decompress the portal system if other therapies have failed. – De Francis et al, Baveno V, J Hepatology, 2010] HE- LT remains the only permanent Rx

Main indications for LTx: complications of ESLD 3. Refractory ascites- carries a mortality of >50% at 2 yrs. More prone for variceal bleed, HRS, SBP. Annual incidence of HRS in cirrhotics with ascites is 8% with median survival of 2 wks in Type I and 6 months in Type II. LT should be considered as soon as HRS is diagnosed. Planas et al, Clini gastro hepatology 2006;4:1385-94 Gines A et al, Gastroenterology 1993;105:229-36

Main indications for LTx: complications of ESLD 4. HPS- [4-47% prevalence] LT is the only curative Rx for HPS 5. PPHTN- 2-8%, associated with higher post transplantation mortality Individual etiologies – viral hepatitis, ALD, NAFLD, HPB malignancy, AIH, Cholestatic disorders, ALF, HCC.

Need for LT CTP and MELD most commonly used PBC/PSC have their own prognostic scores 5-year survival (CTP 7-15) with (ascites, bleeding, HE, SBP, HRS) : 20% to 50% Survival rates 1, 3, and 5 years after LT 88%, 80%, and 75% -Shetty K et al Hepatology 1997 -Kamath PS et al Hepatology 2001 -Freeman RB et al Liver Transpl 2004 -H-C Huang et al. Journal of Gastroenterology and Hepatology 24 (2009) 1716–1724 Predictive accuracy for short-term mortality

In pts with MELD<14, the mortality with LTx > not undergoing LTx Comparison of mortality risk expressed as hazard ratio by MELD score for recipients of liver transplants compared to candidates on the liver transplant waiting list – Merion et al, Am J transplantation 2005;5:307-13

Referred for LT when (CTP > 7 and MELD > 10) or they experience their first major complication (ascites, bleeding, or HE) - AASLD:Karen F et al Hepatology 2005 Berg CL et al Gastroenterology 2007 MELD under estimates – HCC, Cholangio Ca, HE, ascites, HPS, PPHTN, GI bleed etc

Contraindication for LT x x x

Donor Liver Allocation …… Liver Donor In US, patients name and condition is entered in National Registry CTP (CHILD-TURCOTTE - PUGH SCORE) scores in conjunction with United Network for Organ Sharing (UNOS) status determining factor was used for organ allocation in the USA until early 2002. but it did not always ensure that organs were allocated to the sickiest patients with the greatest risk of mortality. Now, Model for End-Stage Liver Disease (MELD) is used for allocating liver to recepients. In India, there is no such national registry or liver transplant centre registry.

Thank you

King’s college hospital indicators of poor prognosis in Acute Liver Failure

Hyperacute Liver Failure 7 days or less Categorization of FHF Based on the time interval between onset of jaundice and encephalopathy Hyperacute Liver Failure 7 days or less Acute Liver Failure 8 to 28 days Subacute Liver Failure 5-24 weeks O’Grady et al.