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?

• 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.

Multi-function, blood-processing “factory”

LIVER FUNCTION TESTS

• ALT

• AST (SGOT)

• ALKALINE PHOSPHATASE

• BILIRUBIN

• PROTHROMBIN TIME/INR

• ALBUMIN

Acute and Chronic Liver Disease

Acute Liver Disease• Infections

– 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

• Acute Liver Failure 8 to 28 days

• Subacute Liver Failure 5-24 weeks

O’Grady et al.

Categorization of FHF Based on the time interval between onset of jaundice and encephalopathy

Aetiology of FHF in india

• 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, 1antitryptin deficiency, Wilsons disease, • Vascular problems (Portal hypertension + liver disease)• Cryptogenic• Others: sarcoidosis, amyloid, schistosomiasis

What is Cirrhosis?What is Cirrhosis?

Definition:

Hepatic necrosis and degeneration combined with

hepatic regeneration and fibrosis leading to

Nodular formationNodular formation

Cirrhosis

Cirrhosis Of Liver

Complications of cirrhosisVariceal haemorrhage

Complications of cirrhosisAscites

Hepato Renal Syndrome

Complications of cirrhosisHepatic 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

Measure 1 point 2 points 3 pointsTotal Bilirubin

(mg/dl)< 2 2-3 >3

Serum albumin (g/dl) >3.5 2.8-3.5 <2.8INR <1.7 1.71-2.3 > 2.3

Ascites None Slight/Suppressed with medication

Moderate despite diuretics/Refractory

Hepatic encephalopathy

None Grade I-II Grade III-IV

 

CHILD-TURCOTTE - PUGH SCORE

CTP score:- Disease severity for pts with ESLD- Used to predict peri-operative mortality in patients with liver disease.

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, 1992–2007O’Leary et al Gastroenterology 2008

Indications for Liver Transplantation

Main indications for LTx: complications of ESLD

1. 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]

2. 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;4:1385-94Gines 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%

Predictive accuracy for short-term mortality

-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

• 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

In pts with MELD<14, the mortality with LTx > not undergoing LTx

• 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

• 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.

…… Liver DonorDonor Liver Allocation

Thank you

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

• Hyperacute Liver Failure 7 days or less

• Acute Liver Failure 8 to 28 days

• Subacute Liver Failure 5-24 weeks

O’Grady et al.

Categorization of FHF Based on the time interval between onset of jaundice and encephalopathy