DAD

1. Indications for Liver
Transplantation
Dr.K.PANDURANGA RAO

2. 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.

3. 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.

4. Microscopic Anatomy

5. 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”

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

7. Acute and Chronic Liver Disease

8. 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)

9. 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.

10. • 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

11. 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%

12. 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

13. What is Cirrhosis?

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

16. Cirrhosis Of Liver

21. Complications of cirrhosis
Variceal haemorrhage

23. Complications of cirrhosis
Ascites

26. Hepato Renal Syndrome

27. Complications of cirrhosis
Hepatic Encephalopathy

34. 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).

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

36. Scoring systems
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
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.

37. 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

38. 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

39. 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

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

41. Indications for Liver Transplantation

42. 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

43. 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

44. 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.

45. 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

46. • 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

47. • 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

48. Contraindication for LT
x
x
x

49. • 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 Donor
Donor Liver Allocation

50. Thank you

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

52. • 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