Liver transplantation can treat acute liver failure, end-stage liver disease, and some liver cancers. It carries risks of surgery, recurrent disease, and long-term immunosuppression. Acute liver failure is the highest priority for liver transplant (LT), defined as severe liver injury within 26 weeks without preexisting disease. Causes include viruses, drugs, and other factors. Cirrhosis may qualify for LT if complications develop from portal hypertension or liver dysfunction. Scoring systems like MELD and CTP predict disease severity and survival to help determine transplant need. Acute liver failure is further evaluated using criteria from King's College Hospital, Clichy, Japan, and models like MELD and ALFED.

1. Dr.M Rath

2. Liver transplantation...
 A definitive treatment option for patients with acute
liver failure, end-stage liver disease and primary
hepatic malignancies.
 Risk benefit analysis:
 Risks of surgery, recurrent disease & long term immuno
suppression.

3. Indications...
 Acute liver failure
 Cirrhosis
 Liver neoplasms
 Metabolic disorders

4. Acute liver failure...
 Highest priority for LT: UNOS status 1.
 Defined by development of severe acute liver injury
with encephalopathy and impaired synthetic function
in a patient without cirrhosis or preexisting liver
disease.
 Cut off illness duration varies: commonly <26weaks
 Viral and drug induced hepatitis are the most common
causes.

5. Causes of acute liver failure: ABCs
A Acetaminophen, Hep A, autoimmune, adenovirus, amanita phalloides
B HBV, Budd-chiari syndrome
C HCV, CMV, Cryptogenic
D Hep D, Drugs & toxins
E HEV, EBV
F Fatty infiltration: Reyes syndrome, AFLP
G Genetic: Wilson disease
H Hypoperfusion(Ischemia, sepsis), HELLP, hepatectomy, heat stroke
I Infiltration by tumor

6. Cirrhosis...
 Transplantation is considered for complications of
portal hypertension or manifestations of compromised
hepatic function.
 Variceal hemorrhage, ascites, encephalopathy:
markers of decompensation.
 MELD >15 or CTP B with portal hypertension
 Transplant evaluation started with MELD>10

7.  Conditions that qualify for MELD exception points:
 HCC
 hepatopulmonary syndrome
 Portopulmonary hypertension
 Familial amyloid polyneuropathy
 Primary hyperoxaluria
 Cystic fibrosis
 Hilar cholangiocarcinoma
 Hepatic artery thrombosis: within 14days of LT

8.  Conditions that do not qualify for standard MELD
exception points:
 PSC with repeated cholangitis
 Refractory ascitis
 Refractory HE
 Refractory variceal hemorrhage
 Portal hypertensive gastropathy: chronic blood loss
 Intractable pruritus in a patient with PBC

9. Liver neoplasms...
 Primary liver neoplasms:
 HCC: single <5cm, up to 3 lesions all < 3cm with no
vascular, nodal or distant metastasis.
 Epitheloid hemangioendethelioma
 Large hepatic adenoma
 NET metastasized to liver:

10. Metabolic disorders...
 Glycogen storage disorders(1&4)
 Tyrosinemis
 Hemochromtosis
 Wilsons disease
 Acute intermittent porphyria
 Alpha 1 antitrypsine deficiency
 Cystic fibrosis
 Familial amyloid polyneuropathy
 Primary hyperoxaluria

11. Contraindications...
 Cardiopulmonary disease that cannot be corrected
 AIDS
 Malignancy outside liver not meeting criteria for cure
 HCC with metastasis
 Intrahepatic cholangiocarcinoma
 Hemangiosarcoma
 Uncontrolled sepsis
 ALF with ICP>50 or CPP<40 mmhg
 Persistent nonadherance to medical care
 Lack of adequate social support

12. Scoring systems...
 Predictive models for estimating disease severity and
survival.
 Helpful in guiding patient care.
Generalized health status Organ specific
APACHE
SOFA
CTP
MELD
MELD-Na
ALFED

13. Scoring systems for chronic liver
disease...
 1964 : Surgeon Charles Gardner Child (with Turcotte)
of the university of Michigan first proposed the
scoring system in a textbook on liver disease.
 For risk stratification of portacaval shunt surgery in
patients with cirrhosis
 1972 : Modified by Pugh et al. in a report on surgical
treatment of bleeding from esophageal varices.
 Nutritional status Prothrombin time

15.  Child-Pugh classification:
 validated for the assessment of surgical risk.
 survival in patients not undergoing surgery.
 associated with the likelihood of developing of
complications of cirrhosis.

16. MELD score...
 Originally developed to predict three-month mortality
following TIPS procedure.
 Data from a population of 231 patients with cirrhosis
who underwent elective TIPS placement.
 The original model included serum bilirubin, serum
creatinine, INR, and etiology of the liver disease
(cholestatic or alcoholic versus other etiologies)

18.  MELD score has been validated in predicting mortality
in several groups of patients:
 patients on the waiting list for liver transplantation
 patients with hepatic decompensation
 ambulatory patients with non-cholestatic liver disease
 patients with primary biliary cholangitis
 Alcoholic hepatitis
 Variceal bleeding
 SBP
 HRS

19.  Used by UNOS in 2002 for prioritizing allocation of
deceased donor livers for transplantation.
 MELD = 3.8*loge(serum bilirubin [mg/dL]) +
11.2*loge(INR) + 9.6*loge(serum creatinine [mg/dL]) +
6.4
 maximum serum creatinine level was set to 4.0 mg/dL

20. MELD-Na and role of
hyponatremia...
 Severity of the hyponatremia is a marker of the
severity of the cirrhosis.
 January 2016, Organ Procurement and Transplantation
Network Policy (MELD Score) was updated to include
serum sodium as a factor in the calculation of the
MELD score.
 MELD-Na = MELD + 1.32 * (137-Na) - [0.033*MELD *
(137-Na)]

21. •linear increase in mortality by 5 percent for each mmol decrease in serum
sodium between 125 and 140 mmol/L .
•Addition of serum sodium to the MELD model elevates the transplant priority
for about 12 percent of listed patients.

23.  A limitation of MELD-Na score: serum sodium levels
may be vulnerable to alterations by diuretic use and
intravenous fluid administration.

25. Modifications...
 Updated MELD: lower weight to SCr and INR, higher
weight to bilirubin.
 Refit MELD: SCr 0.8-3 and INR 1-3
 Integrated MELD: includes Na and age
 MESO: MELD and Na ratio
 MELD-Na
 UKELD

27. ALF...
onset Defining event Illness duration
Trey and
Davidson, 1970
First symptoms encephalopathy 8 weeks
Bernuau et al,
1986
Jaundice encephalopathy 2 weeks: fulminant
2-12 weeks: sub fulminant
O Grady et al,
1993
jaundice encephalopathy 1 week: hyperacute
1-4 week: acute
5-12 weeks: subacute

28. Criteria for ALF
 King's College Hospital Criteria
 Clichy criteria
 Acute liver failure study group of Japan criteria
 MELD score
 CLIF SOFA
Probability of spontaneous recovery must be
compared with risks of surgery and immuno
suppression.

29.  Described in a seminal publication in 1989 by J.G.
O'Grady et al.
 588 patients with from 1973 - 1985 were assessed
retrospectively to determine any particular clinical
features or tests that correlated poorly with prognosis.
 Recommendations for liver transplantation in acute
liver failure were proposed based upon their outcomes.

31.  Sensitivity: 59-69%
 Specificity (in predicting mortality):
 92-95% for paracetamol related ALF
 82% for non paracetamol aetiology
 Increased to 93% with more advanced encephalopathy.

32. Clichy criteria...
 A group of criteria proposed for the survival of
individuals with acute liver failure (viral hepatitis) .
 Two criteria predicted the prognosis of patients with
poor survival:
 Factor V level <20 % of its normal value for age < 30yr.
 Factor V level <30 %f its normal value for age>30yr.
 The positive predictive value of mortality was 82% and
the negative predictive value of mortality was 98%.

33. ALF study group of Japan criteria...

34. MELD in ALF...
 Has been used to predict survival among patients with
acute liver failure.
 In a study of 91 patients with non-acetaminophen-
related acute liver failure, the MELD score was
compared with the King's College Criteria
 MELD score of 32 or higher has sensitivity of 79% and
specificity of 71% in predicting mortality.

37. ALFED model...

38.  four variables:
 arterial ammonia
 serum bilirubin
 INR
 HE >grade II
 increase in mortality with increasing risk scores from 0 to 6
 performance of the ALFED model was superior to the
King's College Hospital criteria and the MELD score.
 ALFED score of ≥4 had a high positive predictive value
(85%) and negative predictive value (87%)

40.  Thank you.