Liver Transplantation Malay Shah, MD Surgical Director, Liver Transplantation Associate Professor of Surgery University of Kentucky Medical Center

Financial Disclosures

Unfortunately, I have no financial commitments or relationships to disclose

1.Discuss indications & contraindications for liver transplant 2. Review allocation of livers for transplantation 3. Discuss the MELD score and its implications for survival with and without transplant

Objectives

Clinical Features of Cirrhosis

Clinical Features of Cirrhosis

Clinical Features of Cirrhosis

Clinical Features of Cirrhosis

Clinical Features of Cirrhosis

Clinical Features of Cirrhosis

THIS ULTIMATELY LEADS TO…

When is Liver Transplant Indicated?

Liver transplantation is indicated in cirrhotic patients when the risk of death without transplant exceeds the risk of death with transplant

Surgical Complications 1% mortality high morbidity

Infections Drug side effects Recurrence of liver disease: HCC,

HepC

Malignancy Risk: Non-melanoma skin CA: RR 30 Kidney: RR 9 HCC and Gyn cancers: RR 5 Bladder, Thyroid, Melanoma, and NHL:

RR 3 Colorectal, Lung: RR 2 Pancreas: RR 1.5 Breast: RR 1.1

10% one-yr mortality

When is Liver Transplant Indicated? Defining the Risks

• Cirrhosis with hepatic decompensation and MELD score ≥ 15 (or Na-MELD ≥ 15): Hep B/C, EtOH, PBC, PSC, biliary atresia, AIH, NASH

• HCC within Milan criteria

• Fulminant liver failure

• MELD EXCEPTIONS : metastatic neuroendocrine tumor, hepatic hydrothorax, recurrent cholangitis, hepatopulmonary syndrome, etc.

Indications for Liver Transplant

Active EtOH use Illicit drug use

Active smoking Noncompliance

Dishonesty Active Malignancy (non-

HCC)

age > 65 COPD

CAD/CHF ESRD

BMI >35

Contraindications for Liver Transplant

• 1985: European Liver Transplant Registry—38% due to HCC

• 5-year survival only 20%!

• 1996: only 10% due to HCC

Lancet 1999; 353: 1253

Hepatocellular Carcinoma Early Experiences with Transplant

Mezzaferro et al, N Eng J Med 1996

Milan Criteria

Historically, liver transplantation for HCC produced horrible results

Milan Criteria Solitary lesion <5cm Two or three lesions, all <3cm No extrahepatic disease 5 year survival rate equivilant to txp w/o HCC

• 2002: 29 points for patients within Milan, and 24 points for stage I HCC (one tumor < 2cm)

• This was shown to give too high of a priority to HCC patients

and disadvantaged non-HCC patients

• Current policy: Patients listed with their calculated MELD score. After a 6 month wait period after listing, they will receive a score of 28.

MELD Exception Points for HCC

all OLT HCC one year 84% 87%

five year 75% 67%

ten year 52% 49.5%

Hepatocellular Carcinoma Survival Compared to Non-HCC Recipients

V. Mazzaferro et al., Ann Surg Oncol 2008;15(4):1001

Variable HR CI (95%) p-value Overall patient survival Milan criteria (in vs. out) 3.1 1.35-6.93 0.007 Tumor-free survival Milan criteria (in vs. out) 5.5 1.39-21.27 0.01 Microsatellites (yes vs. no) 3.6 1.5-8.71 0.004 Microvascular invasion (yes vs. no) 3.4 1.36-8.76 0.009 Tumor grade (G3 vs. G1-2) 3.4 1.04-11.14 0.04

Hepatocellular Carcinoma Prognostic Factors Affecting Survival

1980s: waiting time and “level of care”

1996: disease severity using CTP

score

2002: disease severity using MELD (Model End-Stage Liver Disease)

score

Liver Allocation

Assessing perioperative morbidity and mortality in patients with cirrhosis

Class correlates with the frequency of post-operative complications: liver failure, worsening encephalopathy, bleeding, infection, renal failure, hypoxia, intractable ascites

Child-Turcotte-Pugh Score

Child-Turcotte-Pugh Score

Operative mortality: Class A: 10% Class B: 30% Class C: ~80%

Emergency surgery associated with higher mortality

General consensus for elective surgery:

Class A: elective surgery well tolerated Class B: permissible with preoperative preparation Class C: contraindicated

Child-Turcotte-Pugh Score

5 factors contribute to score, 3 of which are non-modifiable (bilirubin, INR and albumin)

Great subjectivity in encephalopathy and ascites

Easy to “game the system” and increase your patient’s CTP score

Child-Turcotte-Pugh Score Limitations for Transplant

MELD Score = (0.957 * ln(Serum Cr) + 0.378 * ln(Serum Bilirubin) + 1.120 * ln(INR) + 0.643 ) * 10

• INR • Creatinine • Total Bilirubin

• Range: 6 – 40

Model for End Stage Liver Disease Score (MELD)

Goal = determine mortality rates for candidates compared to recipients

Liver Recipient Outcomes

12,996 patients listed from 2001 – 2003

Liver Recipient Outcomes

Liver Recipient Outcomes

Overall, recipients had 79% lower mortality risk than candidates waiting on the list MELD 18-20: 38% lower mortality risk MELD 40: 96% lower mortality risk

8X

MELD 6

15

24

33

40

One yr survival without OLT

97%

86%

16%

<2%

<1%

One yr survival with OLT

86%

86%

84%

76%

74%

• Hyponatremia has been shown to be an independent predictor of death

• Na-MELD = MELD + (135 – Na)*1.59

• Example: • MELD 10, Na 129: Na-MELD is 20

“Sodium MELD” Score

Kim WR et al. N Engl J Med 2008;359:1018-1026.

Kim WR et al. N Engl J Med 2008;359:1018-1026.

MELD can quantify mortality risk in cirrhotic patients post-operatively

Applies to abdominal, orthopaedic and cardiovascular operations

Mortality rates: MELD <7: ~6% MELD 8-11: ~10%

MELD 12-15: ~25%

MELD Score Correlation

QUESTIONS?