Pierluigi ToniuttoSezione di Epatologia e Trapianto EpaticoUniversità di Udine

Trapianto di fegato e organi solidi

Case 1

• 55-yr old white woman • Alcoholic cirrhosis (CTP score 11, MELD 24, status UNOS

2B) • HBsAb+ (500 UI/L), HBcAb-, HBeAg-, HBeAb-• HCVAb-• Oesophageal varices grade I• Tense ascites• Platelet count: 36.000/mm3

• OLT with whole cadaveric liver (HBcAb+) in 2007• Piggyback technique

Case 1

• Arterial, portal and bile duct reconstructions both performedwith end-to-end anastomoses

• Optimal graft reperfusion and function• Discharged from the hospital 19 days after transplant• TAC (blood levels between 10 to 15 ng/ml) + prednisone (25

mg/d) based immunosuppression• Mild residual ascites• Normal renal function

Discuss

• Prophylaxis scheme to avoid HBV reactivation in this recipient

– LAM– HBIG– HBIG+LAM– None– Other

Feray et al. Gut; 2002.

Discuss

• Prophylaxis scheme to avoid HBV reactivation in this recipient

– LAM– HBIG– HBIG+LAM– None– Other

Case 1

• No HBV prophylaxis adopted by the transplant center

2 years later…...

• The patient presented with jaundice• US examination revealed patent vascular anastomoses

without dilation of the biliary tract. Hepatic artery RI: 0.44• ALT 480 UI/L• AST 328 UI/L• GGT 426 UI/L• AF 398 UI/L• BIL T/D 7.3/5.8 mg/dL• HB 13.9 gr/dl• WBC 6980/mm3

• PLT 234000/mm3

Discuss

• Diagnostic work-up of jaundice 2 years post LT

0 1 2 3 4 5 6 7 months

PNFEGDHATPVT

Ischemic/preservation injury

ACRInfections

Biliary complicationsCMV

HCV

CRRec of non HCV primary liver

disease Lympho-proliferative diseaseInfective/toxic liver injury

Potential causes of jaundice in relation to the time elapsed from LT

From: Zakim and Boyer: Taxbook of Hepatology; Saunders; 2006.

Serological markers

• HBsAg+, HBcAb Total/IgM +/+, HBeAg-, HBeAb+• HBV-DNA 976000 UI/ml• HDVAg-• HCV-RNA-

Discuss

• De Novo Vs acquired HBV infection• Best prophylaxis strategy• Liver biopsy

De Novo hepatitis B after LT

HBV prophylaxis in the recipient

Yes No p

DNHB 30/366 (8.2%) 119/422 (28.2%) <0.001

Median onset of DNHB after LT (months)

35 19 0.05

Cholongitas et al. J Hepatol; 2010.

Risk of de novo hepatitis B infection in HBsAg- recipients who receivedliver grafts from HBcAb+ donors AND NO HBV prophylaxis after LT inrelationship to their HBV serological status before LT

Cholongitas et al. J Hepatol; 2010.

Risk of de novo hepatitis B infection in HBsAg- recipients who receivedliver grafts from HBcAb+ donors in relationship to their pre-LT HBVserological status and the use of HBV prophylaxis after LT

Cholongitas et al. J Hepatol; 2010.

Risk of de novo hepatitis B infection in HBsAg- recipients who receivedliver grafts from HBcAb+ donors in relationship to their pre-LT HBVserological status and the type of HBV prophylaxis after LT

Cholongitas et al. J Hepatol; 2010.

Published studies on the course of de novo hepatitis B after LT

Cholongitas et al. J Hepatol; 2010.

Discuss

• Antiviral approach

Published studies on the course and treatment outcomes of denovo hepatitis B after LT

Cholongitas et al. J Hepatol; 2010.

Patient characteristics and outcome according to the choice ofinitial antiviral drug for HBV recurrence

Lee et al. Clin Transpl; 2000.

Cumulative incidence of HBV resistance to LAM, ADV, ETV, LdTand TDF in pivot trials in nucleos(t)ide-naive patients with chronicHBV related hepatitis

EASL Clinical guidelines of HBV. J Hepatol; 2012.

Serological course of de novo hepatitis B after livertransplantation

Su et al. Liver Transpl; 2010.

6 months later…..

• ETV 0.5 mg/d• HBsAg+• HBV-DNA 38 UL/ml• ALT 38 UI/L• AST 28 UI/L• GGT 26 UI/L• AF 101 UI/L• BIL T/D 0.9/0.7 mg/dL• HB 13.7 gr/dl• WBC 7890/mm3

• PLT 216000/mm3

• Creatinine clearance 68 ml/min (CKD-EPI)

Discuss

• How and when to perform antiviral follow-up

Discuss

• Duration (6 Vs 12 months)• Parameter

– HBsAg titre Vs HBV-DNA Vs each of them– AST Vs ALT– Creatinin Vs creatinin clearance– Calcium, phosporus, PTH, vitamin D (at the same time points?)

Criteria for monitoring antiviral therapy in chronic HBV infection: HBV-DNA

EASL Clinical guidelines of HBV. J Hepatol; 2012.

Criteria for monitoring antiviral therapy in chronic HBV infection: renal function

EASL Clinical guidelines of HBV. J Hepatol; 2012.

Discuss

• When to adopt prophylaxis against HBV recurrence inrecipients who get a HBcAb positive donor

Proposed algorithm for allocation and management of HBcAb+ liver grafts

Cholongitas et al. J Hepatol; 2010.