Trapianto di fegato e organi solidi. Pierluigi Toniutto Sezione di Epatologia e Trapianto Epatico Università di Udine

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2 Trapianto di fegato e organi solidi Pierluigi Toniutto Sezione di Epatologia e Trapianto Epatico Università di Udine

3 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: /mm 3 OLT with whole cadaveric liver (HBcAb+) in 2007 Piggyback technique

4 Case 1 Arterial, portal and bile duct reconstructions both performed with 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

5 Discuss Prophylaxis scheme to avoid HBV reactivation in this recipient LAM HBIG HBIG+LAM None Other

6 Feray et al. Gut; 2002.

7 Discuss Prophylaxis scheme to avoid HBV reactivation in this recipient LAM HBIG HBIG+LAM None Other

8 Case 1 No HBV prophylaxis adopted by the transplant center

9 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/mm 3 PLT /mm 3

10 Discuss Diagnostic work-up of jaundice 2 years post LT

11 Potential causes of jaundice in relation to the time elapsed from LT ACR Infections Biliary complications CMV HCV PNF EGD HAT PVT Ischemic/preservation injury CR Rec of non HCV primary liver disease Lympho-proliferative disease Infective/toxic liver injury months From: Zakim and Boyer: Taxbook of Hepatology; Saunders; 2006.

12 Serological markers HBsAg+, HBcAb Total/IgM +/+, HBeAg-, HBeAb+ HBV-DNA UI/ml HDVAg- HCV-RNA-

13 Discuss De Novo Vs acquired HBV infection Best prophylaxis strategy Liver biopsy

14 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) Cholongitas et al. J Hepatol; 2010.

15 Risk of de novo hepatitis B infection in HBsAg- recipients who received liver grafts from HBcAb+ donors AND NO HBV prophylaxis after LT in relationship to their HBV serological status before LT Cholongitas et al. J Hepatol; 2010.

16 Risk of de novo hepatitis B infection in HBsAg- recipients who received liver grafts from HBcAb+ donors in relationship to their pre-lt HBV serological status and the use of HBV prophylaxis after LT Cholongitas et al. J Hepatol; 2010.

17 Risk of de novo hepatitis B infection in HBsAg- recipients who received liver grafts from HBcAb+ donors in relationship to their pre-lt HBV serological status and the type of HBV prophylaxis after LT Cholongitas et al. J Hepatol; 2010.

18 Published studies on the course of de novo hepatitis B after LT Cholongitas et al. J Hepatol; 2010.

19 Discuss Antiviral approach

20 Published studies on the course and treatment outcomes of de novo hepatitis B after LT Cholongitas et al. J Hepatol; 2010.

21 Patient characteristics and outcome according to the choice of initial antiviral drug for HBV recurrence Lee et al. Clin Transpl; 2000.

22 Cumulative incidence of HBV resistance to LAM, ADV, ETV, LdT and TDF in pivot trials in nucleos(t)ide-naive patients with chronic HBV related hepatitis EASL Clinical guidelines of HBV. J Hepatol; 2012.

23 Serological course of de novo hepatitis B after liver transplantation Su et al. Liver Transpl; 2010.

24 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/mm 3 PLT /mm 3 Creatinine clearance 68 ml/min (CKD-EPI)

25 Discuss How and when to perform antiviral follow-up

26 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?)

27 Criteria for monitoring antiviral therapy in chronic HBV infection: HBV-DNA EASL Clinical guidelines of HBV. J Hepatol; 2012.

28 Criteria for monitoring antiviral therapy in chronic HBV infection: renal function EASL Clinical guidelines of HBV. J Hepatol; 2012.

29 Discuss When to adopt prophylaxis against HBV recurrence in recipients who get a HBcAb positive donor

30 Proposed algorithm for allocation and management of HBcAb+ liver grafts Cholongitas et al. J Hepatol; 2010.