Medicine Review Course 2018 Viral Hepatitis In Transplant Recipients

Transcription

1 Medicine Review Course 2018 Viral Hepatitis In Transplant Recipients Tan Chee Kiat Senior Consultant Dept of Gastroenterology and Hepatology Singapore General Hospital 21 July 2018

2 Overcoming Saturday Morning Stupor - Brain Gymnastics

3 Overcoming Saturday Morning Stupor - Brain Gymnastics

4 Brain Gymnastics Are You With Us?

5 Outline of Talk

6 Outline of Talk Viral hepatitis in transplant recipients

7 Outline of Talk Viral hepatitis in transplant recipients

8 Outline of Talk Viral hepatitis in transplant recipients The usual suspects HBV, HCV - what s new The usually not suspected Approach

9 Outline of Talk Viral hepatitis in transplant recipients The usual suspects HBV, HCV - what s new The usually not suspected Approach Integrated with activity slides

10 Hepatitis In a Transplant Recipient ALT AST

11 Hepatitis In a Transplant Recipient AST > ALT ALP ALT AST External factors Medications Systemic infections

12 Hepatitis In a Transplant Recipient ALT AST AST > ALT ALP External factors ALT > AST Viral hepatitis Medications Systemic infections de novo plasma cell hepatitis

13 Viral Hepatitis

14 Viral Hepatitis In Transplant Recipients General points: Usually after the 1 st month May be reactivation or acute infection ALT may not be very high ALT > AST Use antigen / PCR tests for diagnosis rather than IgM antibody FBC is that of a viral picture

15 The Usual Suspects CMV HBV HCV

16 Cytomegalovirus (CMV) Most common viral pathogen after Tx Incidence related to donor vs recipient CMV status & degree of immunosuppression Highest in D+ R- Prophylactic vs preemptive therapy Diagnosis by CMV antigen (cytospin) or CMV PCR

17 Cytomegalovirus (CMV) CMV infection vs CMV disease 1 End organs liver, lungs, GI tract, retina, kidneys Treatment iv ganciclovir / oral valganciclovir 2, foscarnet (2 nd line) 1. Ljungman P. Clin Infect Dis Asberg A. Am J Transplant 2007.

18 The Usual Suspects HBV

19 Hepatitis B - Prologue Easy to diagnose HBV DNA Easy to treat - entecavir (ETV) - tenofovir disoproxil fumarate (TDF)

20 Hepatitis B AASLD Guidance For Patients On Immunosuppressive Therapy Screen HBsAg and anti-hbc total in all pts HBsAg+ve and anti-hbc+ve anti-hbv prophylaxis before IST HBsAg-ve and anti-hbc+ve careful surveillance of ALT, HBV DNA and HBsAg every 1-3 months Use anti-hbv drugs with high resistance barrier i.e. ETV, TDF, TAF Terrault N. Hepatology 2018.

21 Hepatitis B What s New? TAF tenofovir alafenamide As efficacious as TDF Less AEs renal, bone TDF 300 mg TAF 25 mg NH 2 O O O O O P O O O O O N N N N O O HN O O P O N N NH 2 N N

22 The Usual Suspects HCV

23 Hepatitis C - Prologue Easy to diagnose HCV RNA HCV recurrence post-tx 100% Difficult to treat Pegylated interferon injection weekly for 6 months plus daily ribavirin BD Adverse effects +++ Relative contraindication to interferon in transplant recipients (RTx no, LTx maybe) Response rate at best 33-42% 1 1. Arjal RR. Alimentary Pharmacol Ther 2007.

24 Hepatitis C What s New? Very easy to treat How easy is it? - 8 to 12 weeks of once a day tablet - no need to do genotyping - decompensated cirrhotics eligible - point-of-care pin-prick test HCV diagnosis 12 weeks of pan-genotypic DAA no more TCU (cure rate > 95%) or TCU 6 months later with HCV RNA discharge

25 Hepatitis C What s New? DAAs (direct acting antivirals) SOF - sofosbuvir LDV - ledipasvir SIM - simeprevir EBR - elbasvir GZR - grazoprevir DCV - daclatasvir ASV - asunaprevir OBV - ombitasvir PTV - paritaprevir DSV - dasabuvir VEL - velpatasvir VOX - voxilaprevir GLE - glecaprevir PIB - pibrentasvir

26 Hepatitis C - DAAs SOF - sofosbuvir OBV - ombitasvir LDV - ledipasvir PTV - paritaprevir SIM - simeprevir DSV - dasabuvir EBR - elbasvir VEL - velpatasvir GZR - grazoprevir VOX - voxilaprevir DCV - daclatasvir GLE - glecaprevir ASV - asunaprevir PIB - pibrentasvir

27 Hepatitis C - DAAs -buvirs & -asvirs have no DDIs with CNIs SOF - sofosbuvir LDV - ledipasvir SIM - simeprevir EBR - elbasvir GZR - grazoprevir DCV - daclatasvir ASV - asunaprevir OBV - ombitasvir PTV - paritaprevir DSV - dasabuvir VEL - velpatasvir VOX - voxilaprevir GLE - glecaprevir PIB - pibrentasvir

28 Hepatitis C - DAAs Which alphabets did not appear in the list of DDA abbreviations?

29 Hepatitis C - DAAs Which alphabets did not appear in the list of DDA abbreviations? H, J, K, N, Q, U, W, Y (8 alphabets)

30 Hepatitis C - DAAs Trialed in LTx and RTx recipients 1-3 Cure rate (i.e. SVR12) % 1-3 Use of HCV infected donor grafts 4,5 1. Charlton M. Gastroenterology Sawinski D. Am J Transplant Fernandez I. J Hepatol Shah AP. Transpl Infect Dis Goldberg DS. New Engl J Med 2017

31 The Usually Not Suspected HEV EBV HHV6, HHV7, HHV8, HSV, VZV, adenovirus Parvovirus B19,

32 Hepatitis E - Prologue Acute infection without chronicity 4 genotypes GT 1 & 2 humans, contaminated water GT 3 & 4 zoonotic, especially pigs No active treatment

33 Hepatitis E What s New? GT 7 Transmission via camels

34 Hepatitis E What s New? Chronic HEV infection in transplant recipients 1 Up to 60% of solid organ transplant recipients develop chronic HEV after acute infection 2 Defined by presence of HEV RNA >6 months Mainly GT3 3 Ribavirin mg for 12 weeks highly effective in eradication of HEV, esp GT3 4,5 May be transmitted via blood transfusion 6 1. Singh A. Gastroenterol Rep Fujiwara S. J Viral Hepat Legrand-Abravanel F. Emerg Infect Dis Kamar N. N Engl J Med Zhou X Rev Med Virol Baylis SA. Vox Sang 2011

35 The Usually Not Suspected EBV

36 Epstein-Barr Virus Acute EBV infection in EBV seronegative patients is associated with post-transplant lymphoproliferative disease (PTLD) PTLD significantly more common in children 1 Knowledge of recipient s pre-transplant EBV status important 1. Jain A. Ann Surg 2002.

37 Other Human Herpesviruses Hepatitis HHV6, HHV7, HHV8, HSV, VZV, adenovirus Less common HHV6 fever, rash, hepatitis, encephalitis, pneumonitis HHV8 associated with Kaposi s sarcoma HSV mucosal lesions Parvovirus B19 - anaemia

38 Approach to a Transplant Recipient with Hepatitis 5

39 ALT AST 4

40 ALT AST ALT < AST Fever, TW, procal, septic ALP Treat sepsis ALT AST 3

41 ALT AST ALT < AST Fever, TW, procal, septic ALP Treat sepsis Review medication list ALT AST 2

42 ALT ALT < AST AST CMV esp if TW Fever, TW, procal, septic ALP Treat sepsis 1 Review medication list ALT AST Prior HBV, HCV? mucosal lesions? rash? anaemia?

43 Bibliography CMV 1. Ljungman P, Griffiths P, Peya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34: Lumbreras C, Manuel O, Len O, et al., on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH). Cytomegalovirus infection in solid organ transplant recipients. Clin Microb Infect 2014; 20 (Suppl 7): Razonable RR, Humar A. and the AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplantation. Am J Transpl 2013;13: Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 2010; 7: Andrews PA, Emery VC, Newstead C. Summary of British transplantation society guidelines for the prevention and management of CMV disease after solid organ transplantation. Transplantation 2011; 92: Asberg A, Humar A, Rollag H, et al., VICTOR Study Group. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2007; 7: HBV 1. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67(4): HCV 1. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology 2015;148: Sawinski D, Kaur N, Ajeti A, et al. Successful treatment of hepatitis C in renal transplant patients with direct-acting antiviral agents. Am J Transplant 2016;16(5): Fernandez I, Munoz-Gomez R, Pascasio JM, et al. Efficacy and tolerability of interferonfree antiviral therapy in kidney transplant recipients with chronic hepatitis C. J Hepatol 2017;66: Shah AP, Cameron A, Singh P, et al. Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens. Transpl Infect Dis 2017;19:e Goldberg DS, Nazarian SM, Sawinski D, et al. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. New Engl J Med 2017;30Apr Legrand-Abravanel F, Kamar N, Sandres-Saune K, et al. Hepatitis E virus infection without reactivation in solid-organ transplant recipients: France. Emerg Infect Dis 2011; 17: Zhou X, de Man RA, de Knegt RJ, et al. Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review. Rev Med Virol 2013;23: Fujiwara S, Yokokawa Y, Morino K, et al. Chronic hepatitis E: a review of the literature. J Viral Hepat 2014; 21: Kamar N, Izopet J, Tripon S, et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med 2014; 370: Baylis SA, Gartner T, Nick S, Ovemyr J, Blumel J. Occurrence of hepatitis E virus RNA in plasma donations from Sweden, Germany and the United States. Vox Sang 2012; 103: Fang SY, Han H. Hepatitis E viral infection in solid organ transplant patients. Curr Opin Organ Transplant 2017;22: Others 1. Holmes RD, Sokol RJ. Epstein-Barr virus and post-transplant lymphoproliferative disease. Pediatr Transplant. 2002;6: Jain A, Nalesnik M, Reyes J, et al. Posttransplant lymphoproliferative disorders in liver transplantation: A 20-year experience. Ann Surg. 2002;236: Razonable RR. Infections due to human herpesvirus 6 in solid organ transplant recipients. Curr Opin Organ Transplant 15: Eid AJ, Chen SF, AST infectious disease community of practice. Human parvovirus B19 in solid organ transplantation. HEV 1. Lee GH, Tan BH, Teo ECY, et al. Chronic infection with camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk. Gastroenterology 2016;150: Singh A, Seth R, Gupta A, et al. Chronic hepatitis E - an emerging disease in an immunocompromised host. Gastroenterol Rep 2016; gow024. oi: /gastro/gow024.