Management of immunocompromised patients with chronic or resolved HBV infection

Transcription

1 Management of immunocompromised patients with chronic or resolved HBV infection Evangelos Cholongitas Assistant Professor 4 th Department of Internal Medicine Medical School of Aristotle University, Thessaloniki, Greece 24 th International Hepatitis Β & C Meeting of Athens Hadziyannis

2 Financial disclosures Advisor and/or lecturer and/or grants: Abbvie, Bristol-Myers Squibb, Gilead, MSD, Novartis

3

4 Definition: not the same in the studies HBV DNA rise usually reappearance or >1 log increase Reappearance of HBsAg in HBsAg (-)/ anti-hbc (+) reverse seroconversion In the liver: ALT elevation (threshold?) HBV reactivation: HBV-DNA and/or HBsAg HBV-associated hepatitis: reactivation + ALT HBV-associated liver failure/death Non-HBV outcomes: e.g. chemotherapy delay

5 Optimal prophylaxis BUT first screening All candidates should be screened for HBsAg and anti-hbc (A1) Vaccination of HBV seronegative patients (A1) 100 % Screening practices for HBV among specialties (USA) Rheumatologists Dermatologists Oncologists

6 Should we use prophylactic antiviral therapy? Close follow up ETV Huang, JCO 2013 No clinical consequences in either group BUT - No confirmation in all studies - Not practical to do HBV DNA every 1-3 months

7 Risk factors for HBV reactivation Underlying disease hematological rheumatic, solid tumors Treatment anti-cd20 (rituximab) anti-tnf agents Viral factors HBsAg(+) HBsAg(-) / anti-hbcore(+)

8 Prophylaxis in ALL HBsAg (+) expect those: - under AZA, Methotrexate (?) - steroids (regardless of dose for <1 week)

9 EASL for HBsAg-positive patients under immunosuppression Prophylaxis with antiviral agent (A1) - regardless of HBV DNA levels - for 12 months after cessation of immunosuppression Entecavir or Tenofovir if: - HBV-DNA >2000 IU/ml or - >12 months duration of immunosuppression or - in high risk patients* (HASL) * Under anti-cd-20, anthracyclines, >10mg prezolon for 4 weeks

10 Prophylaxis in HBsAg-negative / antihbc-positive under immunosuppression

11 Anti-HBc (+): Is not a rare issue Up to 2 billion people exposed to HBV in HBV endemic regions, over 50% anti-hbc (+)

12 Hepatitis B virus reactivation in HBsAg negative, anti-hbc positive patients receiving immunosuppressive therapy: a systematic review Medline/PubMed search from January 2006 to February 2015 Terms: hepatitis B and reactivation or immunosuppression therapy Inclusion criteria: (1) no use of prophylaxis with NA(s) (2) available data on the incidence of HBV reactivation in relation to - the underlying disease and/or - the immunosuppressive regimen Cholongitas & Papatheodoridis, submitted

13 Hepatitis B virus reactivation in HBsAg negative, anti-hbc positive patients under immunosuppressive therapy: a systematic review Citations retrieved using keyword search terms: n=1120 Records excluded: n=1062 No assessment of HBV reactivation in HBsAg negative patients under immunosuppression without antiviral prophylaxis Further assessment for eligibility: n=58 Studies excluded: n= duplicated: 3 Articles met all inclusion criteria: n=55 (3640 patients) Cholongitas & Papatheodoridis, submitted

14 Hepatitis B virus reactivation in HBsAg negative, anti-hbc positive patients under immunosuppressive therapy: a systematic review Results based on - underlying disease hematological vs non-hematological diseases - immunosuppression therapy rituximab vs non-rituximab agents

15 Patients with HBV reactivation, % Hepatitis B virus reactivation in HBsAg negative, anti-hbc positive patients under immunosuppressive therapy: a systematic review HBV reactivation: 6.5% (236/3640) patients 45% after immunosuppression discontinuation ( days) % 10,9 9, ,6 4,1 2 0 Heamatological diseases Non-heamatological diseases Rituximab Without Rituximab 25/36

16 Patients with HBV reactivation, % HBV reactivation in anti-hbc (+) patients with non hematological diseases 10 % ,7 2,6 1,9 1,5 0 Solid tumors Rheumatic Gastrointestinal Dermatologic 25/36

17 Rates of HBV reactivation in relation to the baseline serum HBV DNA detectability HBVDNA (-) HBV DNA (+) anti

18 Rates of HBV reactivation in relation to the baseline anti-hbs status Anti-HBs (-) anti Anti-HBs (+) anti

19 Patients with HBV reactivation, % Rates of HBV reactivation in solid tumors in relation to their baseline anti-hbs status % 10, Solid tumors Anti-HBs (+) Anti-HBs (-) Patients, n/n 0/50 4/37 25/36

20 Number of patients Management of patients with HBV reactivation Outcome: 174 (74%) of 236 patients with HBV reactivation Antiviral therapy: 148 (85%) of 174 patients N Untreated ETV LAM ADV±LAM ETV or LAM

21 Patients with HBV reactivation who died, % Mortality of patients with HBV reactivation under antiviral therapy 30 % p= ,5 0 Treated with LAM Treated with ETV n/n= 10/59 2/56

22 Prophylaxis in ALL HBsAg (+) expect those: - under AZA, Methotrexate (?) - steroids (regardless of dose for <1 week)

23 In HBsAg negative / anti-hbc positive patients Prophylaxis is needed - hematological diseases and/or under rituximab regardless of anti-hbs and serum HBV-DNA - non-hematological diseases and/or under rituximab-free when detectable HBV-DNA Prophylaxis is not needed - under AZA, Methotrexate - steroids ( for <1 week or <10mg prezolon for >4 weeks) - non-hematological diseases and/or under rituximab free regimens when undetectable HBV DNA and positive anti-hbs

24 Thank you