Hepatitis C & B Co-infection PROJECT ECHO HEPC FEBRUARY 9, 2017 PRESENTED BY: DR. JOHN GUILFOOSE

Transcription

1 Hepatitis C & B Co-infection PROJECT ECHO HEPC FEBRUARY 9, 2017 PRESENTED BY: DR. JOHN GUILFOOSE

2 Intro Shared modes of transmission Viral interactions / concept of a Dominant virs Not ncommon in highly endemic areas, and among sbjects with a high risk of parenteral infections Esp. clinically silent HBV infection Clinical featres of co-infection Progression of liver disease / fibrosis HCC risk Treatment that can reslt in HBV flares and clinical decompensation FDA Boxed Warning for HCV DAAs

3 Epidemiology of HBV/HCV Coinfection Worldwide prevalence of coinfection with HBV and HCV is nknown General estimate from past stdies: Approximately 2 10% of anti-hcv-positive patients are fond to be HBsAg positive May be an nderestimated de to the phenomenon of silent (occlt) HBV infection Testing for HBsAg alone may sbstantially nderestimate the tre prevalence of HBV/HCV coinfection

4 Viral Interactions Between HBV and HCV Patients with combined HBV and HCV infection may show a large spectrm of virologic profiles Virologic response are widely divergent / dynamic over time Possibility that HBV and HCV can alternate their dominance dring different periods of infection

5 Viral Interactions Between HBV and HCV Most HBV/HCV coinfected patients appear to have active HCV and inactive HBV replication HCV infection can directly sppress HBV replication Mediated by HCV core protein Prodces a phenomenon of occlt or serologically silent HBV Undetectable hepatitis B virs srface antigen [HBsAg] Usally Hep B core (+), SAb (-) isolated core (+) Detectable HBV DNA in serm

6 Viral Interactions Between HBV and HCV Fewer patients have high HBV viremia levels and low/ndetectable HCV RNA In some HBV/HCV co-infected patients, each virs exerts its own pathogenetic role Casing a cmlative effect in terms of liver injry May explain the high grade of disease severity freqently observed in some cases of co-infection

7 Clinical Featres of HBV/HCV Coinfection Simltaneos acte hepatitis with HBV and HCV is rare Clinical featres and chronicity rates comparable to patients with acte HBV or HCV infection Patients tended to have delayed appearance and shorter dration of HBsAg HCV sperinfection in patients with chronic HBV: In areas of high prevalence of HBV infection (most common sperinfection scenario worldwide) Significant proportion of flminant/sbflminant hepatitis in HBsAg carriers can attribted to HCV sperinfection More freqent / severe acte HCV symptoms Flminant hepatic failre In cases of HCV sperinfection, hepatitis B e antigen (HBeAg) seroconversion and HBsAg clearance have been reported

8 Clinical Featres of HBV/HCV Coinfection HBV Sperinfection in patients with HCV Less common May be associated with acte deterioration of liver fnction Higher incidence of hepatic encephalopathy / ascite formation w/ sperinfection as compared to acte HBV infection alone One possible case for flminant hepatitis in patients with HCV infection Anti-HCV can disappear dring HBV sperinfection?! Again speaks to this dynamic relationship

9 Fibrosis Progression in HBV/HCV Coinfection Unclear: Findings not consistent from one stdy to next Some stdies show more rapid fibrosis progression (histologic) Also some show higher prevalence of cirrhosis and hepatic decompensation

10 Impact of HBV/HCV Coinfection on Development of HCC Clear: Synergism between HBV and HCV in carcinogenesis and developing HCC Longitdinal stdy Incidence of HCC (per 100 person years) 6.4 in co-infected patients 2.0 in HBV monoinfected 3.7 in HCV monoinfected Cmlative risk of developing HCC at 10 years 45% in co-infected patients 16% in HBV monoinfected 28% in HCV monoinfected Sggestion: patients with HBV/HCV coinfection and known or sspected cirrhosis shold be followed reglarly; every 3 6 months w/ imaging/etc.

11 Treatment of HBV/HCV Coinfection FDA Drg Safety Commnication FDA warns abot the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C 24 cases of HBV reactivation reported to FDA in HCV/HBV co-infected patients treated with DAAs dring from November 22, 2013 to Jly 18, 2016 Two patients died and one reqired a liver transplant Baseline worse liver disease wold be a greatest risk from Hep flare This nmber incldes only cases sbmitted to FDA, so srely additional cases HBV reactivation was not reported as an adverse event in the clinical trials sbmitted for the DAA approvals becase patients with HBV coinfection were exclded from the trials

12 Treatment of HBV/HCV Coinfection Boxed Warning added to the drg labels: Risk of hepatitis B virs (HBV) becoming an active infection again in any patient who has a crrent or previos infection with HBV and is treated with direct-acting antiviral (DAA) medicines for hepatitis C Health care professionals shold screen all patients for evidence of crrent or prior HBV infection before starting treatment with DAAs, and monitor patients sing blood tests for HBV flare-ps or reactivation dring treatment and post-treatment follow-p

13 Treatment of HBV/HCV Coinfection Very limited data regarding therapy of HBV/HCV co-infected patients are available Crrently no established treatment gidelines for these patients Not addressed in HCVgidlines.org Can find opinions

14 Treatment of HBV/HCV Coinfection OPINION Start by characterizing the "dominant" virs by serological and virologic testing Serologically Silent HBV Co-infection HBsAg/anti-HBs-negative patients with positive anti-hbc and HBV DNA negative HBeAg and low level viremia Go ahead and treat HCV w/ close monitoring Active HCV-HBV Coinfection Patients with dally-active HBV/HCV coinfection (i.e. HCV RNA positive, HBeAg positive or HBV DNA > 104 IU/mL) Consider treating HBV first, then HCV w/daas and close monitoring

15 Treatment of HBV/HCV Coinfection Important drg interaction: Viread (tenofovir) and Harvoni (ledipasvir-sofosbvir) May increase the concentration of tenofovir by 1.8- to 2.6-fold Kidney fnction shold be monitored closely