Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct‐acting antiviral therapy

Abstract

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.

Update of the statements on biology and clinical impact of occult hepatitis B virus infection

“…112 Earlier studies suggested that the risk is modest in individuals with OBI receiving tumor necrosis factor inhibitors, but recent studies found that the risk of HBV reactivation is very low in patients receiving these therapies. 103 Similarly, the risk of HBV reactivation is very low in individuals with OBI receiving direct-acting antiviral therapy for hepatitis C. [113][114][115] Given the shared transmission routes for HIV and HBV, and the immune impairment produced by HIV, OBI and HBV reactivations were more frequently reported in patients with acquired immunodeficiency syndrome. Following the widespread use of potent antiretroviral therapies, including antiretroviral agents with anti-HBV activity, reactivation of OBI has become negligible in the HIV population receiving appropriate therapy.…”

Risk of hepatitis B virus reactivation with direct‐acting antivirals against hepatitis C virus: A cohort study from Egypt and meta‐analysis of published data

“…A total of 425 patients positive for HBsAg (including the 37 patients from the Egyptian study), and 1900 patients negative for HBsAg but positive for anti‐HBc were used to estimate the pooled risks. Nine studies (10 articles) were from East Asia, 6 from Europe, 1 from USA and 1 from New Zealand . All of these studies included patients on IFN‐free DAAs regimens for 8‐24 weeks.…”

“…All of these studies included patients on IFN‐free DAAs regimens for 8‐24 weeks. While most of studies reported HCV genotype, only 3 studies reported HBV genotype . Risk of bias in these studies is summarized in Appendix .…”

Hepatitis B Reactivation With Hepatitis C Treatment: Bringing Some Clarity to the Black Box

“…Severe outcomes have also been the subject of case reports. However, Gane et al 12 noted that 7 of 8 patients had an increase in HBV DNA during DAA therapy, but none had an associated hepatitis, and Tamori et al 13 found that only 3 of 22 (12%) had an increase in HBV DNA, all subclinical. Collectively, these data highlight the importance of definitions, something that has plagued the HBV reactivation literature in the setting of immunosuppression.…”