Risk of hepatitis B reactivation in patients treated with direct-acting antivirals for hepatitis C

Abstract

The recent introduction of direct-acting antiviral drugs (DAAs) for treatment of the hepatitis C virus (HCV) has greatly improved the management of HCV for infected patients. These viral protein inhibitors act rapidly, allowing HCV clearance and increasing the sustained virological response rates. However, hepatitis B virus (HBV) reactivation has been reported in HCV/HBV co-infected patients. Hepatitis B reactivation refers to an abrupt increase in the HBV and is well-documented in patients with previously undetected HBV DNA due to inactive or resolved HBV infection. Reactivation can occur spontaneously, but in most cases, it is triggered by various factors. Reactivation can be transient, without clinical symptoms; however, it usually causes a hepatitis flare. HBV reactivation may occur regardless of HCV genotype and type of DAA regimen. HBV screening is strongly recommended for co-infected HCV/HBV patients before initiation and during DAA therapy regardless of HBV status, HCV genotype and class of DAAs used. HBV reactivation can be prevented with pretreatment screening and prophylactic treatment when necessary. Additional data are required to evaluate the underlying mechanisms of HBV reactivation in this setting.

Keywords: Direct-acting antivirals; Hepatitis B; Hepatitis B virus reactivation; Hepatitis C; Pretreatment screening.

Figure 1

Treatment algorithm. Therapeutic options for HCV-HBV co-infected patients. All HCV patients who are about to commence DAA therapy should be assessed for HBV coinfection and accordingly for HDV. Patients who are negative for HBV will be monitored using liver function tests (LFTs) during and after the end of DAA therapy. A flare in ALT/liver biochemistry during this timeframe should prompt the treating physician to reconsider the possibility of an occult HBV infection and to re-test for HBV infection (HBsAg and/or HBV DNA)[36]. Management options for patients who are positive for HBV vary according to their serology results. HBsAg positive patients have the following two options: the “treat first” approach (blue pathway), where HBsAg positive are treated with NA agents (commencing NA therapy even before the start of DAA treatment), or the “test first” option (green pathway) where patients are monitored with HBV DNA and are treated according to the detected levels. Both treatment options are viable and are supported by clinical guidelines[36,37]. HCV: Hepatitis C virus; HBV: Hepatitis B virus; DAA: Direct-acting antiviral; Tx: Therapy; HDV: Hepatitis D virus; CHB: Chronic hepatitis B infection; HBsAg: Hepatitis B surface antigen; anti-HBs: Hepatitis B surface antibody; anti-HBc: Total hepatitis B core antibody; NA: Nucleoside/nucleotide analogue; LFTs: Liver function tests; ALT: Alanine transaminase. Blue pathway, options in accordance with EASL guidelines; green pathway, options in accordance with AASLD - IDSA guidelines.