Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature

Abstract

Chronic hepatitis B (HBV) and C (HCV) coinfection are frequently observed in clinical practice. The interaction between HCV and HBV is complex and not completely understood, and usually results in the suppression of hepatitis B replication by HCV superinfection or coinfection. Cases of hepatitis B reactivation during and after HCV treatment with direct acting antivirals (DDA) have been described, and it is recommended to screen all patients starting DAA therapy for HBV infection markers and to monitor those that have positive markers of HBV infection. HBs antigen (HBsAg) positivity is the main risk factor for HBV reactivation, and this phenomenon is rarer in those with "resolved" HBV infection (negative HBsAg, positive antiHBc antibody (HBcAb) and anti-HBs antibody (HBsAb) positive or negative). The authors present a case of HBV reactivation after HCV treatment with sofosbuvir/ ledipasvir that occurred in a 54-year-old male that was HIV-coinfected and had "resolved" hepatitis B infection (negative HBsAg, positive HBcAb and positive HBsAb). Our case reinforces the need to screen all patients who will start DAA therapy for hepatitis C infection, and alerts clinicians to the need to closely monitor patients with evidence of previous HBV infection no only during treatment but also after HCV treatment with DAAs.

Hepatitis B surface antibody titres and hepatitis B reactivation with direct‐acting antiviral therapy for hepatitis C

“…As outline in methods, 'five different degrees of reactivations can be discriminated among the 32 patients with some form of reactivation: HBV DNA becoming detectable, HBsAg sero‐reversion with HBsAg becoming positive, clinical evident reactivation with rise in ALT, or need for initiation of antiviral therapy, and finally persistent HBsAg with or without death or transplant'. HBV DNA becoming positive was reported in all 32 patients but was intermittently positive with spontaneous resolution in all 19 cases from cohort series (with caveat that 2 patients were lost to follow‐up) and in 2 cases from case series 24,33 , while in 4 patients from case reports 23,25,27,32 , HBV DNA resolved likely partially due to early initiation of HBV antiviral therapy. HBsAg sero‐reversion was reported in no patient from cohort studies but found in 11 of 13 patients published as cases reports and being only intermittently positive in 3 of the 11 patients.…”

“…Of the 32 patients who had HBV reactivation, 13 patients had additionally a transient hepatitis, 1 patient had persistent HBV DNA 22 , and 12 patients had HBsAg sero‐reversion. Of the twelve patients with HBsAg sero‐reversion, 6 had transient hepatitis 22‐25,27,32 , 3 had persistent HBV DNA 28,31,34 , and another three had either a fatal outcome 29,30 or needed a liver transplantation 26 (Table 2); 19 patients had neither evidence of hepatitis, sero‐conversion nor any clinical sequelae.…”

“…Of the 13 cases from case reports, 7 patients were HBcAb-positive and HBsAb-negative, one patient's HBsAb status was not reported 27 , two patients were HBsAb-positive with titres below 10 (<5 and 9.5 iU/mL), while 3 patients were HBsAb-positive with titres above 10 (12.2, 75.4 and >1000). to follow-up) and in 2 cases from case series 24,33 , while in 4 patients from case reports 23,25,27,32 , HBV DNA resolved likely partially due to early initiation of HBV antiviral therapy. HBsAg sero-reversion was reported in no patient from cohort studies but found in 11 of 13 patients published as cases reports and being only intermittently positive in 3 of the 11 patients.…”

“…Of the 32 patients who had HBV reactivation, 13 patients had additionally a transient hepatitis, 1 patient had persistent HBV DNA 22 , and 12 patients had HBsAg sero-reversion. Of the twelve patients with HBsAg sero-reversion, 6 had transient hepatitis [22][23][24][25]27,32 , 3 had persistent HBV DNA 28,31,34 , and another three had either a fatal outcome 29,30 or needed a liver transplantation 26 (Table 2) While reactivation defined by intermitted HBV DNA detectability was found in patients being HBsAb-positive, this seems limited to patients with HBsAb titres <30 iu/mL. The two exceptions were one patient who retrospectively was found to be HBsAg-positive at baseline with an escape variant and one with underlying HIV disease.…”

“…Some studies had reported increasing HBsAb titres during DAA17 , while others have reported decline in titre during antiviral therapy resulting in reactivation 32. The decrease in HBsAb titre could be explained by an increase in HBsAg protein being initially neutralized by HBsAb before the neutralizing capacity is overwhelmed and HBV reactivation with HBsAg positivity becomes evident.…”