Hepatitis B Reactivation: The Catch-22 of DAA Therapy in Hepatitis C Treatment

Abstract

Hepatitis C is a leading cause of cirrhosis in the US, and co-infection or prior infection with Hepatitis B is common. Direct anti-viral agents have revolutionized the treatment of HCV, and new treatment dilemmas emerge in those who have achieved SVR. This case highlights an example of HBV reactivation after successful HCV treatment in a patient with a history of liver transplantation. The patient is a 68-year-old African American man with cirrhosis secondary to HCV (Genotype Ia) and alcohol abuse, who underwent an orthotopic liver transplant in 2011 (HCV positive) after developing hepatocellular carcinoma. In December 2015, he received direct-acting antiviral therapy for HCV, finishing a 12-week course of ledipasvir and sofosbuvir. Post-treatment labs revealed SVR12 in March 2016. In September 2016, he was hospitalized for pancreatitis. Labs drawn at the time of admission showed a non-reactive HBsAg, < 3.10 HBsAb, and isolated reactive HBV core antibody. Repeat labs during hospitalization, which were incidentally drawn one week later, showed reactive HBsAg, HBcAb IgM, and an HBV DNA viral load of >170,000,000. Repeat confirmatory serologies showed similar results, and HBeAg and HBeAb were also positive. No genotype was reported and Hepatitis D antibody was negative. Hepatitis B treatment was initiated with entecavir. In March 2017, he was found to have a malignant neoplasm of the pancreatic head, and he passed away one month later from catheter-associated bacteremia. This case focuses on a new treatment hurdle in direct-acting antiviral therapy for HCV, and one that is more common compared to prior interferon-based therapy. The exact mechanism of HBV reactivation is unknown, but thought to be secondary to HCV-HBV viral interference or by rapid clearance of HCV leading to immune reconstitution, favoring HBV reactivation. Thus, it is vital to monitor patients' HBV status before and after treatment, as per new FDA guidelines. This case proves unique as our patient is an African American male; most cases involve Caucasian or Asian patients, with a greater percentage of women reactivating than men. Additionally, prior to reactivation our patient was isolated HBcAb positive, HBsAg negative. Almost all cases in the literature show reactivation exclusively with patients who are HBsAg positive. This case highlights the importance of monitoring Hepatitis B serologies in patients receiving DAA therapy, including those whose serology show HBcAb positive and HBsAg negative.