Sustained hepatitis D virus-ribonucleic acid negativity after self-discontinuation of short-term bulevirtide therapy: a case report

Abstract Background Chronic hepatitis D virus (HDV) infection represents the most severe form of viral hepatitis and is associated with accelerated progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Bulevirtide (BLV), an entry inhibitor targeting the NTCP receptor, has recently emerged as the standard treatment for chronic HDV infection. Although its efficacy and safety have been demonstrated in clinical trials and real-world studies, the optimal duration of therapy and criteria for treatment discontinuation remain undefined. Case report We report the case of a 60-year-old man with long-standing HIV/HBV/HDV coinfection and previous hepatitis C virus infection successfully treated in 1993. He had previously undergone two courses of pegylated interferon alpha without achieving virological response. BLV monotherapy (2 mg/day) was started alongside tenofovir alafenamide/emtricitabine/rilpivirine for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. Treatment was discontinued after 6 months due to mild headache and myalgia. Despite early treatment interruption, HDV-RNA continued to decline after drug withdrawal, becoming undetectable 10 months later. Viral suppression was confirmed in multiple assessments and remained undetectable for nearly 1 year of follow-up. Throughout this period, liver enzymes remained within the normal range, quantitative HBsAg progressively declined, and liver stiffness decreased from 14 to 7.8 kPa. Conclusions This case illustrates a rare example of sustained HDV-RNA suppression after short-term BLV monotherapy in a non-cirrhotic individual with controlled HIV and HBV infection. The continued decline in viral load after treatment discontinuation may reflect a host mediated-immune control of HDV replication, possibly favored by low HBsAg levels. As the decline in HBsAg preceded BLV initiation, spontaneous clearance and a BLV-associated effect remain competing explanations. While this single observation does not support shortening BLV therapy in clinical practice, it highlights the need to identify predictors of durable virological control after treatment withdrawal to guide more individualized treatment strategies.