Hepatitis D

Hepatitis D virus (HDV) is a defective, subviral RNA agent that requires hepatitis B surface antigen for its own viral envelope and can therefore only infect individuals who are also infected with HBV, either as coinfection (simultaneous acute HBV and HDV infection) or superinfection (HDV acquired by someone already chronically infected with HBV, generally the more clinically severe pattern).

It causes the most severe form of chronic viral hepatitis, with accelerated progression to cirrhosis and hepatocellular carcinoma compared with HBV monoinfection.

Coinfection presents similarly to acute hepatitis B, though may be more severe, with a higher rate of fulminant hepatitis than HBV alone; it is usually self-limiting (following the natural course of the acute HBV infection) if the host clears both viruses.

Superinfection typically presents as an apparent acute flare or worsening in a previously stable chronic HBV carrier, and carries a high rate of progression to chronic HDV infection (over 90%), with accelerated fibrosis progression, more rapid development of cirrhosis, and increased hepatocellular carcinoma risk compared with HBV monoinfection.

Screening for HDV should be considered in any patient with chronic hepatitis B, particularly with unexpectedly severe disease, a disproportionately low HBV DNA relative to disease severity, or from a region/population with higher HDV prevalence.

Anti-HDV antibody is the initial screening test; HDV RNA confirms active infection and quantifies viral load, used both for diagnosis and to monitor treatment response.

• Pegylated interferon-alfa has historically been the primary treatment, given for 48 weeks or longer, though sustained virological response rates are modest and relapse after stopping is common
• Bulevirtide, a novel entry inhibitor blocking HBV/HDV cellular entry, is an increasingly available option (alone or combined with pegylated interferon), representing a significant recent advance in HDV-specific treatment
• Standard HBV nucleos(t)ide analogues (tenofovir, entecavir) suppress HBV replication but have limited direct effect on HDV itself, though they remain important for overall HBV disease control in coinfected patients
• Liver transplantation is considered for decompensated cirrhosis, as per general end-stage liver disease principles
• Regular hepatocellular carcinoma surveillance (6-monthly ultrasound ± AFP) given the elevated HCC risk
• Prevention: since HDV cannot infect without HBV, hepatitis B vaccination prevents HDV infection entirely in those not already HBV-infected

Referral: hepatology for all confirmed cases, given the complexity of treatment and elevated cirrhosis/HCC risk.