Abstract
For the first time, this is a separate Czech recommended practice that focuses only on HDV infection. Until now, HDV infection has been mentioned only in the guidelines on hepatitis B virus (HBV) infection, in the HBV/HDV co-infection chapters.
The European Association for the Study of the Liver (EASL) clinical practice guidelines from July 2023 were the basis for writing this guideline. HDV can co-infect a susceptible host with HBV (co-infection) or superinfect a person chronically infected with HBV.
HBV/HDV coinfection usually leads to acute hepatitis with a wide clinical spectrum ranging from an asymptomatic course, to mild hepatitis, to acute liver failure. However, only a small proportion of cases (around 2 %) progress to chronicity.
In contrast, superinfection with HDV on chronic HBV infection very often leads to severe acute hepatitis, which progresses to chronic hepatitis D (CHD) in up to 90 % of cases and is associated with more severe chronic outcomes than HBV monoinfection. CHD has been shown to progress more frequently and more rapidly to liver cirrhosis than HBV monoinfection.
Globally, an estimate of 4.5-13 % of HBsAg-positive persons are infected with HDV, representing 12-72 million persons infected with HDV in absolute numbers. HDV infection is still rare in the Czech Republic, with a maximum of a few dozen patients, almost exclusively foreigners coming from endemic areas, mainly from Mongolia and other Asian countries.
With the increasing migration of people from endemic areas, the incidence and prevalence of hepatitis D in our country may increase rapidly. Experts estimate that the prevalence of HDV among HBsAg positive patients in the Czech Republic is around 1 %.
Until 2020, interferon (IFN)α-based therapy was the only treatment option for CHD. Gradually, pegylated interferon (PEG-IFN)α treatment proved to be more effective than treatment with conventional (standard) IFNα - 25 vs. 17 % virological response at the end of 48 weeks of treatment.
Subsequently, however, more than half of the patients successfully treated so far experienced virological relapse after treatment. Extending the duration of PEG-IFNα treatment to 2 years did not increase treatment success according to the results of most clinical trials.
Bulevirtide (BLV) is a synthetic lipopeptide consisting of 47 amino acids from the preS1 domain of the large HBsAg protein, which binds to NTCP, thereby preventing HDV from entering the hepatocyte. Clinical trials have tested the efficacy and safety of BLV treatment at doses of 2, 5 and 10 mg once daily subcutaneously, alone or in combination with PEG-IFNα.
As the optimal duration of BLV treatment has not yet been established, it has not yet been possible to assess the sustained virological response, as BLV treatment was not discontinued in the studies. According to the results of clinical trials, a higher dose of BLV (10 mg) provides no benefit compared to a dose of 2 mg once daily.
In July 2020, BLV received conditional marketing authorisation from the European Medicines Agency (EMA) for the treatment of CHD and compensated liver disease, with a recommendation to continue BLV treatment at a dose of 2 mg daily until clinical benefit is seen. The conditional marketing authorisation was switched to a standard marketing authorisation in July 2023.