For the first time, a separate Czech guideline focuses exclusively on hepatitis D virus (HDV) infection. Until recently, HDV infection was only mentioned in guidelines concerning hepatitis B virus (HBV) infection, in chapters on HBV/HDV co-infection. The guideline is based on the July 2023 recommendations from the European Association for the Study of the Liver. HDV can either infect a susceptible host together 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 (approximately 2%) progress to chronicity. In contrast, superinfection with HDV in patients with 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 to liver cirrhosis more frequently and more rapidly than HBV monoinfection. Globally, an estimated 4.5-13% of HBsAg-positive individuals 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 at most 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 the country may increase rapidly. Experts estimate that the prevalence of HDV among HBsAg-positive patients in the Czech Republic is approximately 1%. Until 2020, interferon (IFN) α-based therapy was the only treatment option for CHD. Gradually, treatment with pegylated interferon (PEG-IFN) α proved to be more effective than treatment with conventional (standard) IFNα - 25% vs. 17% virological response at the end of 48 week of treatment. Subsequently, however, more than half of the successfully treated patients experienced a virological relapse. Extending the duration of PEG-IFNα treatment to two years did not increase treatment success, as shown by 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 hepatocytes. Clinical trials have evaluated the efficacy and safety of BLV treatment at doses of 2, 5 and 10 mg administered subcutaneously once daily, alone or in combination with PEG-IFNα. Since the optimal duration of BLV treatment has not yet been established, sustained virological response could not be assessed because BLV treatment was not discontinued in the studies. According to 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 authorization from the European Medicines Agency 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 authorization was changed to a standard marketing authorization in July 2023.