Abstract

The consensus report on the management of chronic hepatitis D virus (HDV) infection, first published in 2014 by the Viral Hepatitis Working Group (VHÇG) of the Turkish Society of Clinical Microbiology and Infectious Diseases, has been updated in light of new treatment options that have recently become available or are currently under development. For this purpose, a dedicated subgroup was established within the VHÇG, and a new consensus report was prepared by reviewing the current literature and international evidence-based guidelines.

Key points emphasized in this report include the following: The risk of developing cirrhosis and hepatocellular carcinoma (HCC) is higher in patients with HDV infection compared to those monoinfected with hepatitis B virus (HBV). In HDV-infected individuals, cirrhosis, HCC, and hepatic decompensation may occur at a younger age. Most patients already present with advanced liver disease and/or cirrhosis at the time of diagnosis. Therefore, screening not only at-risk groups but also all HBsAg-positive patients for HDV and raising awareness of HDV infection is essential.

The issue of standardization in diagnostic tests remains unresolved. HDV RNA should be assessed using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR) assay in all patients who test positive for anti-HDV. A 48-week course of pegylated interferon (PEG-IFN) is recommended for treatment. PEG-IFN should be used cautiously in patients with compensated cirrhosis and is contraindicated in those with decompensated disease. While nucleos(t)ide analogs (NAs) may be recommended in cirrhotic patients with detectable HBV DNA, they are not indicated for the treatment of HDV infection.

Bulevirtide (BLV), approved in Europe in 2020, represents a promising option due to its safety profile—including in compensated cirrhotic patients—its efficacy in long-term treatment, and the improved virological response observed when combined with PEG-IFN. However, despite proven efficacy in clinical trials and real-world settings, BLV is only available in countries with regulatory approval.

Ongoing phase studies are evaluating lonafarnib and nucleic acid polymers (NAPs). The high frequency of gastrointestinal side effects observed in phase 2 and phase 3 trials, along with the need for dose reduction and/or treatment interruption, has limited the use of lonafarnib. A phase 3 trial of pegylated interferon lambda (PEG-IFNλ) was terminated due to adverse effects.

Although an increased incidence of HCC among HDV-infected patients has been observed, surveillance with abdominal ultrasonography every six months is still recommended, while alpha-fetoprotein (AFP) testing is left to the physician’s discretion. A better understanding of HDV pathogenesis, the development of drugs targeting the viral life cycle, and the continuation of phase studies may offer the opportunity to reduce complications in patients with chronic HDV infection, who currently have limited treatment options. We believe that this consensus report will contribute to the improvement of HDV diagnosis and treatment and help address the ongoing burden of delta hepatitis in our country.