Viral hepatitis: Innovations and expectations

Abstract

Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients.

Structure of hepatitis B/D antiviral drug Bulevirtide bound to its receptor protein NTCP

“…BLV has a large interface with NTCP, with 2064 Å 2 buried surface area between them, rationalizing the tight binding of BLV (and by extension preS1) to its receptor. Based on the structural observations, we divided the sequence of the BLV peptide into three sections - the myristoyl group, the “plug” (residues Gly2-Asp20), and the “string” (residues Pro21-Gly48) (Fig.…”

“…Nuclei were stained with Hoechst33342 (Thermo Fisher Scientific) and fluorescence images were analyzed on a DMI6000 B inverted fluorescent microscope (Leica). Qualitative and quantitative preS1- peptide binding was analyzed with the NH2-terminally myristoylated and COOH-terminally AlexaFlour 568-coupled fluorescent myr-preS1 2-48 peptide (further referred to as preS1-AX568 peptide), consisting of amino acids 2-48 of the large HBV sub-genotype D3 surface protein (Biosynthesis). Briefly, HEK293 and HEK-NTCP cells were incubated with 200 nM preS1- AX568 peptide in sodium buffer (142.9 mM NaCl, 4.7 mM KCl, 1.2 mM MgSO4 x 7H2O, 1.2 mM KH2PO4, 20 mM HEPES, 1.8 mM CaCl2 x 2H2O, pH 7.4) or in sodium-free buffer (equimolar substitution of NaCl with choline chloride).…”

“…With approximately 1.5 million individuals infected annually, the hepatitis B virus (HBV) continues to pose a substantial global health challenge, despite the availability of an effective vaccine 1 . HBV, a small, enveloped DNA virus, causes acute and chronic infection of the liver and the chronic form, in particular, significantly contributes to the overall burden of liver-related diseases, such as cirrhosis and hepatocellular carcinoma (HCC) 2,3 . Additionally, co-infection of HBV-infected patients with the hepatitis D virus (HDV), an enveloped RNA satellite virus that uses HBV surface proteins in HBV/HDV co-infected cells for envelopment and infection, enhances the severity of liver disease [4][5][6] .…”

Safety profile, antiviral capacity, and liver protection of a nasal therapeutic vaccine in patients with chronic hepatitis B: Five-year-follow-up outcomes after the end of treatment

“…NUCs can be taken orally and can induce HBV reduction or even negativity of HBV DNA in many patients with CHB (8,9). Approximately 25 years have passed since the entry of NUCs for the treatment of CHB (10)(11)(12). It is now apparent that NUCs cannot be the treatment of choice for CHB due to the following reasons: (1) NUCs cannot eradicate all forms of HBV DNA, especially closed covalently circular DNA (cccDNA), which acts as a template for new DNA formation; (2) NUCs therapy must be used for several years or even for a patient's whole life.…”

Liver Injury and Cell Survival in Non-Alcoholic Steatohepatitis Regulated by Sex-Based Difference through B Cell Lymphoma 6

“…Until recent years, the main causes of chronic liver disease have been alcoholic steatosis, due to excessive alcohol consumption, and viral hepatitis, due to persistent infection with hepatitis B and C viruses (HBV and HCV, respectively). However, with the development of several drugs for HBV and HCV, the number of viral hepatitis cases has decreased, making it possible to eliminate the virus at a considerable rate, especially HCV [ 2 ].…”