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Therapy of Chronic Viral Hepatitis: The Light at the End of the Tunnel?
Biomedicines. 2022 Feb 24;10(3):534. doi: 10.3390/biomedicines10030534.
Giorgio Maria Saracco1, Alfredo Marzano1, Mario Rizzetto1
Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of the viruses. In chronic hepatitis B, long term suppressive treatments with nucleoside/nucleotide analogues have had a dramatic impact on the evolution of liver disease and liver-related complications. However, a conclusive clearance of the virus is difficult to obtain; new strategies that are able to eradicate the infection are currently objects of research. The therapy for Hepatitis D Virus infection is challenging due to the unique virology of the virus, which uses the synthetic machinery of the infected hepatocyte for its own replication and cannot be targeted by conventional antivirals that are active against virus-coded proteins. Recently introduced antivirals, such as bulevertide and lonafarnib, display definite but only partial efficacy in reducing serum HDV-RNA. However, in combination with pegylated interferon, they provide a synergistic therapeutic effect and appear to represent the current best therapy for HDV-positive patients. With the advent of Direct Acting Antiviral Agents (DAAs), a dramatic breakthrough has occurred in the therapeutic scenario of chronic hepatitis C. Cure of HCV infection is achieved in more than 95% of treated patients, irrespective of their baseline liver fibrosis status. Potentially, the goal of global HCV elimination by 2030 as endorsed by the World Health Organization can be obtained if more global subsidised supplies of DAAs are provided.