Investigational therapies for hepatitis C virus infection
- Andrew W Tai, MD, PhD
Andrew W Tai, MD, PhD
- Assistant Professor, University of Michigan Health System
- Staff Physician, Ann Arbor Veterans Administration Health Systems
- Raymond T Chung, MD
Raymond T Chung, MD
- Associate Professor of Medicine
- Harvard Medical School
- Director of Hepatology and Liver Center
- Vice Chief, Gastroenterology Division
- Massachusetts General Hospital
Major research efforts are underway to identify new therapies for chronic hepatitis C virus (HCV) infection that achieve very high sustained virologic response (SVR) rates, lower the incidence of side effects, have few drug-drug interactions, and/or shorten the duration of treatment. The main targets of most new therapies are the HCV-encoded proteins that are vital to the replication and life cycle of the virus. These targets include the HCV-encoded NS2/3 autoprotease, the NS3/4A serine protease, the NS3 RNA helicase, the NS5A protein, and the NS5B RNA dependent RNA polymerase (RdRp). Another line of investigation has focused on host-encoded proteins that are essential for viral replication, such as cyclophilins.
This topic review will summarize the current state of knowledge of some of the investigational therapies for chronic HCV infection, including those whose efficacy appears to have been disproven. These can be divided conceptually into:
●Treatments targeting HCV-encoded proteins
●Treatments targeting host-encoded proteins
●Therapeutic and preventive vaccines
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- HCV REPLICATION MODELS
- DIRECT ACTING ANTIVIRAL (DAA) THERAPY
- Role of HCV 1a versus 1b genotype
- Role of IL28b gene polymorphisms
- NS3/4A protease inhibitors
- NS5A inhibitors
- NS5B polymerase inhibitors
- INTERFERON-FREE DAA COMBINATIONS
- Sofosbuvir and velpatasvir combinations
- Sofosbuvir and ledipasvir combinations
- Ledipasvir, vedroprevir, tegobuvir, and ribavirin
- ABT-493 and ABT-530
- DAAs no longer being developed
- DAA, PEGINTERFERON, AND RIBAVIRIN COMBINATIONS
- TREATMENTS TARGETING HOST-ENCODED FACTORS
- MicroRNA-122 inhibition
- Cyclophilin inhibitors
- HCV VACCINES
- COMPLEMENTARY/ALTERNATIVE MEDICINE
- Silybum marianum (milk thistle)
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS