Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.
BACKGROUND
Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection.


OBJECTIVE
To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection.


METHODS
MEDLINE and EMBASE from inception through 1 November 2016.


METHODS
42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs.


METHODS
Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently.


RESULTS
Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without.


CONCLUSIONS
Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling.


CONCLUSIONS
Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis.


BACKGROUND
Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Oluwaseun
O
Falade-Nwulia
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Catalina
C
Suarez-Cuervo
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
David R
DR
Nelson
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Michael W
MW
Fried
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jodi B
JB
Segal
From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Mark S
MS
Sulkowski
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D016031:Liver Transplantation; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use
D000998:Antiviral Agents; D012254:Ribavirin