Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection

Abstract

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. Purpose To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. Data Sources MEDLINE and EMBASE from inception through 1 November 2016. Study Selection 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. Data Extraction Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently. Data Synthesis 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. Limitations 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. Conclusion Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis. Primary Funding Source Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711)

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…The availability of safe, effective, well‐tolerated therapy substantially facilitates the goal of expanding HCV treatment as recommended in the HCV elimination strategies of the WHO and the NASEM . Overall, DAA regimens successfully cure HCV infection in > 95% of treated persons . Moreover, the development of coformulated, pangenotypic regimens that require relatively short treatment durations has greatly simplified HCV antiviral therapy administration.…”

“…The universal treatment recommendation represents a principal tenet of the HCV guidance along with newly recommended universal hepatitis C screening of adults. The HCV guidance panel urges health care providers caring for adults to encourage hepatitis C screening and treatment (if positive) because DAA therapy is safe and cures HCV infection in most people …”

“…Coincident with the marked increase in drug overdose deaths among PWID in the United States, this pool of donor organs has sadly increased substantially . In stark contrast to this tragic loss of life, the development of safe and highly effective DAA therapy provides an opportunity to consider use of allografts from HCV‐viremic donors in HCV‐negative recipients because iatrogenic HCV infection can be cured with retention of allograft function in the majority of cases. Recent data indicate increasing acceptance of these organs among HCV‐negative recipients .…”

Direct antiviral therapy for hepatitis C and hepatocellular carcinoma: facing the conundrum

“…Direct-acting antivirals (DAA) are new oral drugs, with potent antiviral activity against HCV infection, highly efficacious, relatively safe and well tolerated, that can be used in all categories of patients with chronic HCV infection, including those with more advanced and even complicated liver disease [11] . This has allowed treatment of a huge cohort of patients with liver cirrhosis, obtaining the eradication of HCV infection in the vast majority of them.…”

Hepatitis C

“…Overall rates of serious adverse effects and treatment discontinuation were found to be low (<10%) across all patients. 36 Abstinence from alcohol, maintaining ideal body weight, avoiding hepatitis A or B (via vaccination), and avoiding HIV via safe sex are prudent.…”