Multiple oral direct-acting antiviral regimens associated with sustained virologic response for hepatitis C virus infection
1. Multiple oral direct-acting antiviral (DAA) interferon-free therapies with high SVR rates are available for all six hepatitis C virus (HCV) genotypes.
2. These DAA regimens are highly efficacious and have a good safety profile, which suggests that more patients with HCV infection could possibly be treated and cleared of HCV if improvements are made in detection of HCV and accessing DAA treatment.
Evidence Rating Level: 1 (Excellent)
Study Rundown: An estimated 3.2 to 5 million people in the United States have chronic HCV infection. Untreated HCV infection can result in liver cancer, cirrhosis, or death. Sustained virologic response (SVR), which is indicative of successful HCV infection treatment, is the absence of HCV RNA detection in the blood for 12 weeks or more after completion of treatment. The authors of this systematic review examined the safety and efficacy of Food and Drug Administration (FDA)-approved oral HCV treatments that were interferon-free and included 2 or more DAAs. This review found that interferon-free DAA therapies that provide a high SVR are available for all six HCV genotypes. In patients with HCV genotype 1, 6 therapies had SVR rates above 95%. SVR rates were similar for other HCV genotypes. Generally, rates of treatment discontinuation or serious adverse events were low (<10% of the general HCV patient population). These DAA regimens are highly efficacious and have a good safety profile, which suggests that more patients with HCV infection could possibly be treated and cleared of HCV if improvements are made in detection of HCV and accessing DAA treatment.
A strength of this systematic review is that it provides an update of DAA regimens without interferon. This is important in cases of genotype 1 infection that tend to have poor SVR rates with treatments containing interferon. Limitations of this study include moderate risk of bias in 23 studies and industry funding of all but one study. In addition, several studies were specific to a certain population, which limits the ability to generalize study results.
Click to read the study in Annals of Internal Medicine
Click to read an accompanying editorial in Annals of Internal Medicine
Relevant Reading: Hepatitis C disease burden in the United States in the era of oral direct-acting antivirals
In-Depth [systematic review]: This study used MEDLINE and EMBASE databases from the start date of the database through 1 November 2016 to find English-language randomized controlled trials (RCTs) of chronic HCV infection in adults. Included studies assessed ≥8 weeks of FDA-approved HCV interferon-free therapies including 2 or more DAAs. Forty-two studies were selected, with low risk of bias for 19 studies and moderate risk for 23 studies. Thirty-two studies involved patients with HCV genotype 1 infection, which is the most common genotype in the world. Therapies containing NS3/4A protease inhibitors included Grazoprevir-Elbasivir, Paritaprevir–Ritonavir–Ombitasvir and Dasabuvir, and Simeprevir and Sofosbuvir. Therapies that did not contain NS3/4A protease inhibitors included Daclatasvir and Sofosbuvir, Ledipasvir–Sofosbuvir, and Velpatasvir–Sofosbuvir. In patients with HCV genotype 1 infection without cirrhosis, including those co-infected with HIV, 6 DAA therapies demonstrated SVR rates of >95%. SVR rates were lower (78% to 87%) in patients with decompensated cirrhosis. SVR rates for certain DAA therapies and patient populations were increased by adding ribavirin. However, ribavirin-containing therapies had more adverse events than treatments that did not.
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