From the Journals

Strong support to provide DAA therapy to all patients with HCV



Direct-acting antiviral (DAA) therapy for patients with chronic hepatitis C (CHC) is associated with a lower risk for liver and nonliver complications, as well as a “large and significant” 57% reduction in the risk for death from any cause, a large, real-world analysis finds.

Improved outcomes were seen among patients without cirrhosis, those with compensated cirrhosis, and those with existing liver decompensation, the authors noted.

The findings highlight a “substantial need to provide DAA therapy to all patients with HCV, regardless of disease stage or financial status,” wrote Mindie Nguyen, MD, of Stanford University Medical Center, Palo Alto, Calif., and coinvestigators.

“Additional national efforts are needed to reach and treat U.S. population groups that are underinsured or not insured, incarcerated and otherwise marginalized, such as users of illicit drugs, who are also at higher risk of disease complication and reinfection,” they said.

The study was published online in JAMA Internal Medicine.

CHC and its complications are associated with high rates of illness and death. However, large-scale data on long-term liver and nonliver effects of DAA treatment are limited.

For their study, Dr. Nguyen and colleagues analyzed administrative claims data from 2010 to 2021 for 245,596 adults with CHC, of whom 40,654 had received one or more DAA therapies (without interferon) and 204,942 had not received treatment.

DAA-treated patients were slightly older than their untreated peers (mean age, 59.9 years, vs. 58.5 years) and were more likely to be male (62% vs. 58%) and White (59% vs. 57%), and to have diabetes (26% vs. 25%) and cirrhosis (44% vs. 29%).

For liver outcomes, DAA therapy was associated with a lower incidence of decompensation (28.2 vs. 40.8 per 1,000 person-years; P < .001) and hepatocellular carcinoma (HCC) in compensated cirrhosis (20.1 vs. 41.8; P < .001).

For nonliver outcomes, DAA treatment was associated with a lower incidence of diabetes (30.2 vs. 37.2 per 1,000 person-years; P < .001) and chronic kidney disease (31.1 vs. 34.1; P < .001).

The all-cause mortality rate per 1,000 person-years was 36.5 in the DAA-treated group, vs. 64.7 in the untreated group (P < .001).

In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk for HCC (adjusted hazard ratio [aHR], 0.73), decompensation (aHR, 0.36), diabetes (aHR, 0.74), chronic kidney disease (aHR, 0.81), cardiovascular disease (aHR, 0.90), nonliver cancer (aHR, 0.89), and mortality (aHR, 0.43).

The 57% lower mortality rate observed among DAA-treated vs. untreated patients aligns with a large French study of adults with CHC.

“Because HCV treatment with a DAA regimen is well tolerated for nearly all patients, we believe these findings provide further support for universal HCV treatment coverage for all patients affected by HCV,” Dr. Nguyen and colleagues wrote.

The strengths of this study are its large sample of DAA-treated and untreated patients from diverse racial and ethnic groups from across the United States and from diverse practice settings (not just tertiary centers).

One limitation is that the study cohort included only patients covered by private insurance; therefore, the findings may not be generalizable to individuals who are underinsured or not insured. Miscoding and misclassification are also possible with large claims databases.

Support for the study was provided by Stanford University and the Stanford Center for Population Health Sciences. Dr. Nguyen has received institutional grants and advisory board fees from Gilead Sciences outside the submitted work.

A version of this article first appeared on

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