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Direct-Acting Antivirals Linked to Improved Outcomes in Chronic Hepatitis C

— All-cause mortality rate significantly lower in treated versus untreated group

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Treatment with direct-acting antivirals (DAA) was associated with improved outcomes as well as improved long-term survival among patients with chronic hepatitis C, a retrospective cohort study showed.

For liver outcomes, the incidence per 1,000 person-years of decompensation was 28.2 in the DAA-treated group compared with 40.8 in the untreated group (P<0.001), and the incidence of hepatocellular carcinoma (HCC) in compensated cirrhosis was 20.1 compared with 41.8, respectively (P<0.001), reported Mindie H. Nguyen, MD, MAS, of Stanford University Medical Center in Palo Alto, and colleagues.

As for non-liver outcomes, the incidence of diabetes was 30.2 per 1,000 person-years in the DAA-treated group versus 37.2 in the untreated group (P<0.001), and the incidence of chronic kidney disease was 31.1 versus 34.1, respectively (P<0.001), they noted in .

Of note, the all-cause mortality rate per 1,000 person-years was 36.5 in the DAA-treated group compared with 64.7 in the untreated group (P<0.001).

"Because HCV [hepatitis C virus] 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," Nguyen and team wrote.

The study findings "highlight a substantial need to provide DAA therapy to all patients with HCV, regardless of disease stage or financial status," they added.

In a multivariable regression analysis, treatment with a DAA was independently associated with a significant decrease in the risk of HCC (adjusted HR 0.73), liver decompensation (aHR 0.36), diabetes (aHR 0.74), chronic kidney disease (aHR 0.81), cardiovascular disease (aHR 0.90), non-liver cancer (aHR 0.89), and mortality outcomes (aHR 0.43).

Oral DAA treatments have been widely available since 2014, with studies consistently showing after sustained virologic response. However, "the effects of DAAs on most non-liver comorbidities have not been well documented," and "data for long-term outcomes after DAA treatment are limited."

For this study, Nguyen and colleagues used data on 245,596 adults with chronic hepatitis C from the Optum Clinformatics Data Mart database from 2010 to 2021. Of these patients, 40,654 had received one or more DAA (without interferon) and 204,942 were untreated.

Treated patients were slightly older than untreated patients (mean age 59.9 vs 58.5), and more likely to be male (62% vs 58%) and white (59% vs 57%). Treated patients were also more likely to have diabetes (26% vs 25%) and cirrhosis (44% vs 29%).

Although this study offered a generalized view "compared to studies from specialized liver centers," since it included patients with hepatitis C from a database of over 60 million individuals across all regions of the U.S., "the findings may be more generalizable to the overall population with private health insurance," and not the under-insured or the uninsured, Nguyen and team noted.

Furthermore, because the researchers used a large claims database, miscoding and misclassification were possible.

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    Ingrid Hein is a staff writer for 51˶ covering infectious disease. She has been a medical reporter for more than a decade.

Disclosures

The study was supported by the Stanford Center for Population Health Sciences, which is supported by the National Center for Advancing Translational Science Clinical and Translational Science Award and Stanford University funding.

Nguyen reported grants and advisory board fees from Gilead Sciences. Co-authors also reported relationships with Gilead Sciences and Merck Sharp & Dohme.

Primary Source

JAMA Internal Medicine

Ogawa E, et al "Association of direct-acting antiviral therapy with liver and nonliver complications and long-term mortality in patients with chronic hepatitis C" JAMA Intern Med 2022; DOI: 10.1001/jamainternmed.2022.5699.