New Findings Underscore Need for Universal DAA Therapy for all Persons with Hepatitis C Virus Infection

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In a study of over 245 000 insured US patients with chronic hepatitis C (CHC), direct-acting antiviral (DAA) treatment was associated with a reduced risk of mortality and liver and nonliver outcomes, regardless of disease stage.

“These findings support the need for continued efforts to promote hepatitis C screening for diagnosis and treatment of CHC before onset of complications to prevent liver and nonliver complications and to lower all-cause mortality,” wrote Eiichi Ogawa, MD, PhD, of the department of general internal medicine of the department of general internal medicine at Kyushu University Hospital in Japan, and colleagues in JAMA Internal Medicine.

According to Ogawa and colleagues, the most notable improvement in treatment for hepatitis C virus (HCV) infection since 2014 has been DAA agents.

“HCV elimination by DAAs has been associated with significant reductions in the risk of certain nonliver diseases such as diabetes. However, the effects of DAAs on most nonliver comorbidities have not been well documented. In addition, data for long-term outcomes after DAA treatment are limited,” stated researchers.

To assess the association of HCV elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up, investigators conducted a retrospective study of 245 596 insured patients (mean age, 58.7 years; 41% women) with CHC using the Optum Clinformatics Data Mart database, 2010 to 2021.

Of the total cohort, 40 654 patients (mean age, 59.9 years; 61.6% men) had received ≥1 prescriptions for DAAs (without interferon) and 204 942 participants (mean age, 58.5 years; 58.4% men) were untreated. The main outcomes and measures were incidence (per 1000 person-years) of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease [CKD], cardiovascular disease), and overall mortality.

At baseline, compared to participants in the untreated group, those in the DAA-treatment group were more likely to have compensated cirrhosis (44.2% vs 29.3%; P<.001), HCC (3.1% vs 2.4%; P<.001) and/or diabetes (26.3% vs 25.4%; P<.001), according to study results. Also, the mean Charlson comorbidity index score of the DAA-treated group was significantly higher than that of the untreated cohort (4.0 vs 3.3; P<.001).

Investigators observed that compared to untreated patients, DAA-treated participants had lower incidence of liver-related outcomes, such as decompensation (28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P<.001) and HCC in compensated cirrhosis (20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P<.001), and nonliver outcomes such as diabetes (30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P<.001) and CKD (31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P<.001).

The all-cause mortality rates per 1000 person-years were significantly lower in DAA-treated participants compared with untreated patients (36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P<.001), according to the results.

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

“Additional national efforts are needed to reach and treat US 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,” concluded Ogawa et al. “Our findings advocate for continued efforts to promote hepatitis C screening and early diagnosis and treatment—prior to the onset of CHC complications—to prevent liver and nonliver morbidity and mortality.”

Reference: Ogawa E, Chien N, Kam L, 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. Published online December 12, 2022. doi:10.1001/jamainternmed.2022.5699.