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DAA Therapy Linked With Improved Liver, Mortality Outcomes in Patients With Chronic Hepatitis C


Use of direct-acting antiviral (DAA) treatment (without interferon) was shown to reduce liver and nonliver complications, as well as improve long-term overall survival among patients with chronic hepatitis C.

Direct-acting antiviral (DAA) treatment was associated with reduced liver and nonliver complications and improved long-term overall survival in patients with chronic hepatitis C (CHC), according to study findings published today in JAMA Internal Medicine.

Untreated CHC and its complications are associated with high rates of morbidity and mortality. Recent advancements in management of hepatitis C virus (HCV) through short-course DAA has shown these therapies can achieve a virologic cure for almost all treated patients, regardless of age, cirrhosis status, prior treatment failure history, and presence of comorbidities such as chronic kidney disease (CKD).

“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,” wrote the study authors. “Large-scale data obtained from clinical practices without the selection bias of tertiary care center data are more generalizable and can better inform future public health and policy planning.”

They conducted a retrospective cohort study 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 among insured US patients with CHC from the Optum Clinformatics Data Mart database of deidentified administrative health claims from commercial and Medicare Advantage health plans between 2010 and 2021.

The primary outcome assessed was incidence of liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation, and overall mortality. Additionally, secondary outcomes examined incidence of relevant nonliver events (nonliver cancer, diabetes, CKD, cardiovascular disease) and DAA treatment as factors associated with liver, nonliver, and mortality outcomes in patients with HCV infection.

A total of 245,596 adult patients with CHC (mean [SD] age, 58.7 [12.6] years; 100,809 [41.0%] women; 8652 [3.5%] Asian, 42,854 [17.4%] Black, 29,502 [12.0%] Hispanic, and 139,910 [57.0%] White individuals) were included in the analysis, of which 40,654 patients had received 1 or more prescriptions for DAA medication (without interferon) and 204,942 patients were untreated.

Compared with the untreated patients, DAA-treated individuals were more likely to be male (61.6% vs 58.4%; P < .001) and 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). The mean Charlson comorbidity index of the DAA-treated patients was significantly higher than that of untreated patients (4.0 vs 3.3; P < .001).

Findings indicated that incidence (per 1000 person-years) of liver, nonliver, and mortality outcomes were significantly lower in DAA-treated patients with CHC compared with untreated patients:

  • Liver outcomes: 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)
  • Nonliver outcomes: 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)
  • All-cause mortality rates per 1000 person-years (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P < .001).

Furthermore, multivariable regression analysis data adjusting for age, sex, race and ethnicity showed that DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted HR [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).

As the total study cohort included only patients diagnosed with HCV and covered by private insurance, researchers noted that findings may not be generalizable to individuals who are underinsured or not insured.

“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,” concluded researchers.


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

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