HCV: direct-acting antivirals halve risk for DM

Takeaway

• HCV treatment with direct-acting antivirals (DAAs) is associated with a 47% reduced risk for subsequent diabetes mellitus (DM).

Why this matters

• Magnitude of benefit is greater among patients with more advanced liver fibrosis/cirrhosis.

Study design

• ERCHIVES data for 242,680 HCV-infected US Veterans; 2% received peginterferon-ribavirin (PEG/RBV) and 8.8% were treated with DAAs.
• Treated and nontreated patients were matched by propensity score.
• Primary outcome: incident diabetes >12 weeks postbaseline.
• Funding: Gilead Sciences.  

Key results

• Diabetes incidence was significantly lower in treated vs untreated patients (15.4 vs 20.6 per 1000 person-years [PY]; P<.0001).
• Effect was driven by DAAs (9.89 vs 20.6 per 1000 PY; P<.0001), not PEG/RBV (19.8 vs 20.6 per 1000 PY; P=.39).
• 78.8% achieved sustained virologic response at 12 weeks posttherapy (SVR12).
• Among treated patients, diabetes rate was lower with SVR12 than without (13.3 vs 19.2 per 1000 PY; P<.0001).
• Rate reduction benefit of treatment rose with disease severity. Absolute difference per 1000 PY:
  • 2.9 for fibrosis-4 index (FIB-4) <1.25,
  • 5.7 for 1.26<FIB-4<3.25, and
  • 9.8 for FIB-4 >3.25.
• DAA therapy (HR=0.53; 95% CI, 0.46-0.63) and SVR12 (HR=0.81; 95% CI, 0.70-0.93) predicted reduced risk for diabetes; PEG/RBV did not.
• Diabetes-free survival was significantly longer with DAAs vs PEG/RBV and no treatment (P<.001).

Limitations

• Retrospective design; predominantly male population.