The Impact of Direct-Acting Antiviral Therapy on End-Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders

Hepatology. 2021 Aug;74(2):566-581. doi: 10.1002/hep.31732. Epub 2021 Jul 1.


Background and aims: Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD.

Approach and results: This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group.

Conclusions: Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administrative Claims, Healthcare / statistics & numerical data
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology
  • Databases, Factual
  • End Stage Liver Disease / diagnosis
  • End Stage Liver Disease / epidemiology*
  • End Stage Liver Disease / pathology
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Incidence
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • Severity of Illness Index
  • Substance-Related Disorders / complications
  • Substance-Related Disorders / epidemiology*
  • Young Adult


  • Antiviral Agents