Hepatitis C Reinfection After DAA Therapy Linked to Substance Use, Comorbid HCC

Repeat viremia in adults with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) via direct-acting antiviral (DAA) therapy may be more frequent among younger populations and those with a history of substance use or comorbid hepatocellular carcinoma (HCC), according to study findings published in Clinical Infectious Diseases.

To evaluate real-world trends in repeat HCV viremia after SVR, researchers at Emory University School of Medicine in Georgia analyzed data sourced from the Veterans Health Administration. Adult veterans (N=1129) who received DAAs for chronic HCV between 2014 and 2022 and achieved SVR for at least 12 weeks were eligible for the analysis. Study patients with detectable viremia following treatment were evaluated to determine characteristics of repeat viremia. The researchers also identified a random subset of 110 patients via chart review and grouped them by type of repeat viremia. Definite reinfection was defined by HCV genotype change; probable reinfection by use of injection drugs, new diagnosis of sexually transmitted infection, or incarceration between SVR and repeat viremia without HCV genotype change; and late relapse by HCV genotype change in the absence of reinfection risk factors.

Among the full cohort, 96.4% were men, 42.8% were aged 55 to 64 years, 66.3% were White, 87.0% had substance use disorder, 88.8% had mental health conditions, 48.9% reported unstable housing, 65.4% resided in an urban area, and 50.6% resided in the Southern United States.

The median time to repeat HCV viremia was 1.9 (IQR, 0.8-3.6) years, with the highest frequency of reinfections and relapse observed within the first year after DAA therapy.

Among patients grouped by type of repeat HCV viremia, 25.5% had definite reinfection, 28.5% had probable reinfection, 37.3% had late relapse, and 11.8% had false-positive repeat viremia.

Further analysis of patients with definite or probable reinfection, late relapse, and false-positive viremia showed differences in the respective prevalence of mental health diagnoses (89%, 96%, 68%, and 92%; P =.008), injection drug use (82%, 96%, 0%, and 15%; P =0.000), non-injection drug use (82%, 71%, 22%, and 15%; P =0.000), and comorbid HCC (4%, 0%, 20%, and 8%; P =.026). There were also between-group differences observed with respect to median time to repeat viremia (29, 26, 12, and 27 months, respectively).

Study limitations include reduced generalizability to non-veteran populations, the predominance of men, the reliance on electronic health record data to confirm comorbid diagnoses such as HCC, and potential inaccuracy in the number of definite HCV reinfections.

“This study reinforces important clinical considerations in the care of patients being treated for chronic HCV and highlights future directions for research,” the researchers noted. “[F]urther research into the correlation between hepatocellular carcinoma and late relapse would be valuable,” they added, “given the relationship we have identified between the two and the possibility of viral reservoir.”

References:

Matelski A, Gregoire B, Beste LA, et al. Analysis of repeat hepatitis C viremia after sustained virologic response in a large cohort of U.S. veterans. Clin Infect Dis. Published online January 9, 2025. doi:10.1093/cid/ciaf008

Source: Infectious Disease Advisor