Understanding the Context: HIV, HCV, and HCC
Hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) coinfection pose unique health challenges. In the past decade, direct-acting antivirals (DAAs) transformed HCV treatment, offering high cure rates and improved liver outcomes. However, even after what appears to be a sustained virologic response or cure, researchers have identified a persistent risk for hepatocellular carcinoma (HCC) among people living with HIV who have cleared HCV. This finding has important implications for long-term monitoring and cancer prevention strategies in this population.
The New Insight: HCC Risk Persists Post-DAA Cure
Recent studies indicate that the risk of developing HCC does not vanish after successful DAA therapy. Instead, the likelihood of HCC tends to decline gradually each year following HCV cure, but it remains elevated compared with the general population and with HIV-negative individuals who achieved HCV cure. The persistence of genomic and inflammatory changes caused by long-standing liver injury from HCV—and the combined effects of HIV-related immune dysregulation—may contribute to this ongoing risk. Clinicians emphasize that a history of liver fibrosis or cirrhosis remains a critical predictor for future HCC, even after viral eradication.
Why HIV Coinfection Modifies the Risk Landscape
HIV infection can alter liver disease progression and cancer risk through several pathways. Immune system impairment, antiretroviral therapy interactions, metabolic factors, and co-existing liver conditions can influence how the liver responds after HCV cure. In coinfected individuals, the residual inflammatory environment and ongoing immune activation may sustain a milieu conducive to hepatocarcinogenesis. As a result, cancers can emerge years after the virus has been cleared, underscoring the need for tailored, long-term surveillance in this group.
What This Means for Monitoring and Prevention
Medicine now recognizes that HCC surveillance strategies should extend beyond the point of virologic cure in HIV-HCV coinfection. Key recommendations include:
- Continued liver imaging (e.g., ultrasound) at regular intervals, especially for those with prior cirrhosis or advanced fibrosis.
- Periodic assessment of liver function and fibrosis progression to identify changes that could raise cancer risk.
- Risk-factor modification, including managing alcohol use, metabolic syndrome, and weight, to reduce liver inflammation and damage.
- Coordination of HIV and HCV care with a focus on treating other comorbidities that can influence liver health.
Clinicians may also consider adjunctive risk predictors—such as age, duration of HCV infection, and the extent of prior liver scarring—to refine screening intervals. Shared decision-making with patients is essential to balance the benefits and burdens of ongoing surveillance.
What Researchers Are Watching Next
Ongoing studies aim to quantify the precise magnitude of post-DAA HCC risk in diverse populations and to identify which subgroups most benefit from intensified follow-up. Researchers are also exploring whether specific antiretroviral regimens or support therapies can modulate cancer risk by reducing liver inflammation or fibrosis after HCV cure. The evolving evidence will help clinicians tailor long-term care plans for HIV-HCV coinfected patients.
Bottom Line for Patients and Providers
While DAAs effectively cure HCV in many individuals, the risk of hepatocellular carcinoma can persist in people living with HIV. The good news is that this risk declines with time after treatment, but it does not disappear. Persistent vigilance through regular liver imaging and liver health optimization remains a cornerstone of care for HIV-HCV coinfection, ensuring any new HCC can be detected early and managed promptly.
