This clinical review focuses on practical strategies to help healthcare providers move patients through the hepatitis C virus (HCV) care cascade, from screening and diagnosis to linkage to care and antiviral treatment. HCV remains a major cause of chronic liver disease and premature mortality, and both the World Health Organization and the US Department of Health and Human Services have set goals to eliminate HCV as a major public health threat by 2030. Reaching those goals will require major reductions in new infections and HCV-related mortality, which depends on improving completion of each step in the care cascade.

The review highlights several persistent barriers, including incomplete screening among underserved, uninsured, incarcerated, and people who currently or formerly inject drugs. Approximately 40% of people with HCV in the United States remain unaware of their infection, and many who test antibody-positive are lost before confirmatory RNA testing or treatment linkage. Additional challenges include limited provider capacity, insufficient access to harm-reduction services, and insurance restrictions. The authors emphasize that expanding screening, improving linkage to care, and increasing treatment uptake-especially in primary care, correctional, and substance use treatment settings-will be essential to HCV elimination.

Reference: Lo Re V 3rd, Bhattacharya D, Price J, et al. Executive summary: state-of-the-art review: hepatitis C. Clin Infect Dis. 2025 Sep 16;81(2):217-219. doi: 10.1093/cid/ciaf335. PMID: 40971898.

This multicenter randomized clinical trial evaluated whether nontargeted or targeted hepatitis C virus (HCV) screening was more effective in emergency departments (EDs). Across 147,498 patient visits at 3 urban EDs, patients were randomized to either nontargeted screening, where HCV testing was offered regardless of risk or targeted screening, where testing was offered based on risk assessment. Nontargeted screening led to more completed HCV tests and significantly more new HCV diagnoses: 9867 patients were tested and 154 new diagnoses were identified, compared with 4640 tested and 115 new diagnoses in the targeted screening group.

The findings suggest that nontargeted HCV screening is more effective than targeted screening for identifying new HCV infections in ED settings. However, the study also highlights a major gap after diagnosis: only small proportions of newly diagnosed patients were linked to care, started direct-acting antiviral treatment, completed treatment, or achieved sustained virologic response at 12 weeks. The authors conclude that while broader ED screening can improve case detection, better linkage-to-care and treatment models are urgently needed to turn diagnosis into cure.

Reference: Haukoos J, Rothman RE, Galbraith JW, et al; DETECT Hep C Screening Trial Investigators. Hepatitis C screening in emergency departments: the DETECT Hep C randomized clinical trial. JAMA. 2025 Aug 12;334(6):497-507. doi: 10.1001/jama.2025.10563. Epub 2025 Jul 9. PMID: 40632510.

This retrospective single-center study evaluated long-term outcomes in 243 adults with chronic hepatitis C who received direct-acting antiviral (DAA) therapy and achieved sustained virologic response (SVR) at 12 weeks. Over a median follow-up of 24 months, liver function markers improved after treatment with ALT, AST, and albumin normalizing by the end of treatment and generally remaining stable during follow-up. SVR was durable in most patients: 236 patients remained HCV RNA negative, while 7 had recurrent detectable HCV RNA, most within the first 12 months. After retreatment with a changed DAA regimen, all 7 patients again became HCV RNA negative.

Despite viral clearance, the study found that liver-related risks did not disappear, especially for patients with cirrhosis at baseline. Overall, 24 patients experienced liver-related adverse events, including ascites, hepatic encephalopathy, upper gastrointestinal bleeding, liver failure, death, and hepatocellular carcinoma (HCC). These events were significantly more common in patients with cirrhosis than in those without cirrhosis. HCC occurred in 9 patients, and baseline cirrhosis was an independent predictor of HCC risk. The authors conclude that DAA treatment can produce durable viral eradication and improved liver function, but ongoing surveillance remains necessary after SVR, particularly for patients with cirrhosis or genotype 3b.

Reference: Li M, Li Y, Zhang Y, Wang X, Lin C. Five-year follow-up of sustained virological response with hepatitis C infection after direct-acting antiviral therapy: A single-center retrospective study. Medicine (Baltimore). 2024 Feb 16;103(7):e37212. doi: 10.1097/MD.0000000000037212. PMID: 38363923; PMCID: PMC10869073.