2025/08/15 by Vincent Lo Re, Debika Bhattacharya, Jennifer C. Price +6 · 1 voice
Medicine · #Hepatitis B Virus Studies #Hepatitis C virus research
paper · doi:10.1093/cid/ciaf335
openalex publication_date 2025/08/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Hepatitis C virus (HCV) infection remains a major cause of chronic liver disease and premature mortality worldwide. The World Health Organization and US Department of Health and Human Services have committed to eliminate HCV infection as a major public health threat by 2030 as defined by a 90% reduction in incidence of new HCV infections and 65% reduction in mortality from a 2015 baseline. In this review, we provide strategies for healthcare providers to implement in their practice to enhance patients' completion of the steps along the HCV care cascade, including HCV screening and diagnosis, linkage to HCV care, and antiviral treatment. Improving successful completion of each step within the HCV care cascade will help to alleviate the burden of HCV infection and make the nation's 2030 HCV elimination goals a reality. Although HCV screening is recommended at least once in a lifetime for all persons aged ≥18 years, it has not fully penetrated into certain populations, such as people who are underserved, uninsured, incarcerated, or formerly or currently inject drugs. Consequently, approximately 40% of people with HCV infection in the United States remain unaware of their infection. Furthermore, many persons identified as HCV antibody-positive are lost to follow-up before confirmatory HCV RNA testing or linkage to treatment. There also continues to be barriers to accessing HCV therapy, such as lack of provider capacity for treatment, limited access to harm-reduction strategies, and restrictions to insurer reimbursement. To help to achieve HCV elimination, it will be necessary to increase HCV screening, enhance linkage to care, and increase uptake of HCV treatment (Figure 1), particularly within primary care, correctional, and substance use treatment settings. Overview of approach to management of persons diagnosed with hepatitis C virus infection. Abbreviations: ACLD, advanced chronic liver disease; DAA, direct-acting antiviral; FIB-4, Fibrosis-4 Index for hepatic fibrosis; HCV, hepatitis C virus; INR, international normalized ratio; STI, sexually transmitted infection. *Indicates laboratory test indicated in American Association for the Study of Liver Diseases/Infectious Diseases Society of America simplified direct-acting antiviral treatment algorithm. aRelevant comorbidities include HIV infection, hepatitis B virus coinfection, and other preexisting liver diseases (eg, metabolic dysfunction-associated steatotic liver disease) that might further accelerate liver disease progression in the setting of chronic hepatitis C virus infection. bMedication reconciliation should record currently prescribed medications, over-the-counter therapies, and herbal/dietary supplements. cDrug interactions can be assessed by consulting prescribing information and using online resources (eg, http://www.hep-druginteractions.org/checker). dCirrhosis is considered to be present if any of the following are present: (1) FIB-4 > 3.25; (2) liver stiffness measure >12.5 kPa on vibration-controlled transient elastography; (3) noninvasive serologic test above the proprietary cutoff indicating cirrhosis (eg, FibroSure, Enhanced Liver Fibrosis tests); (4) clinical evidence of cirrhosis (eg, liver nodularity or splenomegaly on imaging, platelet count <150 000/mm3); or (5) prior liver biopsy showing cirrhosis. eHarm-reduction strategies include syringe service programs, safe injection sites, safe drug use education, and substance use treatment. fChild-Pugh score classifies severity of liver disease according to degree of ascites, serum total bilirubin, serum albumin, prothrombin time, and degree of encephalopathy. gLiver cancer surveillance should be performed via liver ultrasound and alpha-fetoprotein testing. To promote HCV screening and treatment in high HCV prevalence settings and outside of traditional specialty practice venues, simplified HCV treatment algorithms have recently been developed that make administering and monitoring antiviral therapy feasible by nonspecialist providers. Successful treatment of HCV infection requires consideration of comorbidities (particularly presence of cirrhosis), current medications and potential drug interactions, patient preferences, and barriers to antiviral adherence. Selection of antiviral therapy and the frequency and type of contact during treatment will depend on shared decision-making between patient and provider. The care team involved in managing HCV infection may include primary care providers, infectious diseases and/or hepatology practitioners, addiction medicine specialists, nurse providers, pharmacists, psychiatrists, case managers, and social workers. Communication among these disciplines can provide diverse perspectives and individualized expertise to promote cure of HCV infection, reduce the risk of HCV-related liver complications, and prevent HCV reinfection. This review provides state-of-the-art approaches to promote HCV screening and diagnosis, facilitate linkage to HCV care, and expand access to direct-acting antiviral-based HCV treatment. The article also presents several case vignettes to emphasize important contemporary aspects of the management of HCV infection across the cascade of care. Author Contributions. Concept and design: V. L. R., J. T. Drafting of the manuscript: V. L. R., J.T. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: V. L. R. Financial support. Funding was not received for the writing of this manuscript.