Broad-range efficacy from new short-course regimens with ledipasvir/sofosbuvir in a single-tablet holds promise for treating persons infected with hepatitis C virus (HCV). Of the estimated 2.7 to 3.9 million Americans chronically infected with HCV, anywhere from 50% to 75% are undiagnosed and untreated.  Nearly half of infected persons report no exposure that would have put them at risk, such as injection- or intranasal drug use, acquiring a tattoo in unregulated parlors, incarceration, needle-stick in a health care setting, and other invasive medical procedures, etc. In its acute phase, HCV is usually asymptomatic and so unsuspected. However, anywhere from 75% to 85% of infected persons will develop a chronic infection, and with it, an increased risk for cirrhosis, hepatocellular carcinoma, and diabetes.
Fortunately, chronic HCV can curable with a sustained virologic response to treatment, leading to reduced risk of diabetes and improved liver histology. Recent studies have focused on finding a short-course, well-tolerated regimen. In May 2014, a multicenter research group reported successful outcomes following three short-course regimens. In a randomized trial, 647 patients infected with HCV genotype 1 uncomplicated by cirrhosis were assigned to three treatment groups: ledipasvir and sofosbuvir for12 weeks, ledipasvir and sofosbuvir for 8 weeks, or ledipasvir and sofosbuvir plus ribavirin for 8 weeks.
Patients on all three regimens developed a high rate of sustained virologic response—12-week regimen, 95%; 8-week, 93%; added ribavirin regimen, 94%. The differences were statistically insignificant. At the end of therapy, only 23 patients relapsed overall. Treatment response did not differ with varying patient characteristics, suggesting that there is no need to tailor treatment regimens for HCV-infected persons who have not been treated before and are currently without cirrhosis. The single-tablet ledipasvir-sofosbuvir combination appears effective across a broad range of patients. Patients taking the regimen with added ribavirin suffered more adverse effect without increase in treatment efficacy.
In 2012 the Centers for Disease Control and Prevention recommended screening guidelines that may help bring about earlier diagnosis, before serious complications occur. With earlier diagnosis, affected persons may be less likely to develop liver disease and other extra-hepatic conditions through early treatment. Current guidelines recommend HCV testing based on known risk factors and clinical indications, and one-time screening for persons born from 1945 to 1965. CDC discourages routine testing among low-risk populations, which can lead to false-positive results.
 Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. N Engl J Med 2013;368:1859-61.
 Kowdly KV, Gordon SC, Reddy KR, et al. Ledipasver and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014; DOI: 10.1056/NEJMoa1402355. Accessed May 9, 2014.
 Screening for hepatitis C virus infection in adults: final recommendation statement. Rockville, MD: U.S. Preventive Services Task Force, June 25, 2013. Accessed May 31, 2014 at http:// www.uspreventiveservicestaskforce.org/ uspstf12/hepc/hepcfinalrs.htm.
–Deborah Kowal, MA, PA, President & CEO, Contraceptive Technology Communications, Inc