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Am Fam Physician. 2021;104(6):626-635

Patient information: A handout on this topic is available at https://familydoctor.org/condition/hepatitis-c.

This clinical content conforms to AAFP criteria for CME.

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Screening recommendations and treatment guidelines for hepatitis C virus (HCV) infection have been updated. People at the greatest risk of HCV infection are those between 18 and 39 years of age and those who use injection drugs. Universal screening with an anti-HCV antibody test with follow-up reflex HCV RNA polymerase chain reaction testing for positive results to confirm active disease is recommended at least once for all adults 18 years and older and during each pregnancy. Any person with ongoing risk factors should be screened periodically as long as the at-risk behavior persists. One-time screening is recommended for patients younger than 18 years with risk factors. For treatment-naive adults without cirrhosis or with compensated cirrhosis, a simplified treatment regimen consisting of eight weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir results in greater than 95% cure rates. Undetectable HCV RNA 12 weeks after completing therapy is considered a virologic cure (i.e., sustained virologic response). A sustained virologic response is associated with lower all-cause mortality and improves hepatic and extrahepatic manifestations, cognitive function, physical health, work productivity, and quality of life. In patients with compensated cirrhosis, posttreatment surveillance for hepatocellular carcinoma and esophageal varices should include abdominal ultrasonography (with or without alpha fetoprotein) every six months and upper endoscopy every two to three years. In the absence of cirrhosis, no liver-related follow-up is recommended.

Hepatitis C virus (HCV) infection, an underdiagnosed and undertreated multifaceted systemic disease, has a protracted chronic phase with hepatic and extrahepatic manifestations that affects an estimated 3.7 million people in the United States.15 From 2010 to 2018, the incidence of acute HCV infection among people 18 to 39 years of age quadrupled because of the opioid epidemic and the associated increase in people who inject drugs.18 Globally, less than 5% of people with HCV have been diagnosed, and less than 1% have received treatment.1,6,7

WHAT'S NEW ON THIS TOPIC

HCV Infection

From 2010 to 2018, the incidence of acute HCV infection among people 18 to 39 years of age quadrupled because of the opioid epidemic and the associated increase in people who inject drugs.

Only 52% of the 3.7 million people in the United States with chronic HCV infection are aware of their disease, and only 37% have received treatment.

The U.S. Preventive Services Task Force and the Centers for Disease Control and Prevention recommend one-time screening for HCV infection in adults 18 to 79 years of age, and periodic screening in adults with ongoing risk factors.

The American College of Obstetricians and Gynecologists recommends screening all pregnant people for HCV infection during each pregnancy.

HCV = hepatitis C virus.

Clinical recommendationEvidence ratingComments
Screen for HCV infection in adults 18 to 79 years of age, during each pregnancy, and for patients with at-risk behavior for as long as the behavior persists.17,20,21 BCenters for Disease Control and Prevention, U.S. Preventive Services Task Force, and American College of Obstetricians and Gynecologists
Anti-HCV antibody testing with follow-up reflex HCV RNA polymerase chain reaction testing is recommended for initial testing.8,15,17,24 CAccurate tests for detecting HCV
Hepatitis A and hepatitis B vaccinations should be administered to people with HCV. A pneumococcal polysaccharide vaccine is indicated for adults 19 to 64 years of age with chronic hepatic disease and cirrhosis.8,15,17,18 CExpert opinion and consensus guideline from the Advisory Committee on Immunization Practices and Centers for Disease Control and Prevention
Adults with HCV infection who meet criteria for treatment with a simplified regimen should be treated with eight weeks of glecaprevir/pibrentasvir (Mavyret) or 12 weeks of sofosbuvir/velpatasvir (Epclusa), regardless of the HCV genotype.8,15,18,40,54 BPlacebo-controlled trials show a > 95%sustained viral response at 12 weeks posttreatment; sustained virologic response is associated with improved patient-oriented outcomes in long-term cohort studies
All people should receive education about preventing HCV transmission and reducing the progression of hepatic disease.8,15,17 CExpert opinion and consensus guideline
RecommendationSponsoring organization
Do not repeat hepatitis C virus antibody testing in patients with a previous positive hepatitis C virus test result. Instead, order hepatitis C viral load testing for assessment of active vs. resolved infection.American Society for Clinical Pathology
Do not repeat hepatitis C viral load testing outside of antiviral therapy.American Association for the Study of Liver Diseases

The World Health Organization and the National Academies of Sciences, Engineering, and Medicine have developed strategies to eliminate HCV by 2030.1,6,7 Strategies include expanded screening, better access to appropriate care, and highly effective direct-acting antiviral medication.1,6,7 The United States is not on track to meet this goal.1,4,6,7 Estimates for 2018 indicated that 52% of people in the United States were aware of their disease, and 37% had received treatment.4 Current barriers to access and treatment include the asymptomatic nature of chronic HCV, lack of access to specialty care, high cost of treatment, insurance guidelines requiring advanced stages of liver fibrosis before approving therapy, substance use and sobriety requirements, and prescriber restrictions (https://stateofhepc.org/).1,615

Transmission

Injection drug use accounts for approximately 60% of acute HCV infections in the United States.1,2,8,15 Men who have sex with men (particularly people with HIV or those who have unprotected anal intercourse), perinatal transmission, and exposure to blood products before 1992 are other sources.2,8,15,16 Nosocomial exposure (e.g., hemodialysis, needlestick) and cosmetic exposure (e.g., tattooing, piercing) are less likely routes of transmission if standard infection-control practices are followed8,15 (Table 12,8,1518).

Community exposure
 Incarceration
 Infants born to a person with hepatitis C virus infection
 Injection drug use
 Men who have sex with men (particularly people with HIV or those who have unprotected anal intercourse)
 Percutaneous or parenteral exposure in an unregulated setting with poor infection control practices
Hospital exposure
 Long-term hemodialysis
 Needlestick injuries
 Receipt of clotting factor concentrate in the United States before 1987
 Transfusion of blood products before 1992
Other
 HIV or hepatitis B infection
 Sexually active person starting pre-exposure prophylaxis for HIV
 Unexplained chronic hepatic disease including abnormal liver enzymes (mild, intermittent or markedly elevated)

Screening

The Centers for Disease Control and Prevention recommends universal HCV screening at least once for all adults 18 years and older and during each pregnancy 19 (Table 2).17 The American College of Obstetricians and Gynecologists recommends screening all pregnant individuals during each pregnancy.20 People at risk, or those who request testing, should be screened periodically for as long as the at-risk behavior persists.17 One-time screening is recommended for patients younger than 18 years with risk factors.17 The U.S. Preventive Services Task Force recommends screening all asymptomatic adults (including people who are pregnant) 18 to 79 years of age and people younger or older who are at high risk of infection.21 Anti-HCV antibody testing (third-generation enzyme-linked immunosorbent assay with 99% sensitivity and specificity) is the screening test of choice with follow-up reflex HCV RNA polymerase chain reaction testing for positive results to confirm the active disease.8,15,17 Point-of-care testing allows for expanded screening.8,22 The OraQuick HCV rapid antibody test is a Clinical Laboratory Improvement Amendments–waived point-of-care test with reliable results (sensitivity, 94.1%; specificity, 99.5%; positive predictive value, 72.7%; and negative predictive value, 99.9%).8,22

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