Applied Evidence

Hepatitis C: Screening changes, treatment advances

Author and Disclosure Information

Changing at-risk populations and treatments are reshaping screening and management. Which regimens are best and what factors influence treatment choices?


› Offer hepatitis C virus (HCV) screening to all patients with identified risk factors, as well as anyone born between 1945 and 1965, regardless of risk factors. B

› Offer human immunodeficiency virus and hepatitis B testing, as well as hepatitis A, hepatitis B, and pneumococcal vaccinations, to all patients with chronic HCV infection. C

› Consider treatment with interferon-free direct-acting antiviral therapies for all patients with chronic HCV infection to reduce liver-related and all-cause morbidity and mortality. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Several recent developments have prompted a renewed focus on the way we screen for, and manage the treatment of, hepatitis C virus (HCV) infection. In 2013, the United States Preventive Services Task Force expanded its HCV screening guidelines to include baby boomers born between 1945 and 1965, regardless of apparent risk factors (TABLE 11).2 The recommendation is based on the high prevalence of chronic HCV in this cohort, estimated to be 4.3%, which is about 4 times higher than that of the general US population.3 It is believed that 75% of chronic HCV infections in the United States are in this cohort. After decades of infection, many in this age group are now presenting with advanced disease, leading to 19,659 HCV-related deaths in America in 2014.4

HCV infection risk factors image

In addition, while HCV incidence in America had been steadily declining, it is now once again on the rise among young, non-urban whites, mainly because of increasing intravenous drug use in this population.5 On a positive note, new highly-effective and better-tolerated treatments are greatly improving the care we can provide.

In light of these factors, family physicians (FPs) are likely to be screening for HCV more than ever before and must be prepared to provide appropriate counseling and initial clinical management for those with positive test results. This article reviews the evaluation and primary care management of HCV-infected patients, as well as approaches to treatment with the newest direct-acting antivirals (DAAs).

Hepatitis C: Screening changes, treatment advances image IMAGE: © JOE GORMAN

The natural history of hepatitis C (and what we’re seeing as boomers age)

Acute HCV infection is rarely symptomatic, but results in chronic infection approximately 75% of the time.6 While some chronically infected individuals remain unaffected, most develop some degree of hepatic fibrosis, and 20% will develop cirrhosis within 20 years of diagnosis.7-9

The rate of progression is variable; factors that result in more rapid progression of liver disease include coinfection with HIV or HBV, overweight or obesity, insulin resistance, male gender, and use of alcohol.7 As the baby boomer cohort has aged, patients infected in their youth are now presenting with the sequelae of decompensated cirrhosis, including ascites, portal vein thrombosis, and thrombocytopenia.

Extrahepatic manifestations of chronic hepatitis C can include fatigue, membrano­proliferative glomerulonephritis, porphyria cutanea tarda, cryoglobulinemia, a higher likelihood of insulin resistance, and possibly lymphoma.10-12

Chronic HCV is also the major contributor to the increased incidence of hepatocellular carcinoma (HCC), which has tripled in the past 2 decades in the United States.13

Although results are inconsistent, studies suggest 5% to 10% of HCV-infected patients will succumb to liver-related death.7

Who you’ll screen

If your patient is at heightened risk of contracting HCV infection (TABLE 11) or was born between 1945 and 1965, you’ll want to screen for infection with an HCV antibody test. A positive antibody test must be followed by testing for hepatitis C viral RNA to confirm whether the patient is chronically infected or is among the approximately 25% of patients who spontaneously clear the virus.6

The prevalence of chronic HCV infection among baby boomers is about 4 times higher than that of the general US population.For the patient with no detectable HCV RNA, no further evaluation or treatment is necessary. HCV viral load itself provides little insight into the rate of progression of the illness, but does correlate with risk of transmission.14 Counseling patients about the full testing protocol before screening can help to reduce anxiety and confusion.

At present, 6 genotypes and multiple subtypes of HCV have been identified; these have important implications for prognosis and treatment.15 HCV genotyping is frequently ordered along with a test for HCV viral load, but may be deferred until after fibrosis staging is performed (more on that in a bit). It may also be deferred if treatment is not planned within the next 12 weeks, as its main clinical use is to guide choice of treatment. Once chronic infection has been confirmed by the presence of HCV viremia, further work-up focuses on evaluating the effects on the host, which, in turn, helps the provider finalize a treatment plan (FIGURE 116).

Initial evaluation of the patient presenting for HCV testing image

Follow initial screening with an evaluation including liver disease staging

Following a screen that comes back positive for HCV, you’ll conduct a more thorough history including questioning about previous or ongoing risk factors for HCV, perform a physical examination that includes looking for signs of liver failure or extrahepatic disease, and order more lab work. Laboratory investigations include a complete blood count; renal and hepatic panels; and testing for human immunodeficiency virus (HIV) antibody, hepatitis B virus (HBV) surface antigen, HBV surface antibody, and HBV core antibody.1,17 Finally, the patient must be evaluated for hepatic fibrosis and cirrhosis to quantify the likelihood of developing liver failure and HCC.

Next Article: