Hepatitis C: How To Fine-Tune Your Approach

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. Over the next few decades, the number of deaths per year due to complications of HCV such as liver failure and hepatocellular carcinoma (HCC) is predicted to more than triple to 36,000 by 2032.¹

Fortunately, major advances in drug therapy have made it possible to cure patients of HCV, and treatment is now less complex, of shorter duration, and better tolerated than it once was. To help family physicians maximize the care they provide to these patients, we’ve summarized screening recommendations from the Centers for Disease Control and Prevention (CDC), innovative alternatives to biopsy for staging liver disease, and counseling points to cover with patients.

A common, usually silent infection with potentially fatal complications

According to the National Health and Nutrition Examination Survey (NHANES), an estimated 2.7 to 3.9 million people in the United States are chronically infected with HCV, about threefourths of whom were born between 1945 and 1965 (the “baby boomer” generation).² However, by adding “unaccounted groups” (eg, incarcerated, homeless, and active duty military) to these estimates, the number of people with HCV is likely more than 5.2 million.³

HCV is a ribonucleic acid (RNA) virus capable of mutating at a high rate to escape detection and clearance by the host’s immune system.⁴ Most patients with HCV are asymptomatic during the acute and chronic phases of infection, and may have a silent infection for decades. In fact, 65% to 75% of patients with HCV are unaware of their infection.⁵

Approximately 20% of chronically infected patients develop cirrhosis after 20 years and, once they do, the annual rate of HCC and liver decompensation is about 5%.^6-8 Risk factors for advancement to cirrhosis includes male sex, alcohol consumption, co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV), immunosuppression, having had HCV infection for a long time, becoming infected with HCV after age 40, and not having responded to previous treatment.⁹

Chronic HCV infection can lead to extrahepatic manifestations such as essential mixed cryoglobulinemia, porphyria cutanea tarda, membranoproliferative glomerulonephritis, lymphoma, and glucose intolerance.¹⁰ There is also growing evidence that HCV infection affects cognitive function in the absence of fibrosis and hepatic encephalopathy. Several studies show that HCV-infected patients score poorly on neuropsychological testing for verbal learning, attention, memory, and executive function.¹¹ This may be related to the expression of receptors for HCV by the brain’s microvascular endothelial cells.¹²

Screening recommendations. Given the high prevalence of HCV infection among baby boomers, the CDC decided in 2012 to recommend one-time HCV screening for all patients born between 1945 and 1965.¹³ This is in addition to risk-based screening for all patients who have a history of injection drug use, those on long-term hemodialysis or with tattoos obtained in unregulated settings, offspring of HCV-infected mothers, and those with health-care associated exposures (TABLE¹³). In 2013, the US Preventive Services Task Force upgraded its recommendation to match those of the CDC.¹⁴

Despite these recommendations, which are expected to increase detection of HCV among asymptomatic persons who do not know they are infected, there remain significant barriers to HCV testing. These include poor access to primary care and preventive services, lack of knowledge and awareness of the disease among patients and providers, and a lack of studies that support a universal screening approach for HCV.^5,15,16 One tool that might help overcome some of these barriers and aid family physicians in the screening process is automatic reminders or standing lab orders for HCV testing in electronic medical records systems.

Screening for HCV can be done using any of the US Food and Drug Administration (FDA)-approved tests for the anti-HCV antibody, which have sensitivities and specificities greater than 99%.¹⁷ A positive screening result should be confirmed with an HCV RNA test. However, for practical purposes, ordering the anti-HCV test with reflex to the HCV RNA test decreases the number of blood draws and office visits required of the patient. The reflex confirmation allows the physician to deliver the patient’s full diagnosis and reduces the psychological distress associated with waiting for confirmatory results. The HCV RNA test (alone) should be used, however, in immunocompromised patients, those who may have had exposure to HCV in the past 6 months, and those suspected of having an HCV re-infection after having cleared the virus.¹⁸