Hey Grandma, Let's Get You Checked for Hep C

Medscape Family Medicine > Best Evidence Review

Charles P. Vega, MD

Aug 30, 2013

Best Evidence Review of the USPSTF Screening Recommendations for Hepatitis C

The Study

Moyer VA; US Preventive Services Task Force. Screening for hepatitis C virus infection in adults: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 Jun 25. [Epub ahead of print]

Introduction

The prevalence of chronic hepatitis C virus (HCV) infection in the United States may have peaked over a decade ago, but there is convincing evidence that middle-aged and older adults born between 1945 and 1965 are at increased risk for infection. The most significant risk factor for chronic HCV infection is prior injection drug use, but the majority of adults with infection do not have this risk factor. Therefore, in additional to regular screening among high-risk groups, the US Preventive Services Task Force (USPTSF) now recommends 1-time screening for chronic HCV infection for adults born between 1945 and 1965.

While this recommendation may seem preposterous when thinking of your own Nana, do you really know what she was up to in 1968? There is good merit for the recommendation, which is discussed below.

Background to the Study

HCV infection is one of the most common chronic infections in the United States. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 indicated that the overall prevalence of HCV infection was 1.6% among adults aged 20-59 years.^[1] This figure includes over 3 million adults with active infection, as defined by a positive HCV RNA test. Moreover, this testing probably underestimated the total prevalence of HCV infection because high-risk populations, including homeless and incarcerated adults, were not included in the research. In a study of over 400 homeless war veterans, the prevalence of HCV infection was 44.0%.^[2]

Evidence of HCV infection is twice as common among women than men and among African Americans than white adults.^[3] The most important risk factor for HCV infection is intravenous drug use. Nearly one half of the cohort that was positive for HCV infection in the NHANES study had this risk factor.^[1] Other significant risk factors for HCV infection include receipt of blood transfusion before 1992, receipt of other blood products before 1987, and other drug use.^[3] Sexual behavior is a less powerful risk factor HCV infection compared with HIV infection, but there is evidence that a history of multiple sexual partners is associated with a higher risk for HCV infection. Many individuals with HCV infection have overlapping risk factors for infection.

Why Screen All Baby Boomers?

Although the authors of the recommendations regarding screening for HCV infection note that the prevalence of HCV infection in the United States appeared to peak in 2001, there is another clear trend in the epidemiology of HCV infection that merits close attention. Persons born between 1945 and 1965 comprise approximately 27% of the total population of the United States, but they account for a disproportionate share of cases of HCV infection.^[4] The prevalence of HCV infection in this age group is 3.25%, and approximately three quarters of active HCV infection cases are encountered among persons born between 1945 and 1965.

Moreover, and more important, persons who are currently in the fifth through seventh decades of life at this time are at the highest risk for complications from HCV infection. They account for 73% of mortality due to HCV infection, and this group is also at the highest risk for hepatocellular carcinoma and cirrhosis.^[4] Therefore, the number of patients needed to treat with anti-HCV therapy in order to prevent additional cases of mortality is lower in this specific older cohort of adults compared with younger adults.

Therefore, it is not only the epidemiologic data that drive the new HCV screening recommendations from the USPSTF, but also an expectation that treatment of heretofore undiagnosed HCV infection can put a substantial dent in the broad clinical impact of HCV. The new recommendations call for 1-time screening for all adults born between 1945 and 1965 (B recommendation: high certainty that the net benefit is moderate, or moderate certainty that the net benefit is moderate to substantial). The anti-HCV antibody is test the best screening tool for these adults.

Limitations and Benefits of Age-Based Screening

Limitations

The authors identify the limitations of the new recommendations. Although age-based screening should identify more patients with HCV infection, they admit that this method may be less efficient than risk-based screening. The potential harms of screening include stigmatization, but also the more tangible and serious complications of the diagnostic work-up of liver disease.

The rate of major complications after percutaneous liver biopsy ranges between 0.09% and 2.3%, with a trend toward higher complication rates in older studies.^[5] Use of ultrasonography to guide liver biopsy may reduce the risk for complications by 30%. However, the authors of the current review note that overall use of liver biopsy is declining with greater reliance on laboratory testing alone to guide treatment. This will reduce the potential harms of screening for HCV infection.

A more serious complication of a large screening campaign for HCV infection among older adults is overdiagnosis, meaning the discovery of infections which would have no impact on the course of the patient's life. Up to 25% of acute infections with HCV may be cleared and do not progress to chronic HCV infection.^[6] Despite the high numbers of patients with chronic HCV infection, only 10%-15% develop cirrhosis. The mean interval from infection to cirrhosis is a matter of debate but is approximately 20 years, and patients without other cirrhosis risk factors, such as chronic alcohol misuse or hepatitis B infection, are less likely to develop cirrhosis.

Benefits of Screening

Nonetheless, acquiring HCV infection at an age older than 40 years is also associated with a higher risk for cirrhosis, making overdiagnosis less of an issue among older adults.^[6] In addition, treatment of chronic HCV infection has resulted in significant improvements in morbidity and mortality outcomes.

In research from 5 large tertiary hospitals in which 530 patients were followed for over 8 years for mortality outcomes, patients with a sustained virologic response (SVR) experienced a 74% reduction in all-cause mortality and a 94% reduction in the risk for liver-related mortality or transplantation compared with patients who did not have an SVR to anti-HCV therapy.^[7] The mean age of participants in this research was 48 years, meaning that many patients included in the new screening recommendation might receive these substantial benefits of anti-HCV treatment.

Furthermore, treatment of chronic HCV infection reduces the risk for hepatocellular carcinoma. In a meta-analysis of 18 studies, SVR reduced the relative risk for hepatocellular carcinoma to 0.24 compared with no SVR.^[8] SVR was similarly effective in reducing the risk for hepatocellular carcinoma in an analysis confined to patients with advanced liver disease.

The new screening methods also appear to be cost-effective. In an analysis of the proposed birth-cohort HCV screening plan proposed by the USPSTF, researchers found that screening would result in over 800,000 new cases of HCV infection identified, at the cost of $2874 per case.^[9] Subsequent treatment for HCV would result in costs of $15,000-$35,000 per quality-adjusted life-year gained, a favorable sum compared with other health interventions. In fact, another analysis found that age-based screening for HCV was more cost-effective than risk factor-based screening, although the authors stress that this is true only if all new cases receive standard triple therapy for their infection.^[10]

Adding to the PCP Tasks

Primary care physicians are asked to do many things. The average number of patient requests of physicians per clinic visit was 5.5 in one study, and this information is now 14 years old.^[11] These requests exclude other important elements of the office visit, such as addressing severe anemia or demonstrating empathy and patience when the patient bursts into tears upon being asked, "So, how's it going?"

Primary care physicians are also the stewards of preventive healthcare, which is a wonderful opportunity and distinct challenge. We need to get screening tests ordered on time for the right patients, and practice shared decision-making each step of the way as we do so.

At first glance, the new screening recommendations from the USPSTF may seem superfluous. However, after reviewing the epidemiology, treatment outcomes, and even cost-effectiveness data, this screening certainly appears to be prudent and beneficial. It should be embraced by primary care physicians. It should also evolve. As the demographics of HCV infection shift, the age-based screening approach will almost certainly need to change as well. An eventual move away from HCV screening will indicate a great victory for the public's health.

Clinical Pearls

• Between 1% and 2% of the adult population in the United States has been found to have chronic HCV infection, although this may be an underestimation once high-risk groups are added to the equation.
• Persons born between 1945 and 1965 bear a disproportionate share of the disease burden of chronic HCV infection, both in terms of higher prevalence and increased rates of complications.
• Treatment that results in SVR among patients with chronic HCV infection substantially reduces the risks for cirrhosis, hepatocellular carcinoma, and mortality.
• The new recommendations from the USPSTF support traditional screening for HCV among high-risk groups but also call for 1-time screening using anti-HCV antibody testing among adults born between 1945 and 1965. If used widely, this screening program should have a positive effect on morbidity and mortality among older adults.

References

1. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.

2. Desai RA, Rosenheck RA, Agnello V, et al. Prevalence of hepatitis C virus infection in a sample of homeless veterans. Soc Psychiatry Psychiatr Epidemiol. 2003;38:396-401.

3. Rustgi VK. The epidemiology of hepatitis C infection in the United States. J Gastroenterol. 2007;42:513-521.

4. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61:1-32.

5. Sporea I, Popescu A, Sirli R. Why, who and how should perform liver biopsy in chronic liver diseases. World J Gastroenterol. 2008;14:3396-3402.

6. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3:47-52.

7. van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584-2593.

8. Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329-337.

9. Rein DB, Smith BD, Wittenborn JS, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156:263-270.

10. Liu S, Cipriano LE, Holodniy M, Goldhaber-Fiebert JD. Cost-effectiveness analysis of risk-factor guided and birth-cohort screening for chronic hepatitis C infection in the United States. PLoS One. 2013;8:e58975.

11. Kravitz RL, Bell RA, Franz CE. A taxonomy of requests by patients (TORP): a new system for understanding clinical negotiation in office practice. J Fam Pract. 1999;48:872-878.

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