Task Force Recommends Hepatitis C Screening for Baby Boomers, but Data Inconclusive

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Adults born between 1945 and 1965 should consider screening for hepatitis C, with a stronger recommendation for people with risk factors such as a history of injection drug use or blood transfusions before 1992, according to draft recommendations from the U.S. Preventive Services Task Force (USPSTF). A set of literature reviews, however, found that data on the benefits of testing are lacking.

The USPSTF recommendation for Baby Boomers without specific risk factors for hepatitis C virus (HCV) infection is weaker than recent guidelines from the Centers for Disease Control and Prevention (CDC), which advise that everyone born between 1945 and 1965 -- that is, 47 to 67 years old -- get tested for HCV at least once regardless of traditional risk factors.

The USPSTF is an independent group of national experts in prevention and evidence-based medicine that makes evidence-based recommendations about clinical preventive services such as screenings, counseling services, and preventive medication.

Summary of Recommendations

HCV is the most common chronic blood-borne pathogen in the U.S., the Task Force noted, with a prevalence of approximately 1.6%. Experts estimate that some 4 million Americans have hepatitis C, but as many as 75% are not aware they are infected. Baby Boomers have highest hepatitis C prevalence, with as many as 1 in 30 thought to be infected. People in this age group often acquired HCV decades ago -- in many cases due to a single exposure such as injection drug experimentation -- and are only now developing advanced liver disease.

Public health experts have estimated that routine 1-time testing of this age group could identify some 800,000 additional people with hepatitis C. This would enable them to be evaluated for liver disease progression and, if appropriate, treated with more effective new therapies now becoming available. A recent studyfound that expanded birth cohort testing is likely to be cost-effective.

USPSTF concluded with "moderate certainty" that screening for HCV infection in adults at increased risk has a "moderate net benefit," while screening the 1945-1965 birth cohort has "at least a small net benefit."

"Since symptoms may not appear until decades after a person is infected, detection and treatment can help prevent liver damage, liver cancer, and deaths from hepatitis C," said Task Force member Kirsten Bibbins-Domingo.

"Based on what we know today, the Task Force concluded that screening provides substantial benefits for people at high risk," she continued. "We also found that screening people from the baby boom generation also provides real, although smaller, benefits. People at high risk have about a 50 percent chance of being infected with hepatitis C, whereas people born between 1945 and 1965 have a three to four percent chance of being infected."

The Task Force is accepting public comment on the draft until December 24, 2012. The recommendations are available online at

http://www.uspreventiveservicestaskforce.org/draftrec2.htm and comments can be submitted at www.uspreventiveservicestaskforce.org/tfcomment.htm. Recently issued recommendations for HIV screening also remain open for comment.

Review of Evidence

The updated recommendation is based in part on 3 reviews of recent research about hepatitis C testing and treatment conducted to inform the USPSTF. Results were published in the November 27, 2012, Annals of Internal Medicine.

Roger Chou from the Oregon Evidence-based Practice Center and Oregon Health and Science University and colleagues searched MEDLINE, the Cochrane Library,clinical trial registries, and other sources to identify relevant research.

The first review attempted to answer whether screening to identify people infected with HCV could lead to interventions that improve clinical outcomes. Searching back to 1947, the authors found no studies that evaluated clinical outcomes associated with screening compared to no screening, or of different risk-based or prevalence-based strategies.

They identified 3 cross-sectional studies in higher-prevalence populations, which found that screening strategies based on multiple risk factors were effective, with sensitivities greater than 90%. In these studies, fewer than 20 at-risk people would need to be tested to identify 1 case of HCV infection. However, they did not find similar evidence to support screening of an age cohort as a whole.

Besides drug injection and blood transfusion, other risk factors for HCV infection include long-term kidney dialysis, being born to a mother with HCV, incarceration, intranasal drug use, getting a tattoo outside a professional setting, and other percutaneous exposures (e.g., needle stick accidents by health care workers, surgery prior to implementation of universal precautions). However, "[e]vidence on tattoos and other percutaneous exposures as risk factors for HCV infection is limited," they wrote.

Data on direct harms of screening were "sparse," the authors said. A large study of nearly 3000 percutaneous liver biopsies in hepatitis C patients with compensated cirrhosis saw no deaths and a 1.1% rate of serious adverse events (mostly bleeding and severe pain). They also found that non-invasive tests "have fair to good accuracy for diagnosing fibrosis and good to excellent accuracy for diagnosing cirrhosis compared with liver biopsy."

"Although screening tests can accurately identify adults with chronic HCV infection, targeted screening strategies based on the presence of risk factors misses some patients with HCV infection," they concluded. "Well-designed prospective studies are needed to better understand the effects of different HCV screening strategies on diagnostic yield and clinical outcomes."

The second review looked at treatment for chronic hepatitis C, a rapidly evolving field. The first HCV direct-acting antiviral agents (DAAs) were approved only last year, augmenting the previous standard-of-care of pegylated interferon plus ribavirin. Several all-oral DAA combinations without interferon are currently under study.

This literature search (again extending back to 1947) focused on randomized trials of antiviral treatment and cohort studies examining associations between sustained virological response, or continued undetectable viral load, after therapy and clinical outcomes.

Interestingly, they found that dual therapy with pegylated interferon alfa-2b (Peg-Intron) plus ribavirin was associated with a lower likelihood of SVR than pegylated interferon alfa-2a (Pegasys) plus ribavirin. For people with HCV genotype 2 or 3, dual therapy for 12-16 weeks was less effective than 24 weeks. For people with genotype 1, triple therapy with pegylated interferon, ribavirin, and either boceprevir (Victrelis) or telaprevir (Incivek) led to higher SVR rates than dual therapy.

The authors found "adequate evidence" that antiviral therapy has "small to moderate harms," such as fatigue, headache, flu-like symptoms, hematological events (e.g., blood cell deficiencies), and rash. "Serious adverse events are self-limited and typically resolve after treatment is discontinued," they wrote. "There is adequate evidence that the harms of treatment are no greater than small." Adding boceprevir increased the risk of hematological adverse events, while telaprevir increased the risk of anemia and rash.

The review authors found a large well-designed cohort study and 18 smaller cohort studies showing that achieving SVR, or a viral cure, was associated with lower all-cause mortality compared with non-response. However, they noted, "No trial evaluated effectiveness of treatment on long-term clinical outcomes."

The third review looked at strategies for reducing the risk of mother-to-infant HCV transmission, which the authors noted is the leading cause of childhood hepatitis C, responsible for up to 4000 new cases each year in the U.S.

This analysis looked at randomized trials and observational studies of delivery mode (vaginal versus cesarean), labor management strategies, and breast-feeding practices and their association with risk of mother-to-child transmission. Current antiviral treatment is contraindicated during pregnancy because interferon and especially ribavirin have the potential to cause birth defects.

They found that 14studies showed no clear association between mode of delivery and HCV transmission risk, though 2 studies reported a link between prolonged duration of ruptured membranes and increased risk of transmission. In addition, 14 studies found no association between breast-feeding and transmission risk.

"No intervention has been clearly demonstrated to reduce the risk for mother-to-infant HCV transmission," the review authors concluded. "Avoidance of breastfeeding does not appear indicated for reducing transmission risk."

12/4/12

References

R Chou, E Barth Cottrell, N Wasson, et al. Screening for Hepatitis C Virus Infection in Adults: A Systematic Review to Update the 2004 U.S. Preventive Services Task Force Recommendation. Annals of Internal Medicine. November 27, 2012 (Epub ahead of print).

R Chou, D Hartung, B Rahman, et al. Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review. Annals of Internal Medicine. November 27, 2012 (Epub ahead of print).

E Barth Cottrell, R Chou, N Wasson, et al. Reducing Risk for Mother-to-Infant Transmission of Hepatitis C Virus: A Systematic Review for the U.S. Preventive Services Task Force. Annals of Internal Medicine. November 27, 2012 (Epub ahead of print).

Other Source

U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Issues Draft Recommendation on Screening for Hepatitis C Virus Infection in Adults. USPSTF Bulletin. November 27, 2012.

AIDS.gov. U.S. Preventive Services Task Force Invites Public Comment on Draft Recommendations Related to HIV & HCV Screening. Blog.AIDS.gov. December 4, 2012.