September 16, 2013

Screen All Boomers for Hep C? Two Docs Disagree

Medscape Family Medicine > Roundtable in Primary Care

Robert W. Morrow, MD, Charles P. Vega, MD

Sep 16, 2013

Editor's Note: The Centers for Disease Control and Prevention (CDC) and the US Preventive Services Task Force (USPSTF) have recommended that all baby boomers (those born between 1945 and 1965) should be screened for hepatitis C virus (HCV). We asked Charles P. Vega, MD, and Robert W. Morrow, MD, Medscape family physician advisors, how realistic these recommendations are in primary care practice. We received 2 different opinions.[1,2]

Dr. Vega: Screening These Adults Is Important, and I'm On Board

The age range described in the recommendations fit the majority of my patient panel: those who have an average of 6 chronic conditions. Getting health maintenance completed can be a struggle, given other competing priorities. So I was highly skeptical about checking hepatitis C status on these sweet older adults.

However, on examining the evidence, this is the generation that bears a disproportionate burden of HCV infection, morbidity, and mortality. Moreover, trials of anti-HCV treatment did include, if not focus on, older adults. These are the studies that demonstrated that sustained virologic response improved cancer and mortality outcomes.

Why hadn't I learned this stuff before? Who knows. But I'm on board. One-time screening is more than reasonable and will save lives.

However, the overall incidence of HCV infection appears to have declined over the past 10 years. This screening recommendation is for a limited time only. (Now, there's a potential new marketing gimmick for the USPSTF!) We should keep that in mind moving forward.

Dr. Morrow: Where's the Evidence Supporting Benefits vs Risks of Screening?

Like most of the subjects raised in these roundtables, this one has some substance that was not initially apparent.

Generally, we screen for a disease when the benefit exceeds the risk. In other words, if we randomize the population to those screened and unscreened, the unscreened group should do worse than the screened group using some objective, patient-centered measure, even if that is the quality-adjusted life-year.

As a disease becomes less likely or prevalent, false-positive findings become more common than true-positives.

For example, a polymerase chain reaction test with high sensitivity and specificity might still yield a rather high false-positive result. We see false-positives with Pap tests for women older than 40 years, and for purified protein derivative tests in general; in the first case, as women get older cervical cancer becomes very rare, and in the other case, tuberculosis is less present in the general population.

A false-positive rate of 1/1000 seems small until after the first million studied!

OK, we don't have the information that the tested group does better than the untested group in measures important to patients. So is this an emergency, and therefore we can't wait for a patient-centered study? We need to see the numbers of measures important to patients. Do screened patients die later, transmit less disease to bystanders, or have less disability compared with unscreened people? Right now, that is assumed but not known.

Aside from fatigue for months, I have several patients in my practice with injury from HCV treatment, including hyperthyroidism. One patient had to have surgery for refractory hyperthyroidism after radioactive iodine, and now has lost much of her voice due to injury during intubation.

Regardless, anecdotes suck, so where are the numbers that are patient-centered, not pharma-centered?

I suppose if we had a real healthcare system, we could conduct this study in a few months of analysis of population databases. Hello, Kaiser, what do you know? Until then, did your laboratory have a new technician who made a methods error that resulted in false-positives, owing to contamination of a hypersensitive test? I think that's why I see several inexplicable HPV-positive tests in women older than 50 years, which go away on repeat tests -- and yes, I don't order the test, but laboratories often run HPV tests without a request.

Show me the analysis, so I can understand why this expensive and not necessarily faultless test -- which can lead to treatments that are expensive and not necessarily faultless or successful -- is truly patient-centered. Until then, we should spend the funds on prevention strategies that work, such as needle exchanges and careful histories.

Dr. Vega: False-Positives Are Rare, and We Can't Wait for Studies

Bob is completely accurate in pointing out how every screening test has both a downside and a potential benefit. In fact, he lists some screening tests, such as for tuberculosis in the general population, that do not make sense because the potential harms outweigh the advantages of testing.

HCV screening for this specific age population is not in that class of testing. The prevalence of HCV among persons born between 1945 and 1965 is 3.25%, which sounds small until one realizes that this represents approximately three quarters of cases of chronic HCV infection in the United States. The infection is underrecognized by clinicians treating these patients, and that is a huge contributor to the overall morbidity and mortality of HCV.

With regard to the potential harms of screening, false-positive HCV antibody tests are extremely rare. New-generation anti-HCV screening yields specificity levels above 99%. Advancements in the evaluation of patients with chronic HCV infection have reduced the need for liver biopsy, which incurred the majority of major complications in the work-up of HCV. Complications from HCV treatment are common, but serious complications are rare. The reductions in the risks for cirrhosis and death with HCV treatment generally outweigh the risks of therapy.

It would be wonderful to have a randomized screening trial with thousands of participants to fully evaluate screening for HCV. But Bob knows that such a study is impractical and won't ever happen. First, it will require years to even set up the research, and many, many more to complete it. Remember that we didn't well understand the basic natural history of chronic HCV infection until study cohorts were followed for decades. Persons born between 1945 and 1965 simply do not have that kind of time to wait.

To respond to another couple issues, screening for HCV only works if patients found to be positive can be quickly referred for further evaluation and therapy. Otherwise, it is a waste of healthcare resources that may be better used elsewhere.

Regarding the timing of HCV screening: Between regular blood testing for the diabetes, hyperlipidemia, and assorted other chronic illnesses common among my middle-age and older adult patients, I don't think it will be a challenge to recommend an anti-HCV antibody test at some point. Simple decision-support software can facilitate reminders regarding such screening. We have had strong success in our practice in using this strategy to implement universal screening for HIV infection.

Dr. Morrow: Forget RCTs; Look at Large Data Sets

Thanks for your thoughtful comments, Charles.

I am certainly not going to joust with the epidemiology folks at the CDC, but a different number for prevalence among blood donors from 2010 shows a falling rate of HCV antibody prevalence by the less specific test methods, down to 0.072%.[3]

My general sense is that we have many ways of estimating the expected rates of transmission and liver failure, and because prior transmission was likely owing to sharing of needles and blood transfusions, we do have good preventive measures.

Prospective randomized controlled trials (RCTs) are but one of the methods to analyze risk vs benefits, and often not the best. Could someone step forward and look at these numbers in large data sets systematically before embarking on a campaign?

As an aside, RCTs to a large measure have gotten us into the mess in which you look for answers to clinical questions in the research literature, and questions that are not answered are found far more commonly using this research method, largely because of the linear nature of the process. If you look at A to B, do you get C more commonly than by chance?

In truth, modern analytics, such as Bayesian approaches, are far more predictive than frequentist methods alone. This is simply to say that someone should be funded to look at whether screening large groups of baby boomers for HCV would lead to predictably better outcomes that matter to patients. Yes, indeed, this can be done with many different large data sets using contemporary analytic methods (but please don't ask this community doc for the details!). Think about how Google tells us about traffic on the highways by looking at the number of cell phones and how fast they are travelling and mapping this to the roadways: instantly and clearly, but indirectly.

From my seat in my family medicine office, as well as an educator: We are told not to screen for domestic violence due to lack of outcomes evidence, and not to screen for gun ownership due to politics, and not to screen for chronic alcoholism (only unsafe behaviors) due to difficulty in treatment. We don't screen for Helicobacter pylori. We don't screen men for Chlamydia and gonorrhea.

Why hepatitis C, and why now?

Dr. Vega: It's Time to Screen Now

Good points. I'd just add that Bob is right: The prevalence of HCV is falling, and this may be due to greater public knowledge and interventions to prevent bloodborne transmission. But the more advanced statistical analyses on screening for HCV has been done, and one study showed that age-based screening was actually more cost-effective than screening on the basis of risk factors.[4] At the end of the day, the screening is imperative now because these older adults are in a time window when screening and treatment should add substantially more years of quality living. That window will not stay open forever, and we as primary care physicians need to understand when it is getting ready to close.

The news that HCV treatment is simplifying and may eventually move to the primary care office should only add to the weight of this recommendation. But that's a topic for a different time.


  1. Garcia J. Hepatitis C: USPSTF recommends all baby boomers be screened. Medscape. June 24, 2013. Accessed September 5, 2013.

  2. Teo CG. Testing for hepatitis C: new guidance. Medscape. July 29, 2013. Accessed September 5, 2013.

  3. Murphy EL, Fang J, Tu Y, et al. Hepatitis C virus prevalence and clearance among US blood donors, 2006-2007: associations with birth cohort, multiple pregnancies, and body mass index. J Infect Dis. 2010;202:576-584. Abstract

  4. 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.



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