Hepatitis C — A Review of the CDC Recommendations for Birth-Cohort Screening

Reau, Nancy, MD
Professor of Internal Medicine
Associate Director of Solid Organ Transplantation
Section Chief of Hepatology
Rush University Medical Center
Chicago, Illinois
Also by this Author 

The hepatitis C virus (HCV) is a serious public health concern, with an estimated 2.7 – 3.9 million people living with infection in the United States1, where it is the leading cause of chronic liver disease. The prevalence of HCV is disproportionately high among those born from 1945 to 1965, who account for approximately three quarters of chronic HCV infections in the U.S.1 Additionally, it is estimated that the majority of those infected have not been diagnosed.2

To address these issues, the Centers for Disease Control and Prevention (CDC) recently published a recommendation for universal HCV screening of those born 1945-1965,3 as a supplement to their existing HCV screening guidelines.4 Dr. Nancy Reau, Associate Professor of Medicine, University of Chicago, reviews the recently issued recommendations, and discusses their significance in the context of other trends in Hepatitis C patient management: the increasing burden of the disease and the high cure rates now achievable.

An Increasing Burden on the Healthcare System

 “The first important issue to recognize is the increasing morbidity and mortality linked to hepatitis C,” says Dr. Reau. Estimates indicate that in the next five years there will be a huge increase in the number of individuals with cirrhosis5, as well as a significant increase in patients who develop liver cancer due to hepatitis C. Several cost analyses have recently been published, demonstrating the strain placed on the health care system by hepatitis C 6,7, in particular by HCV patients with advanced fibrosis, and those with advanced fibrosis, who have clinical decompensation of their liver disease. Even if people aren’t yet aware how critical the situation is they are soon going to be, because over the coming years we’re going to see more and more patients with end-stage problems.”  

The increase in those with severe disease is a factor of demographics, explains Dr. Reau. “It comes down to the fact that 75% of Americans with hepatitis C are in the ‘baby boomer’ category,” she notes. “It’s that group which is aging with hepatitis C and is going to matriculate from mild to moderate disease, and from moderate to severe disease, with its associated complications. If someone has had their liver disease for up to 30 years it’s now that we expect to see advanced fibrosis, and the toll it has on the body.”

CDC Recommendations

The demographics of the HCV population, combined with the high proportion of undiagnosed patients, provide a sound rationale for the new CDC recommendations. In August 2012, the CDC published new testing recommendations for chronic HCV infection to include a one-time HCV antibody test for all patients born between 1945 and 1965.1 “Note, this is an addition to their existing guidelines for risk-based screening, not a replacement,” stresses Dr. Reau. “The new recommendations are intended to complement the guideline that’s in place.”

Successful implementation of the new recommendations will depend on widespread adoption by primary care providers, but Dr. Reau foresees obstacles to achieving this goal. “The complication for primary care providers is that once they propose the test, they will also have to educate patients as to why they’re being screened,” she explains. “There’s concern that this is going to cause needless anxiety in the majority of patients who don’t have hepatitis C, as well concern about the time required to provide appropriate patient education.” It’s important that these concerns are recognized and addressed, since there are clear benefits to identifying and treating the disease as early as possible.

The Importance of Early Detection

“The exciting thing about hepatitis C is that in most cases – around 80% - it’s curable,” notes Dr. Reau. “The earlier we catch it, the easier it is to eradicate it, and prevent a patient from developing manifestations of end-stage liver disease. If the disease hasn’t progressed beyond Stage 2, a patient can maintain a healthy liver, provided they don’t develop liver injury from another insult.”

Even finding the disease late can shift the trajectory of its course and provide benefits for patients. “We know that liver cancer rates are lower in patients who clear the virus, than those that don’t, even in those with cirrhosis.  Recurrence of liver cancer is less in people who are treated for hepatitis C along with their cancer intervention. Also, going into transplant without, rather than with, hepatitis C is certainly favorable for outcomes.”

In addition, eradicating hepatitis C has an impact on extra-hepatic manifestations of the disease; explains Dr. Reau.8 “We know that those infected with hepatitis C are at increased risk of other disorders, including diabetes, certain lymphomas, cryoglobulinemia and other immune-mediated diseases. A recent study of a large Taiwanese population has shown that multiple malignancies were higher in patients with hepatitis C than in patients without hepatitis C. Fatigue and quality of life are, of course, improved when you don't have hepatitis C. So there are numerous reasons to consider therapy, other than the avoidance of cirrhosis.”

Verifying Active Infection

Once someone has tested positive for the HCV antibody further testing is needed to distinguish between active virus, cleared virus or a false positive result. “The next test to perform on everybody is a hepatitis C viral load or nucleic acid test (NAT),” says Dr. Reau. “We recommend doing a quantitative test, not a qualitative test, as the quantitative test is sufficiently sensitive to determine infectivity, and has the advantage of providing a baseline of the viral load.If that's positive, we know the person has hepatitis C. If it’s at a very low level, we might repeat it after at least a month to see if the virus is clearing or if the viral load is increasing.”

Genotyping to Help Guide Therapy

Following verification of active infection, genotyping is performed to determine therapy and duration of therapy.  Most people in the United States are infected with genotype 1, while a minority have genotype 2 and 3.  “Currently, if a patient is genotype 2 or 3 they will just receive pegylated interferon plus ribavirin, while those who are genotype 1 receive a triple therapy which includes the addition of a Direct Acting Agent (DAA).” 

Genetic testing can also identify the genotype of IL28B, a genetic polymorphism that can help predict interferon response, explains Dr. Reau10. “The IL28B genotype can help identify patients likely to be able to shorten treatment. There’s a lot of interest in being able to truncate the duration of therapy for people on DAA-based treatment. If a person without cirrhosis clears virus very early, they have great results with a shorter course of treatment.  Most individuals with the favorable IL28B CC genotype are going to achieve the milestone. This allows us to tell a patient they’re most likely to need only 6 months, rather than 12 months of therapy – an important factor in helping ensure compliance.”

A Positive Outlook

In considering how the field is evolving, Dr. Reau believes the most significant changes will come in response to more effective and tolerable therapies. One such change would be the shift of treatment to primary care providers. “This would be quite feasible once you don't have to determine the regimen, or the duration of regimen, based on pre-treatment factors,” she notes. “Once a regimen is standardized, and there is less concern about making decisions based on treatment response, primary care providers are more likely to be motivated to provide therapy themselves.”

“And once therapy becomes simpler and less cost prohibitive,” continues Dr. Reau, “it’s going to be hard to say that we shouldn’t broaden screening. There is no excuse to miss a curable disease that can lead to significant health problems.”


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Released on Tuesday, February 19, 2013