CDC recommends expanded patient testing

Oct. 19, 2012

Deaths in the United States from hepatitis C virus-related disease are on the rise. In the United States, 2.7 to 3.9 million individuals are living with HCV, according to the U.S. Centers for Disease Control and Prevention (CDC), and about 15,000 die every year. Without treatment, the estimated number of deaths caused by HCV will continue to increase to more than 20,000 per year over the next two decades. Recent studies indicate that approximately 75% of those infected with HCV are unaware of their infection because in most cases there are no symptoms, even after many years of chronic infection.1

The risk for disease is especially high among aging baby boomers who may have acquired the virus in the 1970s and 1980s from a parenteral exposure, such as from a blood transfusion or sharing drug-injection needles. Without showing symptoms, most never learned of their infections. As a result, the CDC has recommended that all baby boomers be tested for infection with HCV to help prevent an expected surge in serious liver diseases.1

The CDC’s action coincides with the 40th anniversary of the first serology tests for hepatitis B (HBV). This breakthrough enabled clinicians to accurately diagnose HBV from a blood specimen. Four decades later, the call for hepatitis testing is louder than ever, and the radioactive isotopes used in the original assays in the 1970s have been replaced by immunoassays and molecular (viral genetic) tests.

“The ticking time bomb”

Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation. Untreated HCV infections can cause inflammation of the liver and progressive liver damage including cirrhosis (scarring of the liver) and cancer, in some cases. Chronic hepatitis C virus may persist for 20 years or more before liver damage is evident. Early diagnosis and treatment not only can prevent downstream complications but can also reduce ongoing transmission of hepatitis.

Infectious disease experts predict a steep increase in HCV-related illness and death in the next two decades, as most HCV-infected individuals in the United States are over 50 years old, probably have been infected for decades, and are vulnerable for developing cirrhosis and liver cancer. The American Association for the Study of Liver Diseases (AASLD) and Trust for America’s Health described the situation candidly: “Hepatitis B and C are ticking time bombs.  If we don’t act now to diagnose the millions of baby boomers and others, we’ll be too late to spare them from developing serious liver diseases.”2

The CDC’s testing recommendation followed a January 2012 report by the Institute of Medicine (IOM), which concluded that chronic liver disease due to infection with HBV or HCV is not widely recognized as a serious public health problem in the United States.3 Further, the IOM stated that current approaches to control these viruses have not been effective, partly due to inadequate resources. The IOM also recommended that measures be taken to educate both healthcare providers and the public about the danger posed by chronic hepatitis.

For individuals born between 1945 and 1965 (baby boomers), the prevalence of HCV infection is five times higher than among other age groups, according to the CDC’s estimates, and this group represents 73% of all HCV-associated mortality. The good news is that new antiviral drugs currently available can cure 65% to 75% of individuals infected with HCV, with even better treatments in development.4

The CDC, therefore, is recommending that baby boomers be tested for HCV to determine their status. The testing algorithm includes an initial antibody test (the most cost-effective method to identify exposure to HCV) followed by a second test (e.g., a viral RNA test) to determine if there is an active infection or if the virus has been eliminated. Approximately 75% of HCV-infected individuals will develop chronic disease, whereas the remaining 25% are able to clear the virus on their own.4 Typically, those infected with HCV will have detectable antibodies in their blood even after they have cleared the virus. Those with active infection may become candidates for treatment. The CDC believes that screening baby boomers will allow thousands to be successfully treated for HCV before serious liver disease occurs.

Interferon, a combination of interferon and ribavirin, and two new protease inhibitor drugs are used to treat hepatitis C. The advent of direct-acting antiviral agents active against different steps of the HCV lifecycle will dramatically change therapy, especially for difficult-to-treat patients. Current drugs, however, still must be used in combination with pegylated interferon alfa plus ribavirin. The first two HCV protease inhibitors were approved in May 2011, and other next-generation agents are currently moving through the development pipeline. Decisions on starting treatment are based on many factors, such as the type of virus, the condition of the liver, and the presence or absence of other medical conditions.

A legacy of advances

The latest therapeutic and diagnostic advances in combating hepatitis worldwide have continued an impressive scientific legacy that achieved significant progress for improving global public health. The array of diagnostic tests and antiviral therapies now available have their roots in  discoveries made decades ago when the major health concern was preventing transfusion-transmitted hepatitis.

In the 1960s, transfusion recipients risked infection with hepatitis B because there was no reliable way to screen donors. Also, doctors treating patients with hepatitis A and B were unable to accurately diagnose and stage these diseases and could not differentiate acute and chronic infections or determine if patients were infectious to others.

In 1965, Dr. Bernard Blumberg discovered the Australia Antigen, a surface protein of the hepatitis B virus, now referred to as hepatitis B surface antigen or HBsAg. It didn’t take long for blood banks to screen blood with this marker to help reduce transfusion-transmitted hepatitis. The only test method available was an agar gel diffusion technique used by Dr. Blumberg. It was a simple test, but results were subjective and difficult to interpret and they lacked appropriate sensitivity.

Among the first commercial assays for detection of the hepatitis B surface antigen was the Ausria test, which was introduced in 1972. A test for hepatitis A became available shortly after this.  Ausria-I, a radioimmunoassay, was described in the Journal of Clinical Microbiology as “a useful sensitive test for the laboratory diagnosis of HBsAg.”5  It was followed by Ausria-II in 1975, which offered greater specificity and produced fewer false positive results.5 Through the 1970s and 1980s, several new tests were introduced to measure different serological markers for hepatitis A and B. They allowed clinicians to accurately stage the infections.

For hepatitis B, a panel of diagnostic markers can help determine if the patient has an acute infection, is an asymptomatic chronic carrier, or is capable of passing the disease to others. The general principles of Ausria II have been carried over to future generations of tests for hepatitis B surface antigen. Today’s automated tests use microparticles instead of quarter-inch beads and different, nonradioactive, reporting signals, but otherwise are similar to Ausria II.

Even though tests for hepatitis B were a major leap forward for making transfusions safer, a type of hepatitis aptly called non-A, non-B hepatitis was still a threat. Discovery of the hepatitis C virus in 1989 allowed development of a serological test for detection of anti-HCV antibodies for blood screening and patient diagnosis.

There is a full line of serological assays to detect and stage HBV and HCV infections. They show an immune response to the hepatitis B and C viruses or viral proteins and can quantify the amount of circulating viral protein. Molecular assays are currently used to show the virus is present (qualitative) or to measure exact viral load levels (quantitative); they have become quite effective for monitoring new drug therapies for hepatitis B and C.

Physicians usually order molecular diagnostic assays for hepatitis B and C following diagnosis with serological tests. Viral load assays are performed initially to determine if the HBV or HCV level warrants treatment. Testing can be continued at regular intervals to monitor therapy. The goal is to ensure that the virus is under control or eradicated as indicated when viral loads fall below detectable levels.

For the past 40 years, diagnostics technology has played a critical role in helping protect the public from hepatitis. Today, diagnostics technology still offers the best hope for many baby boomers who are unaware they are infected and who need to be diagnosed and treated to avoid serious liver disease. The CDC’s timely recommendations will save thousands of lives.

Gerald Schochetman, PhD, is Senior Director, Infectious Disease Diagnostics Research and Development, at Abbott Diagnostics.

George Dawson, PhD, is a Distinguished Research Fellow and Manager, Infectious Disease Diagnostics Research and Development, at Abbott Diagnostics.


  1. Recommendations for the identification of chronic hepatitis infection among persons born during 1945 to 1965. U.S. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Aug. 17, 2012:1-6.
  2. Millions of Americans are living with hidden epidemics of hepatitis B and C, top experts warn (news release). Trust for America’s Health. Sept. 27, 2010.
  3. Colvin HM,  Mitchell AE, eds. Hepatitis and liver cancer:  a national strategy for control of hepatitis B and C. Committee on Prevention and Control of Viral Hepatitis Infections, Institute of Medicine. April 2010:2.
  4. Recommendations for the identification of chronic hepatitis infection among persons born during 1945 to 1965. U.S. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Aug. 17, 2012:10-11.
  5. Interview, Richard Decker, PhD, retired hepatitis and AIDS research scientist, Abbott Diagnostics. June 2012.