News Release

Researchers discover method of predicting drug resistance in hepatitis-B patients

Peer-Reviewed Publication

Georgetown University Medical Center

Researchers at Georgetown University Medical Center have discovered a way to predict which hepatitis-B infected patients will respond successfully to the drug lamivudine--one of the most commonly used treatments for this illness--and which are likely to develop drug resistance or reject the drug altogether. This research was presented today at the 16th International Conference for Antiviral Research in Savannah, Georgia.

Left untreated, chronic hepatitis-B infection can lead to progressive liver disease, liver failure, or primary liver cancer. It affects more than 400 million people worldwide. Despite lamivudine's efficacy in treating hepatitis B (HBV), many doctors do not prescribe the drug until patients become clinically ill for fear that the patient will develop a drug resistance that will render lamivudine and other HBV treatments ineffective. Drug resistance occurs in approximately two thirds of treated patients.

"We have long struggled with one tough question: how do you treat those HBV-positive people who have the best chance at responding to lamivudine treatment and determine those who will fail treatment?," said Dr. John Gerin, professor of microbiology and immunology at Georgetown University Medical Center. "Doctors currently play 'wait and see' – wait until you get sick and then we'll see if lamivudine works. With a precise, predictive system in place, we can give patients immediate and targeted treatment rather than forcing them to wait until they become very ill."

Gerin, along with Dr. Brent Korba, professor of microbiology at Georgetown, and colleagues from Ospedale S. Giovanni Battista in Torino, Italy, followed 26 hepatitis-B positive people through 21-48 months of lamivudine treatment. Seven of those patients, classified as "responders," had permanent remission of the disease. Twelve patients, who were considered "breakthroughs," experienced initial success but then ultimately slid back into active infection due to lamivudine resistance. The remaining seven were "non-responders" who didn't respond to lamivudine treatment at all.

Surprisingly, the researchers detected two separate DNA polymorphisms, or markers, in the virus genome in all breakthroughs and non-responders prior to treatment. None of the responders had these markers. "We looked at a region of the virus that hasn't been routinely studied in depth before," said Korba. "Frankly, we were stunned to see that we could in fact clearly distinguish markers between the three groups and link them directly to that patients' degree of success with lamivudine."

The CDC estimates that 1.25 million Americans are chronically infected with HBV, of whom 20-30% acquired their infection in childhood. One out of 20 people in the United States will get infected with HBV some time during their lives. HBV can be spread through sexual transmission; needle sharing; exposure to needlesticks or "sharps" exposures on the job, or from an infected mother to her baby during birth. The highest rate of HBV occurs in 20-49-year-olds, and death from chronic liver disease occurs in 15-25% of chronically infected persons. The HBV vaccine is the best protection against HBV, which is now routinely administered to infants as part of their standard immunizations.

"In an era of skyrocketing medical costs, the cost savings in not treating patients who will not respond may be a profound public health advantage," said Gerin. "We will continue to work with our colleagues to expand upon and further confirm these findings."

Lamivudine is classified as an antiretroviral drug and is used in treatment of HIV as well as HBV. It works by stopping the spread of the HIV and hepatitis B viruses.

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This study was partially funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID).

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis--or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.


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