SAN FRANCISCO — The extent of hepatitis B viral suppression after 6 months of therapy predicts treatment efficacy and the risk of developing resistance at 1 year, Dr. Ching-Lung Lai said at the annual meeting of the American Association for the Study of Liver Diseases.
A study of 1,367 patients with chronic hepatitis B virus (HBV) infection and viral DNA levels greater than 6 log
Patients with detectable HBV at 6 months had more variable outcomes at 1 year, with higher viral loads at 6 months linked to increased risks for detectable virus, viral breakthrough, and development of drug resistance at 1 year, said Dr. Lai, chief of gastroenterology and hepatology at the University of Hong Kong, and his associates.
“Now we can actually adjust the patient's treatment” by adding or changing drugs if HBV remains detectable at 6 months, he suggested. “Early viral suppression at 6 months is an ideal thing to aim for in the treatment of chronic hepatitis B.”
The main purpose of the phase III, randomized GLOBE study was to compare the efficacy of the investigational anti-HBV drug telbivudine with lamivudine during 2 years of treatment. The temporal relationship between early viral suppression and 1-year outcomes was seen in both treatment groups, but telbivudine worked better to suppress the virus, Dr. Lai said. He is a consultant for and has received funding from Idenix Pharmaceuticals, which is developing telbivudine in collaboration with Novartis Pharma AG.
The relationship between early viral suppression and good 1-year outcomes applied regardless of whether patients were positive or negative for hepatitis B e-antigen (HBeAg) at baseline.
For the analysis, patients were divided into four groups based on viral load at 6 months, as measured with polymerase chain reaction: patients with undetectable levels (below 300 copies/mL), fewer than 3 log
Among HBeAg-positive patients, HBV DNA was undetectable at 1 year in 91% of patients with undetectable levels at 6 months but in only 5% of patients with more than 4 log
Viral breakthrough by 1 year was seen in fewer than 1% of patients who had undetectable HBV DNA at 6 months, regardless of HBeAg status. Breakthrough occurred by 1 year in 14% of HBeAg-positive patients and 24% of HBeAg-negative patients who had more than 4 log
At baseline, all patients had compensated liver disease and ALT levels at 1.3–10 times the upper limit of normal. ALT levels normalized by 1 year in 88% of HBeAg-positive patients and 81% of HBeAg-negative patients who had undetectable HBV DNA at 6 months, indicative of improved liver function. In comparison, ALT levels normalized by 1 year in 53% of HBeAg-positive patients and 41% of HBeAg-negative patients who had a viral load of more than 4 log
In each of the viral load categories, telbivudine achieved greater viral suppression and led to less drug resistance, compared with lamivudine, he added.