Chronic infection with hepatitis B is one of the leading causes of chronic hepatitis and cirrhosis and is possibly the major cause of hepatocellular carcinoma worldwide. While there is no definitive cure, interferon-alfa has been reported to induce remission in 25 to 40 percent of patients. However, follow-up has been limited to one to two years in these patients, which is inadequate to determine their ultimate prognosis. Lau and associates evaluated long-term survival rates and clinical outcomes in patients with chronic hepatitis B who were treated with interfer-on-alfa.
A total of 103 patients with chronic hepatitis B were evaluated after receiving treatment with interferon-alfa in three clinical trials. Before treatment, all of the study subjects had elevated serum levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) for at least six months, and hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA were present in serum. Results of pre-treatment liver biopsies revealed that all patients had histologic evidence of chronic hepatitis B. A beneficial response to treatment was defined as a sustained loss of hepatitis B virus DNA from serum and subsequent clearance of HBeAg within one year of treatment.
Thirty-one patients (30 percent) were considered responders and 72 (70 percent) nonresponders. Responders were more frequently female and black and had a significantly lower level of hepatitis B virus DNA and higher levels of AST and ALT. Of the 31 responders, 10 (32 percent) had cirrhosis, compared with only seven (10 percent) of nonresponders. Reactivation of hepatitis B, defined as reappearance of HBeAg or hepatitis B virus DNA in serum, occurred in two of 31 responders and five of 37 nonresponders. By survival analysis, the rate of mortality from all causes was similar for the two groups nine years after treatment. Liver-related deaths or complications were more frequent among nonresponders than responders, but the difference was not statistically significant. The presence of cirrhosis significantly increased the risk of poor outcome.
The authors conclude that patients with chronic hepatitis B who demonstrate a serologic response to interferon-alfa therapy experience fewer liver-related complications. Improvements are particularly striking among patients who had pretreatment cirrhosis resulting from hepatitis B. Some patients who lost HBsAg still had mildly active liver disease and hepatitis B virus DNA in serum. Portal hypertension and complications of liver disease eventually developed among those with preexisting cirrhosis.