Do guidelines preclude hepatitis B patients from receiving treatment?
Authors: Bulent Degertekin, Anna S. Lok
Journal: Hepatology (2008)

We read with great interest the article by Tong et al.1 in the October 2008 issue of HEPATOLOGY. In this article, the authors determined whether the four published guidelines/algorithm (European Association for the Study of the Liver, American Association for the Study of Liver Diseases, Asian Pacific Association for the Study of the Liver, and US Panel) on hepatitis B treatment correctly identified for treatment patients who subsequently developed hepatocellular carcinoma (HCC) or suffered non-HCC liver-related deaths. Tong et al. retrospectively analyzed the outcome of 369 hepatitis B surface antigen (HBsAg)–positive patients followed for a mean of 7 years, and they reported that if the criteria for antiviral therapy stated in the current treatment guidelines/algorithm had been used, only 20% to 60% of the patients who developed HCC and 27% to 70% of the patients who suffered non-HCC liver-related deaths would have been identified for antiviral therapy. The authors found that the addition of baseline serum albumin, platelet count, and presence of basal core promoter and precore mutations would improve the accuracy of the identification of these patients to 90% to 100%. The authors concluded that if current guidelines were used, a significant proportion of HBsAg-positive patients would be deprived of the possible benefits of antiviral therapy. However, the results of this and other studies on this topic2 need to be interpreted carefully. First, all guidelines recommend that patients who are not initiated on treatment should continue to be monitored and that treatment should be initiated later when the indications arise.3 In this study, the authors focused on laboratory test results at the first visit and did not consider the option of treatment after an initial period of observation. As the authors indicated, alanine aminotransferase (ALT) levels fluctuated during follow-up. Thus, many of the patients would have met treatment criteria at some point during the course of follow-up. Second, 78.5% of the patients were Asians and likely acquired hepatitis B virus (HBV) infection perinatally or during early childhood. The mean age of the patients at recruitment was 48 years, indicating that most of the patients had been infected for more than 4 decades. In light of recent findings that persistently high serum HBV DNA is a predictor of clinical outcomes and significant liver disease may be present in patients with normal ALT, the 2007 American Association for the Study of Liver Diseases practice guidelines recommended that lower HBV DNA and ALT cutoffs be applied to patients older than 40 years and liver biopsies be performed in patients with HBV DNA and ALT values in the grey zone.3 Finally, the authors assumed that had antiviral treatment been administered at presentation, all cases of HCC and liver-related mortality would have been prevented. Clinical studies have shown that antiviral therapy is not effective in improving survival for patients with advanced liver failure.4 Moreover, antiviral therapy decreases but does not completely prevent the risk of HCC.5, 6 We congratulate the authors for conducting this study. However, we caution readers that decisions on hepatitis B treatment should not be based solely on laboratory test results at the first visit. Given the fluctuating nature of chronic HBV infection, all patients should be monitored for life so treatment can be initiated later when the indication arises. Bulent Degertekin*, Anna S. Lok*, * Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI.