Tong et al. recently described the failure of several hepatitis B virus (HBV) treatment guidelines to identify treatment eligibility for a significant proportion of 67 of their patients who went on to develop hepatocellular carcinoma or died of liver-related complications, probably due to disease progression as a result of inadequate viral suppression. 1 However, three of these guidelines were published 2-4 prior to 2006, when the importance of HBV viral burden was less clearly established in terms of HBV-associated disease progression. 5,6 The article by Tong and colleagues is very timely, given that recently published Dutch guidelines as well as the most recent algorithm by Keefe et al. still reinforce the HBV DNA threshold for treatment initiation at 10 5 copies/mL for treatment initiation for all patients, 7 or for patients who are hepatitis B e antigen (HBeAg)-positive, 8 respectively. Using a higher viral load threshold for patients who are HBeAg-positive seems questionable, given that HBeAg has been identified as an independent risk factor for disease progression. In contrast, withholding treatment in patients who are HBeAg-negative with viral load up to 19,999 IU/mL (10 5 copies/mL) and persistently normal alanine aminotransferase (ALT) values seems justifiable. 9 It would be interesting to learn from the authors if all patients, who progressed, would have qualified for treatment following the German guidelines (as summarized in figure 1), which were developed following the criteria according to the workshop of the scientific medical professional societies. 10 In short, these guidelines have a hierarchical approach: (1) All patients with evidence for advanced fibrosis are eligible for antiviral therapy with an agent with a high genetic barrier to resistance (tenofovir or entecavir at present) in the presence of detectable HBV DNA; if no virus is detectable, patients should be re-evaluated every 3-6 months; (2) all patients with a viral load Υ10 4 copies/mL would qualify for therapy if ALT is (a) ΟΎ2Ο« upper limit of normal or (b) histology shows ΥF2 fibrosis or (c) high risk for hepatocellular carcinoma development (male gender, age, family history, or aflatoxin exposure in the past).
If viral load is less than 10 4 copies/mL, patients should be reevaluated every 6-12 months. These guidelines for HBV DNA and ALT thresholds apply to both HBeAg-positive and HBeAg-negative patients. Furthermore, the incorporation of histology into the decision-making process allows for the identification of a greater propor-tion of patients at risk of disease progression, and thus eligible to receive appropriate antiviral therapy.