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In order to persist, the virus needs to have a high rate of replication and some immune\u2010escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non\u2010fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut\u2010off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five\u2010fold cross\u2010validation. The average prediction accuracy was 61%\u2009\u00b1\u20091%, with a sensitivity of 24%\u2009\u00b1\u20091%, specificity of 98%\u2009\u00b1\u20091%, positive predictive value of 92%\u2009\u00b1\u20094% and negative predictive value of 56%\u2009\u00b1\u20091%. BCP\/X, enhancer I and surface\/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non\u2010progression to chronic hepatitis. J. Med. 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