In summary, phosphorylation of Ser33 and Ser52 in K18 may serve as reliable progression markers of chronic hepatitis B. Although it remains to be determined the precise molecular mechanism through which HBV alters K18 phosphorylation, specifically how differential phosphorylation of Ser33 and Ser52 is modulated in hepatocytes at different stages of the liver disease, our study suggests that the two phosphorylation events may underlie different hepatocytic events associated with HBV. This evidence concerns the gene KRT18 and chronic hepatitis B virus infection.