Abstract
BackgroundSeveral recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B.Methodology/Principal FindingsChinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21% (95% CI: 9.69%–14.95%). China had an incidence of 13.38% (95% CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90% (95% CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients' ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C.ConclusionsThe YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patients untreated with lamivudine. These mutations might be the consequence of accumulated base mismatch due to the nature of viral polymerase. More fundamental and clinical studies are needed to clarify the influence of YMDD mutations in hepatitis B progression and antiviral treatment.
Highlights
Hepatitis B virus (HBV) infection has long been a serious public health problem around the world
The YMDD-motif mutations can occur spontaneously with a relatively high incidence in chronic hepatitis B (CHB) patients untreated with lamivudine
The two Chinese databases: China National Knowledge Infrastructure (CNKI) and WanFang were searched for articles related to HBV and YMDD motif mutation from January 2001 to December 2010
Summary
Hepatitis B virus (HBV) infection has long been a serious public health problem around the world. HBV is one of the main causes of acute and chronic hepatitis in humans. 400 million people are infected chronically with HBV worldwide [1]. It has been demonstrated that chronic infection with this virus is linked to the development of cirrhosis and hepatocellular carcinoma, accounting for 0.5–0.75 million deaths per year. Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naıve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B
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