Hepatitis B virus DNA levels at week 4 of lamivudine... : Hepatology (original) (raw)
Viral Hepatitis
Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5-year ideal response
Yuen, Man-Fung1; Fong, Daniel Yee-Tak1; Wong, Danny Ka-Ho1; Yuen, John Chi-Hang1; Fung, James1; Lai, Ching-Lung1
1 From the Departments of Medicine and Nursing Studies, University of Hong Kong, Queen Mary Hospital, Hong Kong
Address reprint requests to: Ching-Lung Lai, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China
E-mail:[email protected]
Received 30 April 2007; Accepted 23 July 2007
Published online 20 November 2007 in Wiley InterScience (www.interscience.wiley.com).
Grant sponsor: Hepatology Research Fund, Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong.
Potential conflict of interest: Nothing to report.
Mr. Daniel Yee-Tak Fong (statistician of the Department of Nursing, University of Hong Kong), one of the coauthors, and Dr. Man-Fung Yuen, the principal investigator, performed the statistical analysis for this study.
Dr. Man-Fung Yuen had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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Abstract
The best time and hepatitis B virus (HBV) DNA level during an early lamivudine treatment period for predicting the long-term outcome are unknown. We aimed to determine the optimal time and HBV DNA level during an early treatment period for the prediction of the response after a 5-year lamivudine treatment. The HBV DNA levels at the baseline, at weeks 2, 4, 8, 12, 16, 24, and 32, and at yearly intervals until year 5 were measured in 74 hepatitis B e antigen (HBeAg)–positive chronic HBV patients receiving lamivudine treatment. Seventeen patients achieved an ideal response [HBV DNA level < 2000 copies/mL (400 IU/mL), HBeAg seroconversion, normal alanine aminotransferase levels, and absence of tyrosine-methionine-aspartate-aspartate (YMDD) mutations] at year 5. Receiver operating characteristic curves showed good predictions as early as week 4. The areas under the curve for weeks 4 and 16 were 0.89 and 0.94, respectively. Predictive indices revealed 4 and 3.6 log copies/mL (2000 and 800 IU/mL, respectively) to be the best cutoff HBV DNA levels for these 2 times, respectively. All patients with HBV DNA levels lower than these respective cutoff levels at the 2 times achieved an ideal response at year 5. Patients with HBV DNA levels above these cutoff values had 83.8% and 87.7% chances of not achieving an ideal response at year 5, respectively. Conclusion: The measurement of the HBV DNA levels at week 4 of lamivudine treatment should be performed in all patients to predict the long-term outcome. The treatment can be continued for those with HBV DNA levels of less than 4 log copies/mL (2000 IU/mL). The addition of or switch to alternative antiviral agents should be considered for patients who fail to achieve this early target. (Hepatology 2007.)
Abbreviations: ALT, alanine aminotransferase; anti-HBe, antibody to hepatitis B e antigen; AUC, area under the curve; CHB, chronic hepatitis B; CI, confidence interval; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; PCR, polymerase chain reaction; ROC, receiver operating characteristic; SE, standard error.
Copyright © 2007 American Association for the Study of Liver Diseases.