Lamivudine is an effective antiviral agent for treatment of patients with chronic hepatitis B and advanced liver diseases. However, long-term lamivudine monotherapy leads to the emergence of lamivudine-resistant hepatitis B virus (HBV) mutants in some patients chronically infected with HBV. Sensitive methods for early detection of lamivudine-resistant mutants will help physicians make clinical decisions in treating patients with HBV infection.
To date, many assays have been used for detection of lamivudine-resistant mutants in patients with Hepatitis B. Differences in sensitivity, specificity, cost, and time required, exist in these methods. Real-time PCR is able to quantitatively detect a small portion of resistant mutants in HBV populations and ligase detection reaction (LDR) is a newly developed method for detection of low abundant mutants in the background of wild-type HBV. However, there are no studies which have compared the clinical performance of the two methods.
A research article to be published on January 7 in the World Journal of Gastroenterology (volume 14, issue 1) addresses this question. It compared LDR and real-time PCR for detection of low abundant YMDD mutations in mixed plasmids and serum samples from 52 lamivudine treated patients. Time required and reagent cost for both assays were evaluated. The research was conducted carefully by an experienced team of investigators.
The article suggested both methods are sensitive and inexpensive for detection of YMDD mutation; but LDR is more sensitive than real-time PCR. The results obtained with both methods were completely concordant in all serum samples. LDR was able to detect as low as 0.01% (100 copies/mL) of YIDD plasmid, while real-time PCR only detected 0.1% (1000 copies/mL) of YIDD plasmid in the background of YMDD plasmid. In addition, the cost of LDR is slightly lower than that of real-time PCR.
However, real-time PCR is much more rapid and requires less manual work than LDR. The total assay time for LDR and real-time PCR was 4.5 and 2.5 h, respectively. Another advantage of the real-time PCR method is it is able to calculate the ratio of mutants to total virus in samples. This will be useful in clinical studies on the dynamics of resistant mutants during lamivudine therapy.
6.1 Reference: Wang XL, Xie SG, Zhang L, Yang WX, Wang X, Jin HZ. Comparison of ligase detection reaction and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B. World J Gastroenterol 2008; 14(1): 120-124
6.2 Correspondence to: Xiao-Ling Wang, 98 West Nantong Road, Subei People's Hospital, Yangzhou 225001, Jiangsu Province, China. Wxlf26@163.com
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6.3 About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
6.4 About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.