Author/Authors :
Rahimi، Rahim نويسنده Department of Internal Medicine,Shiraz University of Medical Sciences,Shiraz,Iran , , Hosseini، Younes نويسنده Gastroenterohepatology Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Fattahi، Mohammad Reza نويسنده Gastroenterohepatology Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Sepehrimanesh، Masood نويسنده Gastroenterohepatology Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Safarpour، Alireza نويسنده Gastroenterohepatology Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Malekhosseini، Ali نويسنده Transplant Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Nejabat، Maryam نويسنده Gastroenterohepatology Research Center,Department of Bacteriology and Virology,Shiraz University of Medical Sciences,Shiraz,Iran , , Khodadad، Mahboobeh نويسنده Gastroenterohepatology Research Center,Shiraz University of Medical Sciences,Shiraz,Iran , , Ardebili، Maryam نويسنده National Research Institute for Science Policy Tehran,Shiraz,Iran ,
Abstract :
Recurrence of Hepatitis B Virus infection in patients undergoing liver transplanted (LT) is a serious and often fatal problem. Lamivudine (LAM) and Hepatitis B Immunoglobulin (HBIG) are widely used to manage hepatitis B recurrence after liver transplantation. However, the outcomes in patients are less elucidated. The current study aimed to evaluate the YMDD motif mutations profile among the patients undergoing LT infected with HBV and treated with LAM/HBIG at least for one year. Thirty patients with liver transplantation due to HBV were enrolled, while DNA level remained under detection limit of 50 IU/mL before transplantation and abnormal higher levels of liver enzymes after LT. The HBV genome detection was performed by two different Polymerase Chain Reaction methods following viral quantification by commercial RealTime PCR. HbsAg detection, besides liver function tests were conducted as complementary assays. To assess nucleotide analogue mutations, the major part of polymerase gene (aa 80 240) was amplified by NestedPCR, introduced to sequencing and subjected to phylogenetic analysis. Totally, according to the laboratory criteria there were 13 cases with detectable HBV genome, while the mean liver enzyme levels were higher in recurrent patients and HBsAg was detected only in four out of the 13 cases. Phylogenetic analysis demonstrated that all isolated genomes belonged to genotype D. Critical M204I mutation, as a proof for resistance to LAM, was detected among 46% of the subjects and natural entecavir resistance (S202I) was also distinguished in one subject. Viral quantification showed higher titer in LAM resistant group in comparison to the group with undetectable drug resistance mutant (P amp;gt; 0.05). Although the patients carrying M204I mutation were more likely to show lack of responses to LAM therapy, LAM replacing by other nucleoside/tide analogs plus HBIG maybe still effective in decreasing hepatitis B recurrence after liver transplantation. However, it is suggested that drug resistance test should be considered by clinicians during therapeutic management to avoid the following viral breakthrough.
