title: YMDD Motif Mutation Profile Among Patients Receiving Liver Transplant Due to Hepatitis B Virus Infection With Long Term Lamivudine/Immunoglobulin Therapy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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 Real-Time 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 Nested-PCR, introduced to sequencing and subjected to phylogenetic analysis.
  
  
  RESULTS
  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 > 0.05).
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Rahim
authors: R
authors: Rahimi
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Seyed Younes
authors: SY
authors: Hosseini
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Mohammad Reza
authors: MR
authors: Fattahi
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Masood
authors: M
authors: Sepehrimanesh
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Alireza
authors: A
authors: Safarpour
authors: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Seyed Ali
authors: SA
authors: Malekhosseini
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran ; Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Maryam
authors: M
authors: Nejabat
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Mahboobeh
authors: M
authors: Khodadad
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran ; National Research Institute for Science Policy Tehran, IR Iran.
authors: Maryam
authors: M
authors: Ardebili
keywords: Drug resistance; Lamivudine; Transplantation