Journal of American Science 2012;8(8) http://www.jofamericanscience.org http://www.jofamericanscience.org editor@americanscience.org 819 Incidence of Genotypic Resistance to Lamivudine Long Term Therapy in Egyptian patients with Chronic Hepatitis B Naglaa Allam 1 , Warda Osman 1 , Mona Hassouna 2 , Anne Abdel-moneim 2 , Ayat Abdallah 3 , Imam Waked 1 1 Department of Hepatology, National Liver Institute, 2 Clinical Pathology Department, National Liver Institute, 3 Environmental Health of the Liver Department, National Liver Institute naglaaallam@yahoo.com Abstract: Background: Lamivudine improves patients' outcome but is reported to be associated with increasing rates of viral resistance. The long-term benefit of lamivudine therapy and resistance rate in HBeAg negative genotype D patients is not fully known. This study aimed to determine the incidence of genotypic resistance to lamivudine therapy in Egyptian patients with chronic hepatitis B. Methods: This follow up study included 50 Egyptian patients with chronic hepatitis B who had received lamivudine 100mg daily for at least 12 months (7 females, age 328years). Patients were followed up for a mean period of 2510 months. Investigations included: liver profile, hepatitis B serology and HCV Abs by ELISA, and HBV DNA by PCR. INNO-LiPA was performed in selected cases. Results: HBV-DNA decreased to <2000 IU/ml in 20 patients (40%), and HBV-DNA became undetectable in 30 (60 %) during the first year of treatment. The rate of relapse with either HBV-DNA reverting to positive or increasing to >2000 IU/ml after initial response was 16 patients during the second year, 3 during the third, 1 during the fourth year of follow up. Breakthrough was observed in 75% of the HBeAg positive group and only 33.3% of the HBeAg negative group. INNO- LiPA was performed for the 20 patients with relapse. Wild type was found in 14 patients; mixed type in 4 and mutant in two patients. Hence mutations were detected in 30% of the tested lamivudine-treated cases. YMDD was detected in 15%. Mean viral load was 7416.00±9232.24 IU/ml compared to 21 900 333IU/ml in the patients with the mutants. Conclusion: Long-term lamivudine therapy is associated with a high response rate with a rather low breakthrough rate in HBeAg negative patients and a low incidence of YMDD mutation. [Naglaa Allam, Warda Osman, Mona Hassouna, Anne Abdel-moneim, Ayat Abdallah, Imam Waked. Incidence of Genotypic Resistance to Lamivudine Long Term Therapy in Egyptian patients with Chronic Hepatitis B. J Am Sci 2012;8(8):819-825]. (ISSN: 1545-1003). http://www.jofamericanscience.org . 123 Keywords: Chronic Hepatitis B, Lamivudine, genotypic resistance. 1. Introduction Chronic hepatitis B continues to be a significant public health problem in Egypt (1) . Of the available treatments for hepatitis B (interferon-alpha (IFN-α), lamivudine, adefovir, entecavir and telbivudine), lamivudine remains the most frequently used drug, mostly because it is the cheapest. Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication, which was proved in several clinical trials to result in a rapid decline of serum HBV DNA levels in a majority of patients and improve patients' outcome (2-4). However despite its good clinical tolerability and moderate antiviral efficacy, it is reported to be associated with rather quick development of resistance (5-7). Furthermore, lamivudine mutations may confer cross-resistance to telbivudine, emtricitabine and entecavir. The mutations related to lamivudine arise during prolonged treatment and the major mutation responsible is located in the YMDD site of the polymerase gene in which the methionine (rtM204) is replaced by either valine (rtV204) or isoleucine (rtI204) (6,8) . The incidence and patterns with which these mutations occur may vary among different populations. Hence, in the present study we aimed to assess the long-term response to lamivudine in Egyptian patients who have been taking lamivudine for more than one year and to determine the incidence of genotypic resistance in relapsed patients. 2. Materials and Methods: This follow up study was conducted at the National Liver Institute, where 50 patients diagnosed with chronic HBV infection (who had been on lamivudine therapy for over one year) were recruited from the hepatology outpatient clinics and followed up during the period from the beginning of January 2009 to January 2012. Informed consent was taken from all participants in the study. All patients were subjected to thorough history taking, abdominal examination and the following investigations: bilirubin, AST, ALT, albumin, GGT, ALP, complete blood picture, prothrombin time and concentration, viral markers; (HBsAg, HBeAg, anti-HBe, anti-HBc, anti-HDV, anti- HCV Abs by Enzyme-linked immunosorbent assay (ELISA), and HBV DNA level by polymerase chain reaction (PCR). Patients were followed up for a mean duration of 2510 months and the relapse rate was noted. Detection of genotypic resistance was performed in the 20 patients who relapsed using INNO-LiPA HBV DR v3 (LiPA HBV GT;