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YMDD Motif (ymdd + motif)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Hepatitis B virus variants in patients receiving lamivudine treatment with breakthrough hepatitis evaluated by serial viral loads and full-length viral sequences

HEPATOLOGY, Issue 3 2001
Chun-Jen Liu
Both viral loads and genome variations have been implicated in the pathogenesis of acute exacerbation of chronic hepatitis B. Hepatitis B exacerbation in patients receiving lamivudine treatment represented a unique setting to clarify their importance. Three organ recipients with posttransplantation hepatitis B exacerbation and 3 patients with chronic hepatitis B were studied. All received lamivudine treatment and their alanine aminotransferase (ALT) levels and hepatitis B virus (HBV) loads were regularly followed. Full-length genomic sequences before and during lamivudine treatment were determined in patients who had breakthrough of serum HBV DNA or elevation of serum ALT. Breakthrough of serum HBV DNA occurred after 6 to 15 months of lamivudine treatment in all. A rapid increase of viral load accompanying the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variant was followed by hepatitis B exacerbation in each patient. The mean number of nucleotide and amino acid substitutions per genome pair was equivalent in immunosuppressed or immunocompetent patients (6.3 vs. 6.3 for nucleotide, P > .05; 6.0 vs. 6.7 for amino acid, P > .05). Changes of nucleotide and amino acid beyond the YMDD motif were distributed along the whole HBV genome but none occurred within the known B-cell epitopes and human leukocyte antigen class I, or II,restricted T-cell epitopes. Our results suggest that a resurgence of viral load rather than changes of the known immunogenic viral epitopes is more closely associated with the development of hepatitis B exacerbation after the emergence of YMDD variants in patients receiving lamivudine treatment. (HEPATOLOGY 2001;34:583-589.) [source]

Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatment

HEPATOLOGY RESEARCH, Issue 2 2010
Mariko Kobayashi
Aim:, Continuous lamivudine treatment is associated with high frequency of drug resistance. We analyzed the incidence of tyrosine-methionine-aspartate-aspartate (YMDD) motif mutant and breakthrough hepatitis (BTH) in hepatitis B virus (HBV) DNA positive patients receiving lamivudine for > 1 year and correlated it with HBV DNA and alanine aminotransferase (ALT) levels to evaluate if these measurements can provide a practical option for monitoring patients in clinical practice and define early switch from lamivudine therapy. Methods:, Of the 929 patients receiving lamivudine for > 1 year, 359 patients who maintained an ALT level of , 40 IU/L during the course of lamivudine treatment were stratified into two groups based on the duration of lamivudine treatment , one receiving lamivudine for < 3 years and the other for , 3 years. Results:, The incidence of YMDD motif in patients receiving lamivudine for < 3 years was 27% in patients with ALT , 20 IU/L, 58% with ALT , 30 IU/L, and 63% with ALT , 40 IU/L, (P = 0.002). The corresponding incidence of BTH was 2%, 7%, and 48% (P < 0.001). The incidence of YMDD motif and BTH in these patients was 7% and 2% with HBV DNA < 2.6 (log copies/mL) and ALT , 20 IU/L, while with ALT at 21,30, the YMDD motif mutant was 16% and BTH was 0%. Conclusion:, Correlation of ALT and HBV DNA levels with YMDD motif mutant and BTH indicates that these measurements can be used in clinical practice for deciding early switch from lamivudine to other suitable antiviral therapies. [source]

Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B,,§

JOURNAL OF MEDICAL VIROLOGY, Issue 7 2009
Fabio Iacomi
Abstract A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125,213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L,+,rtL180M,+,rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D,+,sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0,61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5,34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat. J. Med. Virol. 81:1151,1156, 2009. © 2009 Wiley-Liss, Inc. [source]

Successful treatment of an entecavir-resistant hepatitis B virus variant

JOURNAL OF MEDICAL VIROLOGY, Issue 12 2007
Hiromi Yatsuji
Abstract Emergence of a lamivudine (LAM)-resistant hepatitis B virus (HBV) with amino acid substitutions in the YMDD motif is a well-documented problem during long-term LAM therapy. Entecavir (ETV) is a new drug approved for treatment of HBV infection with or without LAM-resistant mutants. This report describes an ETV-resistant strain of HBV, which emerged after prolonged ETV therapy in a patient who did not respond to LAM therapy. Direct sequence analysis of the ETV-resistant strain showed appearance of amino acid substitution rtS202G in the reverse transcriptase (RT) domain, together with rtL180M,+,M204V substitution that had developed at the emergence of LAM-resistant mutant. In vitro analysis demonstrated that the rtL180M,+,M204V,+,S202G mutant strain displayed a 200-fold and a 5-fold reduction in susceptibility to ETV compared with the wild- type and the rtL180M,+,M204V mutant strain, respectively. Adefovir was effective against the ETV-resistant strain both in vitro and during the clinical course. In conclusion, this study showed that virological and biochemical breakthrough due to ETV could occur in patients infected with LAM-resistant HBV and confirmed that the addition of rtS202G substitution to the rtL180M,+,M204V mutant strain is responsible for ETV resistance and we could treat the resistant mutant successfully. J. Med. Virol. 79:1811,1817, 2007. © 2007 Wiley-Liss, Inc. [source]