Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy

Liu, Kezhou; Hou, Wanwan; Zumbika, Edward; Ni, Qin

doi:10.1631/jzus.2005.b1182

Cited by 13 publications

(5 citation statements)

References 22 publications

(21 reference statements)

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“…In a study by Li Zhou et al. , 16 some patients with YMDD motif mutants had significantly lower HBV DNA and ALT levels compared with baseline values, which might be due to decreased replication efficiency of the HBV mutants.…”

Section: Discussionmentioning

confidence: 95%

“…Similarly, in patients maintaining HBV DNA level in the range of 2.6-5.0 log copies/mL and ALT < 20 IU/L, switching to dual therapy with adefovir in combination with lamivudine depends on the related viral breakthrough. In a study by Li Zhou et al, 16 some patients with YMDD motif mutants had significantly lower HBV DNA and ALT levels compared with baseline In patients treated with lamivudine for 3 years or more, the incidence of tyrosine-methionine-aspartateaspartate (YMDD) motif mutant by alanine aminotransferase (IU/L) level was 58% in 113 patients in group A, 60% in 84 patients in group B, and 80% in 37 patients in group C (P = 0.002), and that of BTH in the corresponding groups was 7%, 14%, and 57% (P < 0.001). (a) Incidence of YMDD mutants over time (P = 0.0015).…”

Section: Discussionmentioning

confidence: 99%

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

Kobayashi¹,

Suzuki

Akuta

et al. 2010

Hepatology Research

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

Kobayashi¹,

Suzuki

Akuta

et al. 2010

Hepatology Research

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“…The only limitation, when compared to other anti-viral agents used in the treatment of chronic hepatitis B, is drug resistance, which may arise during lamivudine therapy. [7][8][9][10][11][12][13][14][15] Factors that may be associated with the development of lamivudine resistance in the literature have been reported as the patient's age, sex, body-mass index, HBeAg positivity, HBV genotype, pathological condition of the liver prior to treatment, pre-treatment serum ALT and HBV-DNA levels. 7,8,12,16 In this study, apart from the factors triggering the development of resistance mentioned in the literature, it has been investigated whether MDR1 gene polymorphism is associated with the development of lamivudine resistance.…”

Section: Discussionmentioning

confidence: 99%

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Şıvgın¹,

Yılmaz²,

Rüstemoğlu³

et al. 2023

KMJ

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Aims: Chronic HBV infection is associated with high morbidity and mortality rate due to increased risk of hepatic cirrhosis and hepatocellular cancer. Treatment modilities and resistance is currently investigated. Several mechanisms were underlying in drug resistance. P-glycoprotein (P-gp), the product of multidrug resistance gene (MDR-1), is well-known mechanism of MDR phenotype. MDR gene C1236T polymorphism is associated with decreased p-gp function. The mutation of MDR gene can affect the clinical course of disease and response rate to treatment. It was aimed to investigate the relationship between MDR gene polymorphism and clinical course and treatment responses in chronic HBV infection in our study. Methods: A total of 90 (male/female:69/21) patients with chronic HBV infection under Lamivudine treatment was enrolled in this study. Mean ages were 49.8±12.6 (range:22-75) years. The patients were categorized as: Treatment responded (group 1: HBV-DNA is negative at 24th week) and treatment refractory (group 2: HBV-DNA is still positive after 24th week). Group 1 was consisted of 51 (M/F: 38/13) and group 2 was consisted of 39 (M/F: 31/9) patients. There was no significant difference between ages and genders of two groups. Histologic activity indexes (HAI), total bilirubin, AST and ALT levels, HBV-DNA titers were significantly higher in the patients in group 2 than group 1 (p<0.05). Results: Genotype distributions; homozygous CC genotype was in 8 (15.7%),heterozygous CT genotype was in 37 (%72.5), homozygous TT genotype wasin 6 (11.8%) in patients at group 1. Homozygous CC genotype was in 13 (33.3%), heterozygous CT genotype was in 21 (53.8%), homozygous TT genotype was in 5 (12.8%) in patients at group 2. CC genotype was more common in group 2 than group 1 (p=0.044). C and T alleles’ frequencies in the group 1 and 2 were 51.96% and 60.26%, 48.04% and 39.74%, respectively (p>0.05). The patients with YMDD mutation positive at group 2 (n:11), 5 (45%) had have CC genotype, 5 (45%) had have CT, 1 (9%) had have TT genotype.The patients with YMDD mutation negative at group 2 (n:8), 3 (37%) patients had have CC and 5 (63%) patients had have CT genotype. CC genotype was more common in the patients with YMDD mutation positive than group 1 (p=0.043). Moreover, CC genotype was more common in the patients with HBV-DNA positive at 12nd month of Lamivudine treatment than group 1 (p=0.042). Conclusion: Consequently; MDR-1 and p-gp polymorphisms are important factors in the clinical course of chronic HBV infection and may influence the treatment responses. In the current study, it was found that the CC genotype of MDR-1 gene C1236T was more common in the patients with lamivudine resistant HBV infection.

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“…The loss of efficacy generally increases over time post LAM treatment, from 14-47% after 1 year to 26-71% after 2 years, 49-57% after 3 years, and 67% after 4 years (Tsubota, 2006). Liu, et al found that the majority of the cases (42/63, 66.6%) with YMDD mutants were detected between 12 and 24 months post therapy (Liu et al, 2005). To the best of our knowledge, there is limited data in terms of the proportion and persistent time during YMDD mutants pathological process.…”

Section: Introductionmentioning

confidence: 99%

Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus

et al. 2021

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Background/Aims: Emergence of tyrosine-methionine-aspartate-aspartate (YMDD) motif in reverse transcriptase is a serious problem in chronic hepatitis B(CHB) patients after Lamivudine (LAM) therapy. However, the relationship between inflammation pharmacological reaction and YMDD mutational patterns of CHB has not been well-characterized. The aim of this study was to investigate the inflammation pharmacological reaction and different YMDD mutants patterns of CHB patients.Methods: We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 CHB patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants.Results: Prevalence of YMDD mutation patterns is different. Among 25 YMDD mutants patients, YIDD was the dominant mutation (72%), followed YVDD (16%) and the hybrid YIDD + YVDD (12%). The time course during the YMDD mutations was also different. 52.4% patients developed the mutation less than 12 months after the LAM therapy. Serum hepatitis B virus (HBV) DNA level in patients with YMDD mutants were significantly higher than that in control and negative groups. Serum HbsAg and HbeAg in patients with YMDD mutants were also higher than those in control and negative groups, despite no significant difference was found forserum HbeAb. ALT and AST levels were also significantly higher in mutants group.Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV.

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Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy

Cited by 13 publications

References 22 publications

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

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

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus

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