High pretransplant HBV level predicts HBV reactivation after kidney transplantation in HBV infected recipients

PURPOSE: HBsAg-positive kidney recipients are at increased risk for mortality and graft failure. The aims of this study were to identify the outcomes of HBsAg-positive recipients who received preemptive antiviral agents after successful kidney transplantation and to analyze risk factors for HBV reactivation. METHODS: We retrospectively reviewed the medical records of 944 patients performed kidney transplantation between 1999 and 2010. RESULTS: HBsAg-negative recipients were 902 patients and HBsAg-positive recipients, 42. Among HBsAg-positive recipients, HBV reactivation was detected in 7 patients and well controlled by switch or combination therapy. Graft failure developed in only one patient due to chronic rejection regardless of HBV reactivation but no deaths occurred. All patients were alive at the end of follow-up and none developed end-stage liver disease or hepatocellular carcinoma. There was statistically significant difference in graft survival between HBsAg-positive recipients and HBsAg-negative. Multivariate analysis identified increased HBV DNA levels (>5 x 10(4) IU/mL) in the HBsAg-positive kidney transplant recipients as a risk factor for HBV reactivation (P = 0.007). CONCLUSION: Effective viral suppression with antiviral agents in HBsAg-positive renal transplant recipients improves patient outcome and allograft survival. Antiviral therapy may be especially beneficial in patients with high HBV DNA levels prior to transplantation.

Analysis of the poor answer situation in chronic hepatitis B with lamivudine treatment / 中国基层医药

Objective To explore the use of lamivudine alone induced the poor response,especially the related factors of the occurrence of YMDD.Methods Retrospective analysis of 160 cases of the poor answering cases after lamivudine treatment,the baseline parameter values,the time appearing to the poor answering and the HBVDNA load in treatment were analyzed,to study their relationship with poor response.Results The lamivudine prolonged,the poor response to the probability gradually increase.The mutation rate in the 12nd month was 19.67％ and in the 36th month was 49.18％ ( P ＜ 0.05 ).Response to the many reasons,the YMDD mutation is the more common one.The relationship among HBVDNA load,ALT level on baseline and the rate of poor response emergence,the YMDD mutation rate was clear.By comparison in groups,the difference was significant (P＜0.05).Conclusion The lower baselins of ALT level,the higher of HBVDNA load,the greater probability of the poor response and the YMDD mutation.

Study on YMDD mutation during Lamivudine therapy of chronic hepatitis B / 临床肝胆病杂志

Objective To investigate the clinical significance of YMDD mutation during Lamivudine therapy on chronic hepatitis B.Methods Fluorometric analysis PCR, ELISA were used to estimate the YMDD mutation, HBVDNA quantative level and HBeAg for HBV of 72 cases with chronic hepatitis B before therapy (0 month), and after Lamivudine therapy for 9,12,18 months.Results The YMDD mutation was not observed in these cases before Lamivudine therapy. The mutation was found in 8 cases (11.1%), 17 cases (23.6%) and 28 cases (38.9%) at 9, 12, 18 month for therapy. The YMDD mutation rate rose with the therapy time lasting (P＜0.05). Moreover, the YmDD mutation rate in the patients with HBVDNA quantity higher than 108 copies/ml was significantly higher than that in the patients with HBVDNA quantity lower than 108 copies/ml (P＜0.005). The YMDD variation rate in patients with HBeAg positive and in patients with HBeAg negative showed no significant difference (P＞0.05). The HBeAg negative conversion rate was significantly higher in non-mutation group than that in mutation group (P＜0.05).Conclusion The serum virus quantity may be regard as an early estimate indication of the development of YMDD mutation during Lamivudine therapy.

Bicycolol tablets in treatment of patients with YMDD mutations of HBV / 中华临床感染病杂志

Objective To evaluate the clinical efficacy and safety of bicyelol tablets in treatment of hepatitis B patients infected with YMDD mutation of HBV. Methods Sixty-eight chronic hepatitis patients infected with HBV YMDD mutants and 100 patients with non-mutants HBV were enrolled in the study. All patients received bicyclol tablets orally 150 mg/d, t. i. d, for 24 weeks. Clinical symptoms, signs and adverse effects were observed, and the blood routine, liver function tests, serum HBV markers and HBV DNA loads were examined at 12th and 24th week of the study, Results After treatment for 24 weeks, the normalization rates of ALT and AST in mutant group were 79.4% ( 54/68 ) and 70. 6% (48/68) ; 11 ( 16. 2% ) patients were markedly effective and 14 (20. 6% ) were effective. Clearance rates of HBeAg and HBV DNA were 27.9% ( 17/61 ) and 17.6% ( 12/68 ), while the seroconversion rate of HBeAg was 14. 7% (9/61). The differences of the above indexes were not statistically significant between mutant group and non-mutant group. Conclusion Bicyciol can both protect liver functions and inhibit virus replication in patients infected with HBV YMDD mutants.

Efficacy of Lamivudine Therapy for Chronic Hepatitis B in Children / 대한소아소화기영양학회지

PURPOSE: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. METHODS: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. RESULTS: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13~58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p>0.05). CONCLUSION: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.

YMDD Mutation and Genotype of HBV / 中华医院感染学杂志

0.05).Genotype B with YMDD mutations in 10 samples were found,including 2 YIDD(M+I) mutations and 8 YVDD(M+V) mutations.Genotype C with YMDD mutations in 68 samples were found,including 44 mutations I(M+I) and 24 mutations V(M+V).There was significant difference in YMDD mutation types between genotypes B and C(?2=5.5,P

Clinical study on YMDD mutation and pre-core C region and core promotor region mutation of the patients with chronic hepatitis B virus receiving lamivudine therapy / 中国基层医药

Objective To mvesugate the Tate of YMDD mutation accompamed with pre-core(region and core promotor region mutation and the clinical significance.Methods YMDD mutation and pre-core(at 1896 nu- cleotide)region and core promotor region(at 1762.1764 nucleotide)mutation were detected from the 122 patients with chronic hepatitis B virus after receiving lamivudine treatment above 6 months.Results 40 cases were tested for YMDI)mutations in 122 HBV patients with lamivudine treatment,and the positive rate of YMDD mutation was 32.8 %.After YMDD mutation,ALT,AST and HBV DNA of the patients significantly increased(P0.05).Conclusion The patients with YMDD mutation had higher rate of pre-core region(at 1896 nucleotide)and basal core promotor region(at 1762, 1764 nucleotide)mutation than those without YMDD mutation,but there was no correlation between the mutation and the deterioration of disease condition and the bad prognosis.

Natural YMDD Motif Mutations of HBV Polymerase in the Chronic Hepatitis B Virus Infected Patients / 대한간학회지

BACKGROUND/AIMS: Lamivudine, a nucleoside analogue has been widely used as an effective antiviral agent for the treatment of patients with chronic hepatitis B infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine very frequently occurs after long-term use of lamivudine. It is well known that the mutation is selected by the lamivudine. We hypothesized that a few mutant strains of YMDD motif are present as quasispacies before the lamivudine treatment, are selected by the treatment, and breakthrough during treatment. We investigated the prevalence of the YMDD motif mutants in patients with chronic hepatitis B infection who had not been treated by antiviral agents before. METHODS: The study included the serums of 40 patients with chronic heptitis B infection, which stored at -70 degrees C. Thirty-four patients had chronic hepatitis and 6 patients had cirrhosis. Thirty-one patients were diagnosed by liver biopsy. The average age and range were 29 years and 13-57 years respectively. None had taken any antiviral agents before. To detect YMDD mutants, YVDD (M552V), and YIDD (M552I), we used direct sequencing and the restriction fragment length polymorphism (RFLP) method. RESULTS: The YMDD mutant was detected by RFLP method in 7.5% (3/40) of the patients with chronic hepatitis B infection, in two patients with chronic hepatitis and one with cirrhosis. All were YMDD+ YIDD mutants. CONCLUSIONS: The YMDD motif mutation occurs spontaneously without antiviral therapy in patients with chronic hepatitis B infection.

Management of hepatic HBV reinfection after liver transplantation / 中国普通外科杂志

Objective To study the effect of antivirus therapy of HBV reinfection and YMDD mutation after liver transplantation. Methods Fifteen of 317 patients with HBV-related end-stage liver diseases received lamivudine ( LAM ) monothereapy, others received combination low-dose hepatitis B immune globulin( HBIG) and LAM (or adefovir dipivoxil, ADV) therapy, as prophylaxis against HBV reinfection after OLT. Hepatitis serum markers, HBsAg, HBeAg, HBcAb-IgM, and HBcAg were detected every 2 weeks by immunohistochemistry. Serum HBV DNA was examined by PCR every 2 weeks. HBsAg and HBcAg in the liver specimens were examined by immunohistochemistry. YMDD mutation was detected by PCR in those patients with recurrence of positive HBV DNA posttransplantation. Results In LAM monotherapy group, 4 developed HBV reinfection out of 15 patients with pretreatment positve HBV DNA. Sixteen of 302 patients with combination HBIG and LAM therapy suffered from posttransplant HBV reinfection, the difference between the two groups was significant (26.7% vs. 5. 30% ,P

Cost-Effectiveness Analysis of 3 Therapeutic Schemes for Chronic Hepatitis B with YMDD Mutation / 中国药房

OBJECTIVE: To evaluate the cost-effectiveness of 3 therapeutic schemes in the treatment of chronic Hepatitis B with YMDD mutation.METHODS: 90 patients were randomly assigned into three groups: the patients in Group A were assigned to receive Adefovir Dipivoxil in combination with Lamivudine for 12 weeks followed by administration of Adefovir alone for 36 weeks;Group B received Adefovir in combination with Lamivudine for 48 weeks,while Group C received Entecavir alone for 48 weeks.The cost-effectiveness of the 3 groups were analyzed.RESULTS: In the three groups(A,B,and C),the cost-effectiveness ratios for HBV DNA negative-conversion ratewere 12 685.6,15 481.3,and 31 462.2,respectively and the incremental cost-effectiveness ratios of Group B and Group C were 29 501.5 and 106 907.8 respectively as against Group A.The cost-effectiveness ratios of the three Groups(A,B,and C) for serum alanine aminotransferase normalization rate were 12 685.6,14 284.9,31 462.2 respectively,and the incremental cost-effectiveness ratios of Group B and Group C were 19 618.5 and 106 907.8 respectively as against Group A.The cost-effectiveness ratios of the three Groups(A,B,and C) for HBeAg/HBeAb seroconversion rate were 76 227.9,93 120.3,and 209 664.0 respectively,and the incremental cost-effectiveness ratios of Group B and Group C were 178 350.0 and 1 267 621.4 respectively as against Group A.In Group A,1 case showed rtA181V mutation and another one showed rtN236T mutation after 48-week treatment.CONCLUSION: Group B(ADV in combination with LAM) is more cost-effective in the treatment of chronic hepatitis B with YMDD mutation.

The comparison of YMDD mutation results detected by direct sequencing and real-time PCR / 解放军医学杂志

Objective To compare the efficiency of detecting YMDD mutations by direct DNA sequencing and real time fluerescence PCR, and to explore the significance of the mutations of drug-resistance gene other than YMDD mutation. Methods 92 serum samples from 89 patients with chronic hepatitis B were collected and all the samples were detected by real-time PCR for YMDD mutation. HBV DNA was extracted from serum and was amplified by nest PCR to achieve HBV P gene RT region sequence. The PCR products were sequenced at both directions, and the sequencing results were contrasted through NTI program. The other 11 known drug-resistance mutation sites at the HBV RT region were also analyzed. Results Among the 37 samples with no YMDD mutation detected by real-time PCR, 33 samples were with M204M (without mutation), 1 sample with M204I and 3 samples with M204V by direct sequencing. Mutation and wild-type standard sequences were all coexisted in the 4 positive samples. There were 7 samples detected with ADV resistant mutation, accounting for 18.9% (7/37). Among the 55 samples with YMDD mutation detected by real-time PCR, 52 samples were detected by DNA sequencing, the accordance rate was 94.5% (52/55); 5 samples with ADV or ETV resistant mutation were detected, accounting for 9.1% (5/55). Conclusions Direct DNA sequencing is a high sensitive, repeatable method to detect drug-resistance mutation at RT region of HBV P gene. The result is well consistent with that attained by real-time PCR. Direct DNA sequencing can also detect various drug-resistance mutations as well as YMDD mutation, which is helpful to generally understand the nucleoside analogue resistant mutation and adopt more reasonable therapy projects against HBV.