Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B

AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis B.METHODS:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited.PKTD was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal hypouricemia.The single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration Kit.RESULTS:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic osteomalacia.Among the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without PKTD.The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration.In contrast,the SNPs were not correlated with PKTD.Logistic regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with PKTD.CONCLUSION:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.

Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients

AIM:To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate(YMDD) mutants(reverse transcription;rtM204I/V) and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus(HBV) infection.METHODS:The data of 61 consecutive Japanese patients with chronic hepatitis B who underwent continuous lamivudine treatment for more than 24 mo and had a virological response were analyzed.Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo(mean,50.8 mo;range,24-90 mo).RESULTS:A mixed mutant-type(YMDD + tyrosine-isoleucine-asparatate-asparatate:YIDD or tyrosine-valineasparatate-asparatate:YVDD) or a mutant-type(YIDD or YVDD) were found in 57.4% of 61 patients at 1 year,78.7% of 61 patients at 2 years,79.6% of 49 patients at 3 years,70.5% of 34 patients at 4 years,68.4% of 19 patients at 5 years,57.1% of 14 patients at 6 years,and 33.3% of 6 patients at 7 years.Of the 61 patients,56(92%) had mixed mutant-or a mutant-type.Only 5(8%) had no mutants at each observation point.Virological breakthrough was found in 26(46.4%) of 56 patients with YMDD mutants,20 of whom had a hepatitis flare-up:the remaining 30(53.6%) had neither a virological breakthrough nor a flare-up.All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment.CONCLUSION:Our results suggest that it is possible to continue lamivudine treatment,even after the emergence of YMDD mutants,up to the time that the patients develop a hepatitis flare-up.

Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients

AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.

Biologically inspired self-organizing networks

Information networks are becoming more and more complex to accommodate a continuously increasing amount of traffic and networked devices,as well as having to cope with a growing diversity of operating environments and applications. Therefore,it is foreseeable that future information networks will frequently face unexpected problems,some of which could lead to the complete collapse of a network. To tackle this problem,recent attempts have been made to design novel network architectures which achieve a high level of scalability,adaptability,and robustness by taking inspiration from self-organizing biological systems. The objective of this paper is to discuss biologically inspired networking technologies.

Long-term lamivudine treatment for chronic,hepatitis B in Japanese patients:A project of Kyushu University Liver Disease Study

瞄准：与长期的肝炎 B 决定很多日本病人的长期的 lamivudine 治疗的功效。方法：在这回顾，多中心试用，有长期的肝炎 B 的 318 个日本病人每天为多达 36 收到了 lamivudine 的 100 mg (中部 21 ) 瞬间。Virological 反应是到浆液 HBV DNA 水平的衰落不到 3.7 木头 copies/mL。当浆液 HBV DNA 的再现在 treatment.RESULTS 期间铺平最小到超过 10 褶层， Virological 突破被定义：Lamivudine 在 6 瞬间在 318 个病人中的 86.8% 个生产了 virological 反应，在在 12 瞬间的 252 个病人中的 80.2% 个，在在 24 瞬间的 133 个病人中的 69.2% 个，并且在在 36 瞬间的 28 个病人中的 53.6% 个。向前逐步的逻辑回归分析证明 HBV DNA 铺平不到 6.8 木头 copies/mL ( P【0.0001 )， HBeAg 否定性( P【0.0001 )， 100 x 10 的一个血小板计数( 9 )在基线的 /L 或更多( P=0.0162 )，并且超过 3.2 木头 copies/mL 的 HBV DNA 水平的衰落在治疗( P=0.0003 )的开始以后在 3 瞬间作为与基线相比铺平显著地与 virological 反应被联系。在有 virological 回答的病人之中， virological 突破在在 1 瞬间 virologically 反应了的 19 个病人中的5.3%个被看见，在在 3 瞬间的 203 个病人中的20.7%个，在在 6 瞬间的 51 个病人中的27.5%个，在在 9 瞬间的 12 个病人中的33.3%个，并且在在 】=5 瞬间的 3 个病人的100%。virological 突破与推迟的 virological response.CONCLUSION 在病人更经常显著地被发现：Lamivudine 治疗能在大多数测试日本病人压制浆液 HBV DNA。没有 HBeAg，长期的功效可能在基线在病人被看见，当肝硬化不在时，并且在有在 HBV 的衰落的病人， DNA 此后不久铺平治疗的开始。