Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation

AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutationssuffer from increased rates of liver fi brosis. METHODS: We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fi-brosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. RESULTS: Fifty two of the patients were categorized as "fast fi brosers" and 116 as "slow fi brosers"; 13% of the "fast fi brosers" carried the PT20210 mutation as compared with 5.5% of the "slow fi brosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fi brosis. CONCLUSION: Carriage of the PT20210 mutation is related to an increased rate of liver fi brosis in HCV patients.

Prevalence of factor V Leiden and prothrombin G20210A in patients with gastric cancer

AIM： To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrombin G20210A, in patients with gastric cancer. METHODS： One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects, comparable for age and sex, were investigated. Factor V Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR. RESULTS： Among the 121 cancer patients, factor V Leiden was found in 4 cases （GA genotype： 3.3%） and prothrombin G20210A in 10 cases （GA genotype： 8.3%）. Of the 130 control subjects, factor V Leiden was detected in 6 cases （GA genotype： 4.6%） and prothrombin G20210A in 8 cases （GA genotype： 6.1%）. No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor V Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects. CONCLUSION： Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.

Effect of heparin on recurrent IVF-ET failure patients

Objective:To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer(IVF-ET)and thrombophilia.Methods:This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures.Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)with a record of three or more previous IVF-ET failures.Participants were randomly distributed into two groups.Group A(n=43)received unfractionated heparin 5000 IU twice daily,and group B(n=43)did not take any antithrombotic drugs.Coagulation abnormalities such as factor桋Leiden(FVL)mutation,methylene tetra hydro folate reductase(MTHFR)mutation and prothrombin mutation(F栻)were evaluated.Age,body mass index,basal follicular stimulating hormone,basal estradiol,duration of infertility,and number of IVF-ET failures were compared between two groups.Results:45.0%and 17.4%of women were pregnant with and without MTHFR and prothrombin mutation,respectively,when they received unfractionated heparin treatment.The implantation rate was more in group A(12.5%)than group B(4.3%)and differences in the fertilization rate of the two groups were observed(27.7%vs.35.9%).The clinical pregnancy rate per cycle was remarkably more in group A(30.2%)than group B(14.0%).Conclusions:Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures.The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group.

凝血酶原基因突变与血栓形成的关系

目的 探讨中国人群血栓形成性疾病患者和正常人凝血酶原基因 2 0 2 10G→A突变的发生率以及该突变与中国人群血栓形成的关系。方法 采用聚合酶链反应———限制性片段长度多态性(PCR RFLP)分析方法 ,对 80例血栓性疾病患者和 80例对照者进行凝血酶原基因 2 0 2 10G→A突变分析。结果 80例患者和 80例对照者中均未发现该突变。结论 凝血酶原基因 2 0 2 10G→A突变不是中国人群血栓形成性疾病的危险因子 ,中国人群中凝血酶原 2 0 2 10A等位基因频率极低。

PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis

AIM To evaluate the different roles of thrombophiliain patients with and without viral etiology. The thrombophilicgenetic factors （THRGFs）, PAI-1 4G-4G, MTHFR677TT, V Leiden 506Q and prothrombin 20210A,were studied as risk factors in 1079 patients with livercirrhosis （LC）, enrolled from January 2000 to January2014.METHODS： All Caucasian LC patients consecutivelyobserved in a seven year period were included; thepresence of portal vein thrombosis （PVT） and BuddChiari syndrome （BCS） was registered. The differencesbetween the proportions of each THRGF with regardto the presence or absence of viral etiology and thefrequencies of the THRGF genotypes with those predictedin a population by the Hardy-Weinberg equilibriumwere registered.RESULTS： Four hundred and seventeen/one thousandand seventy-six patients （38.6%） showed thrombophilia：217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leidenfactor and 41 prothrombin G20210 A, 84 with morethan 1 THRGF; 350 presented with no viral liver cirrhosis（NVLC） and 729 with, called viral liver cirrhosis （VLC）,of whom 56 patients were hepatitis C virus ＋ hepatitisB virus. PAI-1 4G-4G, MTHFR C677TT, the presence ofat least one TRHGF and the presence of 〉 1 THRGF,were statistically more frequent in patients with NVLC vspatients with VLC： All χ 2 〉 3.85 and P 〈 0.05. Patientswith PVT and/or BCS with at least one TRHGF were189/352 （53.7%）. The Hardy-Weinberg of PAI-1 andMTHFR 677 genotypes deviated from that expectedfrom a population in equilibrium in patients with NVLC（respectively χ 2 = 39.3; P 〈 0.000 and χ 2 = 27.94; P 〈0.05）, whereas the equilibrium was respected in VLC.CONCLUSION： MTHFR 677TT was nearly twofold andPAI-1 4G-4G more than threefold more frequently foundin NVLC vs patients with VLC; the Hardy-Weinbergequilibrium of these two polymorphisms confirms thisdata in NVLC. We suggest that PAI-1 4G-4G and MTHFR677TT could be considered as factors of fibrosis andthrombosis mechanisms, increasing the inflammationresponse, and causing the hepatic fibrosis and augmentedintrahepatic vascular resistance typical of LC. PAI-14G-4G and MTHFR 677TT screening of LC patientscould be useful, mainly in those with NVLC, to identifypatients in which new drug therapies based on theattenuation of the hepatic stellate cells activation orother mechanisms could be more easily evaluated.