IL-28B单核苷酸多态性对武汉地区慢性丙型肝炎抗病毒疗效的影响

目的分析武汉地区慢性丙型病毒性肝炎患者的白细胞介素-28B(IL-28B)单核苷酸位点rs12979860多态性对抗病毒治疗的病毒学应答及持续病毒学应答的影响。方法对224例慢性丙型病毒性肝炎患者进行全程联合抗病毒治疗,基线水平进行了IL-28B rs12979860位点基因多态性检测,抗病毒治疗疗程为48周,治疗结束后随访24周,有179例患者完成了全部随访。结果 224例患者IL-28B rs12979860位点基因型以CC型为主占87.1%,CT型占12.9%,未发现TT型,对武汉地区224例慢性丙型肝炎患者予以PEG-IFNα-2a联合RBV治疗48周,治疗结束时病毒学应答(ETVR)率为91.9%(206例),持续病毒学应答率(SVR)为77.7%(174例),复发32例,反弹11例,无应答7例。CC型患者的SVR率明显高于CT型患者(81.0%vs.55.2%),差异有统计学意义(P<0.05)。结论我国武汉地区慢性丙型肝炎患者的IL-28B rs12979860位点基因型以CC型为主,C等位基因频率明显高于T等位基因频率,PEG-IFNα-2a联合RBV治疗慢性丙型肝炎疗效显著,其SVR率可达87.2%。IL-28B rs12979860位点CC型患者的SVR率明显高于CT型,因此宿主IL-28B位点多态性检测对抗病毒疗效的预测有一定价值,可作为丙型肝炎患者抗病毒治疗效果的预测因素之一。     

氟伐他汀治疗老年高胆固醇血症的临床研究

目的：研究氟伐他汀对老年高胆固醇血症的治疗效果并与辛伐他汀比较。方法：采用随机、单盲的方法,６８例老年高胆固醇血症患者随机分为两组,服药前及服药后４周、８周测定血脂（胆固醇、甘油三酯）,同时测血尿素氮、肌酐、ＡＬＴ、肌酸激酶和血糖。结果：治疗后４周ＴＣ分别降低了２３．２％和２２．１％;降低ＬＤＬ－Ｃ分别是２９．１％和２８．２％作用相似;氟伐他汀明显降低血清ＴＧ水平１９．２％;载脂蛋白（ＡＰＯ）Ａ１分别增加了１３．１％和１２．２％;ＡＰＯＢ水平分别下降８．１％和７．０％;分别使脂蛋白Ａ（ＬＰａ）水平降低了３１．１％和２４．０％;治疗８周后疗效与４周比较无明显差异。结论：氟伐他汀治疗老年高胆固醇血症能显著降低Ⅱａ和Ⅱｂ型高胆固醇血症患者ＴＣ、ＬＤＬ－Ｃ,其作用与辛伐他汀相等;氟伐他汀降低ＴＧ作用优于辛伐他汀。     

派罗欣联合利巴韦林治疗慢性丙型肝炎疗效对比

目的：观察聚乙二醇干扰素α-2a（派罗欣）联合利巴韦林治疗慢性丙型肝炎的疗效和安全性。方法：50例患者随机分为派罗欣联合利巴韦林组（观察组）和普通干扰素-α2a联合利巴韦林组（对照组）,比较两组的血液病毒学和生化学变化及不良反应。结果：观察组的病毒学应答率及生化学应答率均明显优于对照组（P〈0.05）,两组的不良反应相似。结论：派罗欣联合利巴韦林治疗慢性丙型肝炎具有良好的抗病毒和改善肝功能的作用。     

氟伐他汀对2型糖尿病72例血脂的影响分析

目的探讨氟伐他汀对2型糖尿病合并高脂血症的调节作用及安全性。方法 72例2型糖尿病合并高脂血症患者,在积极控制血糖基础上,每晚顿服,氟伐他汀40mg疗程8周。结果治疗8周后,血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)明显降低,高密度脂蛋白胆固醇(HDL)升高不明显。结论氟伐他汀是2型糖尿病高脂血症有效调脂药物。     

瑞舒伐他汀和阿托伐他汀对高胆固醇血症患者血浆脂蛋白相关性磷脂酶A2的影响

目的 比较瑞舒伐他汀和阿托伐他汀对高胆固醇血症惠者血浆脂蛋白相关性磷脂酶A2(LpPLA2)活性的影响.方法 本试验为随机、双盲研究.在4周治疗性生活方式改善后,符合入选标准的高胆固醇血症患者随机分入瑞舒伐他汀5 mg组(瑞舒伐他汀5 mg/d)、瑞舒伐他汀10 mg组(瑞舒伐他汀10 mg/d)和阿托伐他汀10 mg组(阿托伐他汀10 mg/d),治疗8周.药物治疗前和治疗8周后测定血清总胆固醇、血清甘油三酯、血清低密度脂蛋白胆固醇、血清高密度脂蛋白胆固醇水平以及血浆Lp-PLA2活性.结果 60例高胆固醇血症患者入选.治疗前各组血脂参数和血浆Lp-PLA2活性相似.治疗8周后,瑞舒伐他汀5 mg组、瑞舒伐他汀10 mg组和阿托伐他汀10 mg组血清低密度脂蛋白胆固醇(LDL-C)水平分别降低35%、41%和36%,血浆Lp-PLA2活性降低幅度分别为15%、17%和15%.血浆Lp-PLA2活性和血清LDL-C水平相关(r=0.507,P=0.00).结论 高胆固醇血症患者瑞舒伐他汀和阿托伐他汀治疗8周后,血浆Lp-PLA2活性均显著下降.血浆Lp-PLA2活性和血清LDL-C水平相关.     

大剂量干扰素联合利巴韦林在无应答慢性丙型肝炎患者再治疗中的应用及护理

目的观察无应答慢性丙型肝炎患者使用大剂量干扰素联合利巴韦林治疗的疗效,并总结相关护理经验。方法将2008年12月至2010年1月首都医科大学附属北京佑安医院接受治疗的无应答慢性丙肝27例患者均给予Peg—IFNα-2a270μg每周皮下注射,联合利巴韦林15mg／（kg·d）,治疗12周后改为Peg—IFNα-2a180μg每周皮下注射,联合利巴韦林15mg／（kg·d）继续治疗,总疗程72周,停药后均随访24周,观察其不良反应同时对出现的不良反应给予相应的护理。结果初始治疗无应答的慢性丙型肝炎患者接受大剂量干扰素联合利巴韦林治疗后,快速病毒学应答（RVR）率为25．9％,治疗结束时病毒学应答（ETVR）率为59．3％,病毒动力学缓慢下降。结论无应答慢性丙型肝炎患者进行大剂量干扰素联合利巴韦林治疗,并同时配和护理干预,可明显改善患者预后,对提高患者生活质量及治疗具有重要意义。     

国产苯扎贝特与氟伐他汀联合治疗混合型高脂血症的疗效与安全性

目的 研究联合应用国产苯扎贝特与氟伐他汀治疗混合型高脂血症的安全性反有效性.方法 选取180例混合性高脂血症患者随机分为两组,单药氟伐他汀组90例,给予氟伐他汀40mg,每晚1次,用药24周;联合治疗组90例,给予氟伐他汀40 mg,每晚1次,苯扎贝特200 mg,每日2次.观察24周.结果 两组均能使患者低密度脂蛋白胆固醇水平较治疗前降低,差异有统计学意义(均P<0.01),联合治疗组能够使患者甘油三酯下降,高密度脂蛋白胆固醇升高,差异亦有统计学意义(均P<0.05).结论 联合应用氟伐他汀40 mg+苯扎贝特400 mg治疗混合型高脂血症优于单用氟伐他汀治疗,并有良好的安全性.     

氟伐他汀治疗高尿酸血症肾病的临床观察

目的:探讨氟伐他汀治疗慢性尿酸性肾病的疗效及机制。方法:对46例高尿酸血症肾病患者随机分为氟伐他汀治疗组和一般治疗组,3个月后观察两组24 h尿蛋白定量、三酰甘油、血肌酐、尿素氮等指标变化。结果:经3个月治疗,氟伐他汀治疗组的24 h尿蛋白定量、三酰甘油明显下降,两组间差异有统计学意义。肌酐、尿素氮虽均有下降,但差异无统计学意义。结论:氟伐他汀能明显减少慢性高尿酸血症患者尿蛋白排出,同时降低三酰甘油和肌酐、尿素氮,有助于减轻高尿酸血症肾病的肾损害。     

氟伐他汀钠胶囊治疗冠心病合并高血脂58例分析

目的探讨氟伐他汀在冠心病合并高血脂治疗中的疗效。方法对冠心病伴高血脂58例给予氟伐他汀治疗,观察并比较患者服药前后血脂变化情况。结果 58例患者治疗后总胆固醇水平下降为(5.2±0.8)mmol/L;甘油三酯水平下降为(2.1±0.9)mmol/L,均较治疗前显著改善(P<0.05)。氟伐他汀对总胆固醇的总有效率为91.4%,对甘油三酯的总有效率为77.6%。结论氟伐他汀降低冠心病合并高血脂患者总胆固醇、甘油三酯水平疗效明显,应用安全,值得临床应用。     

氟伐他汀降肾病高脂血症疗效观察

目的：探讨氟伐他汀对肾病综合征高脂血症的疗效及其副作用和对肝、肾功能的影响。方法检测住院患者６０例应用氟伐他汀为治疗组,４０例应用藻酸双脂钠为对照组,治疗时间为６周。两组治疗前后均查总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、肌酐、尿素氮及转氨酶,采用ｔ检验。结果 治疗组应用氟伐他汀（４０ｍｇ／ｄ）后可显著降低高胆固醇及混合性高脂血症,与对照组相比,Ｐ〈０．０１。结论 氟伐他汀对肾     

Prediction of treatment outcome in chronic hepatitis C patients based on early viral dynamics during high-dose induction interferon and ribavirin therapy

OBJECTIVE: In chronic hepatitis C, early viral load decline after interferon administration is dose dependent and reflects the intrinsic viral susceptibility to the antiviral action of interferon. We examined whether the augmented suppression of susceptible viral loads by high-dose induction interferon could possibly discriminate responsive patients from non-responsive patients at an early stage of treatment. METHODS: Fifty-nine chronic hepatitis C patients were randomly allocated to receive one of two treatment regimens; 3 MU interferon three times weekly plus ribavirin 1,000 mg/day for 24 weeks in the CR group (n = 30), and the same regimen as in the CR group except 10 MU interferon daily for the first week in the HR group (n = 29). Changes in viral loads during the first week of treatment were analyzed in terms of sustained virological response (SVR). RESULTS: The positive predictive values of undetectable (<100 IU/ml) or low serum HCV RNA (<2,000 IU/ml) after 1 week of treatment for SVR were 100% in both treatment groups, whereas the negative predictive values of the low viral titer were 91% in the HR group and 70% in the CR group. CONCLUSION: One-week virological response to high-dose induction interferon/ribavirin combination therapy is more predictive of SVR than conventional combination therapy in chronic hepatitis C.     

Treatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon alpha2a (40 kda; PEGASYS)

BACKGROUND: Although nucleot(s)ide analogues can effectively suppress hepatitis B virus (HBV) replication, many patients experience relapse of hepatitis after cessation of treatment. We aimed to investigate the efficacy of pegylated interferon alpha2a (PEG-IFN-alpha2a) in these difficult-to-treat patients. METHODS: Chronic hepatitis B patients who have received antiviral drugs for > or =12 months and stopped for > or =6 months were treated by 48-week PEG-IFN-alpha2a. Virological response was defined as HBV DNA <10,000 copies/ml and hepatitis B e antigen (HBeAg) seroconversion (for HBeAg-positive patients). RESULTS: A total of 40 patients, 29 HBeAg-positive and 11 HBeAg-negative, with median log10 HBV DNA 7.3 copies/ml and alanine aminotransferase 110 IU/ml were studied. The last antiviral treatment was given for 92 +/- 61 weeks and stopped for 176 +/- 88 weeks. At the end of treatment, 22 (12 HBeAg-positive and 10 HBeAg-negative; 55%) patients had virological response and 16 (7 HBeAg-positive and 9 HBeAg-negative; 40%) patients had undetectable HBV DNA (<100 copies/ml). At 24 weeks post-treatment, 14 (8 HBeAg-positive and 6 HBeAg-negative; 35%) patients had virological response and 9 (5 HBeAg-positive and 4 HBeAg-negative; 23%) patients had undetectable HBV DNA. Two (5%) patients had lost hepatitis B surface antigen. HBV DNA levels at week 24 best predicted sustained virological response (area under curve 0.76, 95% confidence interval 0.60-0.92, P=0.007). At HBV DNA cutoffs of 3 logs and 5 logs at week 24, the sensitivity/specificity for sustained virological response were 50%/85% and 86%/62%, respectively. CONCLUSIONS: PEG-IFN-alpha2a was effective in the treatment of chronic hepatitis B patients who have failed previous antiviral treatment.     

恩替卡韦与替比夫定对治疗HBeAg阳性慢性乙型肝炎患者疗效及预测因素分析

目的 观察恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎（CHB）患者的疗效及预测因素分析. 方法 将159例HBeAg阳性的CHB患者分为恩替卡韦分组（ETV组,81例）和替比夫定组（LDT组,78例）.治疗72周后,观察两组的应答情况[生化学应答率（丙氨酸转氨酶转复率）、完全病毒学应答率（HBV-DNA阴转率）、血清学应答率（HBeAg阴转率及HBeAg血清学转换率）],并且分析在治疗24周HBV-DNA转阴情况对72周疗效的预测影响.结果 两组患者治疗后各时间段的生化学应答率比较均无统计学意义（P均＞0.05）.治疗4周后ETV组和LDT组的HBV-DNA值与治疗前比较差异均具有统计学意义（P均＜0.05）,且治疗24周后ETV组的HBV-DNA值明显低于LDT组（P＜0.05）,但治疗72周后比较两组患者的完全病毒学应答率比较差异不具有统计学意义（P均＞0.05）.治疗各时间点ETV组比LDT组有着更高的血清学应答率,但差异不具有统计学意义（P均＞0.05）.治疗24周HBV-DNA转阴（HBV-DNA＜3lg拷贝/ml）的患者,72周具有更高的生化学应答率及血清学应答率（P均＜0.05）.结论 恩替卡韦与替比夫定对治疗CHB具有很好的疗效及较低的耐药率和不良反应,恩替卡韦在早期抗HBV-DNA优于替比夫定片,且治疗24周的HBV-DNA水平可预测长期疗效.     

Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+ T cells following antiviral treatment of chronic hepatitis B

An increased CD8(+) T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8(+) T cells at these time points predict the virological response to therapy. Peripheral blood CD8(+) T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) β chain variable region (Vβ) gene family was analyzed, and the changes in the numbers of Vβ families with clonal expansions were compared in subjects with (n = 12) and without (n = 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8(+) TCR Vβ families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus -1 [-3 to +4], P = 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P < 0.0001) in responders. Increased numbers of CD8(+) T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8(+) T cells are a potential target for a therapeutic vaccine for chronic hepatitis B.     

2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C

OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS: The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS: The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS: These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.     

Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals

BACKGROUND: Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS: Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. RESULTS: Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. CONCLUSIONS: Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.     

拉米夫定联合阿德福韦酯治疗乙肝肝硬化疗效观察

目的探讨拉米夫定联合阿德福韦酯治疗乙肝肝硬化的疗效、安全性、耐药性。方法选择乙肝肝硬化患者78例,随机分为2组。治疗组31例,口服拉米夫定联合阿德福韦酯各1片;对照组47例,单用拉米夫定或单用阿德福韦酯治疗。均治疗24-48周。结果治疗组治疗12、24个月时病毒学应答、治疗12个月时生化学应答与对照组比较均有显著性差异（均P〈0．01）,未发现严重的不良反应。结论拉米夫定联合阿德福韦酯治疗乙肝肝硬化,不易产生耐药性,并可起互补作用,患者能长期稳定病情。     

Early antiviral treatment of hepatitis C virus recurrence after liver transplantation in HIV-infected patients

OBJECTIVE: To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. METHODS: Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100cells/microl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-alpha2b (1.5 microg/kg/week) and ribavirin (800-1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. RESULTS: Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on antiviral treatment a median of 12 weeks (range: 5-31) after transplantation. After a median follow-up of 24 months all treated patients were alive. Biochemical response was achieved in all patients, although only one achieved a sustained virological response. Mild rejection before HCV recurrence occurred in two cases. Treatment was well tolerated with no episodes of rejection or mitochondrial toxicity. No patient required modification of the antiretroviral regimen. Liver biopsies performed in patients without virological response, 12-34 months after transplantation, showed cirrhosis in two and moderate chronic active hepatitis in the remainder. CONCLUSIONS: Despite early antiviral treatment, severe HCV recurrence after liver transplantation may compromise long-term survival in HIV-infected patients. Improved treatment strategies for these patients are urgently required.     

Abbott RealTime PCR assay is useful for evaluating virological response to antiviral treatment for chronic hepatitis C

This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24 weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r = 0.595, P < 0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24 weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C.     

Lipid-lowering response of the HMG-CoA reductase inhibitor fluvastatin is influenced by polymorphisms in the low-density lipoprotein receptor gene in Brazilian patients with primary hypercholesterolemia

Although the efficacy of fluvastatin (HMG-CoA reductase inhibitor) in the treatment of primary hypercholesterolemia is well documented, a wide interindividual variation treatment response has been observed. We have studied the possible role of the AvaII (exon 13), HincII (exon 12), and PvuII (intron 15) polymorphisms at the low-density lipoprotein receptor (LDLR) gene on lipid-lowering response in 55 patients (36 to 70 years old) with primary hypercholesterolemia treated with fluvastatin for 16 weeks. LDLR genotypes were determined by PCR-RFLP. The results indicate that the AvaII and PvuII polymorphisms influence the cholesterol-lowering response of the HMG-CoA reductase inhibitor Fluvastatin. Patients carrying A+A+ (AvaII) or P1P1 (PvuII) homozygous genotypes presented lower reduction in total cholesterol, LDL-C and apolipoprotein B levels after 16 weeks of treatment with fluvastatin, when compared to other genotypes (P<0.05). Our data also support the previous assumption that the AvaII, HincII, and PvuII polymorphisms of the LDLR gene are associated with variation of serum cholesterol levels. Therefore, the identification of the LDLR genetic profile may provide better prediction of a patient's clinical response to fluvastatin.