Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France

Although risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV‐genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV‐infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti‐HCV treatment who were referred to the 26 participating centers, 8.0% had severe liver disease, 25.7% were infected with HCV‐genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV‐genotype 3 (adjusted odds ratio, multiple imputation (aOR_MI) = 1.6, [95% confidence interval, 95% CI: 1.2–2.1]), HIV infection (aOR_MI = 1.8, [1.2–2.8]), male sex (aOR_MI = 2.0, [1.4–2.8]), age over 40 years (aOR_MI = 2.1, [1.6–2.9]), history of excessive alcohol consumption (aOR_MI = 2.8, [2.1–3.7]), and duration of infection ≥18 years (aOR_MI = 2.9, [2.0–4.3]). This analysis shows that HCV‐genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption, and co‐infection with HIV. These results are in favor of earlier treatment for drug users infected with HCV‐ genotype 3 and confirm the need for concomitant care for excessive alcohol consumption. J. Med. Virol. 82:1647–1654, 2010. 2010 Wiley‐Liss, Inc.     

过氧化物酶体增殖物激活受体γ配体抑制大鼠肝纤维化的实验研究

目的 研究过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptorgamma,PPARγ)配体对大鼠肝纤维化的作用.方法 将Wistar大鼠40只随机分为两组,对照组(20只)和罗格列酮组(20只).所有动物使用饮水中加人质量比0.3‰硫代乙酰胺的方法 制作肝纤维化模型.对照组喂饲普通颗粒饲料.罗格列酮组喂饲含200 ppm罗格列酮的颗粒饲料.喂饲6个月后,用RT-PCR方法 检测肝纤维化大鼠肝脏PPARγ、TGF-β 1 及Ⅰ型前胶原mRNA表达,用Westernblot法检测PPARγ、TGF-β 1 、Ⅰ型胶原及α平滑肌肌动蛋白(α-SMA)表达,用Van Gieson(VG)染色的方法 检测肝组织切片的胶原表达情况.结果 罗格列酮组与对照组相比,PPARγmRNA表达显著增强(t=6.93,P<0.01),TGF-β 1 mRNA(t=3.89,P<0.01)和Ⅰ型前胶原mRNA表达显著降低(t=5.67,P<0.01).PPARγ、TGF-β 1 及Ⅰ型胶原蛋白表达所得结果 与RT-PCR结果 相一致.罗格列酮组与对照组相比,α-SMA表达显著降低(t=3.12,P<0.01).罗格列酮组肝组织切片的胶原染色低于对照组(t=3.47,P<0.01).结论 PPARγ配体能够抑制大鼠纤维化肝脏的胶原产生,在体内具有一定的抗肝纤维化作用.     

保肝利水汤治疗肝硬化腹水84例

目的探讨自拟方保肝利水汤治疗肝硬化腹水的临床疗效。方法168例肝硬化腹水患者,随机分为治疗组和对照组各84例,两组均给予常规综合治疗,治疗组加用保肝利水汤每日1剂,疗程1个月。结果治疗组显效率和总有效率显著优于对照组(P0.05)。结论保肝利水汤可作为治疗肝硬化腹水的一种较好选择。     

门冬氨酸和鸟氨酸联合治疗肝性脑病的疗效观察

目的观察联合使用门冬氨酸和鸟氨酸治疗各种肝硬化引起肝性脑病患者的临床疗效,探讨其对生化指标的影响。方法收集2004-08～2007-08乙肝、丙肝和酒精性肝硬化住院患者84例,住院期间均出现不同程度的肝性脑病,分为门冬氨酸和鸟氨酸治疗组与乙酰谷酰胺治疗组(各42例),治疗5～7d观察2组患者的临床表现,记录临床症状、体征的变化,检测治疗前后患者血氨和肝功能,判断临床疗效变化。结果2组患者均经过5～7d治疗后,门冬氨酸和鸟氨酸治疗组患者显效22例(52.4%),有效16例(38.1%),无效4例(9.5%),无死亡病例,总有效率为90.5%;乙酰谷酰胺治疗组患者显效16例(38.1%),有效14例(33.3%),无效8例(19.1%),死亡4例(9.5%),总有效率为71.4%。2组总有效率比较,差异有统计学意义(P<0.05)。另外,发现门冬氨酸和鸟氨酸治疗组患者的血氨水平比乙酰谷酰胺治疗组显著下降(P<0.05),而2组之间的血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰转肽酶、胆红素和凝血酶原时间均无明显变化(P>0.05)。结论降低血氨是治疗肝性脑病的重要步骤,门冬氨酸联合鸟氨酸是控制肝性脑病发生的有效药物。     

门冬氨酸和鸟氨酸联合治疗肝性脑病的疗效观察

目的观察联合使用门冬氨酸和鸟氨酸治疗各种肝硬化引起肝性脑病患者的临床疗效，探讨其对生化指标的影响。方法收集2004-08-2007-08乙肝、丙肝和酒精性肝硬化住院患者84例，住院期间均出现不同程度的肝性脑病，分为门冬氨酸和鸟氨酸治疗组与乙酰谷酰胺治疗组（各42例），治疗5～7d观察2组患者的临床表现，记录临床症状、体征的变化．检测治疗前后患者血氨和肝功能，判断临床疗效变化。结果2组患者均经过5～7d治疗后，门冬氨酸和鸟氨酸治疗组患者显效22例（52．4％）．有效16例（38．1％），无效4例（9．5％），无死亡病例，总有效率为90．5％；乙酰谷酰胺治疗组患者显效16例（38．1％），有效14例（33．3％），无效8例（19．1％），死亡4例（9．5％），总有效率为71．4％。2组总有效率比较，差异有统计学意义（P〈0．05）。另外，发现门冬氨酸和鸟氨酸治疗组患者的血氨水平比乙酰谷酰胺治疗组显著下降（P〈0．05），而2组之间的血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰转肽酶、胆红素和凝血酶原时间均无明显变化（P〉0．05）。结论降低血氨是治疗肝性脑病的重要步骤，门冬氨酸联合鸟氨酸是控制肝性脑病发生的有效药物。     

肝硬化合并自发性腹膜炎优势菌及耐药分析

目的 探讨肝硬化合并自发性细菌性腹膜炎(SBP)患者腹水感染的优势菌分布及其抗菌药物的敏感性,为临床诊断和合理用药提供可靠的依据.方法 以我院2004年3月至2009年3月诊断为肝硬化合并SBP腹水细菌培养结果阳性的84例住院患者为研究对象,对86株病原菌进行鉴定和药敏分析.结果 腹水中病原菌以大肠埃希菌检出率最高,占48.8%;其次是阴沟肠杆菌和肺炎克雷伯菌.革兰阴性杆菌对第三代头胞菌素耐药性较低,而大肠埃希菌对亚胺培南耐药率为零.结论 对SBP应加强病原菌的检测和药敏试验,并依据药敏结果合理选用抗菌药物.     

Selecting an optimal prognostic system for liver cirrhosis: the model for end‐stage liver disease and beyond

In comparison with the Child–Turcotte–Pugh (CTP) system, recent studies suggested that the model for end‐stage liver disease (MELD) may more accurately predict the survival for patients with cirrhosis. In the US, the liver allocation system was changed in 2002 from a status‐based algorithm utilizing CTP scores to one using continuous MELD severity scores as a reference system in prioritizing adult patients on the waiting list. Direct evidence that demonstrates the benefits of MELD is the fact that the mortality rates of transplant candidates on the waiting list have remarkably decreased after the implementation of the MELD. The MELD score is closely associated with the degree of portal hypertension as reflected by the hepatic venous pressure gradient. Hyponatraemia occurs as a result of advanced cirrhosis, and a serum sodium (Na) level <126 mEq/L at the time of listing for transplantation is a strong independent predictor of mortality. Several MELD‐derived prognostic models that incorporate serum Na into calculation have been proposed in the hopes of further improving the MELD's prognostic accuracy. Additionally, serum parameters such as creatinine and international normalized ratio are subject to interlaboratory variations and may need unifying standardizations. Patients with refractory complications of cirrhosis may need a priority MELD score to prioritize them on the waiting list. Appropriate modifications and the fine‐tuning of the MELD based on well‐designed prospective studies are necessary in solving the current controversial issues.     

胆酸对肝硬化大鼠肝大部分切除术后肝脏功能的影响

目的探讨胆酸对肝硬化大鼠肝切除术后肝脏功能的影响。方法24只肝硬化大鼠肝切除术后随机分为胆酸组和对照组喂养1周,每组12只。对照组给以标准饲料喂养,胆酸组给以含0.2%胆酸的饲料喂养。1周后检测大鼠胆汁分泌速度及胆汁总胆汁酸（TBA）含量,检测肝功能、有丝分裂指数（MI）、增殖细胞核抗原（PCNA）标记指数、细胞核DNA含量。结果胆酸组胆汁分泌速度、胆汁TBA含量、血清ALB含量、MI、PCNA标记指数、细胞核DNA含量均高于对照组（P〈0.01）,血清谷草转氨酶（AST）、谷丙转氨酶（ALT）含量均低于对照组（P〈0.01）。结论胆酸可以增加肝硬化大鼠肝切除术后胆汁分泌速度及胆汁TBA含量,促进大鼠肝功能恢复和肝再生。     

A method of measuring quantitative hepatic function and hemodynamics in cirrhosis: The changes following distal splenorenal shunt

Quantiative measurement is required to define the severity of chronic liver disease and the effects of therapy on its complications. This paper presents a method of such assessment based on measurement of hepatocyte function, liver volume, functional liver blood flow, portal perfusion and cardiac output. Data are presented on 54 patients evaluated prior to, and one year after DSRS for variceal bleeding. Preoperative testing showed that alcoholics (n=24) had significantly (p<0.05) larger liver and smaller spleen volumes than nonalcoholic cirrhotics (n=22) and patients with portal vein thrombosis (n=8), but that the other parameters were not significantly different by etiologies. At one year after DSRS: all groups showed a significant (p<0.01) reduction of 41 per cent in spleen size: liver volume was significantly (p<0.05) reduced in cirrhotics: there was a significantly (p<0.01) greater loss of portal perfusion in alcoholic cirrhosis: liver blood flow showd a significant (p<0.05) rise in alcoholics when compared to nonalcoholics and portal vein thrombosis patients: cardiac output ros in alcoholic cirrhosis: hepatocyte function was not significantly different in any group. This study shows that in patients all doing well clinically one year after DSRS, there are markedly different hemodynamic responses. Further studies on cirrhosis aimed at improving therapy for its complications should include some objective, quentitative assessment, first to define the study population, and second to measure the effect of the therapy.     

阿德福韦酯和恩替卡韦治疗活动性肝硬化患者48周的临床疗效观察

目的观察阿德福韦酯和恩替卡韦治疗活动性肝硬化患者48周的疗效和不良反应。方法将60例活动性肝硬化患者，随机分为阿德福韦酯组30例，给予阿德福韦酯10mg／d；恩替卡韦组30例，给予恩替卡韦0．5mg／a，观察期均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝肾功能、血清学标志物、HBVDNA、肝纤维化标志物及药物不良反应情况。结果两组患者肝功能各项指标的复常率、转阴率、HBeAg转阴率及HBeAg／抗HBe转换率均随着治疗疗程的延长而增加，但两组比较，差异无统计学意义。两组患者均未发现药物相关的肾功能损害。两组中各有2例患者出现轻度不良反应，但均能耐受。结论活动性肝硬化患者48周的抗病毒治疗，恩替卡韦的疗效与安全性均与阿德福韦酯相似，而病毒转阴率较阿德福韦酯高。