中西医结合治疗慢性乙型肝炎临床观察

目的：运用中西医结合方法治疗慢性乙型肝炎。方法：对102例慢性乙肝患者,采用随机分组形式,分为中药组,西药组,中西医结合组,分别予中药复方汤剂加减,西药拉米夫定及两者结合治疗,并分别对肝功能及HBV病毒复制及半年后复发情况进行临床观察。结果：中西医结合组在肝功恢复正常及HBV病毒复制上明显优于中药组及西药组。结论：中西医结合治疗慢性乙型肝炎不仅可以迅速使肝功能恢复正常,同时可以降低患者血中的含量,使HBeAg及HBV-DNA转阴率提高。     

双虎清肝颗粒与胸腺五肽注射液联合治疗慢性乙型肝炎192例的体会

目的中西医结合治疗慢性乙型肝炎的临床体会。方法中西医结合,清热解毒,清除乙肝病毒。调节机体免疫,口服双虎清肝颗粒,双侧足三里穴位注射胸腺五肽各0．5mg。结果192例经治疗4周有效率85．42％,8周有效率86．98％,12周总有效率91．15％。结论中西药联合治疗慢性乙型肝炎效果满意。     

慢性乙型肝炎的中医证型分布特点观察分析

目的研究慢性乙型肝炎中医证型分布特点以及中医证型与理化检查指标的关系。方法回顾性分析整理慢性乙型肝炎住院患者的中医诊断及中医证型占比例,观察慢性乙型肝炎中医证型分布特点;对中医证型与肝功能主要指标进行对比分析。结果慢性乙型肝炎最常见中医诊断为湿阻、占47%,其次主要为胁痛(32.5%)和黄疸(11.6%),中医证型以肝胆湿热证最多、占54.4%,其次为肝郁脾虚证(22.4%)和脾肾阳虚证(17.2%)。肝胆湿热证患者肝功能ALT和AST水平最高,TBIL水平则以肝肾阴虚证最高。结论慢性乙型肝炎中医证型以肝胆湿热证最常见,且中医证型与肝功能指标变化有明显相关性。     

慢性乙型肝炎中医证型与拉米夫丁应答的关系

目的:评价慢性乙型肝炎不同的中医辩证分型与拉米夫丁抗病毒效应的关系。方法:选择慢性乙型肝炎84例,按中医辨证分肝胆湿热42例、肝郁脾虚42例。两组均以拉米夫丁100mg,qd,口服观察用药后第1、2、4、,8、12、52周病人血清乙肝两对半定性和HBV-DNA定量。结果:治疗12周后肝胆湿热、肝郁脾虚两组的HBV-DNA累计阴转率分别为90.6%和71.9%,治疗52周后两组的HBeAg阴转率分别为肝胆湿热65.6%、肝郁脾虚40.6%,P<0.05。HBeAg/抗HBe转换率分别为肝胆湿热34.4%、肝郁脾虚15.6%,P<0.05。结论:慢性乙型肝炎不同的中医辩证分型与拉米夫丁抗病毒效应有一定的相关性。     

复方中药治疗慢性病毒性肝炎肝纤维化的Meta分析

目的:对中药方剂治疗慢性病毒性肝炎肝纤维化的有效性进行评价。方法:检索35年内文献(截止2011年)。将复方中药与对照组(抗病毒或保肝药)的随机临床试验纳入本研究。制定文献纳入标准和文献排除标准。采用Cochrane系统评价员手册和Jadad质量记分法对文献进行质量评价。分析指标为计数资料,用相对危险度(RR)及其95%可信区间(95%C I)表示。结果:共纳入5个临床随机对照试验。慢性病毒性肝炎肝纤维化或代偿期肝硬化共计359例。复方中药在改善肝纤维化与对照组比较合并效应量RR=2.03,95%C I(1.52,2.72),P<0.00001。无不良反应。结论:复方中药有明显的改善肝纤维化(S分期)作用,未见不良反应的报道。     

Looking beyond highly active antiretroviral therapy: drug-related hepatotoxicity in patients with human immunodeficiency virus infection

Management of human immunodeficiency virus (HIV) has become increasingly complex since the introduction of highly active antiretroviral therapy (HAART). Patients with HIV have become exposed to an increasing array of drugs to treat HIV, prevent opportunistic infections and immune dysfunction, and manage comorbid illnesses and therapeutic complications. Hepatic complications have become common and may lead to discontinuation of treatment and significant morbidity. Up to 90% of patients with acquired immunodeficiency syndrome (AIDS) receive at least one drug that can cause hepatotoxicity. Clinicians treating patients with HIV frequently face difficulty distinguishing abnormal liver transaminase levels and toxicities in patients receiving several drugs. Some potential causes of hepatic dysfunction are viral infections, alcohol and substance abuse, and hepatotoxic drugs such as HAART. Recent reports have focused on the hepatotoxicity of HAART and the role of hepatitis viruses to the exclusion of many other agents prescribed for patients with HIV. Many of the common antibiotics, antifungals, antivirals, and ancillary agents prescribed for patients with HIV are independently associated with hepatotoxicity. Clinicians should be aware of the potential non-antiretroviral hepatotoxic agents that are frequently administered in HIV management.     

Duloxetine hepatotoxicity: a case‐series from the drug‐induced liver injury network

Aliment Pharmacol Ther 2010; 32: 1174–1183

Summary

Background Case reports suggest that duloxetine hepatotoxicity may arise, but risk factors, presenting features and clinical course are not well‐described. Aim To describe the presenting features and outcomes of seven well‐characterized patients with suspected duloxetine hepatotoxicity. Methods Patients enrolled in the Drug‐Induced Liver Injury Network Prospective Study underwent an extensive laboratory and clinical evaluation to exclude competing aetiologies of liver injury as well as a standardized assessment for causality and disease severity. Results Between 1/2006 and 9/2009, six of the seven cases of DILI attributed to duloxetine were assessed as definite or very likely. Median patient age was 49 years, six (86%) were women and the median latency from drug initiation to DILI onset was 50 days. Six patients developed jaundice and the median peak alanine aminotransferase in the five patients with acute hepatocellular injury was 1633 IU/L. Ascites developed in one patient and acute renal dysfunction in two others (29%). All patients recovered without liver transplantation even though three had pre‐existing chronic liver disease. Liver histology in four cases demonstrated varying patterns of liver injury. Conclusions Duloxetine hepatotoxicity developed within 2 months of drug intake and led to clinically significant liver injury. A spectrum of laboratory, histological and extra‐hepatic features were noted at presentation.     

中药配合双环醇治疗慢性乙型肝炎57例疗效观察

目的观察中西结合治疗慢性乙型肝炎患者的近、远期疗效。方法将100例慢性乙型肝炎患者随机分为治疗组57例、对照组43例，治疗组服用中药加双环醇片，对照组服用双环醇片，治疗12个月，于治疗前、中、后及停药6个月后检测肝功能及乙肝病毒标志物的变化。结果治疗结束后，两组均能明显改善患者血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、γ-谷氨酰氨基转肽酶（GGT）、白蛋白（A）、球蛋白（G）、总胆红素（TBiL），其中治疗组升高白蛋白、降低球蛋白的作用优于对照组（P〈0．05）。停药6个月后，治疗组在改善ALT、A、G、TBiL方面优于对照组（P〈0．05）；治疗结束后，治疗组HBV-DNA阴转率优于对照组（P〈0．05）。停药6个月后，治疗组（43．9％）与对照组（23．2％）的HBV-DNA阴转率差异有统计学意义，对照组的反跳率（3／43）明显高于治疗组（0）。结论中药加双环醇可降低慢性乙型肝炎患者HBV-DNA含量，改善肝功能，近、远期疗效优于单用双环醇片。     

核苷(酸)类抗肝炎药物对慢性乙型肝炎住院患者肝肾功能的影响

目的：分析核苷（酸）类抗肝炎药物（NAs）对慢性乙型肝炎患者肝肾功能的影响,为临床合理用药提供参考。方法：综合应用某院临床药学管理系统（PASS PharmAssist）、病案质控监测系统和中国医院药物警戒系统检索病历,回顾性分析某院2017年1月至2018年6月因患慢性乙型肝炎而采用NAs药物治疗的患者病例。利用SPSS 23.0软件,采用正态分布、t检验、卡方检验进行单因素分析,把符合单因素分析（P<0.05）的协变量纳入二元logistic分析,以考察多种协变量对NAs药物诱导患者肝肾功能变化的影响。结果：收集到因患慢性乙型肝炎而服用抗肝炎药物的患者病例116份,其中包括男性79例（68.1%）,女性37例（31.9%）,肝功能正常者65例,慢性肝功能不全者51例。在肝功能不全组,NAs药物性肝损加重发生率为17.65%（9/51）,时间为用药后4~13 d;在肝功能正常组,NAs药物性肝损伤发生率为4.61%（3/65）,时间为用药后15~19 d。此外,研究表明NAs药物对肝脏的安全性为恩替卡韦 > 拉米夫定 > 阿德福韦酯 > 替比夫定 > NAs药物联用。在116例患者中肾功能正常者74例,慢性肾功能不全者42例,在肾功能不全组发现患者因服用NAs药物导致血清肌酐升高发生率为14.29%（6/42）,时间为用药后2~10 d,在肾功能正常组未发现NAs药物性肾损伤者。此外,研究表明NAs药物对肾脏的安全性为：NAs药物联用,拉米夫定,阿德福韦酯 > 恩替卡韦 > 替比夫定,相关因素分析表明NAs药物性肝损伤的发生与患者的肝功能不全（OR=5.344,95% CI：1.349-21.167）（P=0.017）有关。结论：NAs药物对患者肝功能和肾功能确实有影响,主要发生在肝功能不全患者身上,但对肝功能正常的患者影响较小。此外,核苷（酸）类抗肝炎药物中拉米夫定对肝脏和肾脏的安全性相对较高。研究结果提示临床在治疗肝功能不全的患者时,应注意调整NAs药物品种或给药剂量并监测患者肝功能指标变化,以确保用药安全。     

Lamivudine. A review of its therapeutic potential in chronic hepatitis B.

Lamivudine is a deoxycytidine analogue that is active against hepatitis B virus (HBV). In patients with chronic hepatitis B, lamivudine profoundly suppresses HBV replication. Clinically significant improvements in liver histology and biochemical parameters were obtained with lamivudine in double-blind, randomised, trials in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B and compensated liver disease. After 52 weeks of treatment, relative to placebo (< or = 25%), significantly more Chinese (56%) or Western patients (52%) treated with lamivudine 100 mg/day had reductions of > or = 2 or more points in Knodell necro-inflammatory scores. Moreover, significantly fewer lamivudine 100 mg/day than placebo recipients had progressive fibrosis in liver biopsies (< or = 5 vs > or = 15%) and fewer lamivudine- than placebo-treated patients progressed to cirrhosis (1.8 vs 7.1%). More lamivudine 100 mg/day than placebo recipients acquired antibodies to HBeAg after 52 weeks (16 vs 4% in Chinese patients and 17 vs 6% in Western patients). ALT levels normalised in significantly more lamivudine than placebo recipients enrolled in these trials. In HBeAg-negative, HBV DNA positive patients with compensated liver disease enrolled in a double-blind, randomised study, HBV DNA levels were suppressed to below the limit of detection (< 2.5 pg/ml) and ALT levels normalised in 63% and 6% of patients treated with lamivudine 100 mg/day or placebo for 24 weeks. Clinically significant improvements in liver histology were obtained in 60% of patients treated with lamivudine for 52 weeks in this study. Lamivudine 100 mg/day for 52 weeks produced similar or significantly greater improvements in liver histology and ALT levels than 24 weeks' treatment with lamivudine plus interferon-alpha. In liver transplant candidates with chronic hepatitis B and end-stage liver disease, lamivudine 100 mg/day alone, or in combination with hepatitis B immune globulin, generally suppressed HBV replication and appeared to protect the grafted liver from reinfection. Lamivudine 100 mg/day suppressed viral replication and improved liver histology in liver transplant recipients with recurrent or de novo chronic hepatitis B. Lamivudine 300 or 600 mg/day reduced HBV replication in HIV-positive patients. The incidence of adverse events in patients with chronic hepatitis B and compensated liver disease treated with lamivudine 100 mg/day or placebo for 52 to 68 weeks was similar. 3.1- to 10-fold increases in ALT over baseline occurred in 13% of patients during treatment with lamivudine 100 mg/day or placebo for 52 weeks. Post-treatment ALT elevations were more common in lamivudine than placebo recipients; however, these generally resolved spontaneously; < or = 1.5% of lamivudine- or placebo-treated patients experienced hepatic decompensation. CONCLUSION: Lamivudine inhibits HBV replication, reduces hepatic necro-inflammatory activity and the progression of fibrosis in patients with chronic hepatitis B, ongoing viral replication and compensated liver disease including HBeAg-negative patients. The drug also suppresses viral replication in liver transplant recipients and HIV-positive patients. Thus, lamivudine is potentially useful in a wide range of patients with chronic hepatitis B and ongoing viral replication.     

评价中医通络消癥汤治疗乙肝肝硬化代偿期肝郁脾虚夹瘀证的临床疗效

目的:分析对乙肝肝硬化代偿期肝郁脾虚夹瘀证患者采用中医通络消癥汤的疗效。方法:选择我院2017年8月至2018年8月收治90例乙肝肝硬化患者,随机分甲组(45例)常规西药抗病毒疗法,乙组(45例)中医通络消癥汤疗法。对比两组疗效。结果:乙组疗效优于甲组,P<0.05。结论:针对乙肝肝硬化代偿期肝郁脾虚夹瘀证患者采取络消癥汤治疗,效果显著,临床上值得推广及应用。     

Adefovir dipivoxil: a review of its use in chronic hepatitis B

Adefovir dipivoxil (Hepsera) is an oral prodrug of the nucleotide analogue adefovir. It is indicated for the treatment of chronic hepatitis B in adults. Adefovir dipivoxil 10 mg/day significantly improved histological, biochemical and virological outcomes in hepatitis B e antigen (HBeAg)-positive and -negative patients, and serological outcomes in HBeAg-positive patients. In two trials, the proportion of adefovir dipivoxil recipients showing histological improvement in the liver was approximately twice that for placebo recipients. In two trials in patients chronically infected with lamivudine-resistant hepatitis B virus (HBV), switching to or adding adefovir dipivoxil was significantly more effective at reducing serum HBV DNA levels than continuing lamivudine monotherapy. In treatment-naive patients, 1 year's treatment with adefovir dipivoxil plus lamivudine had similar efficacy to lamivudine plus placebo; however, lamivudine-resistant HBV emerged in significantly more patients receiving lamivudine plus placebo. Adefovir dipivoxil has also shown efficacy in noncomparative trials in patients with decompensated liver disease, patients co-infected with HIV and patients pre- or post-liver transplantation. Within 96 weeks of treatment with adefovir dipivoxil, a resistance-conferring mutation emerged in viral isolates from 1.6% of patients. In vitro, these isolates remained sensitive to lamivudine, while lamivudine-resistant HBV isolates remained sensitive to adefovir dipivoxil. Adefovir dipivoxil 10 mg/day is generally well tolerated. In a pooled analysis of 48-week data from two trials, there was no marked difference in adverse events or laboratory abnormalities between adefovir dipivoxil and placebo recipients. Within 96 weeks of treatment with adefovir dipivoxil, >1% of patients with adequate renal function developed an increase in serum creatinine levels of >/=0.5 mg/dL above baseline. Within 48 weeks of treatment, increases in serum creatinine levels of >/=0.5 mg/dL above baseline were observed in 13% of pre- and post-liver transplantation patients who generally had renal insufficiency or risk factors for renal dysfunction at baseline. Most patients continued treatment with dosage adjustments. CONCLUSION: Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV. Few resistant HBV mutants have emerged to date. Data from ongoing long-term studies are awaited with interest. Existing treatment options for patients with chronic hepatitis B are limited in both number and effectiveness; the proven efficacy, good tolerability profile and apparently low potential for resistance of adefovir dipivoxil make it a promising new option in the management of this disease.     

慢性前列腺炎致不育症的中西医结合治疗

目的:探讨慢性前列腺炎与不育症的关系及中西医治疗的临床疗效。方法:所有病例均为慢性前列腺炎肾虚湿热瘀阻型患者,服用中药补肾活血汤,结合西医抗生素治疗,观察治疗前后精液、前列腺液各项指标的变化情况及配偶妊娠。结果:总有效率达到96.4%。结论:部分男性不育症为继发于慢性前列腺炎,临床上应充分重视,积极治疗前列腺炎,中西医结合治疗可显著地改善慢性前列腺炎不育症患者的精液质量,提高受孕率。     

中医辨证治疗慢性乙肝e抗原转阴临床研究

目的 观察中医辨证论治慢性乙肝e抗原转阴的临床疗效。方法 125例慢性乙肝病人,其中：治疗组79例（中药组）,分为五型,各型选相对应方药;对照组46例（西药组）,观察治疗前后HBeAg变化。结果 治疗后治疗中药组HBeAg转阴优于对照组（P＜0．005）。结论 中医辨证选方用药对HBeAg转阴有显著疗效。     

Metabolomic approach to understand the acute and chronic hepatotoxicity of Veratrum nigrum extract in mice based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.     

Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction

Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400 mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldolase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (p < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction.     

病毒性肝炎的中医治疗分析

目的：研究分析中医治疗病毒性肝炎的效果。方法选择2012年1月～2013年1月期间在中医门诊接受治疗的92例病毒性肝炎患者，均根据中医辨证分型予以中药治疗。结果本组92例病毒性肝炎患者，经中医辨证治疗后，显效者68例，有效者22例，无效者2例，治疗总有效率是97.83%，未有不良反应出现。随访半年发现，3例患者复发，复发率为3.26%。结论病毒性肝炎应用中医治疗效果较为理想，治标固本，且不会产生严重不良反应，远期复发率较低，具有很高的临床实用及推广价值。     

口服中药联合人工肝治疗重型肝炎的疗效观察

目的:观察口服中药联合人工肝治疗重型肝炎的疗效。方法:176例重型肝炎患者随机分为治疗组与对照组。对照组给予内科基础治疗和人工肝治疗,治疗组在对照组治疗基础上加服中药,疗程为2wk。结果:治疗组与对照组的治愈率分别为45·5%、20·5%(P<0·01);存活率分别为65·9%、40·9%(P<0·05)。结论:口服中药联合人工肝治疗重型肝炎疗效较佳。     

慢性乙型肝炎中医辩证治疗研究

目的探讨中医辩证治疗慢性乙型肝炎的临床疗效。方法100例慢性乙型肝炎患者随机分为治疗组和对照组各50例,治疗组在对照组的基础上加用中药汤剂治疗6个月后判定疗效。结果2个疗程结束后治疗组临床疗效为100%,对照组临床疗效为64.0%,而治疗前后血清标志物变化,治疗后肝功能恢复对比,两组有显著差异(P<0.05)。结论中医辩证治疗慢性乙型肝炎有着较好的疗效,且安全性高,易长期服用。