肺结核患者肿瘤坏死因子-α基因多态性的研究

目的通过病例-对照研究,探讨肿瘤坏死因子-α(TNF-α)基因启动子区-238A/G、-308A/G位点单核苷酸多态性(SNP)与肺结核病的关系。方法采用序列特异性引物PCR(PCR-SSP)及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例TNF-α启动子区-238A/G、-308A/G位点基因多态性。采用直接计数法计算各组基因型频率及等位基因频率,并进行χ2检验;采用SHEsis软件进行单倍型分析。以P值0.05为具有统计学意义。结果2组人群TNF-α启动子区-238A/G、-308A/G位点基因型及等位基因分布频率差异无统计学意义(P0.05);两位点各种单倍型在2组间分布差异无统计学意义(P0.05)。结论TNF-α启动子区-238、-308位点基因多态性与中国汉族人群肺结核病易感性未见关联。     

HBeAg阳性慢性乙型肝炎患者肿瘤坏死因子α基因启动子区-238和-308位点基因多态性分析

目的探讨HBeAg阳性慢性乙型肝炎(CHB)患者肿瘤坏死因子α(TNF-α)基因启动子区-238和-308位点基因多态性及其与血清TNF-α水平的关系。方法对203例HBeAg阳性CHB患者,采用聚合酶链反应-限制性片段长度多态性分析法检测TNF-α-238和-308位点基因多态性;采用ELISA法测定血清TNF-α水平。结果 TNF-α-238G/G、G/A基因型频率分别为84.7%和15.3%,-308G/G、G/A、A/A基因型频率分别为76.8%、22.7%和0.5%;TNF-α-238G/A基因型患者血清TNF-α水平低于G/G基因型(201.2±36.3pg/ml对215.7±34.7pg/ml,x2=4.355,P=0.037),-308G/A基因型TNF-α水平高于G/G基因型(234.6±37.5pg/ml对207.4±32.3pg/ml,x2=14.653,P0.001)。结论 TNF-α-238G/G或-308G/A基因型患者血清TNF-α水平相对较高。     

TNF-α基因多态性与类风湿性关节炎相关性研究

目的:探讨肿瘤坏死因子-α(TNF-α)启动子区-308基因多态性与湖北汉族人类风湿性关节炎(RA)易感性的关系。方法:用聚合酶链反应和限制性片段长度多态性(PCR/RFLP)的方法对113例RA患者及126例健康人进行TNF-α的-308位点多态性分析。结果:RA组与对照组TNF-α的-308位点的基因型频率和等位基因频率G/G、G/A、A/A之间差异无统计学意义(P0.05);并且TNF-α的-308位点的基因多态性与RA活动期指标ESR和CRP高低无关。结论:TNF-α启动子区-308基因多态性不是类风湿性关节炎易感性和严重程度的一个风险因子。     

I型自身免疫性肝炎患者细胞因子基因多态性研究

目的评价肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)启动子基因的多态性在I型自身免疫性肝炎(AIH)易感背景中的作用.方法采用聚合酶链反应扩增后寡核苷酸探针杂交法,在I型AIH(32例)和健康对照者(48例)中,对2个TNF-α启动子多态性位点(-238和-308)和3个IL-10启动子多态性位点(-1082、-819和-592)进行分析.结果 I型AIH患者中TNF-α启动子-308位点鸟嘌呤(G)被替换为腺嘌呤(A)的频率显著高于健康对照组(53.1%对27.1%,RR=3.05,P＜0.05).TNF-238位点和IL-10启动子3个位点的多态性差异无显著性.结论TNF-308位点G被替换为A(TNF-308A)可能是I型AIH的发病机制之一.     

肿瘤坏死因子-α基因多态性与非酒精性脂肪性肝病的关系

目的研究肿瘤坏死因子-α(TNF-α)基因-308位点及-238位点多态性在非酒精性脂肪性肝病(NAFLD)患者中的分布,及其在胰岛素抵抗(IR)和 NAFLD 发病中的地位。方法运用聚合酶链反应-限制性片段长度多态性检测117例 NAFLD 患者 TNF-α基因—308位点及—238位点多态性,其中伴肥胖者60例,非肥胖者57例,同时测定患者空腹血清胰岛素(FINS)及空腹血糖,通过体内平衡代谢指数(HOMA)评估 IR,并与120名健康者对照。结果 NAFLD 患者与正常对照组 TNF-α基因-238位点基因多态性分布差异有统计学意义(29.9%比15.8%,P<0.05),而—308位点差异无统计学意义(P>0.05)。NAFLD 患者血清 HOMA-IR、TNF-α明显高于对照者[2.50±0.68比1.16±0.68,(10.54±3.19)ng/L 比(4.54±3.10)ng/L,P<0.01]。FINS、HOMA-IR 在 TNF-α基因-238位点基因变异组明显高于正常基因型组(P<0.05),但在—308位点变异组差异无统计学意义(P>0.05)。NAFLD 患者中无论肥胖或非肥胖患者均较正常对照人群在 TNF-α基因-238位点多态性分布及HOMA-IR、TNF-α差异有统计学意义(P<0.05)。肥胖及非肥胖的 NAFLD 患者之间 HOMA-IR、TNF-α差异无统计学意义(P>0.05)。结论 NAFLD 患者 IR 与其体重关系不显著,非肥胖 NAFLD患者同样有 IR 发生。TNFα基因-238位点 G/A 变异与 IR、NAFLD 易感性相关,TNFα基因-308位点 G/A 的突变与 IR 易感性不相关。NAFLD 发病与 IR、TNF-α密切相关。     

TNF-α基因启动子多态性与HBV感染转归的关系

目的:探讨中国汉族人肿瘤坏死因子-α(tumor necrosisfactor-α,TNF-α)基因启动子单核苷酸多态性与乙型肝炎病毒(hepatitis B virus,HBV)感染结果之间的关系.方法:慢性乙型肝炎患者131例,HBV感染自愈者165组应用聚合酶链反应-限制性片段长度多态性分析方法,检测HBV感染自愈者和慢性乙型肝炎患者TNF-α基因启动子-238G/A,-308G/A,-857C/T和-863C/A单核苷酸多态性位点基因型.结果:对慢性乙型肝炎组和HBV感染自愈组人群TNF-α基因启动子区域的-238G/A,-308G/A,-857C/T和-863C/A 4个SNP位点进行基因型分析,共发现12种启动子基因型,以GG·GG·CC·CC,GG·GG·CC·CA,GG·GG·CT·CC和GG·GA·CC·CC基因型多见,约占85%.通过对慢性乙型肝炎患者和HBV感染自愈者TNF-α基因启动子4个位点基因型联合分析发现,GG·GG·CC·CC,GG·GG·CC·CA和GG·GA·CC·CC基因型在慢性乙型肝炎组和HBV感染自愈组分布差异有显著性,其中携带GG·GG·CC·CC基因型的个体患慢性乙型肝炎的机会比(odds ratio,OR)为2.15,95%可信区间为1.34-3.45;而携带GG·GG·CC·CA或GG·GA·CC·CC基因型的个体患慢性乙型肝炎的OR分别为0.48(95%可信区间为0.27-0.86)和0.35(95%可信区间为0.14-0.89).HBV感染的清除可能与GG·GG·CC·CA(X2=6.14,P=0.013＜0.05)和/或GG·GA·CC·CC(X2=5.18,P=0.023＜0.05)基因型有关.进一步对各位点单核苷酸多态性分析发现,慢性乙型肝炎患者和HBV感染自愈者TNF-α基因启动子-238G/A、-857C/T位点基因型分布频率差异无显著性,而-308G/A,-863C/A位点基因型分布频率差异有显著性(-308G/A位点,X2=6.53,P=0.011＜0.05,OR=3.05;-863C/A位点,X2=4.33,P=0.037＜0.05,OR=1.69).结论:TNF-α基因启动子-308G/A、-863C/A位点多态性与中国汉族人HBV感染后的结果有关,其中TNF0-α308G/A和/或-863C/A位点A等位基因的存在可能有利于HBV感染的清除.     

肿瘤坏死因子α基因启动子区多态性与乙型肝炎病毒感染相关性的荟萃分析

目的:探讨肿瘤坏死因子α(TNF-α)基因启动子区多态性与乙型肝炎病毒(HBV)持续感染或清除的关系.方法:通过检索PubMed、Embase以及CNKI共纳入18项病例对照研究,采用荟萃分析方法研究TNF-α基因启动子区基因多态性与HBV持续感染或清除的关系,以及采用荟萃回归分析不同研究之间存在异质性的原因.结果:亚洲人群(蒙古人种)中自然痊愈组(904例)-308G/A位点的基因型(GA AA)频率显著高于持续HBV感染组(2303例)(P=0.001),而欧洲人(高加索人种)中持续HBV感染组(256例)-238G/A位点的基因型(GA AA)频率略高于自然痊愈组(195例)(P=0.07),样本量、种族、地区以及研究方法均为影响不同研究之间异质性的因素(P<0.05),使研究之间总变异效应降低了约0.236.结论:TNF-α-308G/A位点多态性可能与感染HBV后的清除有关,而-238G/A位点多态性可能与HBV的持续感染有关,并且样本量、种族、地区以及研究方法因素均可能影响病例对照研究的结果.     

肿瘤坏死因子-α基因启动子区点突变与乙型肝炎相关

目的:调查我国汉族健康人群和乙肝患者中TNF-α基因启动子区点突变的分布特点,并探讨HBV感染与TNF-α基因多态性之间的关系.方法:采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)的方法对健康人群(103例)与HBV患者(232例)的TNF-α基因启动子区-308 G→A单碱基突变多态性进行了分析.结果:TNF-α基因启动子区-308 G→A单碱基突变频率在HBV患者中的分布明显低于健康人群(4.7%vs 9.7%,P＜0.05).不同性别、不同HBV血清标记类型、不同HBV DNA肝炎患者之间TNF-α(-308 G→A)基因型与突变频率均无显著性差异.结论:我国汉族人群TNF-α的基因启动子区-308 nt单碱基多态性可能与HBV的发病及易感性相关.     

肿瘤坏死因子α基因启动子区多态性与乙型肝炎病毒感染相关性的荟萃分析

目的探讨肿瘤坏死因子α(TNF-α)基因启动子区多态性与乙型肝炎病毒(HBV)持续感染或清除的关系.方法通过检索PubMed、Embase以及CNKI共纳入18项病例对照研究,采用荟萃分析方法研究TNF-α基因启动子区基因多态性与HBV持续感染或清除的关系,以及采用荟萃回归分析不同研究之间存在异质性的原因.结果亚洲人群(蒙古人种)中自然痊愈组(904例)-308G/A位点的基因型(GA AA)频率显著高于持续HBV感染组(2303例)(P=0.001),而欧洲人(高加索人种)中持续HBV感染组(256例)-238G/A位点的基因型(GA AA)频率略高于自然痊愈组(195例)(P=0.07),样本量、种族、地区以及研究方法均为影响不同研究之间异质性的因素(P＜0.05),使研究之间总变异效应降低了约0.236.结论TNF-α-308G/A位点多态性可能与感染HBV后的清除有关,而-238G/A位点多态性可能与HBV的持续感染有关,并且样本量、种族、地区以及研究方法因素均可能影响病例对照研究的结果.     

北方汉族慢性乙型肝炎患者TNF-α启动子区基因多态性的分析

目的探讨TNF-α启动子区基因多态性对宿主感染乙型肝炎病毒(hepatitis B virus,HBV)慢性化结局的关联。方法用病例-对照研究方法,291例慢性乙型肝炎患者作为病例组和212例乙型肝炎病毒自限性感染者作为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对TNF-α基因启动子区-238G/A、-857C/T、-863C/A位点进行基因分型。结果携带TNF-α-238 GA基因型、-857 CC基因型是HBV感染后宿主发展为慢性乙型肝炎的易感因素(P0.05);3个位点组成的单体型-238G/-857C/-863A的频率在慢性乙肝组显著高于HBV自限感染组。结论TNF-α启动子区基因多态性可能对宿主感染HBV慢性化结局产生影响。     

Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis

BACKGROUND/AIMS: Tumor necrosis factor (TNF) is considered to play a role in the second hit of non-alcoholic steatohepatitis (NASH). To clarify the effects of TNF in NASH we investigated TNF gene polymorphisms that might influence TNF production were investigated. METHODS: We analyzed 102 patients with non-alcoholic fatty liver disease (NAFLD; 36 with simple steatosis and 66 with NASH) and 100 control subjects. The serum level of soluble TNF receptor (sTNFR)-2 was measured. The TNF-alpha promoter region positions -1031, -863, -857, -308, and -238 and the TNF-beta gene Nco1 polymorphism site were investigated. RESULTS: The level of sTNFR-2 was significantly higher in NASH patients than in those with simple steatosis or control subjects. In the analysis of TNF gene polymorphisms, there were no significant deviations between the group of all NAFLD patients and the control subjects. The carrier frequencies of polymorphisms at positions -1031C and -863A were significantly higher in patients with NASH than in those with simple steatosis. In the multivariate analysis, TNF-alpha promoter polymorphisms proved to be significant independent factors distinguishing NASH from simple steatosis. CONCLUSIONS: TNF polymorphisms, which influence TNF production, might be associated with the progression of NAFLD.     

Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease

BACKGROUND & AIMS: Nonalcoholic fatty liver disease, which can range from fatty liver alone to nonalcoholic steatohepatitis and cirrhosis, is related to insulin resistance. Tumor necrosis factor alpha (TNF-alpha) may induce insulin resistance, and polymorphisms of its promoter have been associated with an increased release of this cytokine. We analyzed (1) the prevalence of insulin resistance, (2) the prevalence of the 238 and 308 TNF-alpha polymorphisms, and (3) the relationship among TNF-alpha polymorphisms, insulin resistance, and the occurrence of steatohepatitis in 99 patients with nonalcoholic fatty liver diagnosed by ultrasonography and confirmed by histologic analysis in the 53 who underwent biopsy. METHODS: Insulin resistance was evaluated by the homeostatic metabolic assessment insulin resistance indices and TNF-alpha polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Insulin resistance was detected in almost all of the patients and was more severe in those with steatohepatitis. The prevalence of the 238, but not of the 308, TNF-alpha polymorphism was higher in subjects with nonalcoholic fatty liver than in controls (31% vs. 15%; P < 0.0001), and patients positive for TNF-alpha polymorphisms had higher insulin resistance indices, a higher prevalence of impaired glucose tolerance, and a lower number of associated risk factors for steatosis. CONCLUSIONS: TNF-alpha polymorphisms could represent a susceptibility genotype for insulin resistance, nonalcoholic fatty liver, and steatohepatitis.     

Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis. The aim of this study is to investigate serum hyaluronic acid (HA), TNF-alpha, IL-8 levels in patients with non-alcoholic steatohepatitis and to assess their potential value as a noninvasive marker for the severity of histopathology. METHODOLOGY: Twenty-eight patients with biopsy-proven NASH, 14 patients with cirrhosis and 15 healthy controls were studied. Histopathological findings were graded and staged. HA, IL-8, TNF-levels were determined using by ELISA test RESULTS: Serum HA levels in patients with NASH were significantly higher than in the healthy control group (P < 0.05). However, the levels in patients with cirrhosis were markedly higher than in patients with NASH and healthy controls (P < 0.001). Serum TNF-alpha levels were significantly higher in patients with NASH and cirrhosis than in healthy controls (P < 0.05). Serum IL-8 levels in patients with NASH (P < 0.001) and cirrhosis (P < 0.05) were significantly higher than in the healthy control group. There was no correlation between serum HA and IL-8, TNF-alpha, ALT and AST levels. Serum HA level in patients with NASH was 187.26 +/- 139.21 and 143.49 +/- 93.14 in stage in stage 2-3 and in stage 0-1, respectively, but the difference was not significant (P > 0.05). CONCLUSIONS: In conclusion, serum HA, IL-8 and TNF-alpha levels increased in patients with NASH. Their relation with the severity of histopathology is not significant. Serum HA levels may be a useful marker to monitor the conversion from fibrosis to cirrhosis. Further studies are needed on this topic.     

Disease-specific mi R-34a as diagnostic marker of nonalcoholic steatohepatitis in a Chinese population

AIM To assess disease-specific circulating micro RNAs(mi RNAs) in non-alcoholic steatohepatitis(NASH) patients.METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease(NAFLD) or chronic hepatitis B(CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of mi R-122,-125 b,-146 b,-16,-21,-192,-27 b and-34 a. The correlations between serum mi RNAs and histological features of NAFLD were determined. The diagnostic value of mi RNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18(CK-18), fibrosis-4(FIB-4), and aspartate aminotransferase to platelet ratio index(APRI), respectively.RESULTS Circulating mi R-122,-16,-192 and-34 a showed differential expression levels between NAFLD and CHB patients, and mi R-34 a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples(P 0.01). Serum mi R-122,-192 and-34a levels were correlated with steatosis(R = 0.302, 0.323 and 0.470, respectively, P 0.05) and inflammatory activity(R = 0.445, 0.447 and 0.517, respectively, P 0.01); only serum mi R-16 levels were associated with fibrosis(R = 0.350, P 0.05) in patients with NAFLD. The diagnostic value of mi R-34 a for NASH(area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but mi R-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.CONCLUSION Circulating mi R-34 a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.     

Tumor necrosis factor alpha promoter polymorphisms influence the phenotypic expression of hereditary hemochromatosis

Severe iron overload usually develops in patients with hereditary hemochromatosis (HHC), but variability in the phenotypic expression of the disease has been reported. This study assessed whether tumor necrosis factor alpha (TNF-alpha) plays a role in phenotypic expression of HHC. Sixty-four patients with HHC and 172 healthy volunteers (controls) were studied. Release of TNF-alpha from stimulated peripheral blood monocytes was measured by enzyme-linked immunosorbent assay, and 308 and 238 TNF-alpha polymorphisms were detected with polymerase chain reaction and restriction fragment-length polymorphism analysis. The relation between TNF-alpha polymorphisms and clinical expression of HHC was evaluated. Patients with HHC released less TNF-alpha than controls, but the difference was significant only in homozygotes for the C282Y mutation. The prevalence of the 308 TNF-alpha polymorphism was similar in patients and controls, whereas the prevalence of the 238 polymorphic allele was significantly lower in patients (3% versus 16%; P =.002). A lower prevalence of cirrhosis was observed in patients with TNF-alpha polymorphism than in those without it (4 of 15 [27%] versus 28 of 49 [57%]), but the difference was not significant (P =.07). In nonhomozygotes for the C282Y mutation, severe liver siderosis was less prevalent in patients with the 308 polymorphism than in those without it (P =.05). Alanine aminotransferase (ALT) values were significantly lower in patients with TNF-alpha polymorphism (P =.006), even when patients with other hepatotoxic factors were excluded. Multivariate analysis showed that TNF-alpha polymorphism was independently associated with ALT values (P =.0008 and P =.045, respectively, in homozygotes and nonhomozygotes for the C282Y mutation) and siderosis in nonhomozygotes (P =.047). Thus, TNF-alpha appears to play a role in HHC by modulating the severity of liver damage. (Blood. 2001;97:3707-3712)     

Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis.

BACKGROUND: Although the pathogenesis of non-alcoholic steatohepatitis (NASH) remains poorly understood, proinflammatory cytokines seem to play an important role in the process of NASH. We have undertaken this study in order to elucidate the role of proinflammatory cytokines and their soluble receptors in NASH patients. METHODS: Serum cytokines and soluble cytokine receptors levels were determined using an enzyme-linked immunosorbent assay kit in 23 patients with NASH, 21 patients with simple steatosis, and 18 healthy volunteers. RESULTS: Patients with NASH had significantly higher serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels than did the simple steatosis patients. Similarly, when compared with simple steatosis, NASH was associated with higher soluble TNF receptor 1 (sTNFR1) and soluble IL-6 receptor (sIL-6R) levels, and a significant positive correlation was seen between the levels of sTNFR1 and aminotranferases in NASH patients. CONCLUSIONS: This study shows that circulating TNF-alpha/sTNFR1 and IL-6/sIL-6R levels are significantly increased in NASH patients as compared with simple steatosis patients and healthy volunteers, and that these increased levels may be implicated in the pathogenesis of NASH.     

TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy

OBJECTIVE: The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy. DESIGN: Genetic case-control association study. METHODS: Individuals were genotyped for the -238 and -308 polymorphisms in the TNF-alpha gene using polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype and allele frequencies for 61 HIV-positive patients with lipodystrophy were compared with (a) 35 HIV-positive patients with no evidence of lipodystrophy and (b) 239 healthy HIV-negative individuals. RESULTS: The frequency of the variant rare -238 allele was significantly different (P = 0.01) in HIV-positive patients with lipodystrophy than in those without lipodystrophy. At the genotype level, a trend towards a difference between patients with and without lipodystrophy was observed (chi2 for linear trend 5.2, P = 0.02). For the -308 polymorphism, no difference was found in genotype and allele frequencies between HIV patients with and without lipodystrophy. CONCLUSIONS: The data suggest that the -238 (but not the -308) promoter region TNF-alpha gene polymorphism is a determinant in the development of HIV-related lipodystrophy. However, the results need to be confirmed in larger numbers of patients as well as in an ethnically diverse population.     

Serum neopterin levels in patients with non-alcoholic steatohepatitis

Aim:  Neopterin is a marker of cell-mediated immunity. It also has a fundamental role in host-defense reactions, including interactions with reactive oxygen intermediates and the promotion of local and systemic oxidative stress. The present study aimed to assess the importance of serum neopterin levels in patients with non-alcoholic steatohepatitis (NASH).
Methods:  Thirty-nine patients with NASH diagnosed by liver biopsy and 32 healthy adults (controls) were enrolled in the study. Serum neopterin levels were measured with an enzyme-linked immunosorbent assay in addition to other biochemical parameters, including liver enzymes. Histopathological examinations were graded as suggested by both the necroinflammatory activity grading system and the NASH scoring system.
Results:  The mean serum neopterin levels were higher in patients with NASH compared to the controls (24.1 ± 16.4 vs 16.2 ± 9.5, P  = 0.019). The histological examination of liver biopsies revealed that 34 of the patients with NASH had grade 1 steatohepatitis and only five patients had grade 2 steatohepatitis. A higher serum mean neopterin level was detected in grade 2 patients compared to grade 1 (40.6 ± 5.6 vs 21.7 ± 16.1, P  = 0.014). A gradual increase was also observed in serum neopterin levels with the increase of the NASH score.
Conclusion:  The serum neopterin levels were significantly higher in patients with NASH compared to the controls, and levels showed an association with the severity of liver damage.     

Inhibitory effect of angiotensin Ⅱ receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

AIM: To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH). METHODS: Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and -smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls. RESULTS: In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes. CONCLUSION: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.