CHANGES OF ANTIBODIES AGAINST ANTIGENS ENCODED BY DIFFERENT REGIONS OF HCV GENOME IN CHRONIC HEPATITIS C PATIENTS TREATED WITH INTERFERON

Twenty patients with chronic hepatitis c were investigated during the treatment with interferon to explore the changes of antibodies to HCV (anti-RCV). Anti-HCV was tested with recombinant immunoblot assay (RIBA) by using three antigens (C22, C33c, and C100-3) encoded by different regions of HCV genome. The changes of individual anti-HCV and ALT were compared with the change of HCV RNA. The results showed that persistent disappearance of serum HCV RNA was closely related to the changes of anti-C33c (P<0. 01) and anti-C100-3 (P<0. 005), but there was no relation between persistent ALT normality and HCV viremia clearance (P<0. 05). In conclusion, monitoring anti-C33c and anti-C100-3 could indicate the changes or HCV viremia. The normalization of ALT after interferon treatment did not indicate disappearance of HCV viremia.

Logistic Regression Analysis of Influencing Factors on Serum ALT and HCV RNA Changes in Patients with Chronic Hepatitis C

Objective This study was undertaken to investigate the influencing factors on serum ALT level and hepatitis C virus(HCV)RNA titer in chronic hepatitis C(CHC)patients.Methods All patients enrolled into this study were anti-HCV positive.Retrospective tracing method was applied to detect serum ALT level and HCV RNA titer and to collect general information of the patients such as genders,age groups,interferon medication history,infection pathways,height and weight.Then the multi-factor analysis was adopted with the application of binominal logistic regression mode.Results The abnormal rate of ALT level was positively correlated to HCV RNA and gender while negatively correlated to interferon medication history and age group,with Wald value of the 4 factors as 39.604,11.823,18.991 and 7.389,respectively.The positive rate of HCV RNA was negatively correlated to interferon medication history and gender while positively correlated to ALT level,with corresponding Wald value of the 3 factors as81.394,7.618 and 27.562,respectively.Conclusions The normal ALT level in HCV infected patients was associated with viral load,age,gender and interferon medication history,while the normal rate of HCV RNA titer was closely associated with gender,interferon medication history and ALT level.

Clearance of HCV RNA in peripheral blood mononuclear cell as a predictor of response to antiviral therapy in patients with chronic hepatitis C

BACKGROUND: The resolution of hepatitis C, evidenced by normalization of liver function and disappearance of hepatitis C virus RNA from serum as determined by conventional laboratory assays, reflects virus eradication. But in interferon treated patients the HCV RNA in serum sometimes could not show the virus in cells. Such factors as virus genotype, HCV RNA contents in serum, HCV specific cellular immunities after treatment were reported to predict the response to interferon therapy. In most patients, HCV RNA could detect the virus in peripheral blood mononucle-ar cell. The aim of this study was to investigate the predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after interferon treatment. METHODS: Sixteen patients with chronic hepatitis C were treated with interferon for 24 weeks, and they all get complete responses at 12 weeks of treatment. At the end of treatment, the HCV RNA in PBMC and serum were detected by RT-PCR, and after stopping treatment, HCV RNA in serum was monitored continually. RESULTS: In 9 patients who were HCV RNA positive in their PBMC at the end of treatment, 8 showed serum HCV RNA positive after 24 weeks and another 1 after 1 year. In 7 patients with negative HCV RNA in their PBMC, only 2 patients relapsed in serum HCV RNA after 1-year follow-up, and others remained viral response after 3.5 years. CONCLUSION: HCV RNA in PBMC at the end of IFN treatment is a predictor of durable response to antiviral therapy in patients with chronic hepatitis C.

Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.

荧光定量巢式逆转录PCR(FQ-nRT-PCR)在检测HCV-RNA中的意义

目的:采用荧光定量巢式逆转录聚合酶链反应(FQ-nRT-PCR)检测丙型肝炎患者外周血清HCV-RNA,探讨HCV-RNA的临床应用价值。方法:用FQ-nRT-PCR和酶联免疫吸附试验(ELISA)分别检测192例HCV感染患者血清,比较HCV-RNA和抗-HCV的临床意义。结果:192例丙型肝炎患者血清标本中,HCV-RNA检出率为75.53%(145/192),抗-HCV检出率为91.66%(176/192)。急性丙型肝炎患者HCV-RNA定量均值达5.21×106拷贝/ml,慢性肝炎次之,肝硬化相对偏低,为5.14×103拷贝/ml。结论:192例丙型肝炎患者抗-HCV检出率高于HCV-RNA检出率,但HCV-RNA对丙型肝炎的早期诊断具有灵敏度高、定量准、假阳性率低等优点,此外在病毒复制水平及抗病毒治疗的疗效评估方面具有重要的临床价值。

2018-2022年我国18家省级血液中心献血者HCV检测结果分析

目的分析我国省级血液中心服务区域献血人群丙型肝炎病毒(hepatitis C virus,HCV)检测数据。方法对我国东中西部不同地区的18家省级血液中心,2018—2022年初次献血和重复献血者抗-HCV和HCV RNA检测数据收集整理,分析献血者中抗-HCV ELISA和抗-HCV ELISA阴性中HCV RNA检测不合格率与年度、血液中心以及初次献血和重复献血者之间的关系。结果2018年—2022年HCV总不合格率从24.61/万逐年减少至15.17/万(χ^(2)=717.71,P<0.01),西部地区为25.72/万最高,东部11.96/万最低(χ^(2)=2382.54,P<0.01);初次献血者抗-HCV ELISA不合格率(30.50/万)比重复献血者(7.42/万)高(χ^(2)=9694.63,P<0.01);各血液中心抗-HCV ELISA阴性中HCV-RNA单独不合格率范围为0~7.54/万。结论我国18家血液中心服务区域献血者的HCV检测不合格率呈逐年降低趋势;HCV检测不合格率存在明显的地域分布差异;与初次献血者相比,重复献血者为HCV检测不合格低危人群;HCV-RNA检测在血液安全方面发挥重要作用。

结合RT-PCR体外扩增检测HCVssRNA的研究

本研究旨在以HCV为平台,在简化RT-PCR基础上,结合体外转录,建立一种特异、高效、简便的检测血清中HCVRNA的体外转录合成系统。本法扩增终产物为特定极性的ssRNA,其特异性经凝胶电泳和斑点杂交确定;RNA定量分析结果显示本法核酸扩增效率高于巢式PCR近20倍。

基于医院感染预警系统的江西省某三甲医院就诊患者HCV微消除模式探索及评价

目的探索并评价江西省某综合医院就诊患者丙型肝炎病毒(HCV)微消除模式,为省内制定消除HCV公共健康危害策略提供参考依据。方法收集该院2021年1月—2022年12月就诊并进行HCV筛查的住院患者相关数据,其中2021年为基线数据,2022年为HCV微消除模式运行数据,分析其性别、年龄、送检科室、抗-HCV阳性率、HCV-RNA阳性率等指标,以专科就诊率、治疗率、失访率分析其运行效果,以SWOT-AHP法定量评价模式发展。结果2021—2022年共有397744例住院患者进行抗-HCV筛查,男女性别比为1.34∶1,平均年龄为54岁,送检科室主要以感染科/消化科为主。62份患者标本HCV基因亚型分型主要以1b亚型(43份)为主,其次为6亚型(9份)。模式运行后首次HCV预警率为81.20%,预警后抗-HCV送检率达93.15%,后续弹窗预警抗-HCV送检率为100%。与2021年比较,2022年HCV住院患者治疗率上升,差异有统计学意义(P<0.05);而专科就诊率、患者失访率差异均无统计学意义(均P>0.05)。模式运行重心坐标计算P(X,Y)=(0.0182,0.0069),位于第一象限。结论江西省某综合医院就诊患者HCV微消除模式可行且成效明显,下一步模式优化应重视SO策略(依靠内部优势,利用外部机会)。

Occult persistence and lymphotropism of hepatitis C virus infection

Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.

慢性丙型肝炎合并非酒精性脂肪肝患者血清25(OH)D水平变化及其与HCV-RNA载量、糖脂代谢的关系

目的 探讨慢性丙型肝炎(CHC)合并非酒精性脂肪性肝病(NAFLD)患者血清25-羟维生素D[25(OH)D]水平及其与HCV-RNA载量、糖脂代谢的关系。方法 选取2018年9月至2021年9月医院收治CHC患者174例,根据是否合并NAFLD分为单纯CHC组(110例)和CHC-NAFLD组(64例),选取同期体检健康成人87例(健康组),使用酶联免疫吸附法检测纳入对象血清25(OH)D水平,生化分析检测糖脂代谢指标,荧光定量PCR法检测CHC患者HCV-RNA载量,spearman相关性分析血清25(OH)D水平与HCV-RNA载量、糖脂代谢指标水平的相关性,logistics回归分析CHC合并NAFLD的危险因素。结果 CHC-NAFLD组、CHC组患者中BMI≥28kg/m^(2)比率、HbA1c、FBG、INS、IR、TG和LDL-C水平显著高于健康组(P<0.05),血清25(OH)D水平显著低于健康组(P<0.05)。CHC-NAFLD组BMI≥28kg/m^(2)比率、HbA1c、FBG、INS、IR、TG、LDL-C水平和HCV-RNA载量显著高于CHC组(P<0.05),血清25(OH)D水平显著低于CHC组(P<0.05)。25(OH)D水平与HbA1c、FBG、IR、TG水平呈负相关(r=-0.426、-0.387、-0.406、-0.514,P<0.001)。25(OH)D<42 nmol/L、BMI≥28 kg/m^(2)、TG≥1.72 mmol/L、HCV-RNA载量≥3.5×10^(6) IU/mL是CHC患者合并NAFLD的危险因素(P<0.05)。结论 CHC合并NAFLD患者血清25(OH)D水平降低,25(OH)D水平与HbA1c、FBG、IR、TG呈负相关且其水平升高会增加CHC患者发NAFLD发生风险。

Prevalence of HCV Antibody and its Associated Factors: A Study from Sentinel Hospitals in China

Objective The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies.Methods Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations.Results HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%–6.93%. Patients who were admitted to the liver disease-related departments(aOR =10.76;95% CI, 10.27–11.28), Internal Medicine(aOR = 2.87;95% CI, 2.75–3.00), and Department of Surgery(aOR = 1.95;95% CI, 1.87–2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older(aOR = 2.74;95% CI,2.69–2.80), testing in infetious disease hospitals(aOR = 2.33;95% CI, 2.26–2.40) and secondary hospitals(aOR = 1.72;95% CI, 1.69–1.75). Patients in sentinel hospitals of the Northeast(aOR = 12.75;95% CI,12.40–13.11), the Central(aOR = 1.65;95% CI, 1.61–1.70), and the West(aOR = 1.78;95% CI, 1.73–1.83)China had higher HCV prevalence than those who were in the Eastern coastal area. Conclusion Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.

丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查价值研究

目的通过对本院2019年1月至2022年9月需进行手术、输血或其他侵入性医疗服务的住院患者的HCV血清学抗体及高敏HCV RNA筛查结果进行回顾性分析,探讨丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查检测价值。方法对本院相关住院患者进行Elecsys Anti-HCV II或(和)高敏HCV RNA检测,统计分析其检测结果。结果HCV血清学抗体检测22443人次,阳性率为0.68%,阳性COI中位数为38.4(1.0~165)。高敏HCV RNA检测34628人次,阳性率0.30%,阳性病毒载量中位数为1.00×10^(6)IU/mL(3.50×10^(1)~4.00×10^(7)IU/mL)。两种方法学均显示45~59岁人群阳性率显著高于其他人群(P<0.001)。两种检测有重合的样本共17785人次,HCV抗体血清学阳性率为0.70%。高敏HCV RNA阳性率0.22%,如以高敏HCV RNA为丙型肝炎现症感染的标准,HCV抗体血清学检测HCV现症感染的灵敏度为100.00%(95%CI 89.09%~100.00%),特异性为99.52%(95%CI 99.41%~99.61%),现症感染阳性预测期PPV为32.00%(95%CI 23.82%~40.18%),阴性预期值为100.00%。HCV抗体血清学检测COI值与高敏HCV RNA检测的病毒载量无线性相关性,COI<10和COI>100的HCV RNA阳性率低。结论HCV抗体检测和高敏HCV RNA均为有效的丙型肝炎筛查手段,需进一步加强对重点人群的丙型肝炎感染管理。

Detection of hepatitis C virus core antigen for early diagnosis of hepatitis C virus infection in plasma donor in China

AIM： To evaluate the efficacy of a new hepatitis C virus （HCV） core antigen assay developed in China. METHODS： After the determination of HCV infection, 49 serial samples were selected from II regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS： Among all of the sequential samples, the original 23 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples （75%） were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples （93.2%） were found HCV RNA-positive in HCV core antigen- positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION： This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period （PWP） plasma donations.

Coinfection of hepatitis B and hepatitis C virus in HIV-infectedpatients in south India

AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA) using commercially available ELISA kits; HBsAg, HBeAg/ anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV. RESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co-infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV RNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV RNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.

HCV不同标志物检测结果比较分析

目的分析丙型肝炎病毒抗原、抗体及核酸标志物实验室检测结果之间的关联性。方法用丙型肝炎病毒抗体(HCV-Ab)、丙型肝炎病毒核酸(HCV-RNA)扩增(PCR)荧光定量、丙型肝炎病毒核心抗原(HCV-CAg)及丙型肝炎病毒抗原(HCV-Ag)检测试剂盒,分别检测血清或血浆样品中的HCV-Ab、HCV-RNA、HCV-CAg和HCV-Ag丙型肝炎病毒4种标志物,对检测结果之间的关联性进行分析。结果在1551份血清或血浆样品中,共检出HCV-Ab阳性样品565份(36.43%)、HCV-Ag(游离抗原)阳性样品48份(3.09%)、HCV-RNA阳性样品317份(20.44%)、HCV-CAg阳性样品25份(1.61%),HCV-Ab及HCV-RNA检出率明显高于抗原检出率(P<0.01),其阳性样品检出率按高低顺序依次为HCV-Ab、HCV-RNA、HCV-Ag和HCV-CAg。结论 4种标志物的检测可以联合运用,能有效降低HCV-Ab检测带来的漏检风险。

Hepatitis C virus: Virology, diagnosis and management ofantiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

Autoantibodies and hepatitis C virus genotypes in chronic hepatitis C patients in Estonia

AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region. RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%), TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases, sera were positive for two autoantibodies (ANA and SMA). AMA, PCA and LKMAI were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%) patients. CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1:10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.

Interleukin-12 as a Genetic Adjuvant Enhances Hepatitis C Virus NS3 DNA Vaccine Immunogenicity

Hepatitis C virus (HCV) chronic infection is a worldwide health problem, and numerous efforts have been invested to develop novel vaccines. An efficient vaccine requires broad immune response induction against viral proteins. To achieve this goal, we constructed a DNA vaccine expressing nonstructural 3 (NS3) gene (pcDNA3.1-HCV-NS3) and assessed the immune response in C57BL/6 mice. In this study, the NS3 gene was amplified with a nested-reverse transcriptase-polymerase chain reaction (RT-PCR) method using sera of HCV-infected patients with genotype 1a. The resulting NS3 gene was subcloned into a pcDNA3.1 eukaryotic expression vector, and gene expression was detected by western blot. The resultant DNA vaccine was co-administered with interleukin-12 (IL-12) as an adjuvant to female C57BL/6 mice. After the final immunizations, lymphocyte proliferation, cytotoxicity, and cytokine levels were assessed to measure immune responses. Our data suggest that co-administration of HCV NS3 DNA vaccine with IL-12 induces production of significant levels of both IL-4 and interferon (IFN)-γ (p<0.05). Cytotoxicity and lymphocyte proliferation responses of vaccinated mice were significantly increased compared to control (p<0.05). Collectively, our results demonstrated that co-administration of HCV NS3 and IL-12 displayed strong immunogenicity in a murine model.

Epidemiological Analysis on Reported Hepatitis C Cases in China from 2012 to 2016

Viral hepatitis is an important challenge to public health worldwide.As hepatitis B is well controlled due to vaccination,the disease burden caused by the spread of hepatitis C has become increasingly prominent.Hepatitis C is an infectious disease that is mainly blood-borne.The rate of chronicity ranges from 55% to 85% after people are infected with the hepatitis C virus （HCV）.

Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.