益肝康治疗慢性乙型肝炎肝纤维化365例疗效观察

目的探讨中药益肝康对慢性乙型肝炎、肝纤维化的疗效。方法将365例慢性乙型肝炎患者随机分为两组,治疗组（305例）给予益肝康袋装浓缩煎剂1袋,每日2次,对照组（60例）给予葡醛内酯（肝太乐）0．2g,每日3次,水飞蓟宾140mg,每日3次,治疗6个月。分别于治疗前后记述症状,观察肝、脾变化,检测肝功能、血清肝纤维化指标,肝组织病理,进行疗效评价。结果治疗组和对照组血浆透明质酸、层黏连蛋白和Ⅲ型前胶原水平间差别有统计学意义,（185．13±10．84）μg／L vs（121．43±10．91）μg／L,（175．03±7．14）pg／L vs （142．86±14．66）μg／L,（153．37±20．96）μg／L vs （128．00±18．52）μg／L（P〈0．01）;同时,治疗组患者症状改善,肝、脾回缩,肝功能明显好转,白蛋白水平升高。结论益肝康是治疗慢性肝病、肝纤维化的有效药物。     

Advanced liver fibrosis and care continuum in emergency department patients with chronic hepatitis C

Background

FIB-4, a non-invasive serum fibrosis index (which includes age, ALT, AST, and platelet count), is frequently available during ED visits. Our objective was to define 1-year HCV-related care outcomes of ED patients with known HCV, for the overall group, and both those with and without advanced fibrosis.

Hunting for fibrosis progression genes in hepatitis C patients

HCV (hepatitis C virus) represents one of the major health problems worldwide, as almost 170 million people are infected and most of these develop a chronic disease, often with the progression to cirrhosis and its complications. In the present issue of Clinical Science, Iwata and co-workers report an association between a variant of a gene regulating bile acid levels, ABCB11 1331T>C (where ABCB11 encodes ATP-binding cassette, subfamily B, member 11), and the progression to cirrhosis in patients with HCV, but not in fatty liver patients. They correlate this genetic variant with increased serum bile acid levels as a marker of cholestasis. These findings have important implications for researchers working to dissect the molecular mechanisms underlying liver fibrogenesis and disease progression; however, the implications for clinical hepatologists are less immediate.     

Interferon therapy as chemoprevention of hepatocarcinogenesis in patients with chronic hepatitis C

Hepatocellular carcinoma (HCC) is currently a very common malignancy and its incidence is increasing, both in Japan and the USA. Persistent hepatitis C virus (HCV) infection is a major risk factor for the development of HCC. A number of large-scale retrospective cohort studies have demonstrated that interferon therapy reduces the incidence of HCC not only in sustained virological responders but also in transient biochemical responders without the elimination of HCV. We also demonstrated that retreatment with interferon at certain intervals reduced the incidence of HCC in patients with chronic hepatitis C, even if eradication of HCV was not achieved by retreatment. We cannot, however, explain how a transient normalization of serum alanine aminotransferase levels induced by a maximum 6 months of interferon treatment reduces the incidence of HCC during the progression of chronic hepatitis to cirrhosis or HCC, which requires dozens of years. In this article, we discuss how interferon treatment might reduce the incidence of HCC even in transient biochemical responders, especially in view of antiproliferative or antioxidative activity of interferon-alpha.     

Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C.

BACKGROUND: The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity. METHODS: A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients. RESULTS: The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4. CONCLUSIONS: The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.     

慢性乙肝患者肝纤指标与肝损关系研究

目的研究慢性乙型肝炎（CHB）患者肝纤维化指标透明质酸（HA）、Ⅲ型前胶原（PⅢP）、层黏连蛋白（LN）、IV型胶原（IVC）与肝功能损害的关系。方法以65例正常体检人员为对照,比较CHB中度组（89例）、CHB重度组（72例）及肝硬化组（34例）HA、PⅢP、LN、IVC变化特点,及相应肝功能情况。结果 HA、PⅢP、LN、IVC在CHB中度、重度组及肝硬化组中均有不同程度的升高,丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）在CHB中度、重度组升高,在肝硬化组中降低并出现倒置。结论在CHB患者中肝纤维化指标HA、PⅢP、LN、IVC结合传统肝功能监测指标ALT、AST更能准确反映肝脏纤维化及肝功能受损程度。     

苦参素对慢性乙型肝炎患者血清肝纤维化指标影响的研究

目的 观察苦参素对慢性乙型肝炎患者肝纤维化指标的影响.方法 60例慢性乙型肝炎患者随机分为治疗组(一般保肝治疗 苦参素)和对照组(一般保肝治疗),治疗前后检测肝功能,用放射免疫法检测血清肝纤维化指标透明质酸(HA)、层黏蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)和Ⅳ型胶原(CⅣ).结果 治疗组治疗后HA、LN、PC-Ⅲ和CⅣ水平较治疗前及对照组治疗后均显著降低(P＜0.05或P＜0.01).结论 苦参素是能降低肝纤维化指标,有一定的抗肝纤维化作用.     

慢性丙型肝炎患者血清HCV-RNA水平与抗-HCV抗体和肝纤指标水平相关性分析

目的探讨丙型肝炎患者RNA水平与抗-HCV抗体和肝纤指标水平的关系。方法收集96例慢性丙型肝炎患者的血清,实时荧光定量PCR测定HCV-RNA和ELISA法检测抗-HCV抗体。化学发光法检测LN、PCⅢ、CⅣ及放免法检测HA。并对抗-HCV抗体、HCV-RNA水平与血清肝纤指标之间的关系进行分析。结果本研究的96例抗-HCV抗体阳性的慢性丙型肝炎患者中,HCV-RNA阳性52例,阳性率为54.2%。随着抗-HCV抗体的S/CO值升高,HCV-RNA检出率也在增高,分别为9.5%、37.1%和92.5%。高病毒载量组与低病毒载量组比较,血清HA、LN、PCⅢ及CⅣ水平的差异无统计学意义(P0.05)。结论慢性丙肝患者HCV-RNA阳性检出率与抗-HCV抗体的S/CO值有关,S/CO值越高,HCV-RNA阳性率越高。而RNA水平与肝纤指标水平没有相关性。     

Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B

Introduction: Many noninvasive tests have been studied for the diagnosis and determining the liver fibrosis score (LFS). In this study, we aimed to research the correlation of mean platelet volume (MPV) and stage of liver fibrosis in patients with chronic hepatitis B (CHB). Patients and Methods: Fifty‐nine patients with CHB were enrolled retrospectively into the study. Age–sex matched 25 healthy subjects were used as control group. The following data were obtained from computerized patient registry database: HBV‐DNA level, hepatitis B e‐antigen seropositivity, liver enzymes and function tests, white blood cell count, platelet count, hemoglobin, histological activity index, LFS, and MPV. Patients were divided into two groups: patients without significant fibrosis (F0, F1, or F2) (Group 1) and patients with advanced fibrosis (F3, F4) (Group 2). Results: A statistically significant increase in MPV was seen in patients with CHB compared with healthy controls (8.49±0.84 fl vs.7.65±0.42 fl, P<0.001). Receiver operating characteristic curve analysis suggested that the optimum MPV level cut‐off points for CHB was 8.0 fl, with sensitivity, specificity, PPV, and NPV of 68, 76, 86, and 50%, respectively. MPV levels were significantly higher in Group 2 (8.91±0.94 fl, P: 0.009) compared with Group 1 (8.32±0.74 fl). ROC curve analysis suggested that the optimum MPV level cut‐off points for Group 2 was 8.45 fl, with sensitivity, specificity, positive and negative predictive value of 77, 59, 45, and 85%, respectively. Multivariable logistic regression model, which consisted of HAI, ALT, HBV‐DNA, platelet count, and MPV, was performed. We showed that MPV was independently associated with advanced fibrosis (P: 0.031). Conclusion: We suggest that MPV might help in the assessment of fibrosis in CHB. It should not be considered a stand‐alone test for this use owing to nonspecificity with other diseases. J. Clin. Lab. Anal. 25:162–165, 2011. © 2011 Wiley‐Liss, Inc.     

HCV genotype as a predictor of response to interferon therapy in patients with chronic hepatitis C

Hepatitis C virus(HCV) genotype is one of the most important predicting factors of response to interferon(IFN) therapy in patients with chronic hepatitis C. According to the molecular evolutionary analysis, HCV is classified into six major genotypes. The patients infected with genotype 1 show high HCV RNA levels and poor response to IFN therapy compared to those with genotype 2 or 3. No sufficient data are observed on response to IFN in patients with genotype 4 to 6. When PEG-IFN plus ribavirin therapy is introduced, high proportion of patients without genotype 1 must show complete response. In the near future, to predict good response to IFN therapy, it will be necessary to know whether patients have HCV genotype 1 or not.     

Development and progression of gastroesophageal varices in patients with chronic hepatitis C

Evaluation of: Fontana RJ, Sanyal AJ, Ghany MG et al. Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C. Gastroenterology 138(7), 2321–2331 (2010).

Hepatitis C virus infection is the leading cause of chronic liver disease in the western world. Chronic liver diseases may cause, through portal hypertension, the development of gastroesophageal varices, which can then bleed. We assess the findings of a study aimed at identifying the incidence of de novo varix development and their progression in patients with chronic hepatitis C and advanced fibrosis. This study was a substudy of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. The HALT-C trial was designed to determine whether pegylated interferon (PEG-IFN) at low dose can reduce the rate of disease progression in these patients. Approximately 26% of patients developed de novo varices and 35.2% of patients with varices at baseline had variceal progression or bleeding during the 4-year follow-up. The authors examine demographic, clinical, laboratory, virological, endoscopic and histological factors associated with the development and progression of gastroesophageal varices. PEG-IFN-α2a therapy did not reduce the risk of development or progression of gastroesophageal varices.     

Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C.

BACKGROUND: Circulating levels of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinase (MMP)-2 are investigated as parameters for the diagnosis of fibrosis in chronic liver disease. We evaluated their diagnostic potential in comparison to hepatic histology, serum hyaluronate and standard liver function tests. METHODS: Commercially available ELISA assays were used to study circulating values of TIMP-1 and MMP-2 (Bindazyme, Biotrak, Quantikine) in patients with chronic hepatitis C (CAH; n=59), hepatitis C virus-induced cirrhosis (n=19) and 30 healthy controls. Hepatic histology was evaluated using the Hepatitis-Activity-Index according to Ishak et al. [J. Hepatol., 22 (1995) 696-699], quantifying separately inflammatory activity and fibrosis. RESULTS: Normal ranges for TIMP-1 and MMP-2 values differed for the different assays. Nevertheless, the various assays showed similar diagnostic ability and linear correlation. MMP-2 values were similar in controls and in CAH patients with and without fibrosis, but increased significantly in cirrhosis. TIMP-1 values showed a steady increase from normal to CAH without fibrosis, hepatitis with fibrosis, and cirrhosis. The diagnostic potential of serum MMP-2 to detect fibrosis was low with a sensitivity of 7% in the two assays used and an overall diagnostic efficiency of 56% and 58%. The potential of circulating MMP-2 to detect cirrhosis was higher with sensitivities of 74% and 83% and specificities of 96% and 100%, resulting in a diagnostic efficiency of 92% in the different assays. Plasma TIMP-1 values detect fibrosis with a sensitivity of 52% and 67% and a specificity of 68% and 88% resulting in overall efficiency rates of 68% and 71%, respectively. TIMP-1 values detect cirrhosis with 100% sensitivity but only 56% and 75% specificity. The diagnostic potential of circulating TIMP-1 was similar to that of hyaluronate and better than that of enzymes or albumin values. CONCLUSION: Plasma values of TIMP-1 and MMP-2 are able to detect cirrhosis with high sensitivity. TIMP-1 values also detect fibrosis with comparable efficiency. Regular determinations of both TIMP-1 and MMP-2 in CAH patients may be used as indicators of increasing fibrosis and the development of cirrhosis.     

Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis

OBJECTIVE AND METHODS: We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. RESULTS: Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P 相似文献   

Progression of liver fibrosis in patients coinfected with hepatitis C virus and human immunodeficiency virus undergoing antiretroviral therapy

As the immunosuppression caused by human immunodeficiency virus (HIV) accelerates the progression of hepatitis C virus (HCV)-related liver fibrosis, the immune reconstitution associated with highly active antiretroviral therapy (HAART) may have the opposite effect. However, hepatotoxicity related to HAART could enhance the progression of liver fibrosis. Some retrospective studies have shown that therapy with the protease inhibitors may be associated with less severe liver fibrosis, whereas nevirapine use seems to correlate with faster progression. Low-grade liver toxicity associated with nevirapine could account for this effect. However, other studies have not confirmed these findings. Long-term prospective studies are needed to analyse the impact of antiretroviral drugs on the progression of HCV-related liver disease. Meanwhile, no specific recommendations can be made on the use of individual drugs or drug classes in HIV/HCV-coinfected patients. Most importantly however, the inherent benefits of HAART largely outweigh the risk of enhancing fibrosis progression. Additionally, in coinfected patients, other factors that promote fibrogenesis, such as alcohol consumption, should be avoided. Antiviral treatment of chronic hepatitis C could also reduce the risk of liver damage associated with HAART.     

Efficacy of interferon therapy in elderly patients with chronic hepatitis C

OBJECTIVE: We assessed the efficacy and safety of interferon (IFN) monotherapy in 84 elderly patients aged > or =65 years with chronic hepatitis C in a retrospective cohort study. METHODS: Twenty-two of the 84 elderly patients were treated with IFN at a dose of 6 million units daily for 6-8 weeks, 18 patients were treated 2-3 times a week for 24 weeks and 44 patients were treated daily for 2-8 weeks and 2-3 times a week for 16-24 weeks. RESULTS: A sustained virological response (SVR) occurred in 35.7% (30/84) of the patients by intention-to-treat analysis. Multivariate analysis showed that patients achieved a significant SVR when: (1) serum HCV-RNA level before IFN therapy was <100 KIU/ml (p < 0.0001) and (2) staging of liver fibrosis was mild (p = 0.040). Eleven (13.1%) patients discontinued the IFN regimen due to adverse events. Regarding factors predicting discontinuation of IFN, univariate analysis showed that patients aged >70 years were prone to drop out of therapy due to adverse events in IFN therapy (p = 0.009). CONCLUSION: Our results suggest that IFN administration is suitable for 65- to 70-year-old patients with chronic hepatitis C without genotype 1b and high virus load.     

Significant liver damage in patients with bleeding disorders and chronic hepatitis C: non-invasive assessment of liver fibrosis using transient elastography

Summary.  Background: Many patients with bleeding disorders have been infected with the hepatitis C virus (HCV), mainly with genotype 1. Antiviral treatment is only effective in 50% of these patients and is often accompanied by serious side effects. Consequently, careful selection of patients for treatment is warranted. Liver biopsies are generally not performed in these patients because of increased bleeding risk and high costs. We therefore assessed liver fibrosis and cirrhosis non-invasively using liver stiffness measurement (LSM). Methods: We enrolled 124 patients with bleeding disorders and chronic hepatitis C. Liver fibrosis was assessed by LSM using Fibroscan^®. In order to assess the validity of LSM in our hands, a separate group of 63 patients without bleeding disorders infected with HCV were evaluated with both LSM and biopsy. Results: In the validation study, liver elasticity was highly correlated with histological fibrosis stage (correlations coefficient 0.73, P  < 0.001). Based on LSM, 18% of patients with bleeding disorders and chronic hepatitis C had severe fibrosis, and 17% had cirrhosis after 34 years of infection (range 14–40). However, the prevalence of cirrhosis based on laboratory and ultrasonographic findings was only 7%. Independent risk factors for an increase in LSM were older age at infection, higher body mass index, presence of viral co-infection, and male gender. Fifteen out of 59 patients (25%) with an apparent indication for treatment (significant fibrosis by LSM) agreed to start antiviral therapy within 3 months. Conclusions: We found an unexpected high number of patients with significant fibrosis and cirrhosis in patients with bleeding disorders and hepatitis C detected by LSM, with considerable impact on the management of the disease.