Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure

Fluroquinolone antibiotics have been reported to have antiviral properties against RNA viruses, including hepatitis C virus (HCV). In the present study, five patients with advanced liver disease secondary to chronic HCV received 500 mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as antiviral agents for chronic HCV in patients with advanced liver disease appears to be limited.     

CC族趋化因子受体基因多态性在乙型肝炎肝硬化中的作用

目的 研究CC族趋化因子受体基因多态性与乙型肝炎肝硬化之间的关联及其在乙型肝炎肝硬化发生、发展中的作用.方法 采用聚合酶链反应(PCR)扩增及聚合酶链反应一限制性片段长度多态性(PCR-RFLP)检测技术,对121例乙型肝炎肝硬化患者和138例正常人群中CCR5△32、CCR2-64I、CCR5-promoter-59029G/A的基因多态性分布差异进行检测.结果 CCR5△32等位基因突变在肝硬化和正常人群中均很少发生,在121例肝硬化和138例正常人群中均未发现CCR5△32等位基因突变个体.CCR5-promoter-59029A/A基因型的比例在肝硬化人群中较正常人群高(22.3%vs 14.5%,P＜0.05),而对照组中,CCR5-promoter-59029G/G基因型的比例较肝硬化组高(42.O%vs 31.4%,P＜0.05).在肝硬化组中CCR5-promoter-59029G/A基因型的分布在丙氨酸转氨酶(ALT)正常和异常组问的差别具有统计学意义:正常组CCR5-promoter-59029G/G基因型的比例高于酶学异常组(40.4%vs23.4%,P＜0.05),CCR5-promoter-59029A/A基因型的比例较酶学异常组低(15.8%vs 28.1%,P＜0.05).CCR2-64I基因多态性在肝硬化和正常人群中的差异无统计学意义.结论 CCR5-promoter-59029A/A基因型对于肝硬化是不利因素,它增强细胞免疫反应并导致肝细胞炎症加重(ALT升高)从而促进肝硬化的发展.     

Monoclonal immunoglobulinopathy in chronic active hepatitis and liver cirrhosis

The clinico-laboratory and morphological studies were performed to examine and characterize 15 patients with chronic active hepatitis and liver cirrhosis mainly of viral etiology, going in association with monoclonal immunoglobulinopathy. The diagnostic difficulties determined by the syndrome of monoclonal immunoglobulinopathy are demonstrated. The results of a long follow-up (up to 17 years) of the indicated patients' group are provided. A possible role is discussed of hepatitis B virus as a source of long antigenic stimulation in the origin of monoclonal immunoglobulinopathy in chronic diffuse diseases of the liver.     

Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases

BACKGROUND: Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases. METHODS: Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16). RESULTS: A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns. CONCLUSIONS: These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.     

Significance of serum matrix metalloproteinases and their inhibitors on the antifibrogenetic effect of interferon-alfa in chronic hepatitis C patients

OBJECTIVE AND METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determination of deposition and breakdown of the extracellular matrix. To investigate the antifibrogenetic effect of interferon-alpha (IFN-alpha) treatment on factors regulating hepatic fibrosis, serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels were measured by the one-step sandwich enzyme immunoassay in 27 patients with chronic hepatitis C and compared with the histological status of the patients before and at the end of treatment. RESULTS: After 6 months of IFN-alpha treatment, the histological status of liver fibrosis showed improvement in 9 patients (IF group) and no change or a worsening in 18 patients (NIF group). Compared with pretreatment levels, in the IF group, IFN treatment caused a significant increase in the MMP-1/TIMP-1 ratio. In the NIF group, however, the MMP-1/TIMP-1 ratio tended towards a decrease; moreover, there was not only a significant increase in TIMP-2 levels but also a tendency towards an increase in TIMP-1 levels. CONCLUSION: These results suggested that an elevated MMP-1/TIMP-1 ratio may ameliorate liver fibrosis by interferon in cases of chronic hepatitis C, whereas elevated levels of TIMP-1 and TIMP-2 might impede improvement.     

Diagnostic implications of extracellular matrix proteins in chronic hepatitis and hepatic cirrhosis

Enzyme immunoassay measured concentrations of basic extracellular matrix proteins, collagen type 3 (C-3) and fibronectin, in blood plasm of 119 patients with chronic hepatic diseases. 30, 16, 18, 6 and 49 of them had chronic hepatitis of minimal activity (MiACH), that of moderate activity (MACH), intermediate activity (CHIA), high activity (HACH) and hepatic cirrhosis (HC), respectively. The highest C-3 level occurred in C-stage HC, the lowest--in MiACH. Fibronectin was the highest in HACH, minimal--in C-stage HC. C-3 and fibronectin levels correlated with severity of mesenchymal-inflammatory syndrome in CH and HC; in CHIA, HACH and in B-stage HC--with cytolysis markers. A direct relationship was found between protein-synthetizing function of hepatocytes and fibronectin levels in CHIA, HACH and HC while it was inverse in relation to C-3 amount in HC. Thus, tests for plasm C-3 and finronectin expand potentialities of laboratory diagnosis of the process activity in CH and HC, allow prediction of probability of CH transformation into HC.