Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C

AIM：To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C （CHC）.METHODS： Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group （stage 0）. Twentyfive patients with sustained virological response （SVR） to interferon （IFN） therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness （LS） was performed by elastography.RESISTS： Medians （50% levels） of LS were 4.1 （3.5-4.9）, 6.3 （4.8-8.5）, 8.8 （6.8-12.0）, 14.6 （10.5-18.6）, and 22.2 （15.4-28.0）, respectively, in the fibrosis stages 0-4 （P 〈 0.001）. LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 （3.5-5.6）, 5.2 （4.4-6.8）, 6.8 （6.1-7.6）, and 6.1 （3.6-7.9）, respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide.CONCLUSION： LS correlated well with the histological stage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.

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.

Natural history of major complications in hepatitis C virus-related cirrhosis evaluated by per-rectal portal scintigraphy

AIM: To examine the correlation between the porto-systemic hypertension evaluated by portal shunt index (PSI) and life-threatening complications, including hepatocellular carcinoma (HCC), liver failure (Child-Pugh stage progression), and esophagogastric varices. METHODS: Two hundred and twelve consecutive subjects with HCV-related cirrhosis (LC-C) underwent per-rectal portal scintigraphy. They were allocated into three groups according to their PSI: group Ⅰ, PSI≤10%; group Ⅱ, 10%<PSI<30%; and group Ⅲ, 30%≤PSI. Of these, selected 122 Child-Pugh stage A (Child A) subjects were included in analysis (a mean follow-up period of 5.9±5.4 years, range 6 mo-21 years). RESULTS: No significant correlation between PSI and cumulative probability of HCC incidence was observed. Cumulative probability of Child A to B progression was tended to be higher in group Ⅲ than in group Ⅰ, and significantly higher in group Ⅲ than in group Ⅱ (62% vs 34%, 62% vs 37%; P = 0.060, <0.01; respectively). Cumulative probability of varices tended to be higher in group Ⅲ than in group Ⅰ (31% vs 12%, P = 0.090). On multivariate analyses, significant correlation between PSI and Child A to B progression was observed, and no significant correlation between PSI and HCC incidence or varices progression was observed. CONCLUSION: Patients with LC-C of Child A will progress to Child B rapidly after their PSI reaches 30% or higher. PSI can be used to predict occult progressive porto-systemic shunting and liver failure non-invasively. It indicates that PSI may play an important role in follow-up of the porto-systemic hypertension gradient for outpatients with LC unlike hepatic venous catheterization.