A new index for non-invasive assessment of liver fibrosis

AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.

Effect of herbal medicine Juzentaihoto on hepatic and intestinal heat shock gene expression requires intestinal microflora in mouse

AIM: To evaluate the role of intestinal microflora in the effects of multi-herbal medicine on gene expression in the gut and liver. METHODS: The multi-herbal medicine Juzentaihoto (JTX) was administered to five germ-free mice and regular mice for 2 wk. Among the results of the comprehensive gene chip analysis of the intestine and liver, we featured heat shock proteins (HSPs) 70 and 105 because their gene expression changed only in the presence of microflora. Real-time RT-PCR was performed to confirm the expression levels of these HSP genes. To determine whether JTX acts directly on the HSP genes, sodium arsenite (SA) was used to induce the heat shock proteins directly. To examine the change of the intestinal microflora with administration of JTX, the terminal restriction fragment polymorphism (T-RFLP) method was used. To identify the changed bacteria, DNA sequencing was performed. RESULTS: Heat shock protein gene expression,documented by gene chip and real-time RT-PCR, changed with the administration of JTX in the regular mice but not in the germ-free mice. JTX did not suppress the direct induction of the HSPs by SA. T-RFLP suggested that JTX decreased unculturable bacteria and increased Lactobacillus johnsoni. These data suggested that JTX changed the intestinal microflora which, in turn, changed HSP gene expression. CONCLUSION: Intestinal microflora affects multi-herbal product JTX on the gene expression in the gut and liver.

Changes of shear-wave velocity by interferon-based therapy in chronic hepatitis C

AIM: To evaluate the changes of shear-wave velocity(Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C.METHODS: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon(IFN) plus ribavirin(RBV). Vs value(m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment(EOT), 1 year after EOT, and 2 years after EOT.RESULTS: In patients with a sustained virological response(SVR)(n = 41), Vs significantly decreased at EOT [1.19(1.07-1.37), P = 0.0004], 1 year after EOT [1.10(1.00-1.22), P = 0.0001], and 2 years after EOT [1.05(0.95-1.16), P < 0.0001] compared with baseline [1.27(1.11-1.49)]. In patients with a relapse(n = 26), Vs did not significantly decrease at EOT [1.23(1.12-1.55)], 1 year after EOT [1.20(1.12-1.80)], and 2 years after EOT [1.41(1.08-2.01)] compared with baseline [1.39(1.15-1.57)]. In patients with a nonvirological response(n = 20), Vs did not significantly decrease at EOT [1.64(1.43-2.06)], 1 year after EOT [1.66(1.30-1.95)], and 2 years after EOT [1.61(1.36-2.37)] compared with baseline [1.80(1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28(1.04-1.40)] than in non-SVR patients [1.56(1.20-1.83)](P = 0.0142).CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.