).q RSNA, 2014 Purpose:To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. Materials and Methods:The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. Results:SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P , .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). Abbreviations: AUC = area under the ROC curve CI = confidence interval CLD = chronic liver disease DANA = difference between the mean fibrosis stage of advanced fibrosis and the mean fibrosis stage of nonadvanced fibrosis HCV = hepatitis C virus ROC = receiver operating characteristic SWE = shear-wave elastography Author contributions:Guarantors of integrity of entire study, A.E.S., M.D.; study concepts/study design or data acquisition or data analysis/ interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, A.E.S., M.D., A.V., J.M.N., K.E.C.; clinical studies, A.E.S., A.V., A.K.B., J.M.N., K.E.C., R.T.C.; statistical analysis, M.D., E.F.H.; and manuscript editing, A.E.S., M.D., A.V., R.T.C. Funding:R.T.C. supported by the National Institutes of Health (grant DK078772).Conflicts of interest are listed at the end of this article. (1), with as many as 150 000 new cases diagnosed each year (2)-20% of which had cirrhosis at presentation. The multiple causes of CLD follow a common pathway of progressive liver fibrosis, ultimately culminating in cirrhosis. These include hepatitis C virus (HCV), hepatitis B virus, nonalcoholic fatty liver disease, and alcoholic liver disease (3). Although the prevalence of major causes of CLD remains stable, data from the National Health and Nutrition Examination Surveys show that nonalcoholic fatty liver disease will be a substantial burden on the prevalence of CLD in the United States (1). Advanced fibrosis, cirrhosis, and hepatocellular carcinoma develop in about 17%-55% of patients with HCV ...

HIV/HCV coinfection leads to accelerated hepatic fibrosis progression, with higher rates of cirrhosis, liver failure, and liver death than does HCV mono-infection. However, the profibrogenic role of HIV on hepatocytes and hepatic stellate cells (HSC) has not been fully clarified. We hypothesized that HIV, HCV induce liver fibrosis through altered regulation of the production of extracellular matrix and matrix metalloproteinases. We examined the fibrogenesis- and fibrolysis-related gene activity in LX2 HSC and Huh7.5.1 cells in the presence of inactivated CXCR4 and CCR5 HIV, as well as HCV JFH1 virus. The role of reactive oxygen species (ROS) upon fibrosis gene expression was assessed using the ROS inhibitor. Fibrosis-related transcripts including procollagen α1(I) (CoL1A), TIMP1, and MMP3 mRNA were measured by qPCR. TIMP1 and MMP3 protein expression were assessed by ELISA. We found that inactivated CXCR4 HIV and CCR5 HIV increased CoL1A, and TIMP1 expression in both HSC and Huh7.5.1 cells; the addition of JFH1 HCV further increased CoL1A and TIMP1 expression. CXCR4 HIV and CCR5 HIV induced ROS production in HSC and Huh7.5.1 cells which was further enhanced by JFH1 HCV. The ROS inhibitor DPI abrogated HIV-and HCV-induced CoL1A and TIMP1 expression. HIV and HCV-induced CoL1A and TIMP1 expression were also blocked by NFκB siRNA. Our data provide further evidence that HIV and HCV independently regulate hepatic fibrosis progression through the generation of ROS; this regulation occurs in an NFκB-dependent fashion. Strategies to limit the viral induction of oxidative stress are warranted to inhibit fibrogenesis.

Introduction Acute hepatitis C virus infection is associated with high rates of spontaneous clearance and variable rates of treatment-induced clearance. The benefit of early treatment versus awaiting spontaneous clearance is unknown, as is the optimal timing of treatment. Methods We performed a MEDLINE and EMBASE search for the time period 1950 to October 2008. All English language abstracts using the search terms acute hepatitis C, hepatitis C and acute and hepatitis C and acute disease or acute infection were reviewed. Bibliographies were reviewed. Results Twenty-two studies including 1075 patients met inclusion criteria. The sustained virologic response (SVR) rate for treated patients was 78%, significantly higher than 55.1% in untreated patients (OR =3.08, 95% CI 1.8-4.8 p value<0.0001). Mean time from diagnosis to spontaneous clearance was 9.7 weeks (SD 6.5). SVR rates varied inversely with time from acute HCV diagnosis. SVR rates for treatment within 12 weeks was 82.5% (95% CI 75.6-89.3), significantly better than the clearance rates in untreated patients (p<0.001). Response rates fell to 66.9% for treatment between 12 and 24 weeks, and decreased further to 62.5% for treatment beyond 24 weeks. Conclusions Rates of viral clearance in treated patients with acute hepatitis C virus infection were significantly higher than that in untreated patients. Treatment rates were highest when treatment was initiated within 12 weeks of diagnosis. Based on these findings, we would advocate a 12 week period of observation for spontaneous clearance before treatment initiation. If no clearance has occurred by 12 weeks, treatment should be initiated.

Background and Aims-HCV related liver disease is one of the most important complications in persons with HIV, with accelerated fibrosis progression in coinfected persons compared to those with HCV alone. We hypothesized that HIV coinfection increases HCV related hepatocyte apoptosis and that HCV and HIV influence TRAIL signaling in hepatocytes.