rome and Hepatitis-C--Chronic

HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p<0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p<0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established.

Topics: Antiviral Agents; Blood Glucose; Cohort Studies; Diabetes Complications; Hepacivirus; Hepatitis C, Chronic; Humans; Kinetics; Liver Cirrhosis; Retrospective Studies; Rome; Viral Load

Association between hepatitis C virus (HCV) infection and diabetes has been widely postulated. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycaemic control. The aim of our study was to evaluate the glycaemic control modifications in a case series of HCV-positive diabetic patients receiving DAAs. We retrospectively evaluated 149 HCV-positive patients in two different institutions affiliated with Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with type 2 diabetes mellitus (19% of total population) who were receiving different interferon-free regimens. During-treatment fasting glucose (FG) values were available for 21 patients, and analysis revealed a statistically significant reduction (p 0.007); reduction mean value was -52.86 mg/dL. A glycated haemoglobin (A1C) value during treatment (at weeks 4, 8 and/or 12) was available for ten patients, and the analysis revealed a statistically significant reduction (p 0.021) with a reduction mean value of -1.95%. Six patients (23%) needed to reduce hypoglycaemic drugs, eight of ten patients showed reduction of A1C and 14 (67%) of 21 patients showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, body mass index and HIV status. In order to avoid hypoglycaemic events, diabetic patients receiving DAAs should be closely monitored for reduction of hypoglycaemic drugs. Furthermore, in our opinion, diabetes could be considered as an element to prioritize treatment in those patients with no apparent liver disease.

Topics: Adult; Aged; Antiviral Agents; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hepatitis C, Chronic; Humans; Male; Middle Aged; Retrospective Studies; Rome

We report herein the 10-year outcome of the Tor Vergata weaning off immunosuppression protocol in hepatitis C virus (HCV) liver transplant patients. Thirty-four patients who had received a liver graft for HCV-related cirrhosis were enrolled in a prospective study in which they were progressively weaned off immunosuppression. The primary endpoints were feasibility and safety of the weaning; the second aim was to assess fibrosis progression. At the 10-year follow-up, of the eight original tolerant patients, six remained IS-free. Of the 26 individuals who could not be weaned, 22 were alive. When the baseline biopsies were compared with the 10-year biopsies, the tolerant group showed no differences in staging, whereas the nontolerant group showed a significant increase in staging. The fibrosis progression rates calculated for the tolerant and the nontolerant groups were -0.06 ± 0.12 and 0.1 ± 0.2, respectively (P = 0.04). Furthermore, with the last taken biopsies, nine nontolerant patients were showing frank cirrhosis versus no cirrhosis among the tolerant patients. After a 10-year follow-up of a Tor Vergata weaning protocol, 6/34 patients completed follow-up without reinstitution of immunosuppression and this appeared beneficial regarding a reduction in fibrosis progression.

Topics: Age Factors; Aged; Biopsy, Needle; Cohort Studies; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Hepatitis C, Chronic; Hospitals, University; Humans; Immunohistochemistry; Immunosuppression Therapy; Immunosuppressive Agents; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Retrospective Studies; Risk Assessment; Rome; Sex Factors; Survival Analysis; Time Factors; Transplantation Immunology; Treatment Outcome

Notwithstanding numerous evidences implicating toll-like receptor-4 (TLR4) in the pathogenesis of chronic hepatitis C virus (HCV) infection, the localization and level of TLR4 expression in the liver of patients with hepatitis C have never been investigated. We aimed to evaluate, by means of immunohistochemistry and real-time PCR (rt-PCR), hepatic TLR4 expression in patients with chronic HCV infection. Fifty patients who had undergone liver biopsy and 11 patients transplanted because of chronic HCV infection, and 12 controls free of liver disease, were included in the study. Each case was analyzed by immunohistochemistry for TLR4, α-smooth muscle actin and cytokeratin-7 (CK-7), and a subgroup of patients and all controls by rt-PCR for TLR4. Immunohistochemistry for α-smooth muscle actin was used to derive a score of activation of hepatic stellate cells and portal/septal myofibroblasts, while immunohistochemistry for CK-7 was used to evaluate and count hepatic progenitor cells, interlobular bile ducts and intermediate hepatocytes. In patients, the parenchymal elements responsible for the highest TLR4 level of expression were hepatic progenitor cells and biliary epithelial cells of interlobular bile ducts. Double-labeling experiments between anti-TLR4 and anti-CK7, anti-CD133, anti-CD44, anti-neural cell adhesion molecule, anti-epithelial cell adhesion molecule and anti-sex determining region Y-box 9, confirmed these findings. TLR4-positive hepatic progenitor cells and interlobular bile ducts were significantly correlated with the stage of liver disease (P<0.001), the grade of inflammation (P<0.001), and the activity of portal/septal myofibroblasts (P<0.001). rt-PCR study confirmed an increased TLR4 expression in the 26 patients analyzed with respect to controls (P<0.001). TLR4 expression positively correlated with fibrosis (P<0.05) and inflammation (P<0.05). The present results suggest that TLR4 expression by hepatic progenitor cells and biliary epithelial cells contributes to the progression of liver damage in the course of chronic HCV-related infection.

Topics: Adult; Aged; Analysis of Variance; Bile Ducts; Biomarkers; Biopsy; Case-Control Studies; Chi-Square Distribution; Disease Progression; Epithelial Cells; Female; Hepatic Stellate Cells; Hepatitis C, Chronic; Hepatocytes; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Male; Microscopy, Fluorescence; Middle Aged; Myofibroblasts; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rome; Stem Cells; Toll-Like Receptor 4

Histology is the gold standard by which to diagnose and score hepatic fibrosis. Recently, it has been proposed that hepatic magnetic resonance spectroscopy (MRS) could provide an accurate representation of the disease process. The aim of this study was to correlate the in vivo high-field (3-Tesla) (1)H MRS features of noncirrhotic chronic hepatitis C patients stratified according to the histopathological stages of fibrosis.. Six healthy controls and 23 patients with biopsy-proven precirrhotic hepatitic C virus (HCV)-related liver disease were included. The subdivision of patients into the histopathological stages of fibrosis was based on the Ishak fibrosis (F) scoring system: mild hepatitis (0< or =F< or =1), moderate (2< or =F< or =3) and severe hepatitis (4< or =F< or =5). For correlation analysis, the Spearman nonparametric test was used. Differences between groups were calculated with the nonparametric Mann-Whitney U test. A p value <0.05 was considered significant. The particular metabolite content was evaluated in relative units (RU), according to the pattern metabolite/H(2)O=area of the metabolite x1,000/area of nonsuppressed water.. A significant statistical difference was observed between control vs. mild and moderate vs. severe disease severity in choline-containing compounds (CCC)/H(2)O ratios (p=0.0379 and p=0.0003) and in glutamine/glutamate (Glx)/H(2)O ratios (p=0.004 and p<0.0001), whereas a statistically significant difference in the lipid/H(2)O ratios was achieved only between control vs. moderate and between moderate vs. severe stages of disease (p=0.011 and p=0.0030).. High-field (1)H MRS successfully differentiates between mild/moderate vs. severe stages of chronic hepatitis and can be considered a complement to most standard imaging protocols in the liver.

Topics: Aged; Case-Control Studies; Diagnosis, Differential; Female; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Magnetic Resonance Spectroscopy; Male; Middle Aged; Retrospective Studies; Rome; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric