Luminita Bonyhay

Fibrogenic impact of high serum glucose in chro nic hepatitis C

BACKGROUND/AIMS There is considerable variability in the rate of fibrosis progression in patients with chronic hepatitis C, most of which is related to factors so far unknown. We tested the hypothesis that high serum glucose and overweight might contribute to this variability. METHODS Seven hundred and ten patients with chronic hepatitis C with a known duration of infection and no hepatitis B virus or human immunodeficiency virus coinfection were studied. Significant fibrosis was defined as bridging fibrosis including cirrhosis. Variables were tested for their association with significant fibrosis. RESULTS In univariate analyses both serum glucose and body mass index were associated with fibrosis. In multivariate analyses, age at infection, duration of infection, serum glucose and daily alcohol intake but not body mass index were independently associated with significant fibrosis. Patients with high serum glucose had been contaminated at an older age and had features of the metabolic syndrome, including steatosis more frequently, as well as faster fibrosis progression rates. High serum glucose was associated with intermediate and advanced, but not with early, fibrosis stages. A high serum glucose was associated with a higher relative risk for significant fibrosis than overweight. CONCLUSIONS High serum glucose, is an independent co-factor of fibrosis in chronic hepatitis C with a higher pro-fibrogenic impact than overweight.

Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC) : Results of a phase II study

New systemic therapies are needed to improve the prognosis of patients with advanced‐stage hepatocellular carcinoma (HCC). In a Phase II trial involving previously untreated patients with advanced HCC, the more favorable schedule from a previous pilot study was evaluated.

Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest)

BackgroundBiochemical marker combinations, including α2-macroglobulin, haptoglobin, apolipoprotein A1, γ-glutamyl transpeptidase, and total bilirubin (all part of FibroTest) plus alanine aminotransferase (all part of ActiTest), are being developed as alternatives to liver biopsy in patients with chronic hepatitis C and other various chronic liver diseases. Considering this premise, the primary aim of this study was to assess the impact of meal intake on FibroTest and ActiTest results. Such studies are very important for patients, as many clinical errors have been related to the absence of baseline evidence.ResultsIntra-individual variation was assessed for the 6 above components and for FibroTest and ActiTest, by measuring time dependent variations before and one hour after a standard meal in 64 subjects. These consisted of 29 healthy volunteers and 35 patients with chronic liver diseases. Meal intake had no significant impact on any of the six components, or on FibroTest or ActiTest, as assessed by repeated measure variance analyses (ANOVA all p > 0.90); the Spearman correlation coefficient ranged from 0.87 (total bilirubin) to 0.995 (γ-glutamyl transpeptidase). The coefficients of variation (CV) between fasting and postprandial measurements fluctuated for the six components from 0.09 (apolipoprotein A1) to 0.14 (α2-macroglobulin), and from 0.09 for FibroTest to 0.13 for ActiTest. In contrast, meal intake had a significant impact on triglycerides (ANOVA p = 0.01, CV = 0.65) and glucose (ANOVA p = 0.04, CV = 0.31). As for the prediction of liver injury, the concordance between fasting and postprandial predicted histological stages and grades was almost perfect, both for FibroTest (kappa = 0.91, p < 0.001) and ActiTest (kappa = 0.80, p < 0.001).ConclusionsThe intra-individual variation of biochemical markers was low, and it was shown that measurements of FibroTest, ActiTest and their components are not significantly modified by meal intake. This fact makes the screening of patients at risk of chronic liver diseases more convenient.

Real-Time Shear Wave versus Transient Elastography for Predicting Fibrosis: Applicability, and Impact of Inflammation and Steatosis. A Non-Invasive Comparison.

Background and Aims Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. Methods We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. Results A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2–90.8), was significantly higher than that of TE, 85.6%(84.0–87.0; P<0.0001). In patients with non-advanced fibrosis (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI) 0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs 0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar results. Conclusions Elasticity results including very low minimal signal in the region of interest should be considered not reliable. 2D-SWE had a higher applicability than TE, the reference elastography, with less impact of inflammation and steatosis especially in patients with non-advanced fibrosis, as presumed by blood tests. Trial Registration ClinicalTrials.gov NCT01927133

Net Emergence of Substitutions at Position 28 on NS5A of Hepatitis C Virus Genotype 4 in Patients Failing Direct-Acting Antivirals by Next-Generation Sequencing

More data on resistance of HCV genotype (GT) 3 and 4 to direct-acting antivirals (DAAs) are still needed. Here we investigated the presence of resistance-associated substitutions (RASs) pre- and post-treatment and their emergence under DAAs in HCV GT3- and GT4-infected patients failing DAA regimens by next-generation sequencing (NGS). Sanger sequencing and NGS were performed on NS5B and NS5A in plasma samples prior to and post treatment of 13 patients. Positions implicated in resistance to anti-NS5A and anti-NS5B in the literature were analysed. No baseline RASs was detected in NS5B but one GT4r virus developed the mutation S282T at failure. In NS5A, pre-existing RASs or polymorphisms were detected in viruses of 6/10 patients (L28M for a GT4a, M28V for a GT4r, L30R for a GT4a, 2 GT4d and 1 GT4r, and T58P for a GT4d) by Sanger sequencing and in viruses of 7/10 patients by NGS. Additional baseline minority substitutions detected by NGS were Y93H in a GT3a, L28M in a GT4a and GT4d, and L28F in a GT4d virus. At failure, these substitutions were found at a frequency of 100%. Y93H was detected alone at baseline, whilst L28M and L28F were accompanied by polymorphisms L30R or L30R + T58P. Use of NGS in patients failing DAAs and infected by HCV GT3 and GT4 revealed the emergence of specific patterns of substitutions in NS5A and NS5B, in particular substitutions at position 28 in NS5A in GT4 virus, highlighting the need to list these substitutions in guidelines for resistance interpretation.