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Background In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. Aim To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. Methods A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5-15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. Results During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [ HR (95% CI)] [2.98 (95% CI 1.78-4.99); P < 0.0001] or severe steatosis [1.86 (1.34-2.58); P = 0.0002] was associated with an increased risk of mortality. In a multivariate Cox model adjusted for confounders: the presence of advanced fibrosis was associated with overall mortality [1.95 (1.12-3.41); P = 0.02]; advanced fibrosis at baseline [ n = 50/677; 1.92 (1.04-3.55); P = 0.04] and progression to advanced fibrosis during follow-up [ n = 16/127; 4.8 (1.5-14.9); P = 0.007] were predictors of cardiovascular events in patients with type-2 diabetes. In patients with a Framingham-risk score ≥20%, the presence of advanced fibrosis was predictive of cardiovascular events [2.24 (1.16-4.33); P < 0.05]. Conclusions Liver biomarkers, such as FibroTest and SteatoTest, have prognostic values in patients with metabolic disorders. FibroTest has prognostic value for predicting overall survival in patients with type-2 diabetes and/or dyslipidaemia. In type-2 diabetes, FibroTest predicted cardiovascular events and improved the Framingham-risk score. [ABSTRACT FROM AUTHOR]

. Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 ( P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count. [ABSTRACT FROM AUTHOR]

Background FibroTest has been validated for the diagnosis of liver fibrosis in patients with chronic hepatitis C. Aim To compare FibroTest with a new proteome-based model for the prediction of advanced liver fibrosis. Methods Sera from 191 consecutive patients with simultaneous liver biopsy and FibroTest on fresh sera were used for retrospective mass spectrometry analysis. A new fibrosis index was constructed combining proteomic peaks, selected on differential expression according to fibrosis stages in logistic regression analyses. The main end point was the diagnosis of advanced fibrosis on liver biopsy. Results Eight out of 1000 peaks were selected for the construction of the proteomic index. The area under the receiver operating curve (AUROC) of the proteomic index was 0.88 (95% CI: 0.82–0.92), significantly greater than the FibroTest AUROC of 0.81 (95% CI: 0.74–0.86; P = 0.04); the AUROC of the proteomic and FibroTest combination was 0.88 (95% CI: 0.83–0.92). Seven of the eight selected peaks were highly associated with the FibroTest score, with different patterns of association with the five components of FibroTest. Conclusions A proteomic index combining eight peaks had an excellent accuracy value for the diagnosis of advanced fibrosis in patients with chronic hepatitis C. However, despite a statistical significance, the small improvement delivered by proteomics impairs clinical applications because of its cost and its variability compared with the well validated FibroTest. [ABSTRACT FROM AUTHOR]

Background The best technique to estimate portal hypertension (PHT) is to measure the hepatic venous pressure gradient (HVPG), which is an invasive method. Aim To assess the relationship between the Fibrotest (Biopredictive, Paris, France) and the presence and degree of PHT in patients with liver disease, and to determine if the Fibrotest can diagnose severe PHT, defined by HVPG ≥ 12 mmHg, in cirrhotic patients. Methods Patients who underwent a transjugular liver biopsy were prospectively included. HVPG was measured, and classification of histological lesions assessed. The same day, blood samples for Fibrotest were performed. Results A total of 130 patients were included (no or minimal fibrosis: 12%, moderate fibrosis 17%, cirrhosis 71%). There was a significant correlation between Fibrotest and HVPG (Pearson correlation coefficient = 0.58, P < 0.0001), also weaker in cirrhotic patients (Pearson correlation coefficient = 0.24, P = 0.02). In cirrhotic patients, Fibrotest was significantly higher when there was a severe PHT (0.87 ± 0.15 vs. 0.73 ± 0.14, respectively, P = 0.02). The areas under the receiver operating characteristic curves for the diagnosis of severe PHT was 0.79 ± 0.07, not different from that of platelets and Child-Pugh score. Conclusion In patients with liver disease or cirrhosis, Fibrotest is correlated with the presence and degree of PHT. Other studies are needed to confirm these results, especially in non-decompensated cirrhotic patients. [ABSTRACT FROM AUTHOR]

Background Mortality related to complications of cirrhosis is increasing in patients with insulin-resistance factors. Hyperlipidaemic patients have multiple risk factors of insulin resistance. It is impossible to perform liver biopsy in such a large number of hyperlipidaemic patients to identify patients with advanced liver fibrosis or with steatohepatitis (non-alcoholic steatohepatitis, NASH). Aims To use the non-invasive biomarkers, FibroTest (FT), SteatoTest and NashTest, and to assess the prevalence of advanced liver disease in a large population of hyperlipidaemic patients. Methods A consecutive cohort of hyperlipidaemic patients was followed prospectively in a lipid centre and the sera were analysed retrospectively. Results A total of 2834 subjects were included: 1909 hyperlipidaemic patients and 925 blood donors (BD). Advanced fibrosis was identified by FT in 53/1909 (2.8%) hyperlipidaemic patients vs. 0/925 BD (0%) ( P < 0.0001); advanced steatosis in 569/1893 hyperlipidaemic patients (30.1%) vs. 8/164 (4.9%) BD ( P < 0.0001) and NASH in 132/1893 (7%) vs. 0/164 (0%), respectively ( P < 0.0001). There was a highly significant and linear association between the number of metabolic syndrome factors and liver disease prevalence – the highest being for type 2 diabetics: advanced steatosis 66%, NASH 24% and advanced fibrosis 6%. Conclusions The prevalence of fibrosis, steatosis and NASH in hyperlipidaemic patients appears to be high (3%, 30% and 7%, respectively). Biomarkers could be useful for screening of advanced fibrosis and NASH in patients with several metabolic syndrome factors, to prevent liver mortality. [ABSTRACT FROM AUTHOR]

A liver fibrosis index was recently prospectively validated in a cross-sectional study where patients infected by hepatitis C virus (HCV) had only one biopsy and no longitudinal follow-up. The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference. One-hundred and sixty-five patients who had had two interpretable liver biopsies and at least one stored serum sample before IFN treatment were selected. Seventy-eight patients received 3 MU of IFN-α thrice weekly for 24 weeks and 87 followed a reinforced regimen for 48 weeks. A fibrosis index combining five biochemical markers (α2-macroglobulin, haptoglobin, apolipoprotein A1, γ-glutamyl transpeptidase (GGT) and total bilirubin adjusted for gender and age) as well as hyaluronic acid was assessed on 461 samples available at baseline, at the end of treatment and at the end of follow-up (72 weeks). There was a significant decrease of the fibrosis index score among the 17 sustained virologic responders, from 0.33 ± 0.06 (mean ± SE) at baseline to 0.18 ± 0.06 at 72 weeks in comparison with 92 nonresponders (from 0.41 ± 0.03 at baseline to 0.44 ± 0.03 at 72 weeks; P < 0.001) and in comparison with 56 relapsers (from 0.36 ± 0.03 at baseline to 0.32 ± 0.03 at 72 weeks; P =0.05). No significant differences were observed for hyaluronic acid. Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis., Aim: To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis., Methods: We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high-risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2-macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha-fetoprotein., Results: A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3-9.4]. LCR1 and LCR2 time-dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high-LCR1 then high-LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0-99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5-98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis)., Conclusions: In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133., (© 2018 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non-alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver-related death., Aim: To validate the 10-year prognostic value of FibroTest in NAFLD for the prediction of liver-related death., Method: Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre-included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan-Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti-viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population., Results: 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow-up was 6.0 years (0.1-19.3). Ten year survival (95% CI) without liver-related death in patients with NAFLD was 0.956 (0.940-0.971; 38 events) and 0.832 (0.818-0.847; 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905-0.978)/1638 (342-7839) and even higher than in patients with CHC 0.875 (0.849-0.901; P = 0.01)/2657 (993-6586)., Conclusions: The FibroTest has a high prognostic value in NAFLD for the prediction of liver-related death. (ClinicalTrials.gov number, NCT01927133)., (© 2018 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)