Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin.

Background & Aims: BI 207127 is a potent non-nucleoside hepatitis C virus (HCV) NS5B polymerase inhibitor in vitro.

Methods: In this double-blind, placebo-controlled study, 57 HCV genotype (GT)-1 patients (n=27 treatment-naïve [TN]; n=30 treatment-experienced [TE]) with compensated liver disease were randomised for 28-day treatment with 400, 600, or 800 mg BI 207127 three times daily (TID) or placebo (only TN) in combination with peginterferon alfa 2a and ribavirin (PegIFN/RBV). Plasma HCV RNA was measured by Roche COBAS TaqMan assay.

Screening for liver fibrosis by using FibroScan(®) and FibroTest in patients with diabetes.

Background: Patients with diabetes are at risk for nonalcoholic fatty liver disease leading to cirrhosis. Existing guidelines do not advocate screening for liver related complications amongst persons with diabetes.

Aim: The aim of this prospective study was to identify patients with severe liver fibrosis amongst patients hospitalized for their diabetes, using non-invasive methods, and to evaluate factors associated with severe fibrosis.

Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®.

Background & Aims: Unreliable results of liver stiffness measurement are obtained in 16% of cases and are independently associated with body mass index (BMI) greater than 30 kg/m(2). A new FibroScan® probe (XL probe) was designed specifically for obese patients. The aim of this study was to evaluate the accuracy of liver stiffness measurement using M and XL probes of Fibroscan® for the diagnosis of fibrosis and cirrhosis in a large cohort of patients.

Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive.

Unlabelled: The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis.

Relative performances of FibroTest, Fibroscan, and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis C: a step toward the truth in the absence of a gold standard.

Background & Aims: Liver fibrosis stage is traditionally assessed with biopsy, an imperfect gold standard. Two widely used techniques, FibroTest®, and liver stiffness measurement (LSM) using Fibroscan® have been validated using biopsy, and therefore the true performances of these estimates are still unknown in the absence of a perfect reference. The aim was to assess the relative accuracy of FibroTest, LSM, and biopsy using methods without gold standard in patients with chronic hepatitis C (CHC) and controls.

FibroTest and Fibroscan performances revisited in patients with chronic hepatitis C. Impact of the spectrum effect and the applicability rate.

Background: Two widely used biomarkers of fibrosis, FibroTest and liver stiffness measurement (LSM), have been mostly validated in patients with chronic hepatitis C (CHC) using the standard area under the ROC curve (sAUROC) which is not the most appropriate method due to the risk of fibrosis spectrum effect. Furthermore the performance of these biomarkers have not been assessed in "intention to diagnose" which takes into account the failures and non-reliable results.

Aim: The aim was to compare the accuracy of FibroTest and LSM for the diagnosis of fibrosis using sAUROC, the pairwise comparison of fibrosis stages by Obuchowski measure (wAUROC), and these AUROCs reassessed after taking into account the applicability rates.

Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study.

Background & Aims: Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC).

Pharmacological exposure to ribavirin: a key player in the complex network of factors implicated in virological response and anaemia in hepatitis C treatment.

Ribavirin remains today a pivotal drug in the treatment of hepatitis C; in standard double therapy, as well as in triple combination with direct antiviral agents, ribavirin reduces relapse and can double the sustained virological response obtained with peginterferon alone or in association with direct antiviral agents. In the complex network of interacting factors determining sustained virological response independently of known predictive factors related to host and virus, two modern tools are emerging: polymorphisms in the IL28B gene and very early exposure to ribavirin. The use of a pharmacokinetic-pharmacodynamic model of early ribavirin exposure to adjust the dose individually would help promote a safer ribavirin use and improve sustained virological response.

A new combination of blood test and fibroscan for accurate non-invasive diagnosis of liver fibrosis stages in chronic hepatitis C.

Objectives: Precise evaluation of the level of liver fibrosis is recommended in patients with chronic hepatitis C (CHC). Blood fibrosis tests and Fibroscan are now widely used for the non-invasive diagnosis of liver fibrosis. Detailed fibrosis stage classifications have been developed to provide an estimation of the liver fibrosis stage from the results of these non-invasive tests.

Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C.

Background & Aims: Liver stiffness can be measured noninvasively to assess liver fibrosis in patients with chronic hepatitis C. In patients with chronic liver diseases, level of fibrosis predicts liver-related complications and survival. We evaluated the abilities of liver stiffness, results from noninvasive tests for fibrosis, and liver biopsy analyses to predict overall survival or survival without liver-related death with a 5-year period.

A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease associated with increased morbidity and mortality. Ursodeoxycholic acid (UDCA) may have antioxidant, anti-inflammatory, and antifibrotic properties and may reduce liver injury in NASH. To date, no studies have assessed the efficacy and safety of high-dose UDCA (HD-UDCA) in patients with NASH.

A protective role for CD154 in hepatic steatosis in mice.

Unlabelled: Inflammation and lipid metabolism pathways are linked, and deregulation of this interface may be critical in hepatic steatosis. The importance of the dialog between inflammatory signaling pathways and the unfolded protein response (UPR) in metabolism has been underlined. Herein, we studied the role of CD154, a key mediator of inflammation, in hepatic steatosis.

Transient elastography for the diagnosis of liver fibrosis.

Transient elastography (FibroScan(®)) is a noninvasive method proposed for the assessment of liver fibrosis in patients with chronic liver diseases by measuring liver stiffness. It can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. FibroScan is validated for the diagnosis of significant fibrosis and cirrhosis in chronic hepatitis C, in recurrence of hepatitis C after liver transplantation, in co-infected HIV-HCV patients, in chronic hepatitis B, in chronic cholestatic diseases, in alcoholic disease and in nonalcoholic fatty liver disease.

Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes.

There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.

Assessment of liver fibrosis with transient elastography and FibroTest in patients treated with methotrexate for chronic inflammatory diseases: a case-control study.

Background & Aims: Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX-liver toxicity. The aim of this case-control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX.

Feasibility of liver transient elastography with FibroScan using a new probe for obese patients.

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2-10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI) > or =30 kg/m(2).

Methods: For each patient, LSM was performed using both M probe (currently available and dedicated to patients with standard morphology) and XL probe (dedicated to overweighed patients).

Gastric variceal bleeding uncovering a rare association of CREST syndrome, primary biliary cirrhosis, nodular regenerative hyperplasia and pulmonary hypertension.

A 73-year-old woman was admitted after the first upper gastric tract haemorrhage due to gastric variceal bleeding. A CREST syndrome associated with Hashimoto's thyroiditis, Gougerot-Sjögren syndrome, cryoglobulinaemia and complicated with severe pulmonary hypertension was diagnosed. Liver histology found precirrhotic lesions of primary biliary cirrhosis (PBC) and nodular regenerative hyperplasia (NRH).

Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease.

Unlabelled: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology.

Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations.

Unlabelled: Liver stiffness measurement (LSM) based on transient elastography (TE, FibroScan) is gaining in popularity for noninvasive assessment of liver fibrosis. However, LSM has limitations, which have not yet been thoroughly evaluated. We prospectively investigated the frequency and determinants of LSM failure and unreliable results over a 5-year period, based on 13,369 examinations (134,239 shots).

Prospective comparison of two algorithms combining non-invasive methods for staging liver fibrosis in chronic hepatitis C.

Background & Aims: Non-invasive assessment of liver fibrosis is a challenging area. Several methods have been proposed in patients with chronic hepatitis C (CHC) but their performance may be improved when they are combined as suggested by recently proposed algorithms using either transient elastography (TE) and Fibrotest (FT) (Castera) or AST-to-Platelet Ratio Index (APRI) and FT (SAFE biopsy). The aim of this prospective study was to compare the performance of these two algorithms for diagnosing significant fibrosis and cirrhosis in 302 CHC patients.

Usefulness of noninvasive tests in nodular regenerative hyperplasia of the liver.

Background: The only way to diagnose nodular regenerative hyperplasia (NRH) is liver biopsy.

Aim: To evaluate in a prospective study the performance of noninvasive liver investigations in patients with NRH.

Methods: All consecutive patients with NRH who were being followed up in our unit from 2004 to 2007 were included.

The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis.

Background And Aims: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm.

Methods: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included.

Overestimation of liver fibrosis staging using transient elastography in patients with chronic hepatitis C and significant liver inflammation.

Background: Transient elastography (TE) is a non-invasive method that allows liver fibrosis staging on the basis of hepatic stiffness measurements. Little is known about the influence of chronic liver inflammation on the stiffness of hepatic tissue.

Methods: A total of 112 patients with chronic hepatitis C underwent a liver biopsy and TE.