Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia

Heavy drinkers are at risk for a spectrum of histologic alcohol-related liver injury: steatosis, alcoholic steatohepatitis (ASH), alcohol-related fibrosis, and cirrhosis. Alcoholic hepatitis (AH), the clinical entity associated with severe ASH, has high short-term mortality. The standard-of-care therapy, prednisolone, has limited efficacy and many side effects; no other treatment has consistently shown survival benefit. The National Institute on Alcohol Abuse and Alcoholism (NIAAA)-funded Alcoholic Hepatitis Consortia carry out translational research on pathophysiologic mechanisms, genetic and environmental risk factors, phase II clinical trials, and development of biomarkers. The consortia members were convened by the National Institutes of Health to address diagnostic criteria and practical issues related to clinical AH research, and to develop a set of common data elements to harmonize ongoing and future trials. This was accomplished through 3 face-to-face meetings of the investigators and representatives of the National Institutes of Health, and subsequent electronic communications over the course of 6 months. Evidence for the recommendations was based on published trials and observational data from several of the consortia members. A draft manuscript was iteratively reviewed by members of the consortia. The goal was to reach agreements on recommendations and definitions that could facilitate trial design, and simultaneously be tested by research groups pooling their data. The recommendations made here are specifically directed to achieve better uniformity in clinical trials, rather than serving as clinical practice guidelines

Could caregiver reporting adherence help detect virological failure in Cameroonian early treated HIV-infected infants?

International audienceAbstractBackgroundViral load is still the marker of choice for monitoring adherence to combined antiretroviral therapy (cART) and confirming the success of HIV treatment. Unfortunately it is difficult to access in many resource-poor settings. We aimed to measure the performance of caregiver reporting adherence for detecting virological failure in routine practice during the first 2 years after cART initiation in infants.MethodsPEDIACAM is an ongoing prospective cohort study including HIV1-infected infants diagnosed before 7 months of age between November 2007 and October 2011 in Cameroon. Adherence was assessed using a questionnaire administered every 3 months from cART initiation; the HIV-RNA viral load was determined at the same visits. Virological failure was defined as having a viral load ≥ 1000 cp/mL at 3 and 12 months after cART initiation or having a viral load ≥ 400 cp/mL at 24 months after cART initiation. The performance of each current missed and cumulative missed dose defined according to adherence as reported by caregiver was assessed using the viral load as the gold standard.ResultscART was initiated at a median age of 4 months (IQR: 3–6) in the 167 infants included. The cumulative missed dose showed the best overall performance for detecting virological failure after 12 months of cART (AUC test, p = 0.005, LR + =4.4 and LR− = 0.4). Whatever the adherence reporting criterion, the negative predictive value was high (NPV ≥ 75 %) 12 and 24 months after cART initiation, whereas the positive predictive value was low (PPV ≤ 50 %).ConclusionsThe adherence questionnaire administered by the health care provider to the infants’ caregivers is not reliable for detecting virological failure in routine practice: its positive predictive value is low. However, the cumulative missed dose measurement may be a reliable predictor of virological success, particularly after 12 months of cART, given its high negative predictive value

Peroxisome Proliferator-Activated Receptors in HCV-Related Infection

The topic of peroxisome proliferator-activated receptors has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases such as chronic infection with hepatitis C virus (HCV). PPARs contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differentiation, and cell cycle. In vitro experiments and animal studies showed that PPARα discloses anti-inflammatory property, and PPARγ discloses anti-inflammatory, antifibrogenic, and antiproliferative properties in the liver. Experimental and human studies showed impaired PPARs expression and function during HCV infection. The available nonhepatotoxic agonists of PPARs may constitute a progress in the therapeutic management of patients chronically infected with HCV

Peroxisome Proliferator-Activated Receptors in HBV-Related Infection

Thirty years after its discovery, the hepatitis B virus (HBV) still remains a major global public health problem. Worldwide, two billion subjects have been infected, 350 million have a chronic infection and more than 600 000 die annually of HBV-related liver disease or hepatocellular carcinoma; new infections occur because of the presence of a large reservoir of chronic carriers of the virus. Since a decade several studies describe the interrelations between HBV and nuclear receptors and more particularly the peroxisome proliferator-activated receptors (PPARs). After a brief introduction, this review will make a rapid description of HBV incidence and biology. Then a report of the literature on the role of PPARs on viral transcription and replication will be developed. Finally, the role of HBV on PPARγ expression and activity will be discussed. Concluding remarks and perspectives will close this review

Alcohol-related liver disease: Areas of consensus, unmet needs and opportunities for further study

A joint meeting of the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) was held in London on September 30 and October 1, 2017. The goals of the meeting were to identify areas of broad agreement and disagreement, develop consensus, and determine future directions to ultimately reduce the burden, morbidity, and mortality of alcohol-related liver disease (previously termed alcoholic liver disease). The specific aims of the meeting were to identify unmet needs and areas for future investigation, in order to reduce alcohol consumption, develop markers for diagnosis and prognosis of disease, and create a framework to test novel pharmacological agents with pre-specified treatment endpoints

Étude des propriétés mécaniques, viscoélastiques et chimiques de films minces de mélanges de polymères

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Photothermal AFM-IR Depth Sensitivity: An Original Pathway to Tomographic Reconstruction

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