Liver Cirrhosis

Sleep-wake abnormalities are common in patients with cirrhosis but their evaluation is time consuming and laborious. The aim of this study was to assess the validity of a simple Sleep Timing and Sleep Quality Screening questionnaire (STSQS) against an established sleep quality questionnaire and daily sleep diaries.

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular carcinoma (HCC); nevertheless, the drug was authorized without restrictions based on liver function. Therefore, we planned to test sorafenib efficacy and safety in patients with HCC and deteriorated liver function (CP-B).

Methods: This was an open-label, multicenter, randomized phase 3 trial. Patients with HCC, no previous systemic therapy, and CP-B score 7-9 were assigned 1:1 to best supportive care alone (control arm) or with standard dose sorafenib (experimental arm). Overall survival (OS) was the primary endpoint. To detect a 0.70 HR of death, with 80% power, and two-tailed α error 0.05, 234 events were required. The study closed prematurely because of slow accrual. Descriptive analyses are reported.

Results: From 2012 to 2017, 13 Italian centers randomized 35 patients. In total, 28 deaths were recorded, 12 without and 16 with sorafenib; median OS was 4.9 (95%CI: 1.2-5.6) and 3.5 months (95%CI: 1.3-5.3), respectively. At least one severe adverse event was reported in 2/15 (13.3%) without and 9/17 (52.9%) patients with sorafenib.

Conclusions: This trial failed its planned enrolment goal, showing the difficulty in performing clinical trials with drugs already registered with a label broader than what available evidence supports.

The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Global prevalence of non-alcoholic fatty liver disease (NAFLD) and of NAFLD-hepatocellular carcinoma (HCC) is estimated to grow in the next years. The burden of NAFLD and the evidence that NAFLD-HCC arises also in non-cirrhotic patients, explain the urgent need of a better characterization of the molecular mechanisms involved in NAFLD progression. Obesity and diabetes cause a chronic inflammatory state which favors changes in serum cytokines and adipokines, an increase in oxidative stress, DNA damage, and the activation of multiple signaling pathways involved in cell proliferation. Moreover, a role in promoting NAFLD-HCC has been highlighted in the innate and adaptive immune system, dysbiosis, and alterations in bile acids metabolism. Several dietary, genetic, or combined mouse models have been used to study nonalcoholic steatohepatitis (NASH) development and its progression to HCC, but models that fully recapitulate the biological and prognostic features of human NASH are still lacking. In humans, four single nucleotide polymorphisms (PNPLA3, TM6SF2, GCKR, and MBOAT7) have been linked to the development of both NASH and HCC in cirrhotic and non-cirrhotic patients, whereas HSD17B13 polymorphism has a protective effect. In addition, higher rates of somatic ACVR2A mutations and a novel mutational signature have been recently discovered in NASH-HCC patients. The knowledge of the molecular pathogenesis of NAFLD-HCC will be helpful to personalized screening programs and allow for primary and secondary chemopreventive treatments for NAFLD patients who are more likely to progress to HCC.

Background: This study compares two methods of liver elasticity determination, Shear Wave Elasticity (SWE) and Trancient Elastography (VCTE-Fibroscan). Images will be provided by a group of patients with chronic parechymal liver diseases which will be compared against histological liver biopsy findings of the same patients.