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International audience; Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients. REDD1 deficiency protected mice from the development of hepatic steatosis induced by high-fat diet (HFD) without affecting body weight gain and glucose intolerance. This protection was associated with a decrease in the expression of lipogenic genes, SREBP1c, FASN, and SCD-1 in liver of HFD-fed REDD1-KO mice. Healthy mitochondria are crucial for the adequate control of lipid metabolism and failure to remove damaged mitochondria is correlated with liver steatosis. Expression of markers of autophagy and mitophagy, Beclin, LC3-II, Parkin, BNIP3L, was enhanced in liver of HFD-fed REDD1-KO mice. The number of mitochondria showing colocalization between LAMP2 and AIF was increased in liver of HFD-fed REDD1-KO mice. Moreover, mitochondria in liver of REDD1-KO mice were smaller than in WT. These results are correlated with an increase in PGC-1α and CPT-1 expression, involved in fatty acid oxidation. In conclusion, loss of REDD1 protects mice from the development of hepatic steatosis.

Macrovesicular steatosis (MS) is a major risk factor for liver graft failure after transplantation and pathological microscopic examination of a frozen tissue section remains the gold standard for its assessment. However, the latter requires an experienced in-house pathologist for correct and rapid diagnosis as well as specific equipment that is not always available. Smartphones, which are must-have tools for everyone, are very suitable for incorporation into promising technology to generate moveable diagnostic tools as for telepathology. The study aims to compare the microscopic assessment of nonalcoholic fatty liver disease (NAFLD) spectrum in liver allograft biopsies by a smartphone microscopy platform (DIPLE device) to standard light microscopy. Forty-two liver graft biopsies were evaluated in transmitted light, using an iPhone X and the microscopy platform. A significant correlation was reported between the two different approaches for graft MS assessment (Spearman's correlation coefficient: r = .93; p < .001) and for steatohepatitis feature (r = .56; p < .001; r = .45; p < .001). Based on these findings, a smartphone integrated with a cheap microscopy platform can achieve adequate accuracy in the assessment of NAFLD in liver graft and could be used as an alternative to standard light microscopy when the latter is unavailable.

Aliment Pharmacol Ther 2011; 33: 961–968 Summary Background Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C or the irritable bowel syndrome (IBS). Aim In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in chronic hepatitis C and IBS. Methods We enrolled 81 patients with chronic hepatitis C, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured. Results Fatigue scores were significantly more elevated in patients with chronic hepatitis C and IBS than in healthy subjects. Patients with chronic hepatitis C but not IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared with healthy subjects. In patients with chronic hepatitis C and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with chronic hepatitis C [OR = 2.019, P = 0.02, CI 95% (1.01–1.23)]. Conclusions In patients with chronic hepatitis C, the severity of fatigue is associated with a low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in chronic hepatitis C. The underlying mechanism of fatigue in IBS does not seem to involve carnitine.

Aims: The aims of this study were to determine whether alcohol consumption or cessation influences transient elastography (TE) measurements and whether TE is a useful tool to monitor alcoholic patients. Patients: Twenty-three consecutive heavy drinkers (20 men and 3 women; mean age 47.2 years) admitted for a 7-day hospitalization for alcohol detoxification were included. On admission (D0), a detailed medical history was taken and the following laboratory tests were performed [aspartate aminotransferase (ASAT), gamma glutamyltransferase (γGT), and carbohydrate-deficient transferrin (CDT) levels, and Fibroscan®]. All examinations were repeated on D8, D30, and D60. Variation in the median Fibroscan value of >20% was considered significant. Results: After 1 week of detoxification, the % variation in TE was −21.67 ± −27.6%. The median variation in TE between D8 and D60 was −20% in the abstinent group and 32% in the relapse group (p = 0.007). An increase in proportion of patients with a significant decrease in TE was observed with an increased duration of abstinence: 41.7% at D8 and 66.7% at D60. TE values were significantly correlated with ASAT, γGT, and CDT at D0 and D8, and with ASAT and γGT at D60. Conclusions: TE in alcoholics is influenced by major variations in the biochemical activity of the disease. The kinetics of variation of TE suggest that this method may be useful to assess alcohol abuse and control.

Aliment Pharmacol Ther 2010; 32: 1315–1322 Summary Background Non-invasive approaches are useful to differentiate simple steatosis from non-alcoholic steatohepatitis (NASH) in obese and morbidly obese patients. Aim To develop a new scoring system to diagnose definitive NASH. Methods Preoperative clinical and biological data including serum caspase 3-generated cytokeratin-18 fragments (CK18) and surgical liver biopsies were obtained from 464 morbidly obese patients who had undergone bariatric surgery. The cohort was divided into two groups: training group (n = 310) and validation group (n = 154). Definitive NASH was defined according to Kleiner’s classification with a Non-alcoholic fatty liver disease Activity Score (NAS) ≥5. Results Alanine aminotransferase (ALT), CK18 fragments and the presence of metabolic syndrome were independent predictors for discriminating patients with NAS ≥5 in the training group. These three parameters were used to carry out a scoring system for the prediction of NAS ≥5. Whereas serum CK18 fragment alone had an area under the receiver operating characteristic (AUROC) curve = 0.74, AUROC curves of the scoring system were 0.88 and 0.83 in the training group and the validation group, respectively. Conclusion A simple and non-invasive composite model (the Nice Model) including metabolic syndrome, ALT and CK18 fragments is able to predict accurately a non-alcoholic fatty liver disease activity score ≥5 in morbidly obese subjects.

Aliment Pharmacol Ther 2010; 32: 225–232 Summary Background Life-threatening bleeding caused by early spontaneous slippage of rubber bands has been described after variceal ligation in cirrhotic patients. Aim To determine the predictive factors of this complication in cirrhotic patients. Methods Among 605 patients, 21 patients (mean age 56.6 ± 13.5 years) developed 23 spontaneous band slippages with bleeding on post banding ulcer, as confirmed by endoscopy. Cirrhosis was alcoholic in 13 patients (62%), post viral hepatitis in three (14%) and from other causes in five (24%). A case-control study was performed comparing 17 from these patients who presented the complication after a first ligation with 84 of the 584 controls who underwent first endoscopic variceal ligation without bleeding complication. Results Bleeding occurred 13.5 days ± 7.3 (2–29) following ligation. Eleven patients died following the bleeding complication (52%). Using a multivariate analysis, previous upper variceal digestive bleeding [OR 12.07, 95%CI (2.3–63.43)], peptic oesophagitis [OR 8.9, 95%CI (1.65–47.8)], high platelet ratio index (APRI) score [OR 1.54, 95%CI (1.11–2.16)] and low prothrombin index [OR 0.54, 95% CI (0.31–0.94)] were independent predictive factors of bleeding. Conclusions Bleeding related to post-banding ulcer is a rare, but severe complication. The proposed predictive factors should be looked for and minimized before variceal ligation.