D. Amoruso

Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins.

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70‐kg person) were added for 8 weeks to the drinking water of rats who were being fed a high‐fat, high‐calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two‐fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF‐α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator‐activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF‐α and interferon‐γ and increased anti‐inflammatory interleukin‐4 and interleukin‐10. Conclusion: Our data demonstrate that coffee consumption protects the liver from damage caused by a high‐fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β‐oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (HEPATOLOGY 2010;52:1652‐1661)

Grown-up coeliac children: the effects of only a few years on a gluten-free diet in childhood

Aim : To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re‐exposed to gluten after only a few years and now on a gluten‐containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten‐free diet after childhood diagnosis.

Garlic extract prevents CCl4-induced liver fibrosis in rats: The role of tissue transglutaminase

BACKGROUND AND AIM Tissue transglutaminase contributes to liver damage in the development of hepatic fibrosis. In a model of neurodegeneration, the therapeutic benefit of cystamine has been partly attributed to its inhibition of transglutaminase activity. Garlic extract contains many compounds structurally related to cystamine. We investigated the anti-fibrotic effect of garlic extract and cystamine as specific tissue transglutaminase inhibitors. METHODS Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl(4)) for 7 weeks. Cystamine or garlic extract was administrated by daily intraperitoneal injection, starting from the day after the first administration of CCl(4). Hepatic function, histology, tissue transglutaminase immunostaining and image analysis to quantify Red Sirius stained collagen deposition were examined. Reverse transcription-polymerase chain reaction to detect alpha-SMA, IL-1beta and tissue transglutaminase expression and Western blot for tissue transglutaminase protein amount were performed. Transglutaminase activity was assayed on liver homogenates by a radio-enzymatic method. RESULTS Transglutaminase activity was increased in CCl(4) group and reduced by cystamine and garlic extract (p<0.05). Treatment with cystamine and garlic extract reduced the liver fibrosis and collagen deposition, particularly in the garlic extract group (p<0.01). Moreover, the liver damage improved and serum alanine aminotransferase was decreased (p<0.05). Tissue transglutaminase immunolocalised with collagen fibres and is mainly found in the ECM of damaged liver. Alpha-SMA, IL-1beta, tissue transglutaminase mRNA and tissue transglutaminase protein were down-regulated in the cystamine and garlic extract groups compared to controls. CONCLUSION These findings concurrently suggest that transglutaminase may play a pivotal role in the pathogenesis of liver fibrosis and may identify garlic cystamine-like molecules as a potential therapeutic strategy in the treatment of liver injury.

Etiology of and risk factors for transient and persistent aminotransferase elevation in a population of virus-free blood donors: a multicentre study.

AIM We evaluated the etiology and risk factors for transient and persistently elevated aspartate and/or alanine aminotransferase levels in virus-free blood donors. METHODS INCLUSION CRITERIA HBsAg/HBV-DNA and anti-HCV/HCV-RNA negative blood donors with elevated aspartate aminotransferase and/or alanine aminotransferase, observed in 5 blood transfusion centres in Italy from 2004 to 2005. Aspartate aminotransferase/alanine aminotransferase levels were measured at entry and every 2 months during a period of 6 months. RESULTS 291 individuals were evaluated (144 with persistent and 147 with transient abnormal aminotransferases). High body mass index was the most frequent (75.5%) etiological factor and was more common in the persistent elevated levels group, compared to the transient elevated levels group (82.0% vs 65.3%; p<0.01). Excessive alcohol intake (>2 units/day) was reported in 23.6%, with no differences between the two groups. Instead, recent use of medication or paint exposure were most frequently associated with transient elevated levels than persistent elevated levels (61.6% vs 23.3% for drugs and 13.7% vs 4.3% for paint, p<0.001). Considering the participants with transient elevated levels as controls, the multivariate analysis showed that high body mass index was the only independent predictor of persistent elevated aminotransferase levels (OR=5.3; 95%CI=1.88-13.42 for those with body mass index>29.9). CONCLUSIONS In virus-free blood donors, excessive body mass index is the most frequent etiological factor of abnormal aminotransferases and it is the sole risk factor associated with persistently elevated aminotransferases.