Sezione di Gastroenterologia
Sezione di Gastroenterologia
Thabet K.,University of Sydney |
Chan H.L.Y.,Chinese University of Hong Kong |
Petta S.,Sezione di Gastroenterologia |
Berg T.,Section of Hepatology |
And 5 more authors.
Hepatology | Year: 2017
Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patients underwent gene expression analysis to assess the functional consequences of rs641738 on hepatic MBOAT7 expression. The minor allele (T) of rs641738 was associated with greater inflammation (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.95; P = 0.001) and fibrosis (OR = 1.31; 95% CI, 1.19-1.92; P = 0.01). Risk allele frequency in whites (0.43) was greater than in Chinese (0.24), translating to a larger size effect in the former. The rs641738 (T) allele was associated with lower hepatic MBOAT7 expression (P = 0.008), and the latter was associated with serum liver enzymes and inflammation. Neither patatin-like phospholipase domain-containing protein 3 rs738409 nor transmembrane 6 superfamily member 2 rs58542926 polymorphisms influenced disease severity. Conclusion: In patients with CHB, MBOAT7 rs641738 influences hepatic inflammation and fibrosis stage. © 2017 by the American Association for the Study of Liver Diseases.
Musso G.,Gradenigo Hospital |
Anty R.,French Institute of Health and Medical Research |
Anty R.,University of Nice Sophia Antipolis |
Petta S.,Sezione di Gastroenterologia
Current Pharmaceutical Design | Year: 2013
This review is part of a special issue dealing with various aspects of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We will focus on promising treatments of NASH with antioxidants and drugs that interfere with lipid metabolism.The other therapies of interest, such as diet, behavioral changes, and insulin sensitizers are presented elsewhere. Oxidative stress is believed to play a key role in the pathogenesis of NASH and other liver diseases. Antioxidants aimed at improving chronic alcoholic or viral liver diseases have been an object of study for some time. However, only a few high quality, randomized, versus placebo-controlled, double-blinded trials have been carried out to assess these drugs. Vitamin E is currently the most widely assessed antioxidant. Several questions need to be answered, including long-term tolerance and efficacy of vitamin E in particular subsets, such as diabetes and NASH-related cirrhosis. Other antioxidants are promising, and should be assessed using the standards of evidence-based medicine. NAFLD frequently coexists with hyperlipidemia and carries an increased risk of cardiovascular disease (CVD). Furthermore, altered lipid metabolism is thought to be central to the pathogenesis of liver injury in NASH. Therefore, lipid-lowering drugs are attractive therapeutic tools in the treatment of NAFLD. Statins have ameliorated surrogate markers of steatosis in several randomized controlled trials, but their impact on liver histology is unknown. They have, however, been found to be the only class of lipid-lowering drugs that reduces cardiovascular risk in NAFLD. Preliminary evidence suggests that ezetimibe, an inhibitor of intestinal and hepatic cholesterol absorption, may improve liver histology, but its impact on the risk of CVD and on clinical outcome remains to be determined. Despite strong experimental evidence supporting the use of omega-3 polyunsaturated fatty acids in NAFLD, the studies published on humans have consisted of small sample sizes and had a number of methodological flaws, including the absence of post-treatment histology. Association of antioxidants and/or lipid-lowering drugs plus other drugs of interest in NASH, such as insulin sensitizers, warrant investigation. However, as promising as these drug treatments may continue to be, they should be associated with diet and modifications in lifestyle. © 2013 Bentham Science Publishers.
Petta S.,Sezione di Gastroenterologia |
Grimaudo S.,Sezione di Gastroenterologia |
Tripodo C.,University of Palermo |
Cabibi D.,University of Palermo |
And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Background/Aims: Low 25-hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity. Methods: Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by Western blot for quantification and by immunohistochemistry for morphological distribution. Results: Liver VDR protein was mainly localized in hepatocytes and cholangiocytes, and its expression by a Western blot was similar in chronic hepatitis C (CHC) and controls (1.83 ± 0.97 vs 2.18 ± 0.62, P = .14) but was lower in autoimmune hepatitis (0.84 ± 0.14, P .001). The expression was lower in CHC with severe necroinflammatory activity (1.44 ± 0.87) vs both controls and CHC with grade 1-2 inflammation (1.94 ± 0.97, P = .01 and P = .03, respectively) but higher compared with autoimmune hepatitis (P = .007). A similar difference was observed in CHC patients with F3-F4 fibrosis whose VDR expression (1.51 ± 1.07) was also lower compared with controls and CHC with F0-F2 fibrosis (1.98 ± 0.89, P = .02 and P = .04, respectively) but higher vs autoimmune hepatitis (P = .003). At multivariate logistic regression analysis, low VDR protein expression remained associated with severe necroinflammatory activity and severe fibrosis (odds ratio 0.543,95% confidence interval 0.288-0.989, P = .04; and odds ratio 0.484,95% confidence interval 0.268-0.877, P = .01, respectively) in CHC after correction for clinical, biochemical, and histological features. Conclusion: In a cohort of G1CHC patients, the hepatic expression of VDR protein is associated with the severity of both liver fibrosis and inflammation. © 2015 by the Endocrine Society.