P. Nohra

Background Only a small proportion of alcoholic patients develop advanced liver disease, suggesting that factors other than alcohol intake may influence alcoholic liver disease ( ALD ) progression. We have shown that body mass index ( BMI ) is an independent risk factor for fibrosis in alcohol‐induced liver disease and that adipose tissue inflammation is correlated with liver lesions in alcoholic patients. The aim of this study was to determine whether visceral adipose tissue, as assessed by abdominal height measurement, affected individual susceptibility to fibrosis in alcoholic patients. Methods We included 127 consecutive alcoholic patients with abnormal liver test findings for whom liver histology data were available. Abdominal height was measured with a H oltain‐ K ahn abdominal caliper. We carried out univariate comparisons followed by multivariate regression analysis, to investigate the relationship between abdominal height and fibrosis score. Results Abdominal height ( p < 0.005), waist circumference ( p < 0.05), fasting blood glucose concentration ( p < 0.05), serum triglyceride concentration ( p < 0.05), serum bilirubin ( p < 0.005), and BMI ( p = 0.05) were higher, whereas high‐density lipoprotein ( HDL ) cholesterol level ( p < 0.01) was lower in the 72 patients with significant (F2–F4) fibrosis than in the 55 patients with F0–F1 fibrosis. In multivariate regression analysis, only abdominal height (β = 7.2, p < 0.002) was independently and positively correlated with fibrosis score, which was also negatively correlated with HDL cholesterol level (β = −1.04, p < 0.05). Conclusions We provide the first demonstration that abdominal height may be a predictor of significant fibrosis in patients with ALD . Our findings support a role for visceral fat accumulation, independent of BMI and of metabolic syndrome criteria, in the onset of alcoholic liver damage.

S369(CBR1 and CBR2) are substantially upregulated during liver injury and mediate pro-and anti-fibrogenic effects upon binding of either endocannabinoids or exogenous cannabinoids.CBR1 has received increased attention after daily cannabis smoking was found to be an independent risk factor for the progression of fibrosis chronic hepatitis C and a mediator of alcoholic steatosis.Aims and Methods: To investigate the role of CBRs in alcoholic liver disease (ALD), 56 paraffin-embedded and 24 frozen liver tissues from patients with different severities of ALD were analyzed.CB1 immunohistochemistry was performed with polyclonal anti-CB1 antibodies.CBR1 and CBR2, procollagen a1(I) (PCI) and alpha-smooth muscle actin (aSMA) transcription was quantified by TaqMan PCR.For in vitro experiments, human hepatic stellate cells (HSC) were treated with acetaldehyde, a toxic and profibrogenic metabolite of alcohol, at 50-200mM for 6 and 24 h in serum-free conditions.Results: CBR1 immunostainings in ALD revealed expression of CBR1 predominantly in fibrotic septas of liver sections showing advanced fibrosis, whereas in tissues with no or low fibrosis stages CBR1 immunoreactivity was faint or absent.At mRNA level, CBR1 showed a trend toward an increase with fibrosis stage to which CBR2 expression showed a rather inverse correlation.CBR1 induction did not correlate with PCI mRNA in ALD.In vitro, acetaldehyde induced CBR1 mRNA about 2-fold after 24 h of incubation at 200mM, whereas CBR2 mRNA was unaffected.Conclusions: CBR1 expression correlates with fibrosis progression in ALD, which is, at least to some degree, triggered by acetaldehyde.Thus, it can be speculated that cannabis smoking may potentially aggravate development of fibrosis in ALD.