1020 IMPROVED SURVIVAL IN PATIENTS WITH ADVANCED ALCOHOLIC HEPATITIS (AAH) WITH A COMBINED TREATMENT ASSOCIATING A NON-ABSORBABLE ANTIBIOTIC RIFAXIMIN TO CORTICOIDS PLUS URSODEOXICHOLIC ACID (UDCA)

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.