Significance of Inflammatory and Angiogenic Marker Profile in Alcoholic Liver Disease Pathogenesis: A Case Control Study Involving Northeast Indian Cohorts.

Background/Aims Alcoholic liver disease (ALD) encompasses a spectrum of hepatic injury, ranging from simple steatosis to cirrhosis. Limited literature suggests that pro-inflammatory conditions and hepatic angiogenesis influence the pathophysiology of ALD. This study aimed to explore the usefulness of plasma inflammatory and angiogenic biomarkers for noninvasive evaluation of susceptibility to ALD and progression to severity. Methods Blood samples were collected from clinically proven ALD cases (n=150: chronic liver disease [CLD], 110; cirrhosis, 40), alcoholic without liver disease (AWLD; n=93) and healthy controls (HC; n=274). Key inflammatory markers tumor necrosis factor (TNF)-α and NF-kBp65 and their target iNOS along with eNOS and COX-2 was studied at mRNA level by real-time PCR. Serum TNF-α, NF-kBp65, VEGF and PDGF-BB concentrations were analyzed using enzyme-linked immunosorbent assay. Results Serum TNF-α was increased in alcoholic-CLD (21.85±2.907 pg/mL) and cirrhosis (22.65±4.646 pg/mL) cases compared to HC (20.462±4.719 pg/mL) and AWLD (19.725±5.738 pg/mL; p=not significant). NFkBp65 was significantly increased in CLD compared to HC (p=0.034) and AWLD (p=0.048); and positively significantly correlated with higher fibroscan based liver stiffness measurement (LSM) score, SGOT levels and serum TNF-α expression. Vascular endothelial growth factor (VEGF) levels were significantly higher in CLD cases compared to HC (p=0.043) and AWLD (p=0.049) subjects showing the association with disease severity. iNOS mRNA expression fold change was higher in CLD (6.132±4.132 folds) and cirrhosis (1.272±0.937 folds) cases compared to HC, whereas it was comparable in AWLD (1.08±0.319 folds) subjects. COX-2 mRNA expression was also increased in CLD (2.431±1.395 folds) compared to AWLD subjects. The higher iNOS mRNA expression in ALD cases correlated significantly with increased TNF-α and NF-kBp65 expression. VEGF expression in turn correlated significantly with TNF-α levels in ALD cases, and LSM score. Conclusions The present data underlines the specificity and importance of the state of oxidative stress mediated by chronic alcohol and resulting in inflammatory and angiogenic conditions relating to the pathogenesis of ALD, especially CLD conditions; and therefore the above panel of markers holds prognostic significance as well as therapeutic potentials. [ABSTRACT FROM AUTHOR]