27: Altered immune modulation is key to alcoholic liver disease development and severity: A Northeast India based study

Abstract

Alcoholic liver disease (ALD) is a major cause of mortality and morbidity worldwide. Abnormal cytokine metabolism is a major feature in patients with alcoholic hepatitis and/or cirrhosis, and levels correlates with markers of the acute phase response, liver function, and clinical outcome. ALD is a major health and socio-economic problem in Northeast India (NEI), where alcoholic consumption (majorly indigenously prepared) is customary in the tribal communities. Aim To delineate the role of differential expression/modulation of important cytokines in the development of ALD and its progression to advance liver disease. Methods The study included clinically proved cases of ALD along with comparative cohorts of alcohol consumers without liver disease, age and sex matched healthy controls from different parts of NEI. Differential cytokine profile was studied by FACS analysis (Th1/Th2 kit, BD) and confirmed with magpix magnetic bead based multiplex ELISA. Results There is a distinct role of higher Th1 modulation in ALD development, with significantly higher expression of IFN- γ and IL-12 in cirrhosis cases. Importantly, altered expression of important Th2 cytokines like IL-6 and anti-inflammatory cytokines IL-10 plays a major role in the development of cirrhosis; whereas gradient down-regulation in IL-4 expression correlated with disease development and severity ( Table 1 ). Similarly, higher expre-ssion of TNF- α at mRNA and protein levels correlated with disease severity. Conclusion Th1 biased modulation is key to ALD development and severity. Hence new strategies to target cytokine metabolism as a form of therapy for ALD may be suitable approach to attenuate liver injury.