Enhanced susceptibility to alcohol-induced bacterial translocation, immune activation, and persistent inflammation in patients with alcoholic hepatitis: a prospective observational study

Abstract

Abstract Up to 30% chronic heavy drinkers develop a spectrum of severe alcoholic liver diseases, including alcoholic hepatitis (AH). Alcohol-induced impairment of intestinal integrity and microbial translocation into the portal vein lead to immune activation and play a major role in the pathogenesis of AH. To better understand why AH develops only in some heavy drinkers and the effect of alcohol abstinence on immunity, we conducted a prospective study to compare plasma LPS levels and peripheral blood immunoprofiles between 68 AH patients and 65 heavy drinkers without liver disease (HDC) who were followed up to 12 months. Plasma samples were also obtained from 31 health donors (HD). Plasma LPS was detected in a higher portion of AH patients than HDC (80% vs 49%) at baseline, and in only 8% HD. However, LPS levels were not different between AH an HDC subjects with detectable LPS. Compared with HDC, AH patients had higher baseline plasma levels of sCD14, sCD163, sICAM-1, sVCAM-1, IL-22, TNF-α, IL-8, IP10, IL-4, IL-6, IL-9, IL-10, FGF2, IL-7, IL-15, and TGF-α, but lower levels of the anti-inflammatory chemokine MDC. AH patients also had more activated, yet dysfunctional monocytes, T cells, and B cells as they expressed higher levels of CD38 and CD69, but lower levels of HLA-DR, CD80, and CD86. In spite of having significant bacterial translocation, HDC showed little evidence of immune activation. With alcohol abstinence, levels of many dysregulated immune markers normalized in AH patients. However, TNF-α, IL-8, IL-10, sCD163, and sVCAM-1 levels remained higher. Conclusion AH patients were more susceptible to alcohol-induced bacterial translocation and immune activation. Alcohol abstinence reduced but did not fully reverse immunological abnormalities.