Organ–Organ Crosstalk and Alcoholic Liver Disease

Abstract

Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well-understood. Given the poor prognosis of treating clinically-relevant alcoholic liver disease (ALD) (i.e., alcoholic hepatitis (AH) and cirrhosis), additional research is required to develop more effective therapies. While the stages of ALD have been well-characterized, targeted therapies to prevent or reverse this process in humans are still needed. Better understanding of risk factors and mechanisms underlying disease progression can lead to the development of rational therapies to prevent or reverse ALD in the clinic. A potential area of targeted therapy for ALD may be organ–organ communication in the early stages of the disease. In contrast to AH and end-stage liver diseases, the involvement of multiple organs in the development of ALD is less understood. The impact of these changes on pathology to the liver and other organs may not only influence disease progression during the development of the disease, but also outcomes of end stages diseases. The purpose of this review is to summarize the established and proposed communication between the liver and other organ systems that may contribute to the development and progression of liver disease, as well as to other organs. Potential mechanisms of this organ–organ communication are also discussed.

Endocrine Adiponectin‐FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury

“…79 Endocrine adiponectin-FGF15/19 axis controls adipose and gut to liver communication arm of an adipose-intestine-liver partnership in response to alcohol challenges. However, other organs such as muscle, bone, spleen and brain may be within this communication axis regulated by the adiponectin-FGF15/19 axis and ethanol.…”

The Matrisome, Inflammation, and Liver Disease

“…[38][39][40][41][42] No matter the etiology, chronic liver diseases share a well-documented, common natural history, which ranges initially from simple steatosis, to inflammation and necrosis (steatohepatitis), to fibrosis and cirrhosis. [43][44][45][46] Fibrosis may improve with removal of insult, but reversal of severe stages of fibrosis/cirrhosis is more limited. 47 Cirrhosis is often considered an end-stage liver disease and requires liver transplant.…”

“…[63][64][65] We recently demonstrated that the hepatic matrisome changes robustly to acute injury (e.g., acute lipopolysaccharide), even under conditions in which the ECM appears histologically unchanged. 45 These subhistologic transitional changes to the matrisome appear to resolve after acute injury 66,67 (►Fig. 1); with chronic injury, the transitional matrisome is replaced by collagenous scarring in the liver, which is again in-line with subcutaneous wound healing.…”

Brain Crosstalk with Other Organs in ICU Patient

“…This can be explained through the well-known classic example of hepatic encephalopathy during decompensation of chronic liver disease and alcoholic liver disease. 29 This crosstalk is linked through gut-related pathological changes such as increased permeability, altered microbiome of the gut, leading to "gut dysbiosis." 30 The brain essentially requires glucose for its metabolism which is generated in high amounts by the liver.…”