Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury

Abstract

Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.

Keywords: alcoholic liver disease; apoptosis; cellular toxicity; cytochrome P450; cytokines; fibrosis; inflammation; microsomal ethanol oxidizing system; reactive oxygen species.

Figure 1

The elution pattern with separation of the MEOS from catalase and ADH activities. Using ion exchange DEAE column chromatography and a continuous KCl grading starting with 0 and increasing up to 0.5 M KCl (bright yellow), eluates started with the void volume recovered up to around 220 mL. The highest peak represents the protein curve (light red) assessed as E_280nm. The left-sided peak below represents the catalase peak. ADH is the lowest peak. Starting with an elution volume at 330 mL, the microsomal components appears. Cytochrome P450 (blue) can be seen around 440 mL that decreases in the further course up to 900 mL, the second peak at 500 mL represents E_280nm (light red), followed by a third peak at 580 mL with two shoulders, and by a fourth peak at 740 mL representing MEOS (green). At 750 mL, the reductase peak emerges (light violet), followed by the phospholipids peak (dark violet) at 790 mL elution volume. Modified from the original figure published in a previous report [8].

Figure 2

MEOS and other exogenous substrates. This schematic sequence of events at the microsomal level was expanded and modified from a figure previously published in an open-access journal [13].

Figure 3

Catalytic CYP 2E1 cycle of MEOS. CYP reaction with Fe²⁺ is generated; after splitting off the oxidized substrate (ethanol), Fe²⁺ is oxidized again. CYP became then again free and is oxidized again.

Figure 4

Co-triggering role of MEOS, CYP 2E1, and ROS in alcoholic liver disease.

Figure 5

Proposed clinical therapy and monitoring of patients during hospitalization. Proposed clinical therapy and monitoring of patients during hospitalization.