Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances

Abstract

Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and physiological/cell signaling pathways include fibrinolysis, osteopontin, transforming growth factor-b-SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non-alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

“…PS acyl chains were identified by the assignment of fatty acids as [1] neutral loss of sn1 carboxylic acid and serine from precursor ion ([M−H] -) at m/z 439, [2] neutral loss of sn2 carboxylic acid and serine from precursor ion at m/z 419, [3] loss of sn2 acyl chain as ketene (RCH− −C − −O) and serine from precursor ion at m/z 437, and [4] the presence of sn1 carboxyl ions at m/z 283 and sn2 carboxyl ions at m/z 303.…”

“…Correspondingly, several lines of evidence suggest that cofactor exposures and disease processes contribute to ALD. For example, a key factor promoting acute alcoholic hepatitis, the precursor to progressive ALD, is binge drinking superimposed on chronic heavy alcohol abuse [3]. The very high rates of chronic hepatitis B or C virus infections in patients with alcoholic cirrhosis [4] suggest that virus-mediated injury can also serve as a cofactor in ALD.…”

Non-invasive assessment of fatty liver

“…Az alkohol okozta májkárosodás spektruma színes a steatosison keresztül a gyulladáson át a fi brosisig, majd cirrhosisig. A májkárosítás kórfolyamata több útvonalon történik, amelyben gyulladásos folyamatoknak, a redoxérzékeny transzkripciós faktorok aktivá-lódásának, immunfolyamatoknak, a reaktívoxigén-gyö-kök termelésének, a lipidperoxidációnak van szerepe [13]. A jellemző szövettani eltérések: macrovesicular steatosis, neutrophil lobularis beszűrődés, ballondegeneráció, Mallory-Denk-testek, portalis és pericelluláris fi brosis.…”

Pulmonary consequences of alcoholism: A critical review

“…These properties facilitate its ability to saturate practically all bodily tissue types. Even though the most widely recognised target organ damage is alcohol-related liver dysfunction, overall there are roughly 60 types of diseases and injuries that have been linked to alcohol use 6 . Other commonly recognised targets of alcoholism include the central nervous system, the heart and the pancreas, all of which contribute to significant morbidity and mortality for the individual.…”