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SHR Neuro Cancer Cardio Lipid Metab Microb

Abuja, PM; Zatloukal, K; Denk, H.
Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.
Int J Mol Sci. 2021; 22(22): Doi: 10.3390/ijms222212545 [OPEN ACCESS]
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Leading authors Med Uni Graz

Abuja Peter Michael

Co-authors Med Uni Graz

Denk Helmut

Zatloukal Kurt

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Abstract:

Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propose that SH develops in four phases with transitions: (i) priming lowers stress defence; (ii) triggering leads to acute damage; (iii) adaptation, possibly associated with cellular senescence, mitigates tissue damage, leads to the phenotype, and preserves liver function at a lower level; (iv) finally, senescence prevents neoplastic transformation but favours fibrosis (cirrhosis) and inflammation and further reduction in liver function. Escape from senescence eventually leads to hepatocellular carcinoma. This hypothesis for a pathomechanism of SH is supported by clinical and experimental observations. It allows organizing the various findings to uncover remaining gaps in our knowledge and, finally, to provide possible diagnostic and intervention strategies for each stage of SH development.

Find related publications in this database (Keywords)

steatohepatitis

pathomechanism

metabolism

stress defence

mitochondrial damage

hypoxic signalling

senescence

cirrhosis

hepatocellular carcinoma

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