Synergy between NAFLD and AFLD and potential biomarkers

Fatty liver (hepatosteatosis) is the earliest abnormality in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) due either to metabolic risk factors associated with insulin resistance and/or metabolic syndrome in the absence of alcohol consumption or to chronic alcohol abuse. When unchecked, both NAFLD and AFLD lead to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and eventual death. A number of common mechanisms contribute to the above various stages of hepatocyte injury, including lipotoxicity, endotoxin release, oxidative and ER stress leading to increased pro-inflammatory cytokines that stimulate hepatic fibrogenesis and cirrhosis by activating the quiescent hepatic stellate cells (HSC) into myofibroblasts. Significantly, patients with either NAFLD or AFLD respond favorably to early treatment modalities to reduce hepatic fat accumulation and consequent increased inflammatory signalling and activation of hepatic stellate cells. Although the pathogenic pathways associated with NAFLD and AFLD are seemingly similar, differentiation of the molecular mechanism/s of the pathogenesis of these liver diseases is critical in identifying the unique molecular signatures, especially in the early diagnosis of NAFLD and AFLD. Current clinical practice requires the invasive biopsy procedure for the conclusive diagnosis of NAFLD and AFLD. Micro RNAs (miRNAs) are ∼22 nucleotide non-coding sequences that bind to the 3'-untranslated region of target transcripts and regulate gene expression by degradation of target mRNAs or inhibition of translation. Emerging studies may prove to establish miRNAs as excellent non-invasive tools for the early diagnosis of various stages of liver diseases.