The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

Abstract

Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed. ( J CLIN EXP HEPATOL 2015;5:147-158)

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

“…It has been suggested that insulin resistance plays a pathogenic role in kidney disease progression by worsening renal hemodynamics by activation of the sympathetic nervous system, sodium retention and down-regulation of the natriuretic peptide system 42 , making insulin resistance a possible mechanistic link between NAFLD and CKD. NF-kB pathway activation in NASH increases the transcription of a variety of proinflammatory genes that can amplify systemic chronic inflammation 43,44 . Hence, the increased intra-hepatic cytokine production that occurs in NAFLD/NASH is likely to play a pathogenic role also in the development of extra-hepatic complications, such as CVD and CKD.…”

Supplementation With 2:1 Ratio of N-6:n-3 Polyunsaturated Fatty Acid Improves Liver Steatosis and Serum Cytokine Levels in Young Obese Balinese Women: A Randomized Clinical Trial

“…NAFLD is the most common liver disorder and is the leading cause of hepatocyte injury and fibrosis. NAFLD is also associated with chronic liver diseases such as cirrhosis [4][5][6][7][8].…”

“…The first hit initiates LS, and the second hit stimulates inflammatory processes. These two conditions may result in hepatocyte injury and fibrosis [4,5]. NAFLD is asymptomatic, undetectable, and progressive.…”

“…The prevalence of LS is higher among patients with obesity and type 2 diabetes (70-80%), and as many as 25-70% of these patients eventually develop chronic liver diseases such as NASH and fibrosis [6][7][8]. Obesity, a high-fat diet, a genetic predisposition, and microbiota have been identified as risk factors for NAFL [4][5][6][7][8]. In obese patients associated chronic inflammatory states, the adipose tissue releases more pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, whereas the release of IL-10 is decreased.…”

“…In obese patients associated chronic inflammatory states, the adipose tissue releases more pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, whereas the release of IL-10 is decreased. Moreover, the levels of pro-inflammatory cytokines, such as TNF-α and IL-16, produced by the liver and adipose tissue are elevated during the activation of nuclear factor kappa B. TNF-α involves in inflammatory and metabolic alterations nearly stage of liver injury, leading to increased cytokines synthesis, which in turn induces cell migration, initiate fibrotic processes, and influence the progression of NAFL to NASH [4][5][6][7][8]. By contrast, IL-10 inhibits the synthesis of pro-inflammatory cytokines such as interferon-γ, IL-2, IL-3, and TNF-α.…”