Therapeutic interventions of acute and chronic liver disorders: A comprehensive review

Table 1 Summarized the common pathological mechanisms of acute and chronic liver diseases

Disease	Mechanism	Model	Findings	Ref.
ALF	N-acetyl-p-APAP	Mice model	The hazardous metabolite N-acetyl-p-benzoquinone depleted GSH and caused mitochondrial oxidative stress and necrosis	[6]
	Innate immunity, apoptosis, and cytokine release	Bio-samples from roughly 2000 patients with ALF	Generated pro-inflammatory mediators and oxidative stress, vasodilatation of the peripheral microcirculatory, hypoxia, lactic acidosis, and hypotension	[8]
	MiR-122 and miR-192	APAP in mice	Increased miR-122 and miR-192 levels after acute hepatic poisoning with acetaminophen in mice before transaminases	[82]
	MiRNAs	ALF in mice	Up-regulated miR-155, miR-146a, miR-125a, miR-15b, and miR-16	[83]
			Down-regulated miR-1187
Acute liver injury	MiRNAs	Acetaminophen or carbon tetrachloride in male rats	Down-regulated miR-29c_AS, miR298, miR327, miR342, miR370, miR376c, miR494, and miR503	[66]
			Upregulated miR-153, miR-302b AS, miR-337, miR-363, miR-409-5p, and miR-542-3p
	MiR-122	I/R mouse model	Elevated miR-122 level	[67]
	MiR-192	APAP induced liver injury in mouse	Dose- and exposure-dependent elevation of miR-192 level	[79]
HBV	MiRNAs	Pooled sera obtained from HBV patients	Up-regulated miR-122 level. miR-122 could inhibit HBV replication in Huh7 and HepG2 cells	[84]
	MiR-155	Human hepatoma cells	MiR-155 enhances innate antiviral immunity by promoting JAK/STAT signaling pathway by targeting SOCS1	[86]
HCV	MiR-122	Human hepatoma Huh-7.5 cells	MiR-122 is the predominant miRNA in the liver tissue. 2’-O-methyl antisense oligonucleotide depletion of miR-122 also inhibits HCV genotype 2a replication and infectious virus production	[89]
	MiRNAs	Human hepatoma cells	MiR-24, miR-149, miR-638, and miR-1181 were identified to be involved in HCV entry, replication, and propagation	[90]
Alcoholic steatohepatitis	MiRNAs	In vitro (RAW 264.7 macrophage) and in vivo (Kupffer cells of alcohol-fed mice)	Up-regulated miR-155 expression both in vitro and in vivo	[94]
			Increased TNF alpha production in response to miR-155 induction
			Increased expression of miR-155 and miR-132 in the total liver
	MiRNAs	Bile duct ligation rat model	Down-regulated miR-150 and miR-194 expression	[98]
	MiRNAs	Human stellate cell line	Up-regulated miR-199 and miR-200 led to higher expression of fibrosis-related genes in an HSC cell line	[97]
NAFLD and alcoholic liver disease	Autophagy	In-vivo	Activation of macroautophagy and CMA eliminated damaged mitochondria, lessens oxidative stress, and promotes regeneration	[136]
Liver cancer	Autophagy	Oncogene-driven cancer models	Protein kinase C promotes autophagy and oxidative phosphorylation
			ROS generation, which through Nrf2 drives HCC through cell-autonomous and non-autonomous mechanisms
Liver cirrhosis	Hepatocyte	In-vivo	Activation of hepatic stellate cells by damaged hepatocytes	[18]
	Hepatic stellate cell	In-vivo	The activated hepatic stellate cells produce endothelin-1, TGF-β, and cytoglobin that share in the process of fibrogenesis	[24]
	Sinusoidal endothelial cells SECs	Co-culture with freshly isolated SECs	Differentiated SECs prevent HSC activation and promote reversion of activated HSCs to quiescence through VEGF-stimulated NO production	[32]
	Kupffer cells	Mouse model	Enhanced death ligand expression	[35]
			Inhibition of hepatocyte apoptosis with a caspase inhibitor prevented Kupffer cell activation
			Hepatic stellate cell activation

ALF: Acute liver failure; APAP: Aminophenol; HBV: Hepatitis B virus; HCV: Hepatitis C virus; SECs: Sinusoidal endothelial cells; VEGF: Vascular endothelial growth factor; HSCs: Hepatic stellate cells; TGF-β: Tumor growth factor-beta; CMA: Chaperone-mediated autophagy; HCC: Hepatocellular carcinoma; Nrf2: Nuclear factor erythroid 2-related factor 2; NAFLD: Non-alcoholic fatty liver; TNF: Tumor necrosis factor; GSH: Glutathione; ROS: Reactive oxygen species; miRNA: MicroRNA.