Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Table 1 The information of effects of current conventional medicines on the treatment of alcoholic liver disease

Medicine/compound	Type of model	Dosage/duration	Effects	Mechanisms	Ref.
Corticosteroid	RCT in severe AH	Prednisone (30 mg/d, 30 d)	Lower mortality AH group compared to antioxidant treated group		[37]
	RMT and double blind trials in severe AH	Methylprednisolone (32 mg within 7 d) and 28 d treatment and then tapered over 2 wk and discontinued	Decrease short-term mortality of patients with AH		[160]
Pentoxifylline	A double-blind, placebo-controlled trial	400 mg orally 3 times daily for 4 wk	Decrease in the risk of Progressing hepatorenal syndrome; Improve short-term survival in patients with AH		[42]
	A RCT followed by open study in severe AH patients	400 mg/d, orally for 4 wk and then tapered by 5 mg/wk for 7 wk	Better reduced mortality compared to prednisolone in AH		[161]
SAM	Ethanol-LPS-induced fibrotic rats	10 mg/kg bw, ip	Attenuate oxidative stress and HSC activation	Inhibition of TGF-β signaling pathway	[50]
	Double-blind, placebo-controlled trial in 220 patients with AH and cirrhosis	1600 mg/d orally	Decreased serum markers of cholestasis; Improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell		[162]
PPAR-α agonists	C57BL/6J mice with ethanol (27.5% of total calories)	0.1% Wy-14643 for 4 wk	Decreased serum and hepatic fat accumulation	Enhancement of hepatic FA oxidation pathway; Increased PPAR-α mRNA expression by 5-fold	[163]
	C57BL/6J mice with 4 % ethanol (Ethanol feeding for 12 wk)	Wy-14643 (50 mg/kg per day) for last 2 wk	Decreased serum AST and ALT Dropped on score of hepatic steatosis and hepatocyte ballooning	Repress PI3K and COX-2 expression; Enhance adiponectin and HO-1; Increase SIRT1 protein expression	[164]
	C57BL/6J mice with ethanol containing diet (29% of total calories)	Rosiglitazone (3 mg/kg bw/d) for 2 wk	Reduced hepatic triglyceride content; Reduced AST and ALT	Upregulated level of adiponectin and its receptors; Enhance SIRT1-AMPK signaling pathway	[55]
Metformin	C57BL/6 mice TNF knockout mice PAI-1 knockout with ethanol (6 g/kg ig)	200 mg/kg ip for 4 d prior to ethanol administration	Reduced ALT; Prevented hepatic fat accumulation	Prevention of the upregulation of PAI-1	[57]
Metadoxine	HepG2, CFSC-2G and HSC treated with ethanol (50 mM) and acetaldehyde (175 µM)	10µg/mL for 24 h	Reduced peroxidation and oxidized GSH content	Decrease collagen secretion and IL-6, IL-8 and TNF-α secretion	[69]
Carvedilol	Male Wistar rats with ethanol (5%) fed	10 mg/kg per day for last 7 d of total 49 d	Reduced hepatic TG level and the accumulation of fatty droplets within hepatocytes;	Down-regulated FAS and SREBP-1, and up-regulated PPAR-α;	[56]
			Inhibited ethanol-induced the thickening of zone 3 vessel walls	Reduced the activation of HSCs with decrease induction of TGF-β1 and collagen
Propylthiouracil	Male Sprague-Dawley rat with ethanol consumption (36%)	50 mg/kg per day of Wy-14643 for last 2 wk for the last 5 d of 4-6 wk diets with alcohol	Increased hepatic blood flow; Reduces oxidative stress		[71]
Colchicine	RCT in 74 patients with cirrhosis	1 mg/d for 4.4 yr	Reduced serum N-terminal peptide of type III procollagen levels		[70]

AH: Alcoholic hepatitis; AMPK: 5’ adenosine monophosphate-activated protein kinase; ALT: Alanine transaminase; AST: Aspartate aminotransferase; bw: Body weight; COX-2: Cyclooxygenase-2, FA: Fatty acid; FAS: Fatty acid synthase; GSH: Glutathione; HepG2: Hepatoma G2 cell-line; HO-1: Heme oxygenase-1; HSC: Hepatic stellate cells; IL-6: Interleukin 6; IL-8: Interleukin-8; LPS: Lipopolysaccharide; mRNA: Messenger ribonucleic acid; P13K: Phosphoinositide 3-kinase; PAI-1: Plasminogen activator inhibiter-1; PPAR-α: Peroxisome proliferator-activated receptor-α; RCT: Randomized controlled trial; RMT: Respiratory muscle training; SIRT1: Sirtuin 1; SREBP1: Sterol regulator element binding protein 1; TG: Triglycerides; TGF-β: Tissue growth factor-β; TNF: Tumour necrosis factor; TNF-α: Tumour necrosis factor-α.