Severe alcoholic hepatitis-current concepts, diagnosis and treatment options

Table 2 Summary of potential molecular targets and novel targeted therapies for alcoholic hepatitis

Key element of the pathogenesis	Treatment	Effect	Clinical trial
FXR dysregulation	OCA[67]	FXR agonist	Moderately severe AH (placebo vs OCA)
Altered gut integrity	Zinc[68]	Restoration of gut integrity	Severe AH
	LGG[69]	Probiotic effect	Mild to moderate AH (placebo vs LGG)
	Rifaximin[70]	Intestinal decontamination	Severe AH (steroid vs steroid + rifaximin)
Innate immune activation	Imm 12-E[71]	Anti-LPS antibody	Severe AH (steroid vs steroid + low/high dose Imm 12-E)
	Anakinra[57,58,72]	IL-1RA	Severe AH (steroid vs anakinra + pentoxifylline + zinc)
	Rilonacept[57,58]	IL-1 inhibitor	Severe AH with response to steroid at day 7 (steroid vs steroid + rilonacept)
	Mycophenolate mofetil	IMPDH inhibitor	Severe AH without response to steroid at day 7 (standard of care vs steroid + mycophenolate)
Sterile necrosis and apoptosis	Emricasan[54]	Pancaspase inhibitor	Severe AH with steroid contraindications (placebo vs emricasan)
Impaired regeneration	G-CSF[63,64]	HPC mobilization	Severe AH without response to steroid at day 7 (placebo vs G-CSF)
	IL-22[59,73,74]	Hepatoprotective effect	Only preclinical studies

FXR: Farnesoid X receptor; OCA: Obeticholic acid; AH: Alcoholic hepatitis; LGG: Lactobacillus GG; LPS: Lipopolysaccharide; IL-1RA: Interleukin-1 receptor antagonist; IL-1: Interleukin-1; IMPDH: Inosine-5’-monophosphate dehydrogenase; G-CSF: Granulocyte-colony stimulating factor; HPC: Hepatic progenitor cell; IL-22: Interleukin-22.