Severe alcoholic hepatitis-current concepts, diagnosis and treatment options

Table 1 Components of clinical scoring systems to assess prognosis in alcoholic hepatitis

	Bilirubin	PT/INR	Cr/BUN	WBC	Age	Albumin	Potassium	Change in bilirubin from day 0 to day 7
MDF[10]	+	+	-	-	-	-	-	-
MELD[6]	+	+	+	-	-	-	-	-
GAHS[7]	+	+	+	+	+	-	-	-
ABIC[5]	+	+	+	-	+	+	-	-
Lille[9]	+	+	+	-	+	+	-	+
MAGIC[8]	+	+	+	-	-	-	+	+

PT/INR: Prothrombin time/international normalized ratio; Cr/BUN: Creatinine/blood urea nitrogen; WBC: White blood cell; MDF: Maddrey’s discriminant function; MELD: Model for end-stage liver disease; GAHS: Glasgow alcoholic hepatitis score; ABIC: Age, serum bilirubin, INR, and serum creatinine; MAGIC: Model for alcoholic hepatitis to grade severity in an Asian patient cohort.

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.