Diagnostic and Therapeutic Strategies for Severe Alcoholic Hepatitis

Won Kim

doi:10.4166/kjg.2015.65.1.4

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Kim: Diagnostic and Therapeutic Strategies for Severe Alcoholic Hepatitis

Review Article

Korean J Gastroenterol 2015;65(1):4-11.

Published online: 4 October 2015

DOI: https://doi.org/10.4166/kjg.2015.65.1.4

Diagnostic and Therapeutic Strategies for Severe Alcoholic Hepatitis

Won Kim

Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea

Correspondence to: Won Kim, Department of Internal Medicine, SMG-SNU Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 156-849, Korea. Tel: +82-2-870-2233, Fax: +82-2-831-2826, E-mail: drwon1@snu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol abstinence is the sine qua non of therapy for AH and, in the milder forms, is prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure such as acute kidney injury and infection, which has a major impact on survival and thus should be closely monitored. Patients with severe ASH have a drastic short-term mortality of up to 40–50%. Specific therapies should be considered for patients with severe ASH at risk of early death. Corticosteroids are the standard of care for patients with severe ASH. When corticosteroids are contraindicated, pentoxifylline may be an alternative option. Steroid responsiveness should be evaluated on the basis of Lille score. Tactically, we should explore novel therapeutic targets to suppress inflammation based on cytokine profiles, promote hepatic regeneration, limit innate immune responses, and restore altered gut mucosal integrity in severe ASH.

Keywords: Alcoholic steatohepatitis, Infection, Renal insufficiency, Corticosteroids, Pentoxifylline

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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
MDF¹⁰	+	+	−	−	−	−	−	−
MELD⁶	+	+	+	−	−	−	−	−
GAHS⁷	+	+	+	+	+	−	−	−
ABIC⁵	+	+	+	−	+	+	−	−
Lille⁹	+	+	+	−	+	+	−	+
MAGIC⁸	+	+	+	−	−	−	+	+

Cr, creatinine; WBC, white blood cell; MDF, Maddrey's discriminant function; MELD, model for end-stage liver disease; GAHS, Glasgow alcoholic hepatitis score; ABIC, age-bilirubin-INR-creatinine score; 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	OCA⁵⁵	FXR agonist	Moderately severe AH (placebo vs. OCA)
Altered gut integrity	Zinc⁵⁶	Restoration of gut integrity	Severe AH
	LGG⁵⁷	Probiotic effect	Mild to moderate AH (placebo vs. LGG)
	Rifaximin⁵⁸	Intestinal decontamination	Severe AH (steroid vs. steroid+ rifaximin)
Innate immune activation	Imm 12-E⁵⁹	Anti-LPS antibody	Severe AH (steroid vs. steroid+ low/high dose Imm 12-E)
	Anakinra^60-62	IL-1RA	Severe AH (steroid vs. anakinra+ pentoxifylline+ zinc)
	Rilonacept^60,61	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	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-22^65-67	Hepatoprotective effect	Only preclinical studies

FXR, farnesoid X receptor; OCA, obeticholic acid; AH, alcoholic hepatitis; LGG, lactobacillus GG; LPS, lipopolysaccharide; IL, interleukin; IL-1RA, IL-1 receptor antagonist; IMPDH, inosine-5'-monophosphate dehydrogenase; G-CSF, granulocyte-colony stimulating factor; HPC, hepatic progenitor cell.

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