Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival

Table 1 GRADE summary of findings: Severe alcoholic hepatitis treatments

Intervention	Comparator	Outcome	No. of Studies	Study design	Certainty (GRADE)	Effect estimate	Comments
Corticosteroids[13,14]	Placebo[13]	90-day mortality	1	RCT	↑↑↑↑ (high)	OR 1.02 (P = 0.87)	No benefit observed
	Non-treatment[14]		1	Observational study	↑↑↑ (moderate)	HR 0.92 (P = 0.871)	Downgraded one level due to study design
Pentoxifylline[13]	Placebo	90-day mortality	1	RCT	↑↑↑↑ (high)	OR 0.97 (P = 0.81)	No benefit observed
Anakinra + zinc[15]	Prednisone	90-day survival	1	RCT	↑↑↑ (moderate)	HR 0.34 (P = 0.018)	The findings across studies are inconsistent
Anakinra + zinc + pentoxifylline[16]	Methylprednisolone	90-day survival	1	RCT	↑↑ (low)	HR 0.69 (P = 0.28)	HR reported without CI; precision cannot be assessed. Downgraded one level due to serious imprecision
G-CSF[17]	Corticosteroids	90-day survival	1	Observational study	↑↑↑ (moderate)	HR 0.38 (P < 0.01)	Strength: Large cohort with global scope; Weakness: Needs RCT validation
	Standard medical treatment				↑↑↑ (moderate)	HR 0.26 (P < 0.01)
Amoxicillin-clavulanate + prednisolone[18]	Prednisolone	90-day mortality	1	RCT	↑↑↑↑ (high)	HR 0.78 (P = 0.30)	No significant effect
FMT[19]	Prednisolone	90-day survival	1	Randomized control trial	↑↑↑↑ (high)	HR 0.528 (P = 0.044)	Promising results; small sample
ELAD[20]	Standard of care	91-day survival	1	RCT	↑↑↑↑ (high)	HR 1.03 (P = 0.90)	No benefit observed

OR: Odds ratio; HR: Hazard ratio; CI: Confidence interval; G-CSF: Granulocyte colony-stimulating factor; RCT: Randomized control trial; FMT: Fecal microbiota transplantation; ELAD: Extracorporeal liver assist device.

Table 2 Summary of included studies evaluating 90-day survival or mortality in severe alcoholic hepatitis

Ref.	Intervention	Study design	n (intervention/control)	Effect estimate (90-day survival)	Effect estimate (90-day mortality)	Statistical significance	Country
Thursz et al[13], 2015	PRED	Multicenter, RCT	277/276	-	OR 1.02 (95%CI: 0.77-1.35)	P = 0.87	United Kingdom
	PTX		276/276	-	OR 0.97 (95%CI: 0.73-1.28)	P = 0.81
Arab et al[14], 2021	Corticosteroids	Multicenter, retrospective	1225/2155	-	HR 0.92 (95%CI: 0.33-2.56)	P = 0.871	Global
Gawrieh et al[15], 2024	Anakinra + zinc	Multicenter, phase IIb RCT	74/73	HR 0.34 (95%CI: 0.14-0.83)	-	P = 0.018	United States
Szabo et al[16], 2022	Anakinra + PTX + zinc	Multicenter, RCT	53/50	HR 0.69	-	P = 0.28	United States
Singh et al[17], 2025	G-CSF	Multicenter, retrospective	224/10800 (steroids)	HR 0.38 (95%CI: 0.23-0.62)	-	P < 0.01	Global
			224/8573 (standard medical treatment)	HR 0.26 (95%CI: 0.17-0.41)	-	P < 0.01
Louvet et al[18], 2023	Amoxicillin-clavulanate + PRED	Multicenter, RCT	142/142	-	HR 0.78 (95%CI: 0.47-1.27)	P = 0.30	France/Belgium
Pande et al[19], 2023	FMT	Single center, RCT	60/60	HR 0.528 (95%CI: 0.279-0.998)	-	P = 0.044	India
Thompson et al[20], 2018	ELAD	Multicenter, open-label RCT	96/107	HR 1.03 (95%CI: 0.69-1.53)	-	P = 0.90	United States/United Kingdom/Australia

PRED: Prednisolone; PTX: Pentoxifylline; OR: Odds ratio; HR: Hazard ratio; CI: Confidence interval; G-CSF: Granulocyte colony-stimulating factor; RCT: Randomized control trial; FMT: Fecal microbiota transplantation; ELAD: Extracorporeal liver assist device.