Critical care hepatology: A narrative review of current concepts and management

Table 2 Key evidence guiding vasoactive therapy in acute and acute-on-chronic liver failure

Ref.	Population (n)	Design	Intervention	Comparator	Primary outcome	Key findings	Clinical relevance
Cavallin et al[94], 2015	Cirrhosis, HRS (n = 49)	RCT	Terlipressin 3-12 mg/day CTI + albumin	Midodrine + octreotide + albumin	Renal recovery	Terlipressin superior: Partial/complete response 70% vs 29% (P = 0.01); complete response 56% vs 5% (P < 0.001)	First head-to-head terlipressin vs midodrine/octreotide; terlipressin clearly favoured
Boyer et al[95], 2016	Cirrhosis, HRS-1 (n = 196)	RCT	Terlipressin 1 mg every 6 hours + albumin	Placebo + albumin	CHRSR	CHRSR 19.6% vs 13.1% (P = 0.22; NS); creatinine reduction significantly greater (P < 0.001); survival similar	Phase 3; missed primary endpoint; HRS reversal predicted 90-day survival; more ischaemic AEs
Piano et al[96], 2018	298 patients with cirrhosis and type 1 HRS, stratified by ACLF grade	Retrospective multicenter cohort study	Terlipressin + albumin	Comparison according to ACLF grade (ACLF-1, ACLF-2, ACLF-3) rather than a separate treatment arm	Response to treatment (serum creatinine < 1.5 mg/dL at end of therapy) and 90-day mortality	Treatment response declined with increasing ACLF severity: 60% in ACLF-1, 48% in ACLF-2, and 29% in ACLF-3 (P < 0.001). ACLF grade and baseline creatinine were independently associated with treatment response. ACLF grade independently predicted 90-day mortality irrespective of HRS reversal	Key study establishing ACLF grade as determinant of terlipressin response; EASL-CLIF criteria
Arora et al[97], 2020	ACLF (n = 120)	RCT	Terlipressin 2-12 mg/day CTI + albumin	Noradrenaline 0.5-3 mg/hour + albumin	HRS-AKI reversal day 7; 28-day survival	Terlipressin superior: HRS reversal 40% vs 17% (P = 0.004); survival 48% vs 20% (P = 0.001); less RRT 57% vs 80% (P = 0.006)	APASL ACLF criteria; open-label; landmark ACLF-specific RCT
Wong et al[98], 2021	Cirrhosis, HRS-1 (n = 300)	RCT	Terlipressin + albumin	Placebo + albumin	HRS reversal	Verified HRS reversal 32% vs 17% (P = 0.006); no significant survival benefit; respiratory failure more frequent with terlipressin	Largest placebo-controlled terlipressin trial; pivotal study underlying FDA approval
Wong et al[99], 2022	ACLF (n = 299)	Post-hoc	Terlipressin + albumin	Placebo + albumin	Respiratory failure by ACLF grade; 90-day survival	RF with terlipressin 30% in ACLF grade 3 vs 9.4% grade 1-2 (P = 0.0002); 90-day survival lower in grade 3 terlipressin arm. Use with caution in ACLF grade 3	Basis for FDA black box warning; terlipressin contraindicated in ACLF grade 3 with hypoxia
Jindal et al[100], 2024	ACLF (n = 60)	RCT	Early terlipressin (after 12 hours volume expansion)	Standard terlipressin (after 48 hours albumin challenge)	28-day mortality; AKI reversal	Early terlipressin: Lower mortality (17% vs 43%, P = 0.03); greater AKI reversal; regression of ACLF stage	First study on timing; supports early AKI intervention before 48 hours window in ACLF
Gupta et al[101], 2025	ACLF + septic shock (n = 70)	RCT	Terlipressin 2.6 mcg/kg/minute	Noradrenaline 0.1 mcg/kg/minute	MAP > 65 mmHg at 6 hours	Noradrenaline superior: MAP target achieved 74% vs 14% (P < 0.001); 3- and 7-day mortality higher with terlipressin	Terlipressin INFERIOR in septic shock context; noradrenaline first-line for ACLF septic shock

This table summarizes key studies on vasoactive therapy in acute-on-chronic and acute liver failure. Evidence is largely derived from cirrhosis and acute-on-chronic liver failure, where terlipressin improves hepatorenal syndrome reversal without consistent survival benefit, with reduced efficacy in advanced acute-on-chronic liver failure. While terlipressin may outperform norepinephrine for renal recovery in selected patients, norepinephrine remains first-line in septic shock. Data in acute liver failure are limited and suggest differing cerebral hemodynamic effects, supporting cautious use. HRS: Hepatorenal syndrome; RCT: Randomised controlled trial; CTI: Continuous terlipressin infusion; NS: Not significant; AEs: Adverse events; ACLF: Acute-on-chronic liver failure; EASL-CLIF: European Association for the Study of the Liver-Chronic Liver Failure; APASL: Asian Pacific Association for the Study of the Liver; FDA: Food and Drug Administration; RF: Respiratory failure; AKI: Acute kidney injury; MAP: Mean arterial pressure; CHRSR: Confirmed hepatorenal syndrome reversal; RRT: Renal replacement therapy.