S1247 Progress in Drug Therapy for Hepatorenal Syndrome: A Systematic Review of Clinical Studies in the Last 3 Years

Abstract

Introduction: Rapid deterioration of kidneys in patients with severe liver injury i-e., cirrhosis is termed a hepatorenal syndrome (HRS). Hemodynamic instability due to increased splanchnic blood flow, systemic vasodilation, and renal vasoconstriction might cause HRS, and the goal of the drug therapies is to improve systematic circulation. This article aims to review the efficacy and safety of drug therapies tested in the last 3 years in HRS patients. Methods: We searched PubMed, Embase, Cochrane, and WOS from 1/1/2019 till 05/15/2022. We screened 520 articles and included 3 clinical trials (N=462) and 5 observational studies (N=1,034) with >5 patients providing data about the safety and efficacy of drugs. All case reports, case series, review articles, meta-analyses, and clinical studies with irrelevant populations were excluded. Results: In 8 studies, 708 patients were treated with terlipressin +albumin, 73 with noradrenaline, 22 with midodrine + albumin, 28 with midodrine+ albumin+ octreotide, 82 with other vasoconstrictors, and 121 with albumin only. In two clinical studies (N=416), HRS patients treated with terlipressin + albumin had a reversal in 32%-39.7%, liver transplant (LT) in 12.5%-23%, and death in 51% (11% with respiratory failure) of the patients, versus a reversal in 17%, LT in 29% and death in 45% (2% with respiratory failure) with albumin. In three clinical studies (N=382), HRS patients with terlipressin + albumin had a reversal in 40%-50.2%, overall response (OR) in 41.7%-72.9%, and death in 51% versus a reversal in 16.7%-22.7%, OR in 20%-23% and death in 82% with noradrenaline/other vasoconstrictors. In a retrospective study (N=88), HRS patients treated with midodrine+ octreotide+ albumin had a reversal, LT, and death in 25%, 3.6%, and 39.2%, respectively, versus reversal, LT, and death in 10%, 23%, and 43%, respectively, with non-standard treatment. In a pilot study (N=42), recurrence of HRS was 18% with midodrine vs. 50% with albumin only. (Table) Conclusion: Terlipressin with albumin significantly improved the reversal of HRS and transplants. However, mortality wasn’t improved due to treatment-related adverse effects. Terlipressin with albumin significantly improved the outcomes in HRS patients as compared to noradrenaline with albumin. Standardized albumin + midodrine + octreotide was more effective than non-standardized treatment of HRS. Midodrine with albumin reduced the recurrence of HRS in HRS recovered patients as compared to albumin. More RCTs are needed to confirm these results. Table 1. - Study Phase Treatment therapy N Outcomes Trials Wong et al. 2021 III (RCT) Terlipressin + Albumin (90 days) 199 Reversal of HRS (SCr < 1.5mg/dl) =32%, Renal transplant=29% Liver transplant=23%, Death=51% (11% with respiratory failure) Placebo 101 Reversal of HRS (SCr < 1.5mg/dl) =17%, Renal transplant=39%, Liver transplant=29%, Death=45% (2% with respiratory failure) Sharma et al. 2021 Pilot study (on patients recovered with terlipressin + albumin) Midodrine + albumin 22 Recurrence of HRS=18%, Mean ascitic tap in 2 months=1.9 Albumin 20 Recurrence of HRS=50%, Mean ascitic tap in 2 months=2.6 Arora et al. 2020 RCT Terlipressin + albumin 60 Reversal of HRS (SCr within 0.3mg/dl of baseline) = 40%, Any response (7-days) = 41.7% Survived patients=49% Noradrenaline+ albumin 60 Reversal of HRS (SCr within 0.3mg/dl of baseline) = 16.7%, Any response (7-days)=20%, Survived patients=18% Observational studies Kulkarni et al. 2022 Prospective Terlipressin + Albumin 116 Adverse effects leading to discontinuation=21%, Complete response (SCr within 0.3mg/dl of baseline) = 39.7%, Transplant free patient -at 90 days=57.8%, liver transplant=12.5% Hiruy et al. 2021 Retrospective Albumin+ midodrine+ octreotide (standardized) 28 Full response (SCr within 0.3mg/dl of baseline) =25%, renal replacement=21%, liver transplant=3.6%, 30-day mortality=39.2% Non-standardized treatment 60 Full response (SCr within 0.3mg/dl of baseline) = 10%, renal replacement=45%, liver transplant=23%, 30-day mortality=43% Moore et al. 2020 Retrospective Terlipressin+ albumin 203 Complete response (SCr < 1.5mg/dl) =50.2%, overall response=72.9% Renal transplant=12%, liver transplant=2%, Other vasoconstrictors 22 Complete response (SCr < 1.5mg/dl) =22.7%, overall response=59.1% Giovo et al. 2020 Retrospective Terlipressin+ albumin 24 Response to treatment=67% Noradrenaline+ albumin 13 Response to treatment=23% Nguyen-Tat et al. 2019 Retrospective Terlipressin + albumin for HRS-1 patients 54 HRS reversal=48%, relapse=8%, median OS=89±53 Terlipressin + albumin for HRS-2 patients 52 HRS reversal=46%, relapse=50%, mortality=20%, median OS=239±174 RCT= randomized clinical trial, HRS=Hepatorenal syndrome, SCr=serum creatinine.