PMID- 38285703
OWN - NLM
STAT- MEDLINE
DCOM- 20240131
LR  - 20240206
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 19
IP  - 1
DP  - 2024
TI  - Comparative efficacy of terlipressin and norepinephrine for treatment of 
      hepatorenal syndrome-acute kidney injury: A systematic review and meta-analysis.
PG  - e0296690
LID - 10.1371/journal.pone.0296690 [doi]
LID - e0296690
AB  - The treatment of choice for hepatorenal syndrome-acute kidney injury (HRS-AKI) is 
      vasoconstrictor therapy in combination with albumin, preferably norepinephrine or 
      terlipressin as recommended by recent guidelines. In the absence of larger 
      head-to-head trials comparing the efficacy of terlipressin and norepinephrine, 
      meta-analysis of smaller studies can provide insights needed to understand the 
      comparative effects of these medications. Additionally, recent changes in the HRS 
      diagnosis and treatment guidelines underscore the need for newer analyses 
      comparing terlipressin and norepinephrine. In this systematic review, we aimed to 
      assess reversal of hepatorenal syndrome (HRS) and 1-month mortality in subjects 
      receiving terlipressin or norepinephrine for the management of HRS-AKI. We 
      searched literature databases, including PubMed, Cochrane, Clinicaltrials.gov, 
      International Clinical Trials Registry Platform, Embase, and ResearchGate, for 
      randomized controlled trials (RCTs) published from January 2007 to June 2023 on 
      June 26, 2023. Only trials comparing norepinephrine and albumin with terlipressin 
      and albumin for the treatment of HRS-AKI in adults were included, and trials 
      without HRS reversal as an endpoint or nonresponders were excluded. Pairwise 
      meta-analyses with the random effects model were conducted to estimate odds 
      ratios (ORs) for HRS reversal and 1-month mortality as primary outcomes. 
      Additional outcomes assessed, included HRS recurrence, predictors of response, 
      and incidence of adverse events (AEs). We used the Cochrane risk of bias 
      assessment tool for quality assessment. We included 7 RCTs with a total of 376 
      subjects with HRS-AKI or HRS type 1. This meta-analysis showed numerically higher 
      rates of HRS reversal (OR 1.33, 95% confidence interval [CI] [0.80-2.22]; P = 
      0.22) and short-term survival (OR 1.50, 95% CI [0.64-3.53]; P = 0.26) with 
      terlipressin, though these results did not reach statistical significance. 
      Terlipressin was associated with AEs such as abdominal pain and diarrhea, whereas 
      norepinephrine was associated with cardiovascular AEs such as chest pain and 
      ischemia. Most of the AEs were reversible with a reduction in dose or 
      discontinuation of therapy across both arms. Of the terlipressin-treated 
      subjects, 5.3% discontinued therapy due to serious AEs compared to 2.7% of the 
      norepinephrine-treated subjects. Limitations of this analysis included small 
      sample size and study differences in HRS-AKI diagnostic criteria. As more studies 
      using the new HRS-AKI criteria comparing terlipressin and norepinephrine are 
      completed, a clearer understanding of the comparability of these 2 therapies will 
      emerge.
CI  - Copyright: (c) 2024 Olson, Subramanian. This is an open access article distributed 
      under the terms of the Creative Commons Attribution License, which permits 
      unrestricted use, distribution, and reproduction in any medium, provided the 
      original author and source are credited.
FAU - Olson, Jody C
AU  - Olson JC
AUID- ORCID: 0000-0003-2818-4959
AD  - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, 
      United States of America.
FAU - Subramanian, Ram M
AU  - Subramanian RM
AD  - Department of Medicine, Divisions of Gastroenterology and Hepatology and 
      Pulmonary and Critical Care Medicine, Emory University School of Medicine, 
      Atlanta, Georgia, United States of America.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20240129
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 7Z5X49W53P (Terlipressin)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - 50-57-7 (Lypressin)
RN  - 0 (Vasoconstrictor Agents)
RN  - 0 (Albumins)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Terlipressin/therapeutic use
MH  - Norepinephrine/adverse effects
MH  - *Hepatorenal Syndrome/drug therapy
MH  - Lypressin/adverse effects
MH  - Treatment Outcome
MH  - Vasoconstrictor Agents/adverse effects
MH  - *Acute Kidney Injury/chemically induced
MH  - Albumins/adverse effects
PMC - PMC10824429
COIS- Both JCO and RMS have served as consultants for Mallinckrodt Pharmaceuticals 
      related to terlipressin. This does not alter our adherence to PLOS ONE policies 
      on sharing data and materials. There are no patents, products in development or 
      marketed products associated with this research to declare.
EDAT- 2024/01/29 19:57
MHDA- 2024/01/31 06:42
PMCR- 2024/01/29
CRDT- 2024/01/29 13:36
PHST- 2023/06/29 00:00 [received]
PHST- 2023/12/15 00:00 [accepted]
PHST- 2024/01/31 06:42 [medline]
PHST- 2024/01/29 19:57 [pubmed]
PHST- 2024/01/29 13:36 [entrez]
PHST- 2024/01/29 00:00 [pmc-release]
AID - PONE-D-23-19336 [pii]
AID - 10.1371/journal.pone.0296690 [doi]
PST - epublish
SO  - PLoS One. 2024 Jan 29;19(1):e0296690. doi: 10.1371/journal.pone.0296690. 
      eCollection 2024.