Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002–2018: A Systematic Review and Meta-Analysis

Mary J. Thomson; Arthur Taylor; Pratima Sharma; Anna S. Lok; Elliot B. Tapper

doi:10.1007/s10620-019-05858-2

Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002–2018: A Systematic Review and Meta-Analysis

Mary J. Thomson, Arthur Taylor, Pratima Sharma, Anna S. Lok, Elliot B. Tapper

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24 Scopus citations

Abstract

Introduction: Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress—or lack thereof—in improving outcomes of type 1 HRS over time. Methods: We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. Results: Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4–43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2–51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94–1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96–1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95–1.20, p = 0.26) and 0.97 (95% CI 0.85–1.12, p = 0.70). Conclusion: Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.

Original language	English (US)
Pages (from-to)	1539-1548
Number of pages	10
Journal	Digestive Diseases and Sciences
Volume	65
Issue number	5
DOIs	https://doi.org/10.1007/s10620-019-05858-2
State	Published - May 1 2020
Externally published	Yes

Bibliographical note

Funding Information:
We would like to acknowledge Carol Shannon, who assisted with creating the search strings for this review.

Funding Information:
This study was funded in part by an NIH Training Grant in Epidemiology and Health Services (T32 DK062708—MJT) and an NIH Grant from the Michigan Institute for Clinical and Health Research (KL2 TR002241—EBT).

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Acute kidney injury
Albumin
Antibiotics
Cirrhosis
Hepatorenal syndrome
Hypertension
Liver cirrhosis
Portal
Renal failure
Vasopressors

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title = "Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002–2018: A Systematic Review and Meta-Analysis",

abstract = "Introduction: Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress—or lack thereof—in improving outcomes of type 1 HRS over time. Methods: We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. Results: Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4–43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2–51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94–1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96–1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95–1.20, p = 0.26) and 0.97 (95% CI 0.85–1.12, p = 0.70). Conclusion: Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.",

keywords = "Acute kidney injury, Albumin, Antibiotics, Cirrhosis, Hepatorenal syndrome, Hypertension, Liver cirrhosis, Portal, Renal failure, Vasopressors",

author = "Thomson, {Mary J.} and Arthur Taylor and Pratima Sharma and Lok, {Anna S.} and Tapper, {Elliot B.}",

note = "Funding Information: We would like to acknowledge Carol Shannon, who assisted with creating the search strings for this review. Funding Information: This study was funded in part by an NIH Training Grant in Epidemiology and Health Services (T32 DK062708—MJT) and an NIH Grant from the Michigan Institute for Clinical and Health Research (KL2 TR002241—EBT). Publisher Copyright: {\textcopyright} 2019, Springer Science+Business Media, LLC, part of Springer Nature.",

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doi = "10.1007/s10620-019-05858-2",

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T2 - A Systematic Review and Meta-Analysis

AU - Thomson, Mary J.

AU - Taylor, Arthur

AU - Sharma, Pratima

AU - Lok, Anna S.

AU - Tapper, Elliot B.

N1 - Funding Information: We would like to acknowledge Carol Shannon, who assisted with creating the search strings for this review. Funding Information: This study was funded in part by an NIH Training Grant in Epidemiology and Health Services (T32 DK062708—MJT) and an NIH Grant from the Michigan Institute for Clinical and Health Research (KL2 TR002241—EBT). Publisher Copyright: © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Introduction: Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress—or lack thereof—in improving outcomes of type 1 HRS over time. Methods: We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. Results: Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4–43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2–51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94–1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96–1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95–1.20, p = 0.26) and 0.97 (95% CI 0.85–1.12, p = 0.70). Conclusion: Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.

AB - Introduction: Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress—or lack thereof—in improving outcomes of type 1 HRS over time. Methods: We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019. Results: Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4–43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2–51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94–1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96–1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95–1.20, p = 0.26) and 0.97 (95% CI 0.85–1.12, p = 0.70). Conclusion: Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.

KW - Acute kidney injury

KW - Albumin

KW - Antibiotics

KW - Cirrhosis

KW - Hepatorenal syndrome

KW - Hypertension

KW - Liver cirrhosis

KW - Portal

KW - Renal failure

KW - Vasopressors

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Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002–2018: A Systematic Review and Meta-Analysis

Abstract

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