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

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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.

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Abbreviations

CTP:

Child–Turcotte–Pugh

HRS:

Hepatorenal syndrome

LT:

Liver transplant

MELD:

Model for end-stage liver disease

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

RCT:

Randomized controlled trial

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Acknowledgments

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

Funding

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).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA

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

  2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Arthur Taylor

  3. Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA

    Mary J. Thomson, Anna S. Lok & Elliot B. Tapper

  4. Veterans Affairs Hospital, Ann Arbor, MI, USA

    Elliot B. Tapper

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  1. Mary J. Thomson
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Correspondence to Mary J. Thomson.

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Thomson, M.J., Taylor, A., Sharma, P. et al. Limited Progress in Hepatorenal Syndrome (HRS) Reversal and Survival 2002–2018: A Systematic Review and Meta-Analysis. Dig Dis Sci 65, 1539–1548 (2020). https://doi.org/10.1007/s10620-019-05858-2

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  • DOI: https://doi.org/10.1007/s10620-019-05858-2

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