Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone

Kavish R Patidar^{1

2}, Wanzhu Tu³, Thomas G Cotter⁴, Douglas A Simonetto⁵, Amon Asgharpour⁶, Muhammad Y Jan⁷, Qing Tang³, Yunpeng Yu³, Yang Li³, Moyinoluwa Taiwo⁸, Prashanth Thevkar Nagesh⁹, Srinivasan Dasarathy⁸, Patrick S Kamath⁵, Craig J McClain¹⁰, Naga Chalasani¹, Gyongyi Szabo⁹, Ramon Bataller^{11

12}, Mack Mitchell⁴, Wajahat Z Mehal^{13

14}, Laura E Nagy¹⁵, Vijay H Shah⁵, Samer Gawrieh¹, Arun J Sanyal⁶; AlcHepNet Investigators

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA.
² Department of Internal Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
³ Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA.
⁴ Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA.
⁷ Division of Nephrology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
⁹ Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Louisville, Louisville, Kentucky, USA.
¹¹ Division of Gastroenterology and Hepatology and Nutrition, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹² School of Medicine and Health Sciences, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹³ Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
¹⁴ Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Connecticut, USA.
¹⁵ Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

PMID: 39028887
PMCID: PMC11829732 (available on 2026-04-01)
DOI: 10.1097/HEP.0000000000001019

Clinical Trial

Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone

Kavish R Patidar et al. Hepatology. 2025.

. 2025 Apr 1;81(4):1256-1268.

doi: 10.1097/HEP.0000000000001019. Epub 2024 Jul 19.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA.
² Department of Internal Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
³ Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA.
⁴ Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA.
⁷ Division of Nephrology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
⁹ Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Louisville, Louisville, Kentucky, USA.
¹¹ Division of Gastroenterology and Hepatology and Nutrition, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹² School of Medicine and Health Sciences, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹³ Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
¹⁴ Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Connecticut, USA.
¹⁵ Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

PMID: 39028887
PMCID: PMC11829732 (available on 2026-04-01)
DOI: 10.1097/HEP.0000000000001019

Abstract

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, with death treated as a competing event. Risk factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, HE, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than in PRED (45% [n=33] versus 22% [n=16], p =0.001). AKI phenotypes were similar between the 2 treatment arms ( p =0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n=21 [63.6%] vs. n=8 [50.0%], p =0.035). At baseline, urine-neutrophil-gelatinase-associated lipocalin levels were similar between participants who developed AKI in both treatment arms ( p =0.319). However, day 7 and 14 urine-neutrophil-gelatinase-associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI ( p =0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35, p =0.005).

Conclusions: AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z-treated participants with AKI had higher urine-neutrophil-gelatinase-associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.

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Conflict of interest statement

Wanzhu Tu consults for Bayer. Douglas A. Simonetto consults for BioVie, Evive, Mallinckrodt, PharmaIN, and Resolution. Amon Asgharpour consults for Galectin, Intercept, and Madrigal. Srinivasan Dasarathy received grants from NIH. Patrick S. Kamath received grants from Sequana. Craig J. McClain received grants from Intercept and Target. Naga Chalasani consults for Altimmune, Boehringer Ingelheim, Foresite, Galectin, GlaxoSmithKline, Madrigal, Merck, and Zydus. He received grants from DSM and Exact. He owns stock in Avant Sante and RestUp. Gyongyi Szabo consults and owns stock in Glympse, Satellite, and Ventyx. He consults for Cyta, Durect, Evive, Intercept, LabCorp, Merck, Novartis, Pandion, Pfizer, Surrozen, Takeda, and Terra Firma. He has other interests with Springer and UpToDate. Ramon Bataller consults and advises GlaxoSmithKline and Novo Nordisk. He consults and is on the speakers’ bureau for AbbVie and Gilead. He consults for Boehringer Ingelheim and Resolution. Mack Mitchell consults and advises GlaxoSmithKline and HepaTx. He owns stock and is employed by Amygdala Neuroscience. He consults for Prodigy. He advises Parvus. He received grants from Durect. He owns stock in AbbVie. Vijay H. Shah consults for Ambys Medicines, Durect, Generon Shanghai, GENFIT, HepaRegeniX, Korro Bio, Novartis, and Seal Rock. He advises AgomAb, Akaza, Intercept, Mallinckrodt, Resolution, and Surrozen. Samer Gawrieh consults for Kowa, Pfizer, Spruce, and TransMedics. He received grants from DSM, Sonic Incytes, Viking, and Zydus. Arun J. Sanyal consults and owns stock in GENFIT and NorthSea. He consults for 89Bio, Abbott, AbbVie, AGED, Akero, Albireo, Alnylam, Amgen, Arrowhead, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceutical, Bristol Myers Squibb, Cascade, Chemomab, Cocept, Echosens, Eli Lilly, Gatehouse, Genentech, Gilead, GlaxoSmithKline, HistoIndex, Intercept, Janssen, Mallinckrodt, Mediar, Merck, Myovant, Novartis, Novo Nordisk, Path AI, Pfizer, Poxel, Promed, Regeneron, Roche, Salix, Satellite, Siemens, Surrozen, Takeda, Tern, Variant, and Zydus. He owns stock in Akarna, Diapen, Durect, Exhalenz, Galmed, HemoShear, Inversago, LipoNexus, Rivus, and Tiziana. He has other interests with Elsevier and UpToDate. The remaining authors have no conflicts to report.

References

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Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone

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Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone

Authors

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Abstract

Conflict of interest statement

References

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