Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality

Lukas Hartl; Michael Schwarz; Benedikt Simbrunner; Mathias Jachs; Peter Wolf; David Josef Maria Bauer; Bernhard Scheiner; Lorenz Balcar; Georg Semmler; Benedikt Silvester Hofer; Nina Dominik; Rodrig Marculescu; Michael Trauner; Mattias Mandorfer; Thomas Reiberger

doi:10.1111/apt.18289

Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality

Lukas Hartl, Michael Schwarz, Benedikt Simbrunner, Mathias Jachs, Peter Wolf, David Josef Maria Bauer, Bernhard Scheiner, Lorenz Balcar, Georg Semmler, Benedikt Silvester Hofer, Nina Dominik, Rodrig Marculescu, Michael Trauner, Mattias Mandorfer, Thomas Reiberger

Research output: Journal article (peer-reviewed) › Journal article

9 Citations (Scopus)

Abstract

BACKGROUND AND AIMS: We aimed to characterise insulin-like growth factor-1 (IGF-1) signalling in patients with advanced chronic liver disease (ACLD).

METHODS: Consecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6-9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non-bleeding hepatic decompensation and S5: further decompensation.

RESULTS: In total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF-1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p < 0.001). Patients with CSPH had significantly lower IGF-1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF-1 showed an independent negative association with body mass index (BMI; aB: -1.56; p < 0.001), enhanced liver fibrosis (ELF) test (aB: -8.43; p < 0.001), MELD (aB: -1.13; p = 0.042) and age (per 10 years; aB: -6.87; p < 0.001). IGF-1 exhibited an excellent AUROC (0.856) for the prediction of liver-related death at 6 months of follow-up. Lower IGF-1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95% CI: 0.83-0.98; p = 0.016), acute-on-chronic liver failure (ACLF; asHR: 0.80; 95% CI: 0.68-0.93; p = 0.004) and liver-related death (asHR: 0.76; 95% CI: 0.63-0.91; p = 0.004).

CONCLUSION: Decreased levels of IGF-1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF-1 was independently linked to high BMI. Lower IGF-1 in cirrhosis predicts decompensation, ACLF and liver-related death.

Original language	English
Pages (from-to)	88-98
Number of pages	11
Journal	Alimentary Pharmacology and Therapeutics
Volume	61
Issue number	1
DOIs	https://doi.org/10.1111/apt.18289
Publication status	Published - Jan 2025
Externally published	Yes

Keywords

Humans
Insulin-Like Growth Factor I/metabolism
Female
Male
Liver Cirrhosis/mortality
Middle Aged
Aged
Prospective Studies
Adult
Liver/metabolism
Biomarkers/blood
Hypertension, Portal/physiopathology
Disease Progression
Insulin-Like Peptides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/apt.18289

Cite this

Hartl, L., Schwarz, M., Simbrunner, B., Jachs, M., Wolf, P., Bauer, D. J. M., Scheiner, B., Balcar, L., Semmler, G., Hofer, B. S., Dominik, N., Marculescu, R., Trauner, M., Mandorfer, M., & Reiberger, T. (2025). Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality. Alimentary Pharmacology and Therapeutics, 61(1), 88-98. https://doi.org/10.1111/apt.18289

@article{328e77856bc14928a4398e79e1d59dbe,

title = "Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality",

abstract = "BACKGROUND AND AIMS: We aimed to characterise insulin-like growth factor-1 (IGF-1) signalling in patients with advanced chronic liver disease (ACLD).METHODS: Consecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6-9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non-bleeding hepatic decompensation and S5: further decompensation.RESULTS: In total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF-1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p < 0.001). Patients with CSPH had significantly lower IGF-1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF-1 showed an independent negative association with body mass index (BMI; aB: -1.56; p < 0.001), enhanced liver fibrosis (ELF) test (aB: -8.43; p < 0.001), MELD (aB: -1.13; p = 0.042) and age (per 10 years; aB: -6.87; p < 0.001). IGF-1 exhibited an excellent AUROC (0.856) for the prediction of liver-related death at 6 months of follow-up. Lower IGF-1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95\% CI: 0.83-0.98; p = 0.016), acute-on-chronic liver failure (ACLF; asHR: 0.80; 95\% CI: 0.68-0.93; p = 0.004) and liver-related death (asHR: 0.76; 95\% CI: 0.63-0.91; p = 0.004).CONCLUSION: Decreased levels of IGF-1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF-1 was independently linked to high BMI. Lower IGF-1 in cirrhosis predicts decompensation, ACLF and liver-related death.",

keywords = "Humans, Insulin-Like Growth Factor I/metabolism, Female, Male, Liver Cirrhosis/mortality, Middle Aged, Aged, Prospective Studies, Adult, Liver/metabolism, Biomarkers/blood, Hypertension, Portal/physiopathology, Disease Progression, Insulin-Like Peptides",

author = "Lukas Hartl and Michael Schwarz and Benedikt Simbrunner and Mathias Jachs and Peter Wolf and Bauer, \{David Josef Maria\} and Bernhard Scheiner and Lorenz Balcar and Georg Semmler and Hofer, \{Benedikt Silvester\} and Nina Dominik and Rodrig Marculescu and Michael Trauner and Mattias Mandorfer and Thomas Reiberger",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alimentary Pharmacology \& Therapeutics published by John Wiley \& Sons Ltd.",

year = "2025",

month = jan,

doi = "10.1111/apt.18289",

language = "English",

volume = "61",

pages = "88--98",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

Hartl, L, Schwarz, M, Simbrunner, B, Jachs, M, Wolf, P, Bauer, DJM, Scheiner, B, Balcar, L, Semmler, G, Hofer, BS, Dominik, N, Marculescu, R, Trauner, M, Mandorfer, M & Reiberger, T 2025, 'Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality', Alimentary Pharmacology and Therapeutics, vol. 61, no. 1, pp. 88-98. https://doi.org/10.1111/apt.18289

TY - JOUR

T1 - Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality

AU - Hartl, Lukas

AU - Schwarz, Michael

AU - Simbrunner, Benedikt

AU - Jachs, Mathias

AU - Wolf, Peter

AU - Bauer, David Josef Maria

AU - Scheiner, Bernhard

AU - Balcar, Lorenz

AU - Semmler, Georg

AU - Hofer, Benedikt Silvester

AU - Dominik, Nina

AU - Marculescu, Rodrig

AU - Trauner, Michael

AU - Mandorfer, Mattias

AU - Reiberger, Thomas

PY - 2025/1

Y1 - 2025/1

N2 - BACKGROUND AND AIMS: We aimed to characterise insulin-like growth factor-1 (IGF-1) signalling in patients with advanced chronic liver disease (ACLD).METHODS: Consecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6-9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non-bleeding hepatic decompensation and S5: further decompensation.RESULTS: In total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF-1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p < 0.001). Patients with CSPH had significantly lower IGF-1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF-1 showed an independent negative association with body mass index (BMI; aB: -1.56; p < 0.001), enhanced liver fibrosis (ELF) test (aB: -8.43; p < 0.001), MELD (aB: -1.13; p = 0.042) and age (per 10 years; aB: -6.87; p < 0.001). IGF-1 exhibited an excellent AUROC (0.856) for the prediction of liver-related death at 6 months of follow-up. Lower IGF-1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95% CI: 0.83-0.98; p = 0.016), acute-on-chronic liver failure (ACLF; asHR: 0.80; 95% CI: 0.68-0.93; p = 0.004) and liver-related death (asHR: 0.76; 95% CI: 0.63-0.91; p = 0.004).CONCLUSION: Decreased levels of IGF-1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF-1 was independently linked to high BMI. Lower IGF-1 in cirrhosis predicts decompensation, ACLF and liver-related death.

AB - BACKGROUND AND AIMS: We aimed to characterise insulin-like growth factor-1 (IGF-1) signalling in patients with advanced chronic liver disease (ACLD).METHODS: Consecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6-9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non-bleeding hepatic decompensation and S5: further decompensation.RESULTS: In total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF-1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p < 0.001). Patients with CSPH had significantly lower IGF-1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF-1 showed an independent negative association with body mass index (BMI; aB: -1.56; p < 0.001), enhanced liver fibrosis (ELF) test (aB: -8.43; p < 0.001), MELD (aB: -1.13; p = 0.042) and age (per 10 years; aB: -6.87; p < 0.001). IGF-1 exhibited an excellent AUROC (0.856) for the prediction of liver-related death at 6 months of follow-up. Lower IGF-1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95% CI: 0.83-0.98; p = 0.016), acute-on-chronic liver failure (ACLF; asHR: 0.80; 95% CI: 0.68-0.93; p = 0.004) and liver-related death (asHR: 0.76; 95% CI: 0.63-0.91; p = 0.004).CONCLUSION: Decreased levels of IGF-1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF-1 was independently linked to high BMI. Lower IGF-1 in cirrhosis predicts decompensation, ACLF and liver-related death.

KW - Humans

KW - Insulin-Like Growth Factor I/metabolism

KW - Female

KW - Male

KW - Liver Cirrhosis/mortality

KW - Middle Aged

KW - Aged

KW - Prospective Studies

KW - Adult

KW - Liver/metabolism

KW - Biomarkers/blood

KW - Hypertension, Portal/physiopathology

KW - Disease Progression

KW - Insulin-Like Peptides

UR - https://www.scopus.com/pages/publications/85204535602

U2 - 10.1111/apt.18289

DO - 10.1111/apt.18289

M3 - Journal article

C2 - 39305115

SN - 0269-2813

VL - 61

SP - 88

EP - 98

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

IS - 1

ER -

Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality

Abstract

Keywords

UN SDGs

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