The impact of diabetes and glucose-lowering therapies on hepatocellular carcinoma incidence and overall survival

Theresa J. Hydes; Daniel J. Cuthbertson; Suzanne Graef; Sarah Berhane; Mabel Teng; Anna Skowronska; Pushpa Singh; Sofi Dhanaraj; Abd Tahrani; Philip J. Johnson

doi:10.1016/j.clinthera.2021.12.011

The impact of diabetes and glucose-lowering therapies on hepatocellular carcinoma incidence and overall survival

Theresa J. Hydes, Daniel J. Cuthbertson, Suzanne Graef, Sarah Berhane, Mabel Teng, Anna Skowronska, Pushpa Singh, Sofi Dhanaraj, Abd Tahrani, Philip J. Johnson

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Abstract

Purpose: The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS).

Methods: Data from 1064 patients diagnosed with chronic liver disease (CLD) (n = 340) or HCC (n = 724) were collected from 2007 to 2012. Patients with HCC were followed up prospectively. Univariate and multivariate logistic regression determined HCC risk factors. Kaplan-Meier curves were used to examine survival and Cox proportional hazards analysis estimated hazard ratios (HRs) for death according to use of glucose-lowering therapies.

Findings: Diabetes prevalence was 39.6% and 10.6% within the HCC and CLD cohorts, respectively. The odds ratio for having HCC in patients with diabetes was 5.55 (P < 0.001). Univariate analysis found an increased association of HCC with age, sex, cirrhosis, hemochromatosis, alcohol abuse, diabetes, and Child's Pugh score. In multivariate analysis age, sex, cirrhosis, Child's Pugh score, diabetes status, and insulin use retained significance. Diabetes status did not significantly affect OS in HCC; however, in people with diabetes and HCC, metformin treatment was associated with improved OS (mean survival, 31 vs 24 months; P =0.016; HR for death = 0.75; P = 0.032).

Implications: Diabetes is significantly associated with HCC in the United Kingdom. Metformin treatment is associated with improved OS after HCC diagnosis. Treatment of diabetes should be appropriately reviewed in high-risk populations, with specific consideration of the potential hepatoprotective effects of metformin in HCC.

Original language	English
Pages (from-to)	257-268
Number of pages	12
Journal	Clinical Therapeutics
Volume	44
Issue number	2
Early online date	22 Jan 2022
DOIs	https://doi.org/10.1016/j.clinthera.2021.12.011
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
Theresa J. Hydes was involved with study design, performed data analysis and interpretation, and edited the manuscript. Daniel J. Cuthbertson was involved with study design and data interpretation and wrote the manuscript. Suzanne Graef was involved in study design, data analysis, and interpretation. Sarah Berhane provided statistical advice. Mabel Teng and Anna Skowronska helped with data collection, analysis, and interpretation. Pushpa Singh, Sofi Dhanaraj, and Abd Tahrani helped with data collection. Philip J. Johnson was involved in study concept and design and data interpretation and edited the manuscript.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

Carcinoma, Hepatocellular/epidemiology
Child
Diabetes Mellitus, Type 2/complications
Glucose
Humans
Incidence
Liver Cirrhosis/complications
Liver Neoplasms/epidemiology
Metformin/therapeutic use
Risk Factors

ASJC Scopus subject areas

Pharmacology (medical)
Pharmacology

UN SDGs

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

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10.1016/j.clinthera.2021.12.011Licence: None: All rights reserved

HydesT2022impact Accepted author manuscript, 628 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

Cite this

Hydes, T. J., Cuthbertson, D. J., Graef, S., Berhane, S., Teng, M., Skowronska, A., Singh, P., Dhanaraj, S., Tahrani, A., & Johnson, P. J. (2022). The impact of diabetes and glucose-lowering therapies on hepatocellular carcinoma incidence and overall survival. Clinical Therapeutics, 44(2), 257-268. Advance online publication. https://doi.org/10.1016/j.clinthera.2021.12.011

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abstract = "Purpose: The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS). Methods: Data from 1064 patients diagnosed with chronic liver disease (CLD) (n = 340) or HCC (n = 724) were collected from 2007 to 2012. Patients with HCC were followed up prospectively. Univariate and multivariate logistic regression determined HCC risk factors. Kaplan-Meier curves were used to examine survival and Cox proportional hazards analysis estimated hazard ratios (HRs) for death according to use of glucose-lowering therapies. Findings: Diabetes prevalence was 39.6% and 10.6% within the HCC and CLD cohorts, respectively. The odds ratio for having HCC in patients with diabetes was 5.55 (P < 0.001). Univariate analysis found an increased association of HCC with age, sex, cirrhosis, hemochromatosis, alcohol abuse, diabetes, and Child's Pugh score. In multivariate analysis age, sex, cirrhosis, Child's Pugh score, diabetes status, and insulin use retained significance. Diabetes status did not significantly affect OS in HCC; however, in people with diabetes and HCC, metformin treatment was associated with improved OS (mean survival, 31 vs 24 months; P =0.016; HR for death = 0.75; P = 0.032). Implications: Diabetes is significantly associated with HCC in the United Kingdom. Metformin treatment is associated with improved OS after HCC diagnosis. Treatment of diabetes should be appropriately reviewed in high-risk populations, with specific consideration of the potential hepatoprotective effects of metformin in HCC.",

keywords = "Carcinoma, Hepatocellular/epidemiology, Child, Diabetes Mellitus, Type 2/complications, Glucose, Humans, Incidence, Liver Cirrhosis/complications, Liver Neoplasms/epidemiology, Metformin/therapeutic use, Risk Factors",

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note = "Funding Information: Theresa J. Hydes was involved with study design, performed data analysis and interpretation, and edited the manuscript. Daniel J. Cuthbertson was involved with study design and data interpretation and wrote the manuscript. Suzanne Graef was involved in study design, data analysis, and interpretation. Sarah Berhane provided statistical advice. Mabel Teng and Anna Skowronska helped with data collection, analysis, and interpretation. Pushpa Singh, Sofi Dhanaraj, and Abd Tahrani helped with data collection. Philip J. Johnson was involved in study concept and design and data interpretation and edited the manuscript. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

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AU - Hydes, Theresa J.

AU - Cuthbertson, Daniel J.

AU - Graef, Suzanne

AU - Berhane, Sarah

AU - Teng, Mabel

AU - Skowronska, Anna

AU - Singh, Pushpa

AU - Dhanaraj, Sofi

AU - Tahrani, Abd

AU - Johnson, Philip J.

N1 - Funding Information: Theresa J. Hydes was involved with study design, performed data analysis and interpretation, and edited the manuscript. Daniel J. Cuthbertson was involved with study design and data interpretation and wrote the manuscript. Suzanne Graef was involved in study design, data analysis, and interpretation. Sarah Berhane provided statistical advice. Mabel Teng and Anna Skowronska helped with data collection, analysis, and interpretation. Pushpa Singh, Sofi Dhanaraj, and Abd Tahrani helped with data collection. Philip J. Johnson was involved in study concept and design and data interpretation and edited the manuscript. Publisher Copyright: © 2022 Elsevier Ltd

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N2 - Purpose: The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS). Methods: Data from 1064 patients diagnosed with chronic liver disease (CLD) (n = 340) or HCC (n = 724) were collected from 2007 to 2012. Patients with HCC were followed up prospectively. Univariate and multivariate logistic regression determined HCC risk factors. Kaplan-Meier curves were used to examine survival and Cox proportional hazards analysis estimated hazard ratios (HRs) for death according to use of glucose-lowering therapies. Findings: Diabetes prevalence was 39.6% and 10.6% within the HCC and CLD cohorts, respectively. The odds ratio for having HCC in patients with diabetes was 5.55 (P < 0.001). Univariate analysis found an increased association of HCC with age, sex, cirrhosis, hemochromatosis, alcohol abuse, diabetes, and Child's Pugh score. In multivariate analysis age, sex, cirrhosis, Child's Pugh score, diabetes status, and insulin use retained significance. Diabetes status did not significantly affect OS in HCC; however, in people with diabetes and HCC, metformin treatment was associated with improved OS (mean survival, 31 vs 24 months; P =0.016; HR for death = 0.75; P = 0.032). Implications: Diabetes is significantly associated with HCC in the United Kingdom. Metformin treatment is associated with improved OS after HCC diagnosis. Treatment of diabetes should be appropriately reviewed in high-risk populations, with specific consideration of the potential hepatoprotective effects of metformin in HCC.

AB - Purpose: The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS). Methods: Data from 1064 patients diagnosed with chronic liver disease (CLD) (n = 340) or HCC (n = 724) were collected from 2007 to 2012. Patients with HCC were followed up prospectively. Univariate and multivariate logistic regression determined HCC risk factors. Kaplan-Meier curves were used to examine survival and Cox proportional hazards analysis estimated hazard ratios (HRs) for death according to use of glucose-lowering therapies. Findings: Diabetes prevalence was 39.6% and 10.6% within the HCC and CLD cohorts, respectively. The odds ratio for having HCC in patients with diabetes was 5.55 (P < 0.001). Univariate analysis found an increased association of HCC with age, sex, cirrhosis, hemochromatosis, alcohol abuse, diabetes, and Child's Pugh score. In multivariate analysis age, sex, cirrhosis, Child's Pugh score, diabetes status, and insulin use retained significance. Diabetes status did not significantly affect OS in HCC; however, in people with diabetes and HCC, metformin treatment was associated with improved OS (mean survival, 31 vs 24 months; P =0.016; HR for death = 0.75; P = 0.032). Implications: Diabetes is significantly associated with HCC in the United Kingdom. Metformin treatment is associated with improved OS after HCC diagnosis. Treatment of diabetes should be appropriately reviewed in high-risk populations, with specific consideration of the potential hepatoprotective effects of metformin in HCC.

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KW - Liver Cirrhosis/complications

KW - Liver Neoplasms/epidemiology

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The impact of diabetes and glucose-lowering therapies on hepatocellular carcinoma incidence and overall survival

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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