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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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 languageEnglish
Pages (from-to)257-268
Number of pages12
JournalClinical Therapeutics
Issue number2
Early online date22 Jan 2022
Publication statusPublished - 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


  • 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


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