Liver diseases, transaminases, and hepatobiliary–pancreatic cancer risk - a cohort and Mendelian randomisation study using data from UK Biobank

Q: What was the main objective of this study?

To explore the relationship between liver diseases and hepatobiliary–pancreatic cancers, emphasizing transaminase levels and genetic susceptibility.

Q: How were cancer risks evaluated in the cohort?

Logistic regression models compared cancer risks between liver disease groups and controls and examined associations with transaminase levels and polygenic risk scores.

Q: What did Mendelian randomisation show about causality?

Two-sample Mendelian randomisation indicated causal links between alcohol-associated liver disease and both HCC and intrahepatic cholangiocarcinoma.

Sep 23, 2026

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Objective: Liver diseases are established risk factors for hepatobiliary and pancreatic cancers. This study investigates how liver disease status, transaminase levels, and genetic susceptibility relate to hepatobiliary–pancreatic cancer outcomes. Methods: A large UK Biobank cohort of 449,815 participants was analyzed using logistic regression. Cancer risks were compared across liver disease and control groups, and links between transaminase levels, polygenic risk scores (PRS), and four cancers were assessed. Two-sample Mendelian randomisation tested causal effects. Results: Liver disease and elevated transaminases increased cancer risk (p<0.001). Genetic PRS for ALT/AST associated with higher HCC risk. MR supported causal roles for alcohol-associated liver disease in HCC and ICC. Conclusion: Liver disease patients show higher hepatobiliary–pancreatic cancer risk, with elevated transaminases reflecting genetic predisposition to HCC.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Objective

Methods

Results

Conclusion

Introduction

Global burden of liver diseases and related cancers

Rationale for identifying high-risk factors

What is already known on this topic

Chronic liver injury and genetic predisposition

What this study adds

Transaminase levels and PRS

Mendelian randomisation findings

How this study might affect research, practice or policy

Hepatology Liver diseases, transaminases, and hepatobiliary–pancreatic cancer risk: a cohort and Mendelian randomisation study using data from UK Biobank Yuan Yuan ,1,2 Yong Jiang,2 Chonghui Hu,2 Daixin Wu,3 Huimou Chen,4 Qing Tian,5 Rihua He,2 Tingting Li,5 Tianhao Huang,2 Honghui Jiang,2 Wentao Zhong,1,2 Yuan Chen,6 Jiale Jiang,7 Shangyou Zheng,2 Rufu Chen1,2,5 To cite: Yuan Y, Jiang Y, Hu C, et al. Liver diseases, transaminases, and hepatobiliary–pancreatic cancer risk: a cohort and Mendelian randomisation study using data from UK Biobank. BMJ Open Gastroenterol 2025;12:e001870 . doi:10 . 1136/ bmjgast-2025-001870 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi](https://doi). org/10.1136/bmjgast-2025- 001870 ) . YY, YJ and CH contributed equally. Received 17 April 2025 Accepted 24 June 2025 © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Professor Rufu Chen; [chenrufu@gdph.org.cn](chenrufu@gdph.org.cn) Dr Shangyou Zheng; [zhengshangyou@gdph.org.cn](zhengshangyou@gdph.org.cn) ABSTRACT Objective Liver diseases are established risk factors for hepatobiliary and pancreatic cancers. This study explores the relationship between liver disease and hepatobiliary– pancreatic cancers, focusing on transaminase levels and genetic susceptibility. Methods We conducted a large cohort study using data from 449 815 participants in the UK Biobank. Logistic regression models assessed cancer risks in liver disease versus control groups. The association between transaminase levels, polygenic risk scores (PRS), and hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), biliary tract cancer, and pancreatic cancer was examined. Two-sample Mendelian randomisation (MR) investigated the causal relationships between liver diseases and the four cancers. Results Liver disease and elevated transaminase levels were significantly associated with increased cancer risks (p<0 .001) . Higher alanine transaminase and aspartate transaminase PRS were linked to increased HCC risk (HR=1 .69, 95% CI 1.38 to 2 .08; HR=1 .79, 95% CI 1.46 to 2. 19) . MR analysis revealed a causal link between alcoholassociated liver disease (ALD) and both HCC (OR=1.379, 95% CI 1.109 to 1 .714) and ICC (OR=1 .429, 95% CI 1.130 to 1.807), while metabolic dysfunction-associated steatotic liver disease showed no significant associations. Conclusion Patients with liver diseases have a significantly higher risk of hepatobiliary and pancreatic cancers, and individuals with elevated transaminase levels also exhibit a genetic predisposition to HCC. ALD demonstrates significant causal relationships with HCCand ICC. INTRODUCTION Liver diseases are important global health concerns. Statistics show that liver diseases account for 4% of global mortality.1 Numerous retrospective studies have documented a substantial increase in incidence rates in recent years.2 3 The high incidence of liver diseases poses a significant challenge to the global healthcare system, calling for effective prevention, diagnosis, | WHAT IS ALREADY KNOWN ON THIS TOPIC | | --- | | ⇒ Chronic liver injury and inflammation promoteshepatobiliary–pancreatic carcinogenesis in hepatic disorders, yet the genetic mechanisms driving this pathological progression remain incompletely elucidated.
⇒ Genome-wide association studies have identified single nucleotide polymorphisms linked to elevated alanine transaminase (ALT) and aspartate transaminase (AST), suggesting genetic predisposition in the population.
WHAT THIS STUDY ADDS | | ⇒ Elevated transaminase levels increase hepatobiliary–pancreatic cancer risks.
⇒ High ALT and AST polygenic risk scores (PRS) elevate the risk of hepatocellular carcinoma (HCC; HR=1 .69–1.79), but not intrahepatic chola

FAQs

What was the main objective of this study?

To explore the relationship between liver diseases and hepatobiliary–pancreatic cancers, emphasizing transaminase levels and genetic susceptibility.

How were cancer risks evaluated in the cohort?

Logistic regression models compared cancer risks between liver disease groups and controls and examined associations with transaminase levels and polygenic risk scores.

What did Mendelian randomisation show about causality?

Two-sample Mendelian randomisation indicated causal links between alcohol-associated liver disease and both HCC and intrahepatic cholangiocarcinoma.

Sep 23, 2026

Uploaded by Cart