Abstract
Importance: Artificially sweetened beverages (ASBs) and sugar-sweetened beverages (SSBs) are widely consumed worldwide and have been linked to metabolic disorders, including obesity and type 2 diabetes, which are established risk factors associated with liver cancer. However, prospective evidence examining beverage consumption and liver cancer subtypes remains limited and inconsistent.
Objective: To examine associations between ASB and SSB consumption and risk of incident liver cancer overall and by subtype, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
Design, Setting, and Participants In this pooled analysis of 11 prospective cohort studies (10 US cohorts and 1 European cohort, comprising adults without a history of cancer at baseline), participants were enrolled across cohorts between 1980 and 2009 and followed up through end-of-study dates ranging from 2000 to 2019. The median (IQR) duration of follow-up was 11.4 (10.8-27.9) to 31.4 (27.6-31.5) years. This analysis was conducted between September 2024 and August 2025. Participants were followed up via linkage to state cancer registries or follow-up surveys for incident liver cancer.
Exposures: Self-reported intake of ASB and SSB assessed at baseline using validated food frequency questionnaires and analyzed per 1-beverage/day increment.
Main Outcomes and Measures: Incident liver cancer overall and by subtype (HCC and ICC) identified through cancer registries or medical record review. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence, adjusting for potential confounders, including demographics and lifestyle factors, and weighted-mean meta-analysis of estimates.
Results: A total of 1 518 411 participants (mean [SD] age, 57.8 [10.1] years; 883 832 female [58.2%]) were included in this analysis. During a median (IQR) of 17.8 (12.8–23.5) years of follow-up, 2811 incident liver cancer cases were identified, including 1699 HCC and 444 ICC cases. After multivariable adjustment, ASB intake per 1-beverage/day increase was not associated with liver cancer risk, HCC (10 cohorts), or ICC (6 cohorts). SSB intake per 1-beverage/day increase was not associated with overall liver cancer risk but was associated with increased risk of HCC (HR, 1.10; 95% CI, 1.03-1.18; 10 cohorts) and ICC (HR, 1.15; 95% CI, 1.00-1.32; 6 cohorts). There was no evidence of effect modification by diabetes status.
Conclusions and Relevance: In this study, increased SSB consumption was associated with increased risk of HCC and ICC. There was little evidence that ASB intake was associated with liver cancer risk overall or by subtype.
Summary:
This individual participant data (IDP) pooled analysis of 11 prospective cohort studies, involving more than 1.5 million adults and 2,811 incident liver cancer cases over approximately 18 years of follow-up, investigated whether consumption of low- and no-calorie sweetened beverages (LNCSBs) and sugar-sweetened beverages (SSBs) was associated with liver cancer risk.
The results showed that LNCSB intake was not associated with risk of liver cancer overall, nor with its major subtypes after adjustment for potential confounding factors such as diabetes or obesity status.
The authors concluded that the overall evidence does not support an association between LNCSB consumption and liver cancer in humans, including a specific association between aspartame and HCC.