Liver cancer is a significant global health problem, with increasing incidence and mortality rates. While risk factors like HBV, HCV, aflatoxin, alcohol, tobacco, obesity, NAFLD, and type 2 diabetes are known, the role of dietary factors remains unclear. This study focuses on the relationship between whole grain and dietary fiber intake and the risk of liver cancer and chronic liver disease (CLD) mortality. Whole grains are rich in fiber, vitamins, minerals, and phytochemicals, and have been linked to reduced risk of various diseases, including type 2 diabetes and cardiovascular disease. Some previous research suggested a protective effect of whole grains and dietary fiber against liver cancer, but these studies had limited sample sizes. This study aims to investigate these associations using a large prospective cohort, thereby offering a more robust assessment of the potential protective effects of whole grain and dietary fiber against liver cancer and CLD mortality. The large sample size will allow for a more precise estimation of the effect size and investigation of the impact across different subgroups of the population.

Existing research on the association between diet and liver disease is limited. While known risk factors for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) – the two most common types of liver cancer – include viral infections, aflatoxin exposure, and lifestyle factors, the impact of dietary components like whole grains and dietary fiber remains poorly understood. Two prospective cohort studies previously explored the relationship between dietary fiber and liver cancer risk, showing inverse associations. However, these studies had a limited number of cases, hindering the strength of their conclusions. One study also reported an inverse association for whole grain intake, but with similar limitations. No prior study had examined the connection between whole grain and dietary fiber intake and CLD mortality. This research gap highlights the need for a larger, more comprehensive investigation to determine the protective role of dietary components against liver cancer and CLD.

This study utilized data from the NIH-AARP Diet and Health Study, a large prospective cohort of 485,717 US adults (290,484 men and 195,233 women) aged 50–71 years. Baseline data, including dietary information obtained through a validated food frequency questionnaire (FFQ), were collected in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases (635 HCC, 164 ICC) and 993 deaths from CLD. Whole grain and dietary fiber intake were categorized into quintiles. Cox proportional hazards models were used to assess the association between whole grain and dietary fiber intake (total and from different sources: fruits, vegetables, beans, grains) with liver cancer risk and CLD mortality, adjusting for potential confounders such as age, sex, race, education, BMI, alcohol consumption, smoking status, physical activity, diabetes history, and total energy intake. Sensitivity analyses were conducted to assess the robustness of findings by adjusting for additional dietary factors (HEI-2015) and excluding early cases or heavy drinkers.

The highest quintile of whole grain intake was associated with a 22% lower risk of liver cancer (Hazard Ratio [HR] = 0.78, 95% CI: 0.63–0.96) and a 56% lower risk of CLD mortality (HR = 0.44, 95% CI: 0.35–0.55) compared to the lowest quintile, after adjusting for confounders. The highest quintile of total dietary fiber intake was associated with a 31% reduction in liver cancer risk (HR = 0.69, 95% CI: 0.53–0.90) and a 63% reduction in CLD mortality (HR = 0.37, 95% CI: 0.29–0.48). Significant inverse associations were observed for dietary fiber from vegetables and grains with both liver cancer and CLD mortality. However, no significant association was observed for fiber from fruits. Stratified analyses showed consistent inverse associations across different subgroups (BMI, diabetes status, alcohol consumption, smoking status, and physical activity). Sensitivity analyses yielded similar results.

This study provides strong evidence supporting the protective effects of higher whole grain and dietary fiber intake against liver cancer and CLD mortality. The observed reductions in risk were substantial, suggesting that dietary modifications could be an important component of liver disease prevention strategies. The findings are consistent with previous, albeit smaller, studies and extend the findings to include CLD mortality. The specific benefits from vegetables, beans, and grains highlight the importance of dietary diversity and source-specific effects of fiber. The potential mechanisms underlying these associations may involve several factors, including improved gut health, modulation of inflammation, improved glucose metabolism, and reduced exposure to carcinogens. However, the lack of association observed for fruit fiber highlights the complexity of dietary influences on liver health. Further research is required to fully elucidate the underlying biological pathways and to pinpoint specific dietary components responsible for this protective effect.

This large prospective cohort study demonstrates a strong inverse association between higher whole grain and dietary fiber intake and the risk of liver cancer and CLD mortality. These findings suggest that dietary interventions focusing on increased whole grain and fiber intake, particularly from vegetables, beans, and grains, may offer a valuable approach to liver disease prevention. Further research should explore the specific mechanisms involved and examine these relationships in diverse populations to enhance the generalizability of findings.

Several limitations should be considered. The study relied on self-reported dietary data (FFQ), which is subject to recall bias and measurement error. Information on HBV/HCV infection, critical risk factors for liver disease, was not available for the entire cohort, although the authors argue that the effect of diet is unlikely to be substantially confounded by these factors. The study population was predominantly of European ancestry, potentially limiting generalizability to other ethnic groups. The focus on CLD mortality rather than incidence due to the absence of national CLD registries is also a limitation. The participants were aged 50-71, restricting generalizability to this age group.