Risk Of Liver Cancer Research Articles

The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes.

A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone. Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related (microvascular) and cancer events over 1-5 years. Analysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all-cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1-5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all-cause mortality and several obesity related cancers versus T2D alone. T2D significantly potentiates risk of cardiovascular, malignancy and liver-related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy).

Causal relationship between gout and liver cancer: A Mendelian randomization and transcriptome analysis.

Gout is an inflammatory arthritis resulting from urate crystal deposition, now recognized as part of metabolic syndrome. Hyperuricemia, a hallmark of gout, is associated with various health complications, including liver cancer. Observational studies indicate a link between gout and increased cancer incidence. However, the causal relationship between gout and hepatocellular carcinoma remains uncertain. This study utilizes Mendelian randomization (MR) to explore this connection, minimizing confounding factors commonly present in observational studies. Genome-wide association study data for gout and liver cancer were sourced from the UK Biobank. We selected single nucleotide polymorphisms that are strongly associated with gout and liver cancer as instrumental variables for the analysis. We conducted 2-sample MR analysis using multiple MR methods (MR-Egger, weighted median, inverse variance weighting, and weighted mode) to evaluate causality. Co-localization and transcriptomic analyses were employed to identify target genes and assess their expression in hepatocellular carcinoma tissues. The 2-sample MR analysis indicated a significant causal relationship between gout and heightened liver cancer risk (P_IVW = .014). Co-localization analysis identified phosphatidylethanolamine N-methyltransferase (PEMT) as a crucial gene associated with gout (pH4 = 0.990). Transcriptomic data showed that PEMT expression was significantly higher in normal liver tissues compared to malignant samples (P < .001), and higher PEMT levels correlated with improved survival outcomes (P = .045). Immunohistochemical analysis revealed lower PEMT expression in hepatocellular carcinoma from patients with concurrent gout compared to those without (P < .05). The results indicate that gout increases the risk of hepatocellular carcinoma, with PEMT potentially playing a key role. Although this study focused on European populations, indicating a need for further research in diverse groups, the results emphasize the potential for liver cancer screening in newly diagnosed gout patients. Understanding the relationship between these conditions may inform future clinical practices and cancer prevention strategies.

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.

Causal relationship between ferroptosis-related gene HSPA5 and hepatocellular carcinoma: study based on mendelian randomization and mediation analysis.

To explore the causal relationship between ferroptosis-related gene heat shock protein A5 (HSPA5) and hepatocellular carcinoma (HCC). A two-sample Mendelian randomization (MR) design was employed to evaluate the causal relationships among HSPA5, regulatory T cells (Tregs), and liver cancer. Single nucleotide polymorphisms (SNPs) associated with HSPA5, HCC and Tregs were selected as instrumental variables through publicly available genome-wide association studies (GWAS) databases. MR analysis was used to assess the direct effect of HSPA5 on HCC, followed by two-step MR to analyze the potential mediating role of Tregs. Reverse MR analysis was conducted with liver cancer as the exposure and HSPA5 as the outcome. Inverse variance weighting (IVW) was the primary method for testing causal associations in all MR analyses. Robustness of the results was confirmed through MR Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity of instrumental variables was evaluated using Cochrane's Q statistic, while pleiotropy was tested by MR-Egger intercept and MR-PRESSO, with leave-one-out sensitivity analysis performed for robustness. Data from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were utilized to verify the expression levels of HSPA5 in liver cancer tissues and its correlation with Tregs to reveal the interaction mechanisms between HSPA5 and Tregs in HCC progression and their relationship with patient prognosis. MR analysis showed a positive correlation between elevated HSPA5 expression and liver cancer risk (all P<0.01), while reverse MR analysis found no statistically significant association between liver cancer and HSPA5 (P>0.05). HSPA5 expression was significantly correlated with Tregs function (all P<0.05), and the enrichment of Tregs in the liver cancer microenvironment was positively associated with liver cancer progression (all P<0.05). Mediation analysis indicated that Tregs accounted for 5.00% and 7.45% of the mediation effect between HSPA5 and liver cancer. TCGA and HPA database analysis revealed that both HSPA5 mRNA and protein expression levels were higher in liver cancer tissues compared to normal tissues, and high HSPA5 expression was significantly associated with poor patient prognosis. Immune infiltration analysis confirmed a significant positive correlation between HSPA5 and Tregs, with high Tregs infiltration closely related to HCC progression. Elevated HSPA5 expression is significantly associated with HCC development and poor prognosis. HSPA5 may promote HCC progression by regulating the function of Tregs in the tumor microenvironment.

Research Progress on Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. With the prevalence of overweight and obesity in the Chinese population, NAFLD is no longer a disease exclusive to Western developed countries, and has become one of the most common metabolic diseases in the world. The global prevalence of NAFLD is as high as 37.8%, and the prevalence of NAFLD in the Chinese population is 23.3%. In recent years, with the global epidemic of obesity and metabolic syndrome, the prevalence of NAFLD has gradually increased. The risk factors of NAFLD are closely related to obesity, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia and other diseases. When NAFLD co-exists with these metabolic diseases, it often increases the risk of cirrhosis, liver cancer, and even death. At the same time, it can aggravate other chronic liver diseases, promote disease progression, and is closely related to the occurrence and development of atherosclerosis and type 2 diabetes. With the progression of NAFLD disease, the related clinical burden and economic burden of NAFLD and its impact on patients' quality of life are becoming more and more serious. Therefore, early identification, early diagnosis, early prevention, early treatment and standardized management of NAFLD are conducive to the control of the risk of cirrhosis, liver cancer and cardiovascular diseases. This article will review the epidemiology, hazards, and related risk factors of NAFLD.

Exposure to mycotoxins from the consumption of corn-based breakfast cereals in the United Arab Emirates

Corn-based breakfast cereals, known as cornflakes, have become a common breakfast choice worldwide, recognized for their convenience and versatility. However, mycotoxins can contaminate these products, adversely affecting human health. This study assessed the occurrence of major mycotoxins (AFB1, OTA, DON, ZEA, and FUM) in cornflake stock-keeping units (SKUs) marketed in the United Arab Emirates (UAE). It also evaluated the effect of different independent variables (country of origin, temperature on the production day, storage time, presence of chocolate, bran, and nut ingredients) and estimated the exposure levels of the UAE population to these mycotoxins and the associated risk factors. Seventy-six distinct cornflake SKUs were identified through a market screening and tested for mycotoxins using the Enzyme-Linked Immunosorbent Assay (ELISA) technique. AFB1, OTA, ZEA, FUM, and DON were detected in 23.7, 48.7, 27.6, 9.2 and 88.2% of the samples, respectively. The mean concentrations among positive samples were 2.0, 1.0, 10.14, 584.9, and 90.6 μg/kg, respectively. Except for AFB1, the average mycotoxin levels in samples were below the established limits by the European Union (EU). Among positive samples, none exceeded the US FDA limits for all mycotoxins, and only one exceeded the CODEX limit for FUM. On the other hand, four (5.3%), one (1.3%), one (1.3%), and one (1.3%) SKU exceeded EU limits for AFB1, OTA, FUM, and ZEA, respectively. The country of origin (developing vs. developed countries) exhibited a significant effect on AFB1 presence (p < 0.0001). Furthermore, higher temperature on the production day was associated with significantly higher AFB1 occurrence (p = 0.009). Moreover, the presence of chocolate ingredient had a borderline significant effect on AFB1 (p = 0.05) and a significant effect on OTA (p = 0.002), with higher percentages observed in SKUs containing chocolate. However, no significant effects were found for storage time or the presence of bran and nut ingredients in the cornflakes. On the other hand, the HQ values were below 1 for all mycotoxins, indicating low risk. MoE values exceeded 10,000 among regular cornflake consumers, except for FUM, suggesting minimal risk. Liver cancer risk was 0.0032 cases per 100,000 people per year. Weekly OTA exposure was 0.133 ng/kg BW, below PTWI (Provisional Tolerable Weekly Intake).

The association between empirical dietary inflammatory pattern and risk of cancer and cancer-specific mortality: a systematic review and meta-analysis of prospective cohort studies.

Current evidence indicates a correlation between the inflammatory potential of diet and the risk of cancer and cancer-specific mortality. This study aimed to assess the association between empirical dietary inflammatory pattern (EDIP), which has recently been designed based on the inflammatory potential of the diet, and the risk of cancer and cancer-specific mortality. A systematic literature search was conducted across the PubMed/Medline, Scopus, and Web of Science databases from January 2016 to March 2024. A random effects model was used to calculate the pooled effect size (ES) and 95% confidence intervals (95% CI). Heterogeneity between studies was assessed using the Cochran Q test and the I 2 statistic. From the initial 229 records, 24 prospective cohort studies with 2,683,350 participants and 37,091 cancer incidence cases, as well as 20,819 cancer-specific mortality, were included in our study. Pooled results indicated a significant association between higher adherence to the EDIP and an increased risk of total cancer (ES: 1.10; 95% CI: 1.05-1.15; I 2 = 41.1), colorectal cancer (ES: 1.19; 95% CI: 1.11-1.27; I 2 = 41.1), and liver cancer (ES: 1.48; 95% CI: 1.14-1.94; I 2 = 36.9). However, no significant association between increased adherence to the EDIP and an increased risk of ovarian or endometrial cancer was found. Furthermore, greater adherence to the EDIP was significantly associated with an increased risk of cancer-specific mortality (ES: 1.18; 95% CI: 1.05-1.33; I 2 = 45.4). Our results showed that a diet with higher inflammatory properties is associated with an increased risk of cancer and cancer-specific mortality. PROSPERO registration no. CRD42024496912.

Risk of Malignancy in Indeterminate Liver Nodules Among Patients with Cirrhosis: A Retrospective Cohort Study

BackgroundSeveral studies have shown a higher risk of liver cancer from indeterminate liver nodules, but the exact occurrence and predictors of liver cancer in this group are still unclear. Our aim is to study the development of liver cancer in this population and identify any potential risk factors.MethodsThis retrospective study evaluated cirrhotic patients with indeterminate liver nodules from 2013 to 2023.Data from electronic patient records was analyzed to assess the association between HCC and baseline factors. Subgroup exploratory analysis compared characteristics of patients with de novo HCC and those with nodule transformation HCC.ResultsOut of 116 patients with liver nodules, 19 (16%) developed HCC in up to 7.5-year follow-up. Univariate Cox regression analysis showed a significant association between HCC incidence and smoking [hazard ratio (HR) 2.60, 95% Confidence Interval [CI] 1.01–6.74), nodule diameter exceeding 2 cm (HR 5.41, 95% CI 1.45–20.18), and baseline LI-RADS score 3 (HR 3.78, 95% CI 1.36–19.52). Multivariate Cox regression analysis revealed significant independent associations with nodule diameters 1 cm to < 2 cm (adjusted HR 3.35, 95% CI 1.06–10.60) and greater than 2 cm (adjusted HR 5.85, 95% CI 1.10–31.16), as well as with LI-RADS 3 lesions (adjusted HR 3.75, 95% CI 1.16–12.11) with adjusting other potential predictors and covariates.ConclusionOur findings show a higher incidence of HCC in patients with indeterminate liver nodules, increasing over time and reaching 30% at seven years. Nodules larger than 1–2 cm or LI-RADS 3 lesions pose increased risk for HCC. Enhanced surveillance is necessary given the lack of clear management guidelines.

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.53-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. [Correction added on 19 August 2024, after first online publication: In the preceding sentence, the value '3.534' has been changed to '3.54'.]. No associations were observed for the other medications. Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

Determinants of hepatitis B virus infection among pregnant women in Bench Sheko zone, Southwest Ethiopia: a case-control study.

Hepatitis B Virus (HBV) infection during pregnancy poses serious risks by raising the likelihood of chronic infection in newborns by 90% and the risk of cirrhosis and liver cancer by 25% in chronic infections. This study aimed to identify determinants of HBV infection among pregnant women in the Bench Sheko zone, Southwest Ethiopia. An unmatched case-control study was conducted from May 15 to July 15, 2022, in selected health facilities of the Bench Sheko zone, Southwest Ethiopia. Medical charts were reviewed to collect the HBsAg status of participants, as all pregnant women attending antenatal care underwent routine screening. It involved 228 pregnant women (76 HBV-positive cases and 152 HBV-negative controls). Data were collected using structured questionnaires, and analyzed using SPSS 21. A multivariable logistic regression was performed to identify significant determinants of HBV infection, and statistical significance was declared at p-value <0.05. After controlling potential confounders, having no formal education (AOR = 4.94, 95% CI: 2.01, 8.29; P = 0.007), urban residency (AOR = 2.56, 95% CI: 1.43, 6.86; P = 0.010), history of unsafe abortion (AOR = 3.87, 95% CI: 2.17, 6.98; P < 0.001), sharing sharp materials (AOR = 8.43, 95% CI: 5.54, 10.9; P < 0.001), contact with HBV-infected persons in the family (AOR = 2.18, 95% CI: 1.72, 4.87; P < 0.001), tribal scarification (AOR = 3.23, 95% CI: 1.24, 8.91; P = 0.017), and history of unsafe tooth extraction (AOR = 4.52, 95% CI: 2.18, 9.76; P = 0.039) were identified as significant predictors of HBV infection. The study identifies multiple factors contributing to HBV infection in pregnant women. Therefore, it is crucial to promote safe abortion practices and the responsible use of sharp materials, avoid high-risk contact with infected individuals within the family, raise awareness about the risks associated with tribal scarification while advocating for safer practices, and offer education on safe tooth extraction methods to reduce the risk of HBV.

Liver Cancer Etiology: Old Issues and New Perspectives.

This review aims to synthesize the old issues and current understandings of the etiology of liver cancer, focusing on the diverse causative factors influenced by geographical, socioeconomic, and lifestyle variations across different regions. We highlight significant geographic disparities in liver cancer risk factors. While hepatitis B and C viruses, aflatoxin exposure, and alcohol consumption remain globally established contributors; metabolic dysfunction-associated steatotic liver disease and metabolic syndromes are increasingly prominent in the West. Chronic HBV and aflatoxin continue to dominate as risk factors in Asia and Africa. Dietary factors, metabolic diseases like diabetes and obesity, genetic predispositions, environmental risk factors and lifestyle choices such as smoking and alcohol use play substantial roles in specific populations. Protective factors like coffee and tea consumption, along with aspirin use, vegetables and fruits have shown potential in reducing HCC risk, although findings vary by population and dietary habits. Liver cancer etiology is influenced by various factors that differ by region. Established risk factors include hepatitis B and C, aflatoxin, and alcohol. Emerging risks, such as metabolic dysfunction-associated steatotic liver disease, are more prevalent in Western countries, while aflatoxin and HBV remains significant in Asia and Africa. Diet, metabolic conditions like diabetes and obesity, genetic predispositions, and lifestyle choices also play crucial roles. Coffee, tea, aspirin, vegetables, and fruits may reduce HCC risk, but effectiveness varies. Future research should integrate epidemiology, genetics, and nutrition, with global cooperation and data sharing essential for effective cancer control strategies.

Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study.

α1-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α1-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. In a nationwide nested study, we identified 2702 individuals with α1-antitrypsin deficiency and 26,750 control subjects without α1-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. Individuals with α1-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81-2.63), leukemia (1.76, 1.12-2.79), liver cancer (3.91, 2.23-6.85), and cancer overall (1.25, 1.13-1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55-3.58), 1.83 (1.19-2.81), 4.46 (2.74-7.28), and 1.45 (1.31-1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60-4.95) and skin disease (2.93, 2.19-3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α1-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α1-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.

Association Between Type 1 Diabetes Mellitus and Incident Gastrointestinal Cancer in Korean Population: A Nationwide Retrospective Cohort Study.

The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex. This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers. Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age. The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care.

Immune cells mediate the causal pathway linking circulating complements to cancer: A Mendelian randomization study.

The role of complement in cancer remains controversial. Whether immune cells and inflammatory factors mediate the pathway from complement to cancer has not been fully elucidated. We conducted bidirectional Mendelian randomization (MR) analysis to explore the causal association between complement components and cancer. Meta-analysis was conducted to enhance the robustness of the results. We further explored the mediation roles of immune cells and inflammatory factors in these associations. Our study identified causal associations between 11 complement components and 12 types of cancer. Furthermore, we identified five immune cells as potential mediators: BAFF-R on IgD + CD38- naive B cell mediated 7.434% of the increased risk for liver cancer from C3; CD4 on CD39 + activated CD4 regulatory T cell mediated 12.384% of the increased risk for biliary tract cancer from CD93; CD25 + + CD45RA + CD4 not regulatory T cell and Basophil %CD33dim HLA DR- CD66b- mediated 7.721% and 7.986% of the increased risk of colorectal cancer from MASP1, respectively; CD45RA on resting CD4 regulatory T cell mediated 11.444% of the increased risk of skin cancer from MASP1. This study revealed the causal relationships between complement components and certain cancers, with five immune cells as potential mediators.

Intermittent Fasting on Cancer: An Update

Intermittent fasting (IF) has garnered considerable interest as a dietary intervention with potential therapeutic benefits for various medical conditions, particularly cancer. This review provides a comprehensive update on the effects of IF on cancer, emphasizing its impact on metabolic, hormonal, and cellular mechanisms. IF has been shown to improve glycemic control and reduce liver enzyme levels in patients with non-alcoholic fatty liver disease (NAFLD), suggesting a reduction in liver cancer risk. It can significantly reduce tumor growth and enhance apoptosis in breast cancer by lowering insulin-like growth factor 1 (IGF-1) levels. In patients with polycystic ovary syndrome (PCOS), IF offers superior metabolic and hormonal regulation, potentially lowering cancer risk. IF mitigates chemotherapy-related toxicities, thereby improving patient quality of life. It modulates metabolic pathways, reduces inflammation, and enhances drug delivery in cancer therapy. Personalized dietary strategies, including IF and ketogenic diets, are crucial in cancer care. IF also benefits liver conditions by reducing inflammation and fibrosis, preventing the progression to hepatocellular carcinoma. In obesity-induced triple-negative breast cancer, IF disrupts critical processes involved in cancer progression. In addition, aligning IF with circadian rhythms has shown promise in treating lung cancer. Patient perspectives reveal that IF is feasible and acceptable, improving treatment adherence and quality of life. Overall, IF represents a multifaceted approach to cancer prevention and therapy. This review advocates for further research to establish standardized guidelines for implementing IF in oncology, aiming to develop more effective and holistic cancer treatment strategies.

Air pollutants and primary liver cancer mortality: a cohort study in crop-burning activities and forest fires area.

Northern Thailand experiences high levels of air pollution in the dry season due to agricultural waste burning and forest fires. Some air pollutants can enter the bloodstream, and the liver has the role of detoxifying these along with other harmful substances. In this study, we assessed the effects of long-term exposure to air pollutants on liver cancer mortality in this area. A cohort of 10,859 primary liver cancer patients diagnosed between 2003 and 2018 and followed up to the end of 2020 were included in the study. Extended time-varying covariates of the annually averaged pollutant concentrations updated each year were utilized. The associations between air pollutants and mortality risk were examined by using a Cox proportional hazard model. Metastatic cancer stage had the highest adjusted hazard ratio (aHR) of 3.57 (95% confidence interval (CI):3.23-3.95). Being male (aHR = 1.10; 95% CI: 1.04-1.15), over 60 years old (aHR = 1.16; 95% CI: 1.11-1.21), having a history of smoking (aHR = 1.16; 95%CI: 1.11-1.22), and being exposed to a time-updated local concentration of PM2.5 of 40 μg/m3 (aHR = 1.10; 95% CI: 1.05-1.15) increased the mortality risk. We found that air pollution is one of several detrimental factors on the mortality risk of liver cancer.

Abstract A024: Exploring liver cancer risk factors by birth cohort: An electronic health record (EHR)-based epidemiologic cohort study

Abstract Background: Most hepatocellular carcinoma (HCC) cases in the U.S. have been attributed to chronic hepatitis B (HBV) and hepatitis C virus (HCV) infections, though burden of alcoholic liver disease and metabolic-dysfunction associated fatty liver disease (MAFLD) is rising. Individuals born between 1945-1965 (“the baby boomers”), comprise 25% of the U.S. population but account for 81% of chronic HCV infections and thus bear a disproportionate burden of HCC compared to younger or older cohorts. We examined the association of HCV and other risk factors to liver cancer incidence within liver cancer birth cohorts. Methods: Adults with at least one visit from 2000-2017 to San Francisco Health Network (SFHN), Sutter Health Northern California, and Kaiser Permanente Hawai’i (KPH) were linked to data on incident HCC from the California (SFHN/Sutter) and Hawai’i (KPH) cancer registries through 2017. The three birth cohorts were defined as 1)1895-1944 (“pre-baby boomer”); 2)1945-1965 (“baby boomer”); 3)1966-1999 (“post-baby boomer”). We used Cox proportional hazards regression with age as the timescale to examine association of each risk factor (i.e., HBV, HCV, metabolic syndrome, MAFLD, alcohol use, smoking history) with incident HCC stratified by sex and birth cohort; models were adjusted for site, baseline year, number of encounters, length of active follow-up, race/ethnicity, and cirrhosis. For next steps, we plan to calculate the population attributable fraction for each of these risk factors. Results: From the pooled cohort of 4,248,553 individuals, 2,916 had incident HCC. 15% were born between 1895-1944; 32% from 1945-1965; and 53% from 1966-1999; 55% were females; 39% identified as non-Hispanic (NH) White; 14% as Asian American; 11% as Hispanic; 5% as NH Black. Across all birth cohorts, males and females with active chronic hepatitis B had higher HCC risk compared to those with inactive status. Males and females in the pre-baby boomer and baby boomer cohorts (but not post baby-boomers) with active chronic hepatitis C had higher HCC risk. Males and females in the pre-baby boomer cohort (Hazard Ratio [HR]=2.58, 95% Confidence Interval [CI] 2.01-3.31); HR=2.85, 95% CI 2.03-4.00, respectively) and females in the baby boomer cohort (HR=1.55, 95% CI 1.03-2.32) with metabolic syndrome had higher HCC risk. Having MAFLD was associated with increased HCC risk among males from all three birth cohorts and females in the pre-baby boomer and baby-boomer cohort. Alcohol use was associated with higher HCC among pre-baby boomer males (HR=1.23, 95% CI 1,04-1.46) and baby boomer females (HR=1.39, 95% CI 1.10-1.76). Conclusion: In this racially, ethnically, and socioeconomically diverse cohort, HBV is a significant risk factor in HCC risk across birth cohorts for both males and females, while HCV is among older birth cohorts. Consistent with recent studies, MAFLD is a growing cause across birth cohorts. Understanding the contribution of these risk factors and for whom they are most relevant can help identify targets for intervention to reduce liver cancer burden. Citation Format: Janet N. Chu, Aly Cortella, Alison J. Canchola, Pushkar Inamdar, Sixiang Nie, Mai Vu, Ma Somsouk, Michele M. Tana, Caroline A. Thompson, Chanda Ho, Hashem B. El-Serag, Mi-Ok Kim, Mark Segal, Yihe G. Daida, Su-Ying Liang, Scarlett L. Gomez, Mindy C. Derouen, Salma Shariff-Marco. Exploring liver cancer risk factors by birth cohort: An electronic health record (EHR)-based epidemiologic cohort study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A024.

Metabolic dysfunction‐associated steatotic liver disease and MetALD increases the risk of liver cancer and gastrointestinal cancer: A nationwide cohort study

SummaryBackgroundThe new nomenclature of metabolic dysfunction‐associated steatotic liver disease (MASLD) substituting nonalcoholic fatty liver disease was proposed along with a new category of MASLD with increased alcohol intake (MetALD).AimsWe aimed to explore the cancer risk by MASLD and MetALD.MethodsThis nationwide cohort study included 3,596,709 participants who underwent a health check‐up in 2011 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥30. Participants were categorized into four exclusive groups: MASLD, MetALD, other combination aetiology and no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine–Gray model after adjusting other variables.ResultsDuring the 33.9 million person‐years of follow‐up, 285,845 participants (7.9%) developed cancers. Compared with no SLD, MASLD, MetALD and other combination aetiology had an increased risk of all cancer. Liver cancer risk escalated from no SLD to MASLD (SHR, 1.16; 95% CI, 1.12–1.21), MetALD (SHR, 2.06; 95% CI, 1.92–2.20) and other combination aetiology (SHR, 8.16; 95% CI, 7.69–8.67). Gastrointestinal cancers including oesophagus, stomach, colorectal, biliary and pancreas cancers increased in MASLD (SHR, 1.13; 95% CI, 1.11–1.15), MetALD (SHR, 1.17; 95% CI, 1.14–1.21) and other combination aetiology (SHR, 1.09; 95% CI, 1.05–1.13). A modest increase in lung cancer and hormone‐sensitive cancer was observed with MASLD.ConclusionsThis study showed that MASLD and MetALD are associated with an increased risk of cancer, particularly liver and gastrointestinal cancers. The findings build new evidence for the clinical outcomes of MetALD while highlighting the importance of managing alcohol intake properly in MASLD and MetALD.

Risk prediction model of hepatitis B associated hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common malignant tumors in the world, which is a serious threat to human health. HBV infection is one of the most common causes of hepatocellular carcinoma.The diagnosis of most hepatocellular carcinoma has progressed to the middle and late stage, and the prognosis is poor. Early detection, diagnosis and treatment are important supports to improve the clinical outcome of hepatocellular carcinoma. In recent years, scholars at home and abroad have established various hepatocellular carcinoma risk prediction models, which are conducive to improving the early diagnosis rate of hepatocellular carcinoma and reducing the mortality rate. This article reviews the risk factors and risk prediction models of chronic hepatitis B associated hepatocellular carcinoma, in order to provide reference for HBV-associated liver cancer risk monitoring and management decision.

The loss of hepatitis B virus receptor NTCP/SLC10A1 in human liver cancer cells is due to epigenetic silencing.

HBV is a hepatotropic virus that infects human hepatocytes expressing the viral receptor hNTCP. Without effective antiviral therapy, chronic HBV infection poses a high risk of liver cancer. However, most liver cancer cell lines, including HepG2 and Huh7, do not support HBV infection due to the absence of hNTCP expression, and the mechanism underlying this defect remains unclear. This study demonstrates a significant reduction of hNTCP in hepatocellular carcinoma samples and HepG2 cells compared to normal liver tissues and primary human hepatocytes. Despite identical hNTCP genetic sequences, epigenetic analyses revealed a loss of the activating histone modification H3K27ac near the hNTCP transcription start site in cancer cells. Treatment with histone deacetylase inhibitors restored H3K27ac levels, reactivated hNTCP expression, and rendered HepG2 cells susceptible to HBV infection. These findings highlight the role of epigenetic modulation in hNTCP dysregulation, offering insights into hepatocarcinogenesis and its implications for chronic HBV infection.