Risk Of Liver Cancer Research Articles

Long-term exposure to ambient fine particulate matter and risk of liver cancer in the NIH-AARP Diet and Health Study

BackgroundFine particulate matter (PM2.5) exposure has been associated with liver cancer incidence and mortality in a limited number of studies. We sought to evaluate this relationship for the first time in a U.S. cohort with historical exposure assessment. MethodsWe used spatiotemporal prediction models to estimate annual average historical PM2.5 concentrations (1980–2015) at residential addresses of 499,729 participants in the NIH-AARP Diet and Health Study, a cohort in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan) enrolled in 1995–1996 and followed up through 2017. We used a time-varying Cox model to estimate the association for liver cancer and the predominant histologic type, hepatocellular carcinoma (HCC), per 5 µg/m3 increase in estimated outdoor PM2.5 levels, incorporating a 5-year average, lagged 10 years prior to cancer diagnosis and adjusting for age, sex, race/ethnicity, education level and catchment state. We also evaluated PM2.5 interactions with hypothesized effect modifiers. ResultsWe observed a non-significantly increased risk of liver cancer associated with estimated PM2.5 exposure (Hazard ratio [HR] = 1.05 [0.96–1.14], N = 1,625); associations were slightly stronger for HCC, (84 % of cases; HR = 1.08 [0.98–1.18]). Participants aged 70 or older at enrollment had an increased risk of liver cancer versus other age groups (HR = 1.50 [1.01–2.23]); p-interaction = 0.01) and risk was elevated among participants who did not exercise (HR = 1.81 [1.22–2.70]; p-interaction = 0.01). We found no evidence of effect modification by sex, smoking status, body mass index, diabetes status, or alcohol consumption (p-interaction > 0.05). ConclusionsOur findings in this large cohort suggest that residential ambient PM2.5 levels may be associated with liver cancer risk. Further exploration of the variation in associations by age and physical activity are important areas for future research.

A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk

High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.

Survey of lived experiences and challenges in hepatitis B management and treatment

Almost 300 million people are living with chronic hepatitis B infection worldwide and most remain undiagnosed and at risk for liver cancer. In 2015 the World Health Organization (WHO) developed guidelines for the prevention, care, and treatment of persons with chronic hepatitis B and in early 2023 began to work on updating these guidelines. In March 2023, a self-administered, anonymous online survey was launched, aiming to identify patient preferences related to the clinical management of hepatitis B including current management, treatment, and care experiences, preferences regarding engagement with providers, and preferences related to simplifying hepatitis B care access. A sample of 560 individuals living with hepatitis B (self-identified as HBsAg positive) from 76 countries completed the survey. Key findings demonstrated that less than half (49%, N = 268) of participants regularly visited a doctor to check the health of their liver (every 6–12 months), with 37% of participants prescribed antiviral medication by a specialist (82%, N = 167) or general practitioner (13%, N = 26). Participants reported not being actively involved in care decision making with their providers (42%, N = 217), with an overwhelming majority wanting to participate in hepatitis B management and treatment choices (85%, N = 435). Participants provided qualitative and quantitative details using open-ended responses within the survey about challenges with medication affordability and receiving care from a knowledgeable provider. Overall findings demonstrated key gaps in care, management, and treatment access related to hepatitis B: identifying these gaps can be used to identify areas for improvement along the care continuum for viral hepatitis. The survey found a need for the comprehensive simplification of clinical management and health care services related to hepatitis B. A thematic analysis of the open-ended survey responses highlighted major overarching themes including the cost and access burdens associated with hepatitis B management and treatment, and challenges in finding knowledgeable providers. Results from this mixed methods survey were used to inform the WHO hepatitis B guidelines update. Efforts should continue to explore public health approaches to address barriers and facilitators to testing, care, and treatment for people with hepatitis B to improve awareness of hepatitis B and access, care, and treatment among patients and providers.

Metabolic dysfunction-associated profiles and subsequent site-specific risk of obesity-related cancers among Chinese patients with diabetes: a retrospective cohort study

ObjectivesTo compare metabolic dysfunction-associated profiles between patients with diabetes who developed different obesity-related site-specific cancers and those who remained free of cancer during follow-up.DesignRetrospective cohort study.SettingPublic general outpatient clinics in...

Aspirin in Patients with Viral Hepatitis: Systematic Review and Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a disease demonstrating increasing morbidity and mortality, especially in patients with chronic viral hepatitis. Studies have shown that aspirin can reduce the incidence of liver cancer; however, the degree of benefit in patients with viral hepatitis is unclear. This study focused on the association between aspirin use and HCC risk in patients with chronic viral hepatitis. A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to December 16, 2023. The primary outcome was HCC incidence, and the secondary outcome was gastrointestinal bleeding. The results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analyses were performed by using random or fixed-effects models based on the heterogeneity assessed via the I2 statistic. A total of 13 articles (303,414 participants and 14,423 HCC patients) were included in the analysis. The incidence of HCC in aspirin users was lower than that in non-aspirin users (HR 0.75; 95% CI, 0.68-0.83; P < 0.001; I2 = 90.0%). Subgroup analysis further showed that this effect may be more obvious in HCV patients, non-cirrhotic patients, patients with statins, and long-term aspirin users, but it may have the risk of gastrointestinal bleeding (HR 1.13; 95% CI, 1.07-1.20; P = 0.906; I2 = 0.0%). Our meta-analysis shows that in patients with chronic viral hepatitis, aspirin use is associated with a significantly reduced risk of liver cancer, but attention should be paid to the possible risk of gastrointestinal bleeding, and this conclusion needs further validation in the future.

Role of body mass index and weight change in the risk of cancer: A systematic review and meta-analysis of 66 cohort studies.

This study was designed to evaluate the effects of body mass index (BMI) and weight change on the risk of developing cancer overall and cancer at different sites. We searched PubMed and other databases up to July 2023 using the keywords related to 'risk', 'cancer', 'weight', 'overweight', and 'obesity'. We identified eligible studies, and the inclusion criteria encompassed cohort studies in English that focused on cancer diagnosis and included BMI or weight change as an exposure factor. Multiple authors performed data extraction and quality assessment, and statistical analyses were carried out using RevMan and R software. We used random- or fixed-effects models to calculate the pooled relative risk (RR) or hazard ratio along with 95% confidence intervals (CIs). We used the Newcastle-Ottawa Scale to assess study quality. Analysis included 66 cohort studies. Compared to underweight or normal weight, overweight or obesity was associated with an increased risk of endometrial cancer, kidney cancer, and liver cancer but a decreased risk of prostate cancer and lung cancer. Being underweight was associated with an increased risk of gastric cancer and lung cancer but not that of postmenopausal breast cancer or female reproductive cancer. In addition, weight loss of more than five kg was protective against overall cancer risk. Overweight and obesity increase the risk of most cancers, and weight loss of >5 kg reduces overall cancer risk. These findings provide insights for cancer prevention and help to elucidate the mechanisms underlying cancer development. Reviewregistry1786.

Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea.

Tobacco and alcohol may interact to increase the risk of liver cancer, which might be modified by other risk factors. Their combined effects in the context of metabolic syndrome (MetS) remain unclear. Given the increasing prevalence of MetS, this nested case-control study was conducted to evaluate the combined effects of smoking and alcohol consumption on liver cancer risk with stratification by MetS. We included 15,352 liver cancer patients and 92,112 matched controls who attended the nationwide general health examination during 2009-2019, using a customized database (N = 5,545,835) from the Korean National Health Insurance Service. Liver cancer risk according to smoking and alcohol consumption was estimated using conditional multivariable logistic regression. Additive and multiplicative interactions between these two factors were assessed. Results showed that in men, dual current users were at a significantly higher risk of liver cancer compared with dual nonusers, adjusted odds ratio (aOR) = 1.61, 95% confidence interval: (1.50, 1.72). Interactions were detected between light-to-moderate alcohol consumption (0.1-28 g/day) and heavy smoking (>20 pack-years) on additive scale, relative excess risk due to interaction = 0.34 (0.16, 0.51), attributable proportion = 0.22 (0.11, 0.33), synergy index = 2.75 (1.85, 3.66), and multiplicative scale, aOR for the product term = 1.28 (1.11, 1.49). An additive interaction was also revealed between light-to-moderate drinking and light-to-moderate smoking in the MetS subgroup. In women, light-to-moderate drinking/nonsmoking was negatively associated with the risk in the non-MetS subgroup. In conclusion, a holistic health promotion program should target male dual users of tobacco cigarettes and alcohol, including light-to-moderate users, especially those with MetS.

Assessment of the mode of action of perchloroethylene-induced mouse liver tumors.

Perchloroethylene (PCE) is used as a solvent and chemical intermediate. Following chronic inhalation exposure, PCE selectively induced liver tumors in mice. Understanding the mode of action (MOA) for PCE carcinogenesis in mice is important in defining its possible human cancer risk. The proposed MOA is based on the extensive examination of the peer-reviewed studies that have assessed the mouse liver effects of PCE and its major oxidative metabolite trichloroacetic acid (TCA). Similar to PCE, TCA has also been demonstrated to liver tumors selectively in mice following chronic exposure. The Key Events (KE) of the proposed PCE MOA involve oxidative metabolism of PCE to TCA [KE 1]; activation of the peroxisome proliferator-activated receptor alpha (PPARα) [KE 2]; alteration in hepatic gene expression including cell growth pathways [KE 3]; increase in cell proliferation [KE 4]; selective clonal expansion of hepatic preneoplastic foci [KE 5]; and formation of hepatic neoplasms [KE 6]. The scientific evidence supporting the PPARα MOA for PCE is strong and satisfies the requirements for a MOA analysis. The PPARα liver tumor MOA in rodents has been demonstrated not to occur in humans; thus, human liver cancer risk to PCE is not likely.

Abstract 3428: Association of adipokines and inflammation biomarkers with cancer risk in men

Abstract Using pre-diagnosis fasting plasma samples from 4,040 participants of the Shanghai Men’s Health Study which enrolled 61,464 men ages 40-70 during 2001-2006, we prospectively evaluated the associations of adipokines and inflammation biomarkers with cancer risk. Levels of leptin, resistin, adiponectin, plasminogen activator inhibitor type-1 (PAI-1), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNFa), monocyte chemoattractant protein-1 (MCP-1), and insulin were measured by Luminex assays, and C-reactive protein (CRP), measured by ACE Clinical Chemistry System. Biomarker levels were categorized by tertile distribution. The Cox regression model was applied to derive hazard ratios (HR) and 95% confidence intervals (CI) for cancer risk in association with biomarkers with adjustment for potential confounders. Principle component analysis (PCA) was performed to assess associations with multiple biomarkers, and tertile scores for each component were used in analyses. During 15-years of follow-up, 318 cancer cases were identified, including 85 lung, 49 gastric, 17 liver, and 61 colorectal cancer (CRC) cases. Analyses adjusted for age, education and income showed that 3rd vs 1st tertile of TNFa (HR=1.7, 95%CI=1.0-3.0) and adiponectin (HR=4.0, 95%CI=1.1-14.4) was associated with lung and liver cancer risk, respectively. High levels of leptin, insulin, and CRP were each associated with CRC risk: respective HRs were 2.3 (95%CI=1.1-4.7), 2.1 (95%CI=1.0-4.2), and 2.0 (95%CI=1.1-3.9). After further adjustment for known cancer risk factors, TNFa-lung cancer (HR=1.8, 95%CI=1.1-3.1); leptin-CRC (HR= 3.2, 95%CI=1.3-7.7); insulin-CRC (HR=2.1, 95%CI=1.0-4.5); and CRP-CRC (HR=2.0, 95%CI=1.0-4.0) associations remained statistically significant. The adiponectin-lung cancer association lost significance. PCA identified 4 principal components (PC). High PC1 score (main loadings: TNFa, leptin, and insulin) was associated with CRC risk (HR=2.3, 95%CI=1.1-5.0 for 3rd vs 1st tertile ptrend=0.02). High PC2 score (main loadings: adiponectin, IL-8, MCP-1) and PC3 (main loadings: resistin and PAI-1) were associated with liver cancer risk: HR=5.2 (95%CI=1.1-24.3) for the 3rd vs 1st tertile, ptrend=0.03 and HR=4.7 (95%CI=1.0-21.7), for the 3rd vs 1st tertile, ptrend=0.03, respectively. High PC4 score (main loadings: IL-6 and CRP) was associated with lung cancer risk (HR=1.7, 95%CI=1.0-3.0, for the 3rd vs 1st tertile, ptrend=0.04). These associations, except the PC1-CRC association, lost significance after further adjustment of known cancer risk factors. Our study found that high plasma levels of insulin, CRP, and their combination were associated with CRC risk, high resistin and adiponectin levels with liver cancer risk, and high TNFa levels with lung cancer risk. Some biomarker-cancer associations may be explained by their correlations with known cancer risk factors, especially smoking. Citation Format: Douglas DeMoulin, Hui Cai, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu. Association of adipokines and inflammation biomarkers with cancer risk in men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3428.

Abstract 3943: Refined race and ethnicity categories for an EHR-based cohort to study disparities in liver cancer risk

Abstract Purpose: To develop a schema for harmonized, detailed characterization of race and ethnicity data for an electronic health record (EHR)-based cohort linked to cancer registry data to assess disparities in hepatocellular carcinoma (HCC) risk. Methods: We assembled an cohort of adults with 1+ encounter in 2000-2017 by pooling EHR data from three healthcare systems (Kaiser Permanente Hawai’i, Sutter Health, San Francisco Health Network). EHR data to define sociodemographic and clinical factors were linked to population-based state cancer registries for data on incident HCC (ICD-03 site/histology C22.0/8170-8175) through 2017. We extracted, harmonized and developed schemas to characterize multiple response race and ethnicity data across systems. We used Cox proportional hazards regression to examine disparities in HCC risk across racial and ethnic groups, comparing observations across categorization schema. Results: The cohort included 4,248,553 adults; 2,916 had incident HCC. A race and ethnicity schema that prioritized small populations and disaggregation of heterogenous groups defined 16 categories and was used to analyze pooled data from Kaiser Permanente Hawai’i and Sutter Health. With this schema, we observed variation in HCC risk across ethnic groups that are typically aggregated into larger ethno-racial categories (e.g., Asian American). Compared to non-Hispanic (NH) White males, Vietnamese American males had greater risk of HCC (hazard ratio (HR): 7.42; 95% CI: 4.25, 12.96) as did American Indian/Alaska Native, Black, Chinese American, Hispanic, Native Hawaiian, and Pacific Islander males; Asian Indian, Filipino, Japanese, and Korean American males did not. Among females, every group except American Indian/Alaska Native, Asian Indian American, and Pacific Islander females had greater risk of HCC than the NH White group. Due to less granular data from San Francisco Health Network during our study period, we developed a second, grouped schema aggregating categories from the detailed schema; it resulted in seven race and ethnicity categories and was used to analyze pooled data from all three healthcare systems. Compared to the categorization of race and ethnicity used by the US Census, which also has seven categories, we observed different patterns in HCC risk disparities for the smallest groups (i.e., American Indian/Alaska Native and Native Hawaiian). Conclusions: Analysis of a large EHR-based cohort linked to cancer registry data using a race and ethnicity characterization schema that prioritizes small populations yields valuable knowledge on disparities in HCC risk. Thus, to advance research on health disparities using EHR data, researchers must critically assess racial and ethnic categories typically available from healthcare system data repositories. We offer recommendations to operationalize EHR data on race and ethnicity to facilitate its meaningful use in research. Citation Format: Mindy C. DeRouen, Caroline A. Thompson, Alison J. Canchola, Alyssa Cortella, Pushkar Inamdar, Janet Chu, Sixiang Nie, Mai Vu, Ma Somsouk, Michele M. Tana, Anna D. Rubinsky, Iona Cheng, Mi-Ok KIm, Mark Segal, Chanda Ho, Yihe G. Daida, Su-Ying Liang, Hashem B. El-Serag, Scarlett L. Gomez, Salma Shriff-Marco. Refined race and ethnicity categories for an EHR-based cohort to study disparities in liver cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3943.

Abstract 3461: Shorter leukocyte telomere length and higher risk of primary liver cancer in a prospective cohort study

Abstract Background: Telomeres are conserved tandem repeats at chromosome ends that are vital to maintaining chromosomal stability and preventing degradation. Shorter telomere lengths (TL) are typically associated with older biological age or poor health status and can activate programmed cell death, whereas longer telomere lengths can be indicative of younger age or abnormal replication processes with oncogenic mutations. Previous research has identified a link between telomere length and carcinogenesis, but relatively few studies have investigated TL and primary liver cancer (PLC) risk despite it being one of the leading causes of cancer worldwide. The goal of this analysis was to study this association in a large prospective cohort. Methods: Data was extracted from the Singapore Chinese Cohort Health Study, a cohort of 63,257 men and women aged 45-74 years at enrollment during 1993-1998. Telomere length was measured in peripheral leukocytes of 26,540 participants who provided baseline blood samples, using a validated quantitative polymerase chain reaction (qPCR) method. PLC incidence and death among cohort participants was annually surveilled using the nationwide Singapore Cancer Registry and the National Birth and Death Registry from study enrollment to 2015. For statistical analysis, a t test was performed to examine the differences in TL between participants who developed incident PLC and those who remained free of PLC. Cox proportional hazard method was used to estimate the hazard ratios (HRs) and their 95% confidence interval (CI) of PLC incidence according to TL quartiles. Results: Over a 12-year follow-up, 199 participants developed incident PLC. The relative TL was significantly lower in participants with incident PLC than those without (-6.7%, p &amp;lt; 0.001). Multivariate Cox regression model showed an inverse association between TL quartile and risk of PLC (p for trend = 0.009). Compared with the lowest quartile, HRs (95% CIs) of PLC for the 2nd, 3rd, and highest quartile of TL were 0.78 (0.54-1.12), 0.75 (0.51-1.11), and 0.57 (0.37-0.88), respectively, after adjustment for age, sex, alcohol use, body mass index, and smoking status. Conclusion: The present analysis demonstrated a statistically significant association between shorter telomere length and increased risk of PLC in a large prospective cohort of Singaporean Chinese. This inverse association for PLC is different from those for other cancer types in the same cohort. These results warrant further studies such as using Mendelian randomization to quantify genetic variation in TL with PLC development. Citation Format: Sindhu Karnam, Kathryn Demanelis, Kenneth B. Beckman, Renwei Wang, Jennifer Adams-Haduch, Woon-Puay Koh, Jian-Min Yuan. Shorter leukocyte telomere length and higher risk of primary liver cancer in a prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3461.

Abstract 3434: Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank

Abstract Introduction: The association between adiposity and cancer risk differs between sexes for some cancer types. Methods: We prospectively examined adiposity in relation to cancer incidence according to sex hormones in the UK Biobank. Adiposity was assessed by body mass index (BMI) and visceral adipose tissue (VAT), the latter predicted using determinants of age, height, weight, hip circumference, waist circumference, and race. Serum sex hormone binding globulin (SHBG), testosterone, and estradiol were measured using a biochemistry assay and were classified as high or low based on median levels. Cancer incidence was ascertained using ICD-10 codes through cancer registry linkage. For cancer types showing a sex difference in the association between adiposity and cancer incidence, we assessed multiplicative and additive interaction with sex hormones in men and women separately and corrected for multiple testing using false discovery rate. We used Cox regression to calculate the multivariable hazard ratio (HR) of cancer per increase between the 90th to 10th percentile of adiposity (BMI or predicted VAT). Results: During a median follow-up of 13.1 years, we documented 23,964 and 21,045 incident cancer cases among 217,460 men and 256,163 women, respectively. Adiposity showed a much stronger association with higher risk of colorectal, esophageal, and liver cancers in men than women. In men, BMI was more strongly associated with higher risk of colorectal cancer in low vs. high levels of SHBG (HR (95%CI) of 1.47 (1.31-1.64) vs. 1.12 (0.94-1.33) (adjusted Pinteraction = 0.027). In contrast, BMI showed a stronger association in high vs. low levels of SHBG with esophageal (HR = 2.39 vs. 1.62) and liver cancers (HR = 3.24 vs 1.96) in men (adjusted Pinteraction = 0.038 and 0.027, respectively). Among women, BMI was associated with a higher risk of esophageal cancer in those with low SHBG (HR=1.68) but not in those with high SHBG (HR=0.64) (adjusted Pinteraction = 0.025). Similar patterns were observed for predicted VAT. Men with high SHBG levels and high adiposity (BMI and predicted VAT) had 7.63 (5.08-11.46) and 8.92 (5.72 to 13.90), respectively, times higher risk of liver cancer compared to men with low SHBG levels and low adiposity. No effect modification by estradiol or testosterone was detected for any of the cancers studied. Conclusions: The association between adiposity and colorectal, esophageal, and liver cancer differed by sex. SHBG may be an important factor underlying these differences. Citation Format: LeeAnn Lucas, Yujia Lu, Edward L. Giovannucci, Mingyang Song. Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3434.

Abstract 3811: Impact of antiviral treatment status on risk of extrahepatic cancers in patients with chronic hepatitis C

Abstract Background: Eradiation of hepatitis C virus (HCV) infection has been shown to reduce risk of liver cancer among HCV patients; however, there has been spare data on the effect of antiviral treatment on the risk of extrahepatic cancers. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated whether antiviral therapy impacts the risk of extrahepatic cancers among patients with HCV. Methods: 17,485 HCV patients were included in the study, and they were followed until incidence of cancer including lung cancer, non-Hodgkin lymphoma (NHL), breast cancer or prostate cancer, death, or last follow-up. An extended landmark modeling approach was considered, which included time-varying covariates and propensity score justification for treatment selection bias and used generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. Results: Compared to untreated patients, patients with HCV treatment had significantly lower risk of lung cancer for direct-acting antiviral (DAA) treatment (hazard ratio (HR) = 0.47, 95% CI, 0.30-0.72) and for interferon-based treatment (IFN) (HR = 0.33, 95% CI, 0.20-0.50). The risk of NHL was only reduced among patients receiving DAA treatment. There were no significant associations between HCV treatment and risks of breast and prostate cancer. Conclusion: Both DAA and IFN antiviral treatment independently reduce the risk of lung cancer, while the protective association with NHL was limited among HCV patients with DAA treatment. Our findings support the importance of timely initiation antiviral therapy in chronic HCV-infected patients. Citation Format: Menghua Tao, Jia Li, Trueman Wu, Stuart C. Gordon, Loralee B. Rupp, Sheri Trudeau, Scott D. Holmberg, Anne C. Moorman, Philip R. Spradling, Eyasu H. Teshale, Mark A. Schmidt, Yihe G. Daida, Mei Lu. Impact of antiviral treatment status on risk of extrahepatic cancers in patients with chronic hepatitis C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3811.

Determination and risk assessment of aflatoxin B1 in the kernel of imported raw hazelnuts from Eastern Azerbaijan Province of Iran

Aflatoxin B1 (AFB1) is widespread and seriously threatens public health worldwide. This study aimed to investigate AFB1 in imported hazelnut samples in northwest of Iran (Eastern Azerbaijan Province) using High-Performance Liquid Chromatography with a Fluorescent Detector (HPLC-FLD). In all tested samples AFB1 was detected. The mean concentration of AFB1 was 4.20 μg/kg and ranged from 3.145 to 8.13 μg/kg. All samples contained AFB1 levels within the maximum acceptable limit except for one sample. Furthermore, the human health risk assessment of AFB1 from consuming imported hazelnuts by Iranian children and adults was evaluated based on the margin of exposure (MoE) and quantitative liver cancer risk approaches. The MoE mean for children was 2529.76, while for adults, it was 8854.16, indicating a public health concern. The present study found that the risk of developing liver cancer among Iranian children was 0.11100736 per 100,000 people, and in the Iranian adult population was 0.0314496 cancers per 100,000 people. Since environmental conditions potentially affect aflatoxin levels in nuts, countries are advised to monitor aflatoxin contents in imported nuts, especially from countries with a conducive climate for mold growth.

Integration of hepatitis B virus into patients' sperm genome and its clinical risks.

Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. Forty-eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group-1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group-2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty-eight healthy male donors were included as control. The standard semen parameter analysis, real-time polymerase chain reaction, quantitative real-time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group-1 and Group-2 was not statistically significant. In Test Group-2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18×103 /mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm-derived embryos through fertilization and retained their function in replication, transcription, and translation. Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer.

The association of metabolic syndrome score trajectory patterns with risk of all cancer types.

Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. Four MetS score trajectory patterns were identified: low-stable (n=4657), moderate-low (n=18,018), moderate-high (n=18,288), and elevated-increasing (n=3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR,1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.

Liver transplantation and primary liver cancer in porphyria.

The porphyrias are a heterogeneous group of metabolic disorders that result from defects in heme synthesis. The metabolic defects are present in all cells, but symptoms are mainly cutaneous or related to neuropathy. The porphyrias are highly relevant to hepatologists since patients can present with symptoms and complications that require liver transplantation (LT), and some porphyrias are associated with a high risk for primary liver cancer (PLC). Among the cutaneous porphyrias, erythropoietic protoporphyria (EPP) can lead to cholestatic liver failure where LT cures the liver disease but not the porphyria. In acute porphyria (AP), neurotoxic porphyrin precursors are produced in the liver and LT is a curative treatment option in patients with recurrent severe neuropathic attacks. Patients with AP, mainly acute intermittent porphyria, have a significantly increased risk for PLC that warrants surveillance and adequate follow-up of high-risk groups. LT is well established in both EPP with liver failure and AP with recurrent attacks, but most transplant centres have little porphyria experience and cooperation between transplant hepatologists, and porphyria experts is important in the often-difficult decisions on timing and management of comorbid conditions.

Fiber and whole grain intakes in relation to liver cancer risk: An analysis in 2 prospective cohorts and systematic review and meta-analysis of prospective studies.

The association between fiber or whole grain intakes and the risk of liver cancer remains unclear. We assessed the associations between fiber or whole grain intakes and liver cancer risk among 2 prospective studies, and systematically reviewed and meta-analyzed these results with published prospective studies. A total of 111,396 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and 26,085 men from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were included. Intakes of total fiber and whole grains were estimated from validated food frequency questionnaires. Study-specific HRs and 95% CI with liver cancer risk were estimated using multivariable-adjusted Cox regression. We systematically reviewed existing literature, and studies were combined in a dose-response meta-analysis. A total of 277 (median follow-up = 15.6 y) and 165 (median follow-up = 16.0 y) cases of liver cancer were observed in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, respectively. Dietary fiber was inversely associated with liver cancer risk in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (HR 10g/day : 0.69; 95% CI: 0.55-0.86). No significant associations were observed between whole grain intakes and liver cancer risk in either study. Our meta-analysis included 2383 incident liver cancer cases (7 prospective cohorts) for fiber intake and 1523 cases (5 prospective cohorts) for whole grain intake; combined HRs for liver cancer risk were 0.83 (0.76-0.91) per 10 g/day of fiber and 0.92 (0.85-0.99) per 16 g/day (1 serving) of whole grains. Dietary fiber and whole grains were inversely associated with liver cancer risk. Further research exploring potential mechanisms and different fiber types is needed.

Effects of Interventions for Improving Awareness and Knowledge of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults for Prevention of Liver Cancer-A Randomized Controlled Trial.

Chinese young adults (CYA), who are at an increasing risk of developing nonalcoholic fatty liver disease (NAFLD), which in turn increases the risk of liver cancer, are an ideal target population to deliver educational interventions to improve their awareness and knowledge of NAFLD and consequently reduce their risk of developing NAFLD. The purpose of this study was to determine the efficacy of two interventions to improve awareness and knowledge of NAFLD among CYA for the prevention of liver cancer. Between May and July 2021, 1373 undergraduate students aged 18 to 25years in one university in China completed a web-based, self-administered survey distributed through WeChat app. One week after completion of the baseline survey, all eligible participants were randomly assigned to a pamphlet, a video intervention, or no intervention (control group), with follow-up assessments immediately and 1-month post-intervention. The 7-page pamphlet or 6.5-min video had information on NAFLD. Self-assessments included NAFLD awareness, lean NAFLD awareness, and knowledge scores of NAFLD. About 26% of participants had NAFLD awareness at baseline. Compared with controls, participants in both interventions showed significant improvement of awareness of NAFLD (pamphlet, + 46.0%; video, + 44.3%; control, + 18.7%; OR [95% CI], 3.13 [2.19-4.47] and 2.84 [1.98-4.08]), awareness of lean NAFLD (pamphlet, + 41.2%; video, + 43.0%; control, + 14.5%; OR [95% CI], 2.84 [1.62-4.99] and 2.61 [1.50-4.54]), and knowledge score of NAFLD (pamphlet, + 64.2%; video, + 68.9%; control, - 1.0%; OR [95% CI], 1.62 [1.47-1.80] and 1.67 [1.50-1.86]) at immediately post-intervention. Delivering NAFLD education through a pamphlet or video intervention was effective in improving the awareness and knowledge of NAFLD among CYA.

Statin Use and Liver Cancer Risk: A Meta-Epidemiological Study of Retrospective Cohort Studies by the Types of Constructed Cohort.

Previous systematic reviews of retrospective cohorts (RSC) indicate that statin use decreases the risk of liver cancer. However, the summary effect size (sES) of the randomized controlled trials was not statistically significant. This study aimed to conduct a subgroup meta-analysis based on the types of constructed cohorts. RSCs were selected from previous systematic reviews. Based on the characteristics of the source database (national vs. hospital) and the selection criteria of the subjects (population vs. patients), RSCs were categorized into three types of study cohorts: a national-based population cohort (NPo), national-based patient cohort (NPa), and hospital-based patient cohort (HPa). The sES and 95% confidence intervals were calculated using a random-effects model. The 28 cohorts from 23 RSC were classified into 15 NPa, 7 NPo, and 6 HPa. The sES of 15 NPa decreased the liver cancer risk with statin intake history with statistical significance, but 7 NPo lost statistical significance. The lack of statistical significance in NPo supports the argument that the conclusions of existing systematic reviews on RSC have low validity. It is necessary to conduct a subgroup meta-analysis of the NPo, NPa, and HPa proposed in this study when conducting a systematic review of RSCs, which will evaluate various outcomes of a specific drug intake with time-varying exposure.