• Anti-cancer therapy
• GLP-1 receptor agonists
• Gastrointestinal cancers
• Metabolic syndrome
• Metformin
• Statins

• Humans
• Metabolic Syndrome/drug therapy
• Metabolic Syndrome/complications
• Gastrointestinal Neoplasms/drug therapy
• Animals
• Hypoglycemic Agents/therapeutic use
• Hypoglycemic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology
• Hypolipidemic Agents/therapeutic use
• Hypolipidemic Agents/pharmacology

• Metabolic dysfunction-associated steatotic liver disease
• complication
• extrahepatic complication
• fibrosis diagnosis
• liver complication
• mortality

• Humans
• Fatty Liver/therapy
• Fatty Liver/mortality
• Fatty Liver/diagnosis
• Fatty Liver/complications
• Risk Factors

• Cancer incidence
• Lifestyle
• Metabolic syndrome

• Humans
• Female
• Male
• United Kingdom/epidemiology
• Neoplasms/epidemiology
• Neoplasms/etiology
• Middle Aged
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/complications
• Incidence
• Biological Specimen Banks/statistics & numerical data
• Aged
• Risk Factors
• Life Style
• Healthy Lifestyle
• Adult
• Exercise
• Follow-Up Studies
• UK Biobank

• 82273148 National Natural Science Foundation of China
• 82403798 National Natural Science Foundation of China
• 82172673 National Natural Science Foundation of China
• 2023A1515012396 Natural Science Foundation of Guangdong Province
• 2024A04J5202 Science and Technology Projects in Guangzhou

• Hepatocellular carcinoma
• immunity
• inflammation
• obesity
• risk

• Cancer
• Diabetes
• Metabolic syndrome
• Metformin
• Mortality

• Hepatocellular carcinoma
• Metabolic dysfunction-associated fatty liver disease
• Metabolic dysfunction-associated steatotic liver disease
• Nonalcoholic fatty liver disease
• Steatotic liver disease

• hepatitis B
• hepatitis C
• hepatocellular carcinoma
• meta-analysis
• nonalcoholic fatty liver disease

• Humans
• Non-alcoholic Fatty Liver Disease/therapy
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/diagnosis
• Obesity/complications

• Humans
• Non-alcoholic Fatty Liver Disease/therapy
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/etiology
• Obesity/complications
• Obesity/therapy
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/therapy
• Risk Factors
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Liver Neoplasms/therapy
• Liver Neoplasms/etiology
• Cardiometabolic Risk Factors

• Blood lipids
• Cohort study
• Liver neoplasms
• Meta-analysis

• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/epidemiology
• Risk Factors
• Lipids/blood

• Global burden of disease
• High fasting plasma glucose
• Liver cancer
• Non-alcoholic steatohepatitis

• Humans
• Liver Neoplasms/epidemiology
• Liver Neoplasms/blood
• Liver Neoplasms/etiology
• Male
• Female
• Global Burden of Disease
• Blood Glucose/analysis
• Blood Glucose/metabolism
• Middle Aged
• Aged
• Fasting/blood
• Global Health/statistics & numerical data
• Disability-Adjusted Life Years
• Adult
• Aged, 80 and over
• Prevalence

• HCC
• MASH
• pathogenesis
• progression
• risk factors

• Bile acids
• Diethylnitrosamine
• Lipogenesis
• Liver tumour
• Metabolomics

• Humans
• Mice
• Male
• Animals
• Bile Acids and Salts
• Fructose/adverse effects
• Mice, Inbred C57BL
• Liver Neoplasms/chemically induced

• growth factor signalling
• membrane structure and assembly

• Mice
• Animals
• Proto-Oncogene Proteins c-akt/metabolism
• Epidermal Growth Factor
• Hepatocytes/metabolism
• Receptors, Transforming Growth Factor beta/metabolism
• Transforming Growth Factor beta/metabolism
• Liver Diseases/metabolism
• Cholesterol/metabolism

• Project 437145127 Deutsche Forschungsgemeinschaft (German Research Foundation)
• WE 2554/13-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
• Project 437145127 Deutsche Forschungsgemeinschaft (German Research Foundation)
• DO 373/19-1 Deutsche Forschungsgemeinschaft (German Research Foundation)
• Project 437145127 Deutsche Forschungsgemeinschaft (German Research Foundation)
• DO 373/19-1 Deutsche Forschungsgemeinschaft (German Research Foundation)

• Anthropometric Indicator
• Body Mass Index
• Meta-analysis
• Obesity
• Primary Liver Cancer
• Waist Circumference

• Humans
• Adiposity
• Risk Factors
• Obesity/epidemiology
• Waist Circumference
• Body Mass Index
• Liver Neoplasms/etiology
• Liver Neoplasms/complications

• hepatobiliary cancer
• nested case-control study
• pancreatic cancer
• prospective cohort
• risk stratification

• Humans
• Aged
• Carcinoma, Hepatocellular/epidemiology
• Liver Neoplasms/epidemiology
• Prospective Studies
• East Asian People
• Risk Factors
• Biliary Tract Neoplasms/epidemiology
• Biliary Tract Neoplasms/pathology
• Pancreatic Neoplasms/epidemiology

• 2019YFC1315905 National Key Research and Development Program of China
• 82021005 Natural Science Foundation of China
• WJ2021M102 Health Commission of Hubei Province Scientific Research Project
• 2019kfyXJJS036 Fundamental Research Funds for the Central Universities

• Humans
• Hepatitis B, Chronic/complications
• Carcinoma, Hepatocellular/surgery
• Metabolic Syndrome/complications
• Liver Neoplasms/etiology
• Liver Neoplasms/surgery

• 2021-YT Adjunct Talent Fund of Zhejiang Provincial People's Hospital
• 22QA1411600 Shanghai Science and Technology Committee Rising-Star Program
• 81972726 National Natural Science Foundation of China
• 22ZR1477900 Natural Science Foundation of Shanghai
• 21SG36 Dawn Project Foundation of Shanghai

• Humans
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/epidemiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Risk Factors
• Liver Cirrhosis/complications
• Liver Cirrhosis/epidemiology

• NAFLD
• alcohol use
• cardiovascular disease
• hepatocellular carcinoma
• liver disease
• metabolic syndrome

• Metabolic syndrome
• National Health and Nutrition Examination Survey
• Restricted cubic spline
• Sleep duration

• Humans
• Male
• Female
• Metabolic Syndrome/diagnosis
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/complications
• Nutrition Surveys
• Self Report
• Sleep
• Odds Ratio
• Risk Factors
• Sleep Wake Disorders/complications

• Diabetes mellitus
• Dyslipidemias
• Hepatocellular carcinoma
• Obesity

• Arachidonic Acid/metabolism
• Arylamine N-Acetyltransferase
• Bile Duct Neoplasms/pathology
• Bile Ducts, Intrahepatic/chemistry
• Bile Ducts, Intrahepatic/metabolism
• Bile Ducts, Intrahepatic/pathology
• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/pathology
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/pathology
• Cholesterol/metabolism
• Cytochrome P-450 CYP2C9/genetics
• Cytochrome P-450 CYP2C9/metabolism
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Glucuronosyltransferase
• Humans
• Liver Neoplasms/pathology
• Multigene Family
• Prognosis
• Retinoic Acid 4-Hydroxylase/genetics
• Retinoic Acid 4-Hydroxylase/metabolism
• Vitamin A

Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01–1.24, and 1.12, 95% CI 1.01–1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31–0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.

• association
• generalized additive model
• glucose
• hpv multiple infections

• Adult
• Blood Glucose
• China/epidemiology
• Cross-Sectional Studies
• Female
• Humans
• Middle Aged
• Papillomaviridae
• Papillomavirus Infections/complications
• Papillomavirus Infections/epidemiology
• Precancerous Conditions
• Retrospective Studies
• Squamous Intraepithelial Lesions
• Uterine Cervical Neoplasms/pathology

High-sensitivity C-reactive protein (hs-CRP) levels and metabolic syndrome (MetS) are known to be associated with an increased incidence of different cancers. We aimed to evaluate the effect of MetS combined with high hs-CRP levels on the risk of primary liver cancer (PLC).

Participants were recruited from the Kailuan cohort study and were classified into four groups according to the presence or absence of MetS and inflammation (hs-CRP ≥ 3 or < 3 mg/L). The associations of MetS and inflammation with the risk of PLC were assessed using Cox proportional hazards models.

This study included 92,770 participants. The mean age was 51.4 years old. Over a median follow-up of 13.02 years, 395 participants were diagnosed as PLC. Compared to the control participants without inflammation (hs-CRP < 3 mg/L) and MetS (n = 69,413), participants with high hs-CRP levels combined with MetS (n = 2,269) had a higher risk of PLC [hazard ratios (HR) 2.91; 95% confidence interval (CI), 1.77–4.81], and participants with high hs-CRP levels and without MetS (n = 14,576) had the same trend (HR, 1.36; 95%CI, 1.05–1.75). However, participants with low hs-CRP levels and MetS (n = 6,512) had no significant association with an elevated risk of PLC (HR, 1.18; 95%CI, 0.76–1.82). After excluding participants who had cancer during the first year of follow-up, sensitivity analysis showed the same trend. In addition, co-occurrence of MetS and high hs-CRP levels had significant interactive effects on the risk of PLC between the sexes (P < 0.001) and the patients with HBV infection (P = 0.012).

Participants with co-occurrence of MetS and high hs-CRP levels have an elevated risk of PLC.

Kailuan study, ChiCTR–TNRC–11001489. Registered 24 August, 2011-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050

The online version contains supplementary material available at 10.1186/s12885-022-09939-w.

• Hs-CRP
• Incidence
• Metabolic syndrome
• Primary liver cancer

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver resulting in approximately 800,000 deaths annually. A growing body of research investigating statin use and HCC risk has shown conflicting results. We aim to evaluate the current evidence of statin impact on HCC risk.

We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through May 2019 to identify all studies that evaluated the association between statin use and HCC. We included studies that presented an odds ratio (OR) with a 95% confidence interval (CI) or presented data sufficient to calculate the OR with a 95% CI. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA), Version 3 software, and a Forrest plot was generated. We assessed for publication bias using conventional techniques.

Twenty studies (three randomized controlled trials, six cohorts, and 11 case-controls) with 2,668,497 patients including 24,341 cases of HCC were included in the meta-analysis. Our findings indicate a significant risk reduction of HCC among all statin users with a pooled odds ratio of 0.573 (95% CI: 0.491-0.668, I2= 86.57%) compared to non-users. No publication bias was found using Egger’s regression test or on visual inspection of the generated Funnel plot.

The results indicate that statin use was associated with a 43% lower risk of HCC compared to statin non-users. Further prospective randomized research is needed to confirm the association.

• diabetes mellitus
• excess body weight
• hepatocellular carcinoma
• metabolic syndrome
• non-alcoholic fatty liver disease

• BMI
• HCC
• Hepatocellular carcinoma
• Liver cancer
• Metabolic
• obesity

• Body Mass Index
• Carcinoma, Hepatocellular/epidemiology
• Case-Control Studies
• Humans
• Liver Neoplasms/epidemiology
• Metabolic Syndrome/diagnosis
• Obesity/complications
• Obesity, Metabolically Benign/complications
• Obesity, Metabolically Benign/diagnosis
• Obesity, Metabolically Benign/metabolism
• Overweight/complications
• Phenotype
• Risk Factors

• K01 CA237875 NCI NIH HHS
• P30 CA015083 NCI NIH HHS

• liver cancer

• Cancer Genetic Risk
• Cancer Prevention
• Gastrointestinal Neoplasms
• Molecular Epidemiology

• Adenocarcinoma/complications
• Carcinoma, Hepatocellular/complications
• Esophageal Neoplasms/complications
• Esophageal Squamous Cell Carcinoma/epidemiology
• Female
• Humans
• Liver Neoplasms/complications
• Male
• Metabolic Syndrome/complications
• Metabolic Syndrome/epidemiology
• Pancreatic Neoplasms/complications
• Prospective Studies
• Rectal Neoplasms
• Risk Factors

• 001 World Health Organization
• MC_PC_17228 Medical Research Council
• MC_QA137853 Medical Research Council

• epidemiology
• hepatocellular carcinoma
• metabolic syndrome
• nonalcoholic fatty liver disease
• obesity

• Hepatocellular Carcinoma
• Incidence
• Meta-analysis
• Nonalcoholic Fatty Liver Disease

• Gender-specific effect
• Liver cancer
• Metabolic syndrome
• Non-linear association
• UK Biobank

• Direct-acting antivirals
• Hepatitis C
• Hepatocellular carcinoma
• Obesity

Due to the rapid increase of primary liver cancer incidence and the poor prognosis, it is imperative to identify new modifiable factors such as diet and nutrition for the prevention of liver cancer. Diet high in saturated fatty acids (SFA) has been hypothesized to be associated with increased risk of cancers. However, the associations between dietary fatty acids and liver cancer are not consistent. We aimed to examine the association between dietary total fat, its major components, serum cholesterol, and risk of liver cancer combining current evidence from prospective studies. Our meta-analyses provided new evidence on associations between dietary fats, serum cholesterol, and liver cancer risk. Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and high-density lipoprotein (HDL) were associated with a lower risk of liver cancer with high between-studies variability. Based on our findings, reducing dietary SFA may help to prevent the development of liver cancer.

To quantify the associations between dietary fats and their major components, as well as serum levels of cholesterol, and liver cancer risk, we performed a systematic review and meta-analysis of prospective studies. We searched PubMed, Embase, and Web of Science up to October 2020 for prospective studies that reported the risk estimates of dietary fats and serum cholesterol for liver cancer risk. We carried out highest versus lowest intake or level and dose-response analyses. Higher intake of dietary saturated fatty acids (SFA) was associated with a higher liver cancer risk in both category analysis (relative risk [RR]_{highest vs. lowest intake} = 1.34, 95% confidence interval [CI]: 1.06, 1.69) and dose-response analysis (RR_{1% energy} = 1.04, 95%CI: 1.01, 1.07). Higher serum total cholesterol was inversely associated with liver cancer but with large between-studies variability (RR_{1 mmol/L} = 0.72, 95%CI: 0.69, 0.75, I² = 75.3%). The inverse association was more pronounced for serum high-density lipoprotein (HDL) cholesterol (RR_{1 mmol/L} = 0.42, 95%CI: 0.27, 0.64). Higher intake of dietary SFA was associated with higher risk of liver cancer while higher serum levels of cholesterol and HDL were associated with a lower risk of liver cancer with high between-studies variability.

• cholesterol
• dietary fat
• epidemiological study
• high-density lipoprotein cholesterol
• liver cancer
• low-density lipoprotein cholesterol
• meta-analysis

• Cervical cancer
• HPV
• Metabolic syndrome
• Persistent infection

• African Americans
• Diabetes
• Liver cancer
• Racial disparities

• Black or African American
• Cohort Studies
• Diabetes Mellitus/epidemiology
• Humans
• Liver Neoplasms/epidemiology
• Risk Factors
• White People

• K07 CA225404 NCI NIH HHS
• R01 CA092447 NCI NIH HHS
• U01 CA202979 NCI NIH HHS

• HCC
• Hepatitis B virus
• comorbidities
• diabetes
• hepatocellular carcinoma

There are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014.

We identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation.

A total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990–1994 and 2010–2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08–3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85–1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0–29%, p = 0.037) than in men (2–12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women (p <0.001). From 2000–2004 to 2010–2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77–5.08) for men and 12.7 (95% CI 1.63–545) in women, whereas it decreased or remained stable for other major aetiologies of HCC.

In a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.

•

The burden of HCC arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD) remains unclear.

• AFP, alpha-foetoprotein
• ALD, alcohol-related liver disease
• ALT, alanine transaminase
• ASI, age-standardised incidence
• AST, aspartate aminotransferase
• Fatty liver
• GGT, gamma-glutamyltransferase
• HCC, hepatocellular carcinoma
• HR, hazard ratio
• Hepatocellular carcinoma
• INR, international normalised ratio
• Liver cancer
• MAFLD, metabolic-associated fatty liver disease
• MELD, model for end-stage liver disease
• Metabolic syndrome
• NAFLD, non-alcoholic fatty liver disease
• SIR, standardised incidence ratio
• TACE, transarterial chemoembolisation
• Women’s health

• L-glutamic acid
• hepatocellular cancer
• metabolic syndrome
• metabolomics
• pipecolic acid

• Biomarkers, Tumor
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/etiology
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Metabolic Syndrome/complications
• Metabolic Syndrome/diagnosis
• Metabolomics

• National Natural Science Foundation of China