Risk Of Primary Liver Cancer Research Articles

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.

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.

Primary Liver Cancer Risk and Mortality in Patients With Alcohol-Related Cirrhosis in England and Denmark: Observational Cohort Studies.

Patients with alcohol-related cirrhosis (ALD cirrhosis) have an increased risk of primary liver cancer (hepatocellular carcinoma [HCC] or intrahepatic cholangiocarcinoma [iCCA]). England recommends surveillance for HCC in these patients, while Denmark does not. We performed an observational cohort study using the English Clinical Practice Research Datalink and the nationwide Danish healthcare registries to identify 17,110 English (2000-2016) and 22,122 Danish (1994-2022) patients with diagnosis codes of ALD cirrhosis. We computed and compared incidence rates and cumulative incidence of primary liver cancer, annual ultrasound scan rates, and mortality following diagnosis of primary liver cancer. The overall risk of primary liver cancer was similar in England and Denmark: 5-year risk was 2.24% (95% confidence interval 2.00-2.49) in England (iCCA 0.07%, HCC 2.16%) and 2.36% (2.15-2.57) in Denmark (iCCA 0.05%, HCC 2.30%). The annual rate of ultrasound scans per person was 0.65 (0.63-0.67) in England and 0.44 (0.42-0.46) in Denmark. The 1-year mortality after a diagnosis of primary liver cancer was 59.2% (54.4-64.0) in England and 60.9% (57.4-64.4) in Denmark. The 3-year risks of HCC in those on vs off surveillance in England were 2.3% (1.0-4.6) vs 1.5% (1.0-2.2). The risk of primary liver cancer was the same in English and Danish patients with ALD cirrhosis, and HCCs constituted 97% of primary liver cancers. Mortality with primary liver cancer was equally high in both countries. Notably, in England, where guidance recommends biannual HCC surveillance with ultrasound, patients with ALD cirrhosis were undergoing fewer than 1 ultrasound scan per year.

The Association between the Substitution of Red Meat with Legumes and the Risk of Primary Liver Cancer in the UK Biobank: A Cohort Study.

Primary liver cancer is globally on the rise, partially due to poor diets and sedentary lifestyles. Shifting to more plant-based diets may lower the risk. We aimed to estimate the effect of replacing total red meat, unprocessed red meat and processed red meat with legumes on primary liver cancer in a free-living population. We analyzed data from 126,744 UK Biobank participants who completed ≥ two 24 h diet recalls. Baseline characteristics were collected from the initial assessment visit. Information on liver cancer diagnoses was collected via external linkage to inpatient hospital episodes or central cancer registries. Cox proportional hazards regression models were used to estimate the substitution of 15 g/day of legumes with 15 g/day of total red meat, unprocessed red meat or processed red meat on liver cancer risk, using the leave-one-out food substitution model. During a median follow-up time of 11.1 years, 173 participants developed liver cancer. In the fully adjusted models, no association was observed when substituting 15 g/day of legumes with total red meat (HR: 1.02 (95% CI 0.96-1.08)), unprocessed red meat (HR: 1.00 (95% CI 0.94-1.06)) or processed red meat (HR: 1.09 (95% CI 0.99-1.21)). Overall, little evidence of an association between replacing red meat with legumes and liver cancer was observed. Further research in other study populations with longer follow-up time is warranted.

1347-P: Risk of Primary Liver Cancer following New-Onset of Diabetes—A Longitudinal Study in a Chinese Adult Cohort

1347-P: Risk of Primary Liver Cancer following New-Onset of Diabetes—A Longitudinal Study in a Chinese Adult Cohort

Long-term complications in acute porphyria.

New treatment options and low attack-related mortality have changed the life expectancy of patients with acute porphyria (AP) to that of the general population. Clinicians should therefore be aware of the long-term complications of AP, which typically include chronic neuropathy and encephalopathy, high blood pressure and porphyria-associated kidney disease. Patients have an increased risk of primary liver cancer (PLC), but no increased risk of non-hepatic cancers. Chronic pain occurs in patients with recurrent attacks, combined with chronic fatigue and nausea, leading to poor quality of life. Patients with sporadic attacks may also have chronic symptoms, which should be distinguished from mild recurrent attacks and treated appropriately. Sequels of acute polyneuropathy after an attack should be distinguished from ongoing chronic polyneuropathy, as the management is different. Overestimation of chronic neuropathy or encephalopathy caused by AP should be avoided, and other causes should be treated accordingly. Prevention of recurrent attacks is the best strategy for managing chronic comorbidities and should be actively accomplished. Hormonal interventions in female patients, or in severe cases, prophylactic givosiran or haematin, may be helpful before liver transplantation to prevent recurrent attacks. Regular monitoring can be personalised according to the patient's age, comorbidities and AP activity. Blood pressure, renal function and cardiovascular risk factors should be monitored annually in patients with previous symptoms. Appropriate medication and lifestyle management, including nutrition and hydration, are necessary to prevent complications. As PLC is common, especially in patients with acute intermittent porphyria, bi-annual surveillance after the age of 50 is important.

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 < 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.

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.

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis.

Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

Associations between physical activity and risk of liver cancer: results from a population-based cohort study in Chinese women

Aims : Epidemiological evidence has revealed varying degrees of relationship between physical activity and risk of most cancers, but the association between physical activity and risk for primary liver cancer in Chinese has seldom been reported. This study aims to characterize the associations between different physical activity types and liver cancer risk in Chinese women. Methods: We collected physical activity information through the physical activity questionnaire (PAQ) and assigned a corresponding metabolic equivalent value according to the physical activity compendium. Multivariable-adjusted Cox regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between physical activity and liver cancer. Results : A total of 72,674 females were enrolled in the cohort, with a median follow-up time of 18.12 years. By the end of 2016, 255 females were identified as incident cases of liver cancer. In Multivariable-adjusted Cox regression analysis, total physical activity (TPA), daily living physical activity (DPA) and leisure-time physical activity (LTPA) were not associated with the liver cancer risk in women. The highest tertile vs . none of HRs (95%CIs) were 0.82 (0.58, 1.17) for TPA, 0.80 (0.56, 1.15) for DPA, and 1.15 (0.82, 1.61) for adult LTPA in terms of measures as the METs-hour/week. For each activity, we found that the HRs (95%CIs) were 0.77 (0.55, 1.08) for stair climbing and 0.78 (0.53, 1.15) for participation in housework after further adjusting for body mass index and type 2 diabetes. Conclusion : Null significant results were found in the association between physical activity and female liver cancer risk in China.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease with Increased Alcohol Intake Increase the Risk of Developing Hepatocellular Carcinoma and Incident or Decompensated Cirrhosis: A Korean Nationwide Study

Introduction: This study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD). Methods: From a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health checkups between 2009 and 2010 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model regarding competing risks. Results: A total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR: 1.65; 95% CI: 1.44−1.88), MetALD (SHR: 1.87; 95% CI: 1.52−2.29), and ALD (SHR: 1.86; 95% CI: 1.39−2.49) were associated with an increased risk of PLCa. MASLD (SHR: 1.96; 95% CI: 1.67−2.31), MetALD (SHR: 2.23; 95% CI: 1.75−2.84), and ALD (SHR: 2.34; 95% CI: 1.67−3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD. Conclusion: MASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.

Role of Aflatoxin B1 as A Risk for Primary Liver Cancer in India

The most well-known primary liver cancer in the world is Hepatocellular Carcinoma (HCC). Its prevalence is alarmingly increasing and has drawn public attention on a global scale. With regard to regional variation, racial differences, and socioeconomic level, it occurs more frequently in underdeveloped countries than in industrialised ones. Aflatoxin use is one of the main risk factors for HCC. Aflatoxin B1, a genotoxic hepatocarcinogen, is thought to induce cancer by causing DNA adducts in target liver cells that result in genetic alterations. HCC may result from a mutational impact caused by DNA adducts at the codon 249 hotspot in exon 7 of the P53 tumour suppressor gene, which interacts with the guanine bases of liver cell DNA. Aflatoxin-contaminated food affects about 4.5 billion people worldwide, mostly in developing nations with poor incomes. Treatment of crops that are prone to fungal contamination, proper food handling techniques, and the use of chemopreventive intervention are all part of prevention. Additionally, in order to maintain efficient food regulation systems and reduce the risk of aflatoxins contaminating food, a networked collaboration of several sectors, including public health, agricultural departments, and the media, is needed.

Visceral and ectopic fat are more predictively associated with primary liver cancer than overall obesity from genetic sights: A Mendelian randomization study.

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.

Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case-control study of 188 patients.

Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease characterized by acute attacks and accumulation of the porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Patients with AIP have a high risk of primary liver cancer (PLC). We aimed to assess the association between porphyrin precursor excretion and the risk for PLC in patients with AIP. We studied 48 patients with AIP who developed PLC between 1987 - 2015 and 140 age and sex matched controls with AIP but no PLC. Data on all available urinary PBG and ALA samples collected from 1975 until one year before PLC diagnosis were analyzed and compared between cases and controls using logistic regression. Porphyrin precursor excretion was higher in patients with PLC (PBG median 7.9 (IQR 4.4-21.9) mmol/mol creatinine) than in controls (3.8 (1.2-9.8)) (adjusted odds ratio 1.07, 95% confidence interval: 1.02-1.12). None of the 28 patients with all registered samples below the upper limit of normal (ULN) developed PLC, and only one of the 45 patients with all samples <2x ULN developed PLC. Among non-PLC controls, ALA and PBG levels decreased after age 50-60 while an increasing trend was observed after age 65 among those who developed PLC. Increased urinary porphyrin precursors are associated with a high risk of developing PLC. Patients with normal levels appear to have a low risk while high or increasing ALA and PBG after age 65 indicates high risk, which should be considered in surveillance decisions. This article is protected by copyright. All rights reserved.

Association between air pollution and primary liver cancer in European and east Asian populations: a Mendelian randomization study.

The incidence of primary liver cancer is increasing year by year, with environmental factors playing a non-negligible role. At present, many studies are still disputing whether air pollution is associated with primary liver cancer incidence, and it is difficult to draw causal inferences. Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5-10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1). We used large-scale publicly available genome-wide association studies (GWAS) summary data to conduct MR analyses of European and East Asian populations. Inverse variance weighted (IVW) method was used as the main analysis method, and weighted median model, MR-Egger, simple model and weighted model methods were selected for quality control. Heterogeneity was checked by the Cochran's Q test. The MR-Egger regression and the MR-PRESSO global test detect pleiotropy. The sensitivity analysis was performed using the leave-one-out method. Between air pollution and primary liver cancer in either European (PM2.5: p = 0.993; PM2.5-10: p = 0.833; PM10: p = 0.257; nitrogen dioxide: p = 0.215; nitrogen oxides: p = 0.614) or East Asian (PM2.5: p = 0.718; PM2.5-10: p = 0.362; PM10: p = 0.720; nitrogen dioxide: p = 0.101; nitrogen oxides: p = 0.760) populations were found no statistical association. Notably, there was a causal relationship between nitrogen oxides and Arginase-1, a biomarker associated with hepatocellular differentiation, statistically significant associations remained after deletion for single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency, Body mass index (BMI) and cancers (Beta: 4.46; 95%CI: 0.83-8.08; p = 0.015). There was no heterogeneity or pleiotropy in the results. This MR study found no evidence to support a causality between air pollution and primary liver cancer in European and East Asian populations, but nitrogen oxides may affect hepatocellular differentiation.

FRI-436 - Risk of primary liver cancer in alcohol-related cirrhosis-Danish and English cohort studies

FRI-436 - Risk of primary liver cancer in alcohol-related cirrhosis-Danish and English cohort studies

The Effects of Fatty Acids on Primary Liver Cancer: A Two-Sample Mendelian Randomization Study

Currently, it is unknown whether fatty acids (FAs) and primary liver cancer (PLC) are associated. The cause–effect association was established using a two-sample Mendelian randomization (MR) study. Eligible single nucleotide polymorphisms were selected as instrumental variables from six FAs genome-wide association studies. The outcome involved a total of 260,428 subjects and was a summary of genetic data on PLC from FinnGen biobanks. The principal method inverse variance weighted (IVW) and several other analytical approaches (MR-Egger, Weighted Median, and Maximum likelihood) were tested to determine the causal relationship between different FAs and PLC. Furthermore, sensitivity analyses were performed to determine the stability of the results. The two-sample MR analysis revealed a negative causal relationship between omega-3 FAs and PLC. It was discovered that an increase in each standard deviation (0.53 mmol/L; SD: 0.22) in the genetic levels of omega-3 FAs reduced the risk of PLC by 62.1% through the IVW method [odd ratio: 0.379; 95% confidence interval (0.176, 0.816)]. Nevertheless, other FAs were not statistically correlated with PLC. Additionally, no pleiotropy was found between the two. According to the MR study, consuming omega-3 FAs may help prevent PLC.

Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals.

There is still a lack of knowledge on the association between cholecystectomy and liver disease. This study was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy. PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model. We identified 20 studies with a total of 27 320 709 individuals and 282 670 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR: 1.63, 95% CI: 1.34-1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR: 1.54, 95% CI: 1.18-2.01), a 173% increased risk of cirrhosis (OR: 2.73, 95% CI: 1.81-4.12), and a 46% increased risk of primary liver cancer (OR: 1.46, 95% CI: 1.18-1.82). There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.

High Salt Intake Combined With Hypertension Elevated The Risk Of Primary Liver Cancer: A Prospective Cohort Study

High Salt Intake Combined With Hypertension Elevated The Risk Of Primary Liver Cancer: A Prospective Cohort Study

Pre-diagnostic anti-EBV antibodies and primary liver cancer risk: a population-based nested case-control study in southern China

BackgroundWe aimed to investigate associations between pre-diagnostic anti-Epstein-Barr virus (EBV) antibodies, including interactions with hepatitis B virus (HBV), and risk of primary liver cancer in southern China.MethodsIn a population-based nested case-control study, we measured pre-diagnostic immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) in 125 primary liver cancer cases and 2077 matched controls. We also explored the interaction between HBV surface antigen (HBsAg) and anti-EBV antibodies.ResultsParticipants with positive EBNA1-IgA, positive VCA-IgA or single-positive anti-EBV antibodies had two-fold odds of developing liver cancer, compared with seronegative subjects. The odds ratios (ORs) between the relative optical density of EBNA1-IgA and VCA-IgA and primary cancer, controlling for age and HBsAg, were 1.59 (95% confidence interval (CI): 1.17, 2.14) and 1.60 (95% CI: 1.07, 2.41), respectively. Subjects with both HBsAg and anti-EBV antibody seropositivity were at 50-fold increased risk compared with those negative for both biomarkers (OR: 50.67, 95% CI: 18.28, 140.46), yielding a relative excess risk due to interaction of 30.81 (95% CI: 3.42, 114.93).ConclusionPre-diagnostic seropositivity for EBNA1-IgA and/or VCA-IgA was positively associated with primary liver cancer risk, especially in combination with HBsAg positivity. EBV may interact with HBV in the development of primary liver cancer, and anti-EBV antibodies might be potential biomarkers for primary liver cancer in this high-risk population.