BACKGROUND: Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated.
OBJECTIVE: We aimed to assess the global, regional and national burden of gastrointestinal cancers.
METHODS: Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI).
RESULTS: In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer.
CONCLUSIONS: Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

UNASSIGNED: Smoking is a preventable risk factor for morbidity and mortality in patients with liver disease. This study aims to explore the additional risks of smoking in the development of alcoholic liver disease (ALD), cirrhosis, and hepatocellular carcinoma (HCC) in high-risk drinkers.
UNASSIGNED: Data from the National Health Insurance Service, including claims and health check-up information spanning 2011 to 2017, were used. The overall alcohol consumption was calculated, and ALD was defined based on ICD-10 codes. High-risk drinking was defined as 7 or more drinks for men and 5 or more for women, twice weekly. Half of the high-risk drinkers were smokers, decreasing in men but stable at 20% for women.
UNASSIGNED: ALD prevalence was 0.97% in high-risk drinkers and 1.09% in high-risk drinkers who smoked, higher than 0.16% in social drinkers (p < 0.001). ALD incidence over 3-years was highest in high-risk drinkers who smoked (2.35%), followed by high-risk drinkers (2.03%) and social drinkers (0.35%) (p < 0.001). Cirrhosis and HCC followed similar patterns, with prevalence and incidence was highest in drinkers who smoked. 3-year mortality was 0.65% in high-risk drinkers who smoked, compared to 0.50% in high-risk drinkers and 0.24% in social drinkers (p < 0.001). Smoking increased the incidence of ALD, cirrhosis, and HCC by 1.32, 1.53, and 1.53 times, respectively (all p < 0.001). Gender-specific analysis revealed higher risk ratios (RR) for women in ALD, alcoholic cirrhosis, and HCC, particularly among high-risk drinkers who smoked. Women showed significantly increased RR in ALD (6.08 to 12.38) compared to men (4.18 to 4.40), and similar trends were observed for cirrhosis and HCC.
UNASSIGNED: Smoking significantly heightens the risk of ALD, cirrhosis, and HCC, especially in women, among high-risk drinkers. This emphasizes the importance of smoking cessation, particularly for female patients with ALD.

UNASSIGNED: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD.
UNASSIGNED: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran\'s Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed.
UNASSIGNED: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results.
UNASSIGNED: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.

OBJECTIVE: Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression.
METHODS: The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database.
RESULTS: Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism.
CONCLUSIONS: This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.

OBJECTIVE: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC.
METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis.
RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04.
CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS.
UNASSIGNED: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

BACKGROUND: There is a lack of national-level research on alcohol consumption and the epidemiology of alcoholic liver disease (ALD) in South Korea. This study aims to address the critical public health issue of ALD by focusing on its trends, incidence, and outcomes, using nationwide claims data.
METHODS: Utilizing National Health Insurance Service data from 2011 to 2017, we calculated the population\'s overall drinking amount and the incidence of ALD based on ICD-10 diagnosis codes.
RESULTS: From 2011 to 2017 in South Korea, social drinking increased from 15.7% to 16.5%, notably rising among women. High-risk drinking remained around 16.4%, decreasing in men aged 20-39 but not decreased in men aged 40-59 and steadily increased in women aged 20-59. The prevalence of ALD in high-risk drinkers (0.97%) was significantly higher than in social drinkers (0.16%). A 3-year follow-up revealed ALD incidence of 1.90% for high-risk drinkers and 0.31% for social drinkers. Women high-risk drinkers had a higher ALD risk ratio (6.08) than men (4.18). The economic burden of ALD was substantial, leading to higher healthcare costs and increased hospitalization. Progression rates to liver cirrhosis and hepatocellular carcinoma (HCC) in ALD patients were 23.3% and 2.8%, respectively, with no gender difference in cirrhosis progression.
CONCLUSIONS: The study revealed a concerning rise in alcohol consumption among South Korean women and emphasizes the heightened health risks and economic burdens associated with high-risk drinking, especially concerning ALD and its complications.

UNASSIGNED: Liver disease is linked to series of extrahepatic multisystem manifestations. However, little is known about the associations between liver and eye diseases, especially cataract, the global leading cause of blindness. We aimed to investigate whether severe liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, and liver fibrosis and cirrhosis, were associated with an increased risk of the cataract.
UNASSIGNED: A total of 326,558 participants without cataract at baseline enrolled in the UK Biobank between 2006 and 2010 were included in this prospective study. The exposures of interest were severe liver diseases (defined as hospital admission), including NAFLD, ALD, viral hepatitis and liver fibrosis and cirrhosis. The outcome was incident cataract. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Each liver disease was first treated as a binary time-varying variable to investigate its association with cataract, and then was treated as a ternary time-varying variable to examine the recent (liver disease within 0-5 years) vs. long-term (liver disease > 5 years) state associations with the risk of cataract.
UNASSIGNED: After a median follow-up of 13.3 years (interquartile range, 12.5-14.0 years), 37,064 individuals were documented as developing cataract. Higher risk of cataract was found in those with severe NAFLD (HR, 1.47; 95% CI, 1.33-1.61), ALD (HR, 1.57; 95% CI, 1.28-1.94) and liver fibrosis and cirrhosis (HR, 1.58; 95% CI, 1.35-1.85), but not in individuals with viral hepatitis when exposure was treated as a binary time-varying variable (P = 0.13). When treating exposure as a ternary time-varying variable, an association between recently diagnosed viral hepatitis and cataract was also observed (HR, 1.55; 95% CI, 1.07-2.23). Results from the combined model suggested they were independent risk factors for incident cataract. No substantial changes were found in further sensitivity analyses.
UNASSIGNED: Severe liver diseases, including NAFLD, ALD, liver fibrosis and cirrhosis and recently diagnosed viral hepatitis, were associated with cataract. The revelation of liver-eye connection suggests the importance of ophthalmic care in the management of liver disease, and the intervention precedence of patients with liver disease in the early screening and diagnosis of cataract.
UNASSIGNED: National Natural Science Foundation of China, Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission, Clinical Research Plan of Shanghai Shenkang Hospital Development Center, Shanghai Municipal Key Clinical Specialty Program, the Guangdong Basic and Applied Basic Research Foundation and Shenzhen Science and Technology Program.

OBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD.
METHODS: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence.
RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180.
CONCLUSIONS: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested.
BACKGROUND: ISRCTN41353774.

UNASSIGNED: Although most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.
UNASSIGNED: Using the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.
UNASSIGNED: A total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90-1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91-1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11-1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24-1.75).
UNASSIGNED: We report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels.

UNASSIGNED: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research.
UNASSIGNED: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis.
UNASSIGNED: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators.
UNASSIGNED: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.