[Analysis of global liver cancer statistics].

Liver cancer is a significant contributor to the world's cancer burden. In order to comprehend the variations in its regional, age, gender, and histological subtype distributions as well as its temporal trend, this paper analyzes the worldwide statistical data of liver cancer, including the incidence, mortality, and survival. The findings indicated that the stages of liver cancer control and prevention are heterogeneous among countries and regions. The successful experience of liver cancer control and prevention in some countries should be promoted and disseminated. According to the various national conditions, comprehensive intervention measures, including reducing aflatoxin exposure, promoting vaccination, improving the treatment of chronic hepatitis infection, and implementing early diagnosis and treatment of liver cancer, should be developed.

Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study.

BACKGROUND: Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. METHODS: Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. RESULTS: The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05-0.71). CONCLUSIONS: This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.

Modeling different infectious phases of hepatitis B with generalized saturated incidence: An analysis and control.

Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are significant because worldwide, approximately 250 million people are infected by chronic hepatitis B. The chronic stage is a long-term, persistent infection that can cause liver damage and increase the risk of liver cancer. In the case of multiple phases of infection, a generalized saturated incidence rate model is more reasonable than a simply saturated incidence because it captures the complex dynamics of the different infection phases. In contrast, a simple saturated incidence rate model assumes a fixed shape for the incidence rate curve, which may not accurately reflect the dynamics of multiple infection phases. Considering HBV and its various phases, we constructed a model to present the dynamics and control strategies using the generalized saturated incidence. First, we proved that the model is well-posed. We then found the reproduction quantity and model equilibria to discuss the time dynamics of the model and investigate the conditions for stabilities. We also examined a control mechanism by introducing various controls to the model with the aim to increase the population of those recovered and minimize the infected people. We performed numerical experiments to check the biological significance and control implementation.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.

Productivity loss by cancer stage in patients newly diagnosed with hepatocellular carcinoma: A claims database analysis.

BACKGROUND: New cancer diagnoses are associated with employment decrease, workplace absenteeism, and attributable costs to employers. OBJECTIVE: To estimate the workplace productivity loss in the year following a new diagnosis of early-, intermediate-, or advanced-stage hepatocellular carcinoma (HCC) in commercially insured US adults. METHODS: We conducted a retrospective cohort study using Merative MarketScan commercial claims to identify incident HCC diagnoses from 2010 to 2020. Patients were stratified into early-, intermediate-, or advanced-stage cohorts based on presence of secondary malignancy codes or first treatment received. Mean workdays lost and attributable cost in the year following a new diagnosis were calculated using the Kaplan-Meier sample averages to account for censoring. An exploratory analysis was conducted on subgroups in the early and advanced cohorts to assess productivity loss in patients with and without treatment. RESULTS: Mean workdays lost in the year following a new HCC diagnosis among the early, intermediate, and advanced cohorts was 22.6 days (95% CI = 16.0-29.8), 17.4 days (95% CI = 11.9-23.2), and 19.5 days (95% CI = 15.6-23.6), respectively. Corresponding indirect costs were $6,031(95% CI = $4,270-$7,953), $4,644 (95% CI = $3,176-$6,192), and $5,204 (95% CI = $4,163-$6,298). Early-stage patients without a liver transplant and advanced-stage patients who received systemic therapy had 19.7 (95% CI = 12.7-27.4) and 22.0 (95% CI = 16.6-27.7) mean workdays lost, respectively. CONCLUSIONS: Productivity loss varies by stage and appears to be higher in early-stage patients who receive more intensive treatments in the first year following a new HCC diagnosis.

Deep learning models for predicting the survival of patients with hepatocellular carcinoma based on a surveillance, epidemiology, and end results (SEER) database analysis.

Hepatocellular carcinoma (HCC) is a common malignancy with poor survival and requires long-term follow-up. Hence, we collected information on patients with Primary Hepatocellular Carcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a deep learning with a multilayer neural network (the NMTLR model) for predicting the survival rate of patients with Primary Hepatocellular Carcinoma. HCC patients pathologically diagnosed between January 2011 and December 2015 in the SEER (Surveillance, Epidemiology, and End Results) database of the National Cancer Institute of the United States were selected as study subjects. We utilized two deep learning-based algorithms (DeepSurv and Neural Multi-Task Logistic Regression [NMTLR]) and a machine learning-based algorithm (Random Survival Forest [RSF]) for model training. A multivariable Cox Proportional Hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into a training set and a test set in a 7:3 ratio. The training dataset underwent hyperparameter tuning through 1000 iterations of random search and fivefold cross-validation. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-year, 3-year, and 5-year survival rates was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Area Under the Curve (AUC). The primary outcomes were the 1-year, 3-year, and 5-year overall survival rates. Models were developed using DeepSurv, NMTLR, RSF, and Cox Proportional Hazards regression. Model differentiation was evaluated using the C-index, calibration with concordance plots, and risk stratification capability with the log-rank test. The study included 2197 HCC patients, randomly divided into a training cohort (70%, n = 1537) and a testing cohort (30%, n = 660). Clinical characteristics between the two cohorts showed no significant statistical difference (p > 0.05). The deep learning models outperformed both RSF and CoxPH models, with C-indices of 0.735 (NMTLR) and 0.731 (DeepSurv) in the test dataset. The NMTLR model demonstrated enhanced accuracy and well-calibrated survival estimates, achieving an Area Under the Curve (AUC) of 0.824 for 1-year survival predictions, 0.813 for 3-year, and 0.803 for 5-year survival rates. This model's superior calibration and discriminative ability enhance its utility for clinical prognostication in Primary Hepatocellular Carcinoma. We deployed the NMTLR model as a web application for clinical practice. The NMTLR model have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with primary liver cancer.

Risk Factors and Comorbidities Associated With Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection.

INTRODUCTION/OBJECTIVES: Chronic hepatitis B virus infection (CHBVI) is a major public health problem affecting about 296 million people worldwide. HBV infects the liver, and when it becomes chronic, may cause cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to identify the risk factors and comorbid medical conditions that were associated with HCC in patients who had CHBVI. METHODS: We performed a retrospective electronic medical record review of adult patients diagnosed with CHBVI, who presented to our primary care office between October 1, 2017 and October 21, 2022. Selected variables in patients with CHBVI with HCC (HCC group) were compared to those without HCC (NoHCC group). RESULTS: Among 125 patients with CHBVI, 24% had HCC and 76% did not have HCC. There were higher frequencies of association of certain comorbidities in the HCC group compared to NoHCC group, such as anemia (63.3% vs 26.3%; P < .001), ascites (53.3% vs 1.1%; P < .001), portal hypertension (43.3% vs 0.0%; P < .001), chronic kidney disease (40.0% vs 13.7%; P = .002), and HCV coinfection (13.3% vs 7.4%; P < .001). The logistic regression model showed increased odds of HCC for each year of increase in age (OR = 1.06, 95% CI = 1.01-1.11; P = .014), and increased odds in men (OR = 5.96, 95% CI = 1.71-20.73; P = .005). Although Asians represented the racial majority in both the groups, there was no significant difference in the race distribution between the two groups. CONCLUSION: In patients with CHBVI, increasing age and male sex are factors associated with increased odds of having HCC. Patients with CHBVI and HCC have higher frequencies of association of tobacco use, recreational drug use, anemia, ascites, portal hypertension, chronic kidney disease, and co-infection with HCV.

Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study.

Background and aims: Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study. Methods: Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer's disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses. Results: Multivariable MR analysis showed causal association between Alzheimer's disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer's disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer's disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer's disease, and LIHC susceptibility. Conclusions: A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer's disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.

Liver Cancer Incidence in Kazakhstan: Fifteen-Year Retrospective Study.

OBJECTIVE: The aim is to study the trends of liver cancer (LC) incidence in the regional context in Kazakhstan. METHODS: The retrospective study was done using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in sanitary statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period. RESULTS: Between 2005 and 2019, 13,510 cases of LC were documented, comprising 59.3% males and 40.7% females. Most diagnoses were seen in age groups 55-59 years (13.3%) to 75-79 years (11.7%). LC patients' average age increased from 63.6 to 64.5 years. Incidence rates per 100,000 peaked at ages 65-69 years (35.1±1.0) and 70-74 years (43.3±1.0). LC incidence notably rose in the 70-74 years age group (APC=+0.89), contrasting with declining trends in younger age groups. Regional incidence variations revealed diverse patterns, mostly demonstrating unimodal increases, and some regions displaying bimodal growth. The age-standardized incidence rate was 5.7±0.1 per 100,000, declining from 2005 to 2012 (APC: -3.93), then rising until 2019 (APC: +1.13). Gender-specific standardized rates showed varied trends. Analyses of standardized indicators indicated declining trends in most regions but increased values in specific areas. Thematic maps classified incidence rates based on standardized indicators: low (up to 5.22), average (5.22 to 7.11), high (above 7.11 per 100,000 for the entire population). CONCLUSION: The study on liver cancer in Kazakhstan reveals marked gender and age differences. The standardized incidence rate among men was twofold greater than that among women. A distinct rise in cases was noted among individuals aged 70-74 years. Regional variations in incidence were evident. These findings emphasize the necessity for focused research to comprehend the causes behind these differences, enabling customized interventions for Kazakhstan's population.

Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center.

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.

Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Global Burden and Trends of Primary Liver Cancer Attributable to Comorbid Type 2 Diabetes Mellitus Among People Living with Hepatitis B: An Observational Trend Study from 1990 to 2019.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS: We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS: In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS: The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.

Burden of liver cancer attributable to high fasting plasma glucose: a global analysis based on the global burden of disease study 2019.

OBJECTIVE: Liver cancer is the world's sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. METHODS AND ANALYSIS: We evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. RESULTS: In 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. CONCLUSION: The burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality. This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease. This makes the management of patients more challenging, since physicians must take into consideration two different conditions, the chronic liver disease and the tumor. The underlying liver disease has several implications in clinical practice, because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC, obstacles in surveillance, and differences in the efficacy of the treatment against HCC. A shift in the prevalence of liver diseases has been evident over the last few years, with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance. Therefore, in an era of personalized medicine, it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Gender disparity between first and senior authors on liver cancer research in the top journals of Gastroenterology and Hepatology.

BACKGROUND: Gender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades. METHODS: We conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test. RESULTS: 665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals. CONCLUSION: The findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men.

Epidemiological, Diagnostic and Therapeutic Aspects of Hepatocellular Carcinoma in Morocco: A Case Series and Review of Literature.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver tumor. It is considered a global public health problem given its incidence and high mortality rate. Epidemiological studies on hepatocellular carcinoma in our Moroccan and North African contexts are rare. Hence, our study aims to determine the epidemiological, clinical, paraclinical, etiological and therapeutic aspects of this pathology in our context. MATERIALS AND METHODS: We conducted a descriptive retrospective study on patients with HCC treated by the Hepato-gastroenterology department of the university hospital of Mohammed VI in Marrakech over a period of 7 years spread between 01/01/2015 and 31/12/2021. The epidemiological characteristics, diagnostic methods and therapeutic management of HCC in these patients have been described and analyzed. RESULTS: 100 patients with HCC were identified and included in our study. The average age was 63.3 ± 12.63 years with a male predominance. The predominant etiology was cirrhosis (87% of cases) then viral hepatitis C (35%) and B (27%) and of unknown origin in 29% of cases. HCC revealed cirrhosis in 41% and was diagnosed during cirrhosis surveillance in 36% of cases. The functional signs were dominated by abdominal pain (68%), deterioration of general condition (58%) and abdominal distension (43%). Alfa-fetoprotein was elevated in 73% of cases and was above 400ng/ml in 41% of cases. The diagnosis was mainly radiological in 92% and histological in 8% of cases. The radiological aspects of HCC were dominated by mononodular form (58%), a right lobar location (80%), a diameter greater than 5 cm (58%), a typical vascular aspect (86%) with portal thrombosis in 24% and metastases in 36% of cases, especially in lymph nodes. The majority of cirrhosis in our series was classified as Child-Pugh stage B (46%) at the time of diagnosis and most patients had an advanced stage of HCC with 31% at BCLC C and 28% at BCLC D. 72% of patients received palliative treatment, and only 6% received curative treatment. At the end of the study, 48% of patients had died with an overall survival of 6.5 months. CONCLUSION: Our study achieved its main objective by providing a snapshot of HCC in our context and confirmed that HCC remains with poor prognosis since its diagnosis is often late, limiting the therapeutic choices with a very short median survival. It also noted that the viral etiology remains the main cause of HCC in our population. Therefore, prevention remains the best therapeutic approach against HCC and the need for a national or at least a regional HCC registry in our country is essential in order to develop targeted preventive measures adapted to our context and to improve the diagnostic and therapeutic approaches for our patients.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.