Incidence Of Primary Liver Cancer Research Articles

Incidence of liver cancer in young adults according to the global burden of disease database 2019.

The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. This study analyzed data from the Global Burden of Disease (GBD) study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) associated with primary liver cancer in the young (15-49y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million DALYs in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010-2019. More than half of countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease (MASLD)-attributable primary liver cancer (annual percentage change [APC] +0.87%, 95% confidence interval 0.70-1.05%) and alcohol-attributable primary liver cancer (APC +0.21%, 95% confidence interval 0.01-0.42%). Limitations of the GBD database include reliance on the quality of primary data and possible underestimation of alcohol consumption. Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.

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.

Sex-specific impact of dietary patterns on liver cancer incidence: updated results from two population-based cohort studies in China.

The associations between dietary patterns and liver cancer risk have received much attention, but evidence among the Chinese population is scarce. This study aims to update the results of two cohort studies and provide the sex-specific associations in the Chinese population. This study was based on two cohorts from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). Diet information was collected by validated food frequency questionnaires. Dietary patterns were derived by factor analysis. Cox regression model was utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for associations between dietary patterns and liver cancer risk. During median follow-up years of 11.2 (male) and 17.1 (female) years, 427 males and 252 females were identified as incident primary liver cancer cases. In males, vegetable-based dietary pattern was inversely associated with liver cancer (HRQ4-Q1: 0.67, 95%CI 0.51-0.88, Ptrend < 0.001). Interaction analysis indicated that in males lower vegetable-based dietary pattern score and older age/medical history of chronic hepatitis combined increase the hazard of liver cancer more than the sum of them, with a 114% and 1061% higher risk, respectively. In females, the fruit-based dietary pattern was associated with a reduced risk of liver cancer (HRQ4-Q1: 0.63, 95%CI 0.42-0.95, Ptrend = 0.03). In both males and females, null associations were observed between the meat-based dietary pattern and the risk of liver cancer. A vegetable-based dietary pattern in males and a fruit-based dietary pattern in females tended to have a protective role on liver cancer risk. This study provided updated information that might be applied to guide public health action for the primary prevention of liver cancer.

S1329 A Systematic Time-Trend Analysis of the Global Incidence, Prevalence, and Mortality of Primary Liver Cancer From 1990 to 2019 Using the Global Burden of Diseases Study 2019

S1329 A Systematic Time-Trend Analysis of the Global Incidence, Prevalence, and Mortality of Primary Liver Cancer From 1990 to 2019 Using the Global Burden of Diseases Study 2019

Radiotherapy for Liver Cancer: An International Multi-Centre Pooled Analysis of 925 Cases

Primary and secondary liver cancer incidence is growing and has a poor prognosis. The standard use of radiation has been hampered by studies with a wide range of patients, different management protocols and varied outcomes. To overcome this heterogeneity in the literature, larger and higher-level trials are warranted, but, so far, have been difficult to implement. Therefore, pooled analyses may offer the best way to determine the benefit of radiation, identify treatment parameters needed to optimize treatment techniques, and identify patient factors that allow for better patient selection. Patients with liver cancer treated by radiotherapy at centers in Canada, United States and Australia was pooled. Patient and treatment characteristics were noted, as well as the clinical outcomes of local control within 1 year, recurrence and mortality. Stepwise Cox proportional hazards models were used to identify significant predictors for recurrence and mortality. Patients were stratified by center, and primary versus metastatic disease. A total of 925 patients were included in this study. Mean age was 67 years, and 45% had a primary diagnosis of hepatocellular carcinoma. 1-year local control rate was 80%. Median survival was 1.8 years (1.9 years for primary liver cancer, and 1.4 years for metastatic liver cancer). Higher total dose and BED was associated with better survival. Median time to recurrence was 1.5 years. Higher total dose was associated with lower risk of recurrence CONCLUSION: As one of the largest pooled analyses in hepatic cancer, this international multi-center study provides pragmatic data on clinical outcomes of patients receiving radiotherapy for liver cancer. This database may assist in better selection of patients for future studies and answer questions such as what is the optimal dose and which patients benefit from treatment.

Incidence trends of primary liver cancer in different geographical regions of China from 1978 to 2012 and projections to 2032: An age-period-cohort analysis.

China accounted for 45.3% of new cases of primary liver cancer (PLC) worldwide in 2020. While variations in PLC incidence between different regions of China and decreasing incidence in overall China have been reported, incidence patterns have not been thoroughly explored by region. We examined the nearly status and temporal trends of PLC incidence in different geographical regions in China and project future trends. The age-standardized incidence rate (ASR) was estimated for 1978 to 2012 by different geographical regions and gender in China. Age-period-cohort model was adopted to evaluate age and birth cohort effects on the temporal trend of five registries of China (Hong Kong, Shanghai, Jiashan, Harbin and Zhongshan), Bayesian age-period-cohort model was adopted to project future trends for 2013 to 2032. PLC incidence in China exhibits marked geographical disparity, with the highest incidence in Southwest China, and gender differences being particularly pronounced in South China. While other registries exhibited decreasing trend, Zhongshan exhibited an increasing trend, with the cohort effect showing a marked upward trend for females born in 1916 to 1949 and males born in 1916 to 1962. During 2013 to 2032, the ASR appears to increase by 86.9% for men and 40.0% for women in Zhongshan, while the remaining registries will decline by around 50%. Since the high incidence of hepatitis B virus infection in early birth cohort, recent rise of nonviral risk factors and the severe aging of the Chinese population, it may be critical to tailor future prevention and control strategies for PLC to the distribution of risk factors in different geographical regions.

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.

OS-117 - Socioeconomic disparities and primary liver cancer incidence between 2006 and 2016: analyze by subtypes, a French population-based study

OS-117 - Socioeconomic disparities and primary liver cancer incidence between 2006 and 2016: analyze by subtypes, a French population-based study

Global, Regional, and National Trends in Incidence and Mortality of Primary Liver Cancer and Its Underlying Etiologies from 1990 to 2019: Results from the Global Burden of Disease Study 2019

ObjectivePrimary liver cancer is not only one of the most common causes of cancer deaths but also the second most common cause of premature death worldwide. Understanding the trends in incidence and mortality of primary liver cancer and its etiologies is crucial for development of effective prevention and mitigation strategies. This study aimed to quantify the trends in incidence and mortality of primary liver cancer and its etiologies at the global, regional and national levels using data from Global Burden of Disease (GBD) study.MethodAnnual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of primary liver cancer and its etiologies, including hepatitis B, hepatitis C, alcohol use, nonalcoholic steatohepatitis, and other causes, between 1990 and 2019 were collected from GBD study 2019. Percentage changes in incident cases and deaths and estimated annual percentage changes (EAPCs) in ASIRs and ASMRs of primary liver cancer and its etiologies were calculated to quantify their temporal trends. Correlations of EAPC in ASIRs and ASMRs with socio-demographic index (SDI) and universal health coverage index (UHCI) in 2019 were separately evaluated by Pearson correlation analyses.ResultsGlobally, the incident cases and deaths of primary liver cancer increased by 43.11% from 373 393 in 1990 to 534 365 in 2019 and 32.68% from 365 213 in 1990 to 484 584 in 2019, respectively. ASIR and ASMR of primary liver cancer decreased by an average of 2.23% (95% CI 1.83%, 2.63%) and 1.93% (95% CI 1.55%, 2.31%) per year between 1990 and 2019 worldwide, respectively. ASIRs and ASMRs of primary liver cancer varied between regions, with an increasing trend in ASIR (EAPC = 0.91; 95% CI 0.47, 1.35) and a stable trend in ASMR (EAPC = 0.42, 95% CI − 0.01, 0.85) of primary liver cancer in high SDI region between 1990 and 2019. Nearly half (91/204) of the countries suffered an increasing trend in ASIR of primary liver cancer and more than one-third (71/204) of the countries suffered an increasing trend in ASIRs of primary liver cancer from all etiologies between 1990 and 2019 worldwide. Positive correlations of EAPC in ASIR and ASMR of primary liver cancer with SDI and UHCI were observed in nations with SDI ≥ 0.7 or UHCI ≥ 70.ConclusionPrimary liver cancer remains a major public health concern globally, with an increasing trend in the numbers of incident cases and deaths in the past three decades. We observed an increasing trend in ASIR of primary liver cancer in nearly half of the countries and an increasing trend in ASIRs of primary liver cancer by etiology in more than one-third of the countries worldwide. In line with the Sustainable Development Goals, the identification and elimination of risk factors for primary liver cancer will be required to achieve a sustained reduction in liver cancer burden.

Anthropometric indicators of adiposity and risk of primary liver cancer: A systematic review and dose–response meta-analysis

Background and aimsAdiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. MethodsSystematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. ResultsSixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33–55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26–40.75). ConclusionCentral adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.

Living on the edge: how stromal cells restrict liver cancer invasion

The global incidence of primary liver cancer is increasing and currently ranks amongst the top-five causes of premature death from cancer annually. Like in many solid tumours, liver cancer cells are closely associated with stromal cells, known as non-parenchymal cells (NPCs), in the liver, including fibroblasts and endothelial cells, which normally support liver function and structure. Although single-cell RNA sequencing has begun to unpick the interactions between tumour cells and this non-epithelial microenvironment, these -omic approaches cannot mechanistically resolve how the non-parenchymal stroma interacts with tumour cells, nor can they resolve whether a fibroblast exerts differential outcomes on mutant versus healthy epithelial cells.In this issue of Disease Models & Mechanisms, Liqin Zhu and colleagues describe a novel in vitro microwell culture system to co-culture NPCs with either healthy hepatocytes or tumour cells of intrahepatic cholangiocarcinoma (iCCA), an aggressive type of primary liver cancer. When the authors co-cultured NPCs with primary hepatocytes, the NPCs supported hepatocyte spheroid growth, maintaining the phenotype of the healthy hepatocytes in culture. Interestingly, when cultured with mutant iCCA cells, NPCs supressed the growth of cancer spheroids, suggesting a divergent role of NPCs in tumour growth.To understand the role of these stromal cells in tumour growth further, the authors then co-cultured healthy hepatocytes and tumour cells in their microwell system and found that tumour cells invade and kill healthy hepatocytes. The addition of NPCs to this system significantly limited this process, and in vitro cancer cells were constrained, no longer killing healthy hepatocytes. Following on from this, the authors used an orthotopic transplantation mouse model of liver cancer and liver tumour samples from patients to show that activated myofibroblasts localised at the interface between tumour and normal tissue. Together, the data suggest that, in liver cancer, NPCs, in particular myofibroblasts, form a physical barrier that limits the ability of cancer cells to invade and damage normal tissue.Targeting the tumour microenvironment to limit disease progression is an attractive therapeutic prospect that could be agnostic to the underlying genetic and molecular heterogeneity seen in cancer. However, as NPCs have previously been shown to provide pro-proliferative signals in cancer and modify the intratumoral immune landscape, more research is required to understand the nuanced NPC-epithelial cell relationship in cancer. We should carefully consider the diverse and potentially conflicting roles of NPCs in tumour progression, and advanced in vitro systems, such as those developed by Zhu and colleagues, will help us decipher this.

Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study

Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7cm (interquartile range: 0.5-0.8cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08). Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case–control study

To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26-4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02-3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07-4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95-3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54-5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25-3.94, Ptrend = 0.005). We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.

Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals

Introduction: Simple predictive markers enabling even nonspecialized medical doctors and clinicopathological features of primary liver cancer (PLC) following HCV clearance with direct-acting antivirals (DAAs) are unclear. Methods: The subjects of this retrospective study were 2,476 patients following HCV clearance with DAAs. All patients were confirmed to be PLC-free before and during DAAs. Results: PLC was diagnosed in 73 patients during the follow-up, with an incidence rate per 1 000 person-years of 5.9. The annual rate of PLC during the first 6 years was 0.6%. Multivariate analysis identified gender, GGT, and FIB-4 index as the significant determinants of PLC. According to a combination of these risk factors, the cumulative PLC incidence rates were significantly different among the five subgroups based on the number of PLC risk scores. In 73 patients with PLC, the rates of abnormal AFP, PIVKAII, and serum TERT C228T positive were 37.0, 32.4, and 22.2%. PIVKAII levels in BCLC stage A and B were significantly higher than those in stage 0. In 41 patients, who underwent surgical resection for PLC, maximum tumor diameters of abnormal PIVKAII were significantly larger than those of normal PIVKAII. PLC of abnormal PIVKAII significantly indicated presence of vp more than that of normal PIVKAII, and did not contain well-differentiated HCC. Conclusions: Combination of simple markers, enabling even nonspecialized medical doctors, is useful for the evaluation of PLC risk following HCV clearance with DAAs. However, imaging studies are regularly recommended for the early detection of PLC.

Decrease in liver cancer incidence rates in Bamako, Mali over 28 years of population-based cancer registration (1987-2015).

BACKGROUNDPrimary liver cancer is common in West Africa due to endemic risk factors. However, epidemiological studies of the global burden and trends of liver cancer are limited. We report changes in trends of the incidence of liver cancer over a period of 28 years using the population-based cancer registry of Bamako, Mali.AIMTo assess the trends and patterns of liver cancer by gender and age groups by analyzing the cancer registration data accumulated over 28 years (1987-2015) of activity of the population-based registry of the Bamako district.METHODSData obtained since the inception of the registry in 1987 through 2015 were stratified into three periods (1987-1996, 1997-2006, and 2007-2015). Age-standardized rates were estimated by direct standardization using the world population. Incidence rate ratios and the corresponding 95% confidence intervals (CI) were estimated using the early period as the reference (1987-1996). Joinpoint regression models were used to assess the annual percentage change and highlight trends over the entire period (from 1987 to 2015).RESULTSAmong males, the age-standardized incidence rates significantly decreased from 19.41 (1987-1996) to 13.12 (1997-2006) to 8.15 (2007-2015) per 105 person-years. The incidence rate ratio over 28 years was 0.42 (95%CI: 0.34-0.50), and the annual percentage change was -4.59 [95%CI: (-6.4)-(-2.7)]. Among females, rates dropped continuously from 7.02 (1987-1996) to 2.57 (2007-2015) per 105 person-years, with an incidence rate ratio of 0.37 (95%CI: 0.28-0.45) and an annual percentage change of -5.63 [95%CI: (-8.9)-(-2.3)].CONCLUSIONThe population-based registration showed that the incidence of primary liver cancer has steadily decreased in the Bamako district over 28 years. This trend does not appear to result from biases or changes in registration practices. This is the first report of such a decrease in an area of high incidence of liver cancer in Africa. This decrease may be explained by the changes and diversity of diet that could reduce exposure to aflatoxins through dietary contamination in this population.

Comparison of time trends in the incidence of primary liver cancer between China and the United States: an age-period-cohort analysis of the Global Burden of Disease 2019.

China and the United States (US) ranked first and third in terms of new liver cancer cases and deaths globally in 2020. Therefore, a comprehensive assessment of trends in the incidence of primary liver cancer with four major etiological factors between China and the US during the past 30 years with age-period-cohort (APC) analyses is warranted. Data were obtained from the Global Burden of Disease 2019, and period/cohort relative risks were estimated by APC modeling from 1990 to 2019. In 2019, there were 211,000 new liver cancer cases in China and 28,000 in the US, accounting for 39.4% and 5.2% of global liver cancer cases, respectively. For China, the age-standardized incidence rate (ASIR) consecutively decreased before 2005 but increased slightly since then, whereas the ASIR continuously increased in the US. Among the four etiological factors of liver cancer, the fastest reduction in incidence was observed in hepatitis B virus-related liver cancer among Chinese women, and the fastest increase was in nonalcoholic steatosis hepatitis (NASH)-related liver cancer among American men. The greatest reduction in the incidence of liver cancer was observed at the age of 53 years in Chinese men (-5.2%/year) and 33 years in Chinese women (-6.6%/year), while it peaked at 58 years old in both American men and women (4.5%/year vs . 2.8%/year). Furthermore, the period risks of alcohol- and NASH-related liver cancer among Chinese men have been elevated since 2013. Simultaneously, leveled- off period risks were observed in hepatitis C viral-related liver cancer in both American men and women. Currently, both viral and lifestyle factors have been and will continue to play an important role in the time trends of liver cancer in both countries. More tailored and efficient preventive strategies should be designed to target both viral and lifestyle factors to prevent and control liver cancer.

A prospective cohort study of cigarette smoking, alcohol drinking and liver cancer incidence in Chinese men

Population-based prospective studies on the associations of cigarette smoking, alcohol drinking, and primary liver cancer remain limited in Mainland China. Our study was designed to evaluate such relationships in middle-aged Chinese men. Self-reported habits of cigarette smoking and alcohol drinking were obtained from all cohort members at the baseline survey. The outcomes were identified through in-person follow-up and annual record linkage to multiple statistics of vital and cancer registration. Age-adjusted and multivariable-adjusted hazard ratio (HR) and their corresponding 95% confidence interval (CI) were estimated utilizing the Cox regression model. After a median follow-up of 12.31 years, 329 cases of incident primary liver cancer occurred among 45 266 male participants. Compared with never smoker, former smoker was positively associated with liver cancer risk, with a multivariable-adjusted HR of 1.42 (95% CI 1.02-1.98). Individuals who had smoked for more than 40 years had a 49% increased risk of liver cancer (HR≥40 years 1.49, 95% CI 1.04-2.14). The association of alcohol drinking with liver cancer showed no statistical significance. Our study provided evidence that cigarette smoking was positively associated with an increased liver cancer risk among Chinese men. Attention to such non-viral modifiable risk factors to prevent liver cancer effectively is needed.

Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review.

Simple SummaryPorphyria is a metabolic condition which leads to reduced heme production. While it involves multiple organs systems, porphyria affecting the liver can lead to elevations in hepatic enzymes, progressive fibrosis, cirrhosis and eventually malignancy. Our study looked at the prevalence of liver cancer in patients with porphyria. Overall, we found that patients with porphyria are at increased risk of developing hepatic malignancy. As a result, patients with porphyria should undergo routine surveillance for detecting primary liver malignancy.Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.

Relationships between serum iron and liver diseases in nutrition intervention trials: A nested case-control study

BackgroundSerum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence. MethodsWe performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression. ResultsIndividuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27–3.27, Ptrend=0.011). The association was stronger among HCV-positive participants (Pinteraction=0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05). ConclusionsA significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.

JIM Reading List.

JIM Reading List.