Primary Liver Cancer Mortality Research Articles

Air pollutants and primary liver cancer mortality: a cohort study in crop-burning activities and forest fires area.

Northern Thailand experiences high levels of air pollution in the dry season due to agricultural waste burning and forest fires. Some air pollutants can enter the bloodstream, and the liver has the role of detoxifying these along with other harmful substances. In this study, we assessed the effects of long-term exposure to air pollutants on liver cancer mortality in this area. A cohort of 10,859 primary liver cancer patients diagnosed between 2003 and 2018 and followed up to the end of 2020 were included in the study. Extended time-varying covariates of the annually averaged pollutant concentrations updated each year were utilized. The associations between air pollutants and mortality risk were examined by using a Cox proportional hazard model. Metastatic cancer stage had the highest adjusted hazard ratio (aHR) of 3.57 (95% confidence interval (CI):3.23-3.95). Being male (aHR = 1.10; 95% CI: 1.04-1.15), over 60 years old (aHR = 1.16; 95% CI: 1.11-1.21), having a history of smoking (aHR = 1.16; 95%CI: 1.11-1.22), and being exposed to a time-updated local concentration of PM2.5 of 40 μg/m3 (aHR = 1.10; 95% CI: 1.05-1.15) increased the mortality risk. We found that air pollution is one of several detrimental factors on the mortality risk of liver cancer.

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 study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years 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 disability-adjusted life years 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 and 2019. More than half of the 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-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease 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.

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

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.

Comparison of primary liver cancer mortality estimates from World Health Organization, global burden disease and global cancer observatory.

AimsThis study aims to compare estimates of primary liver cancer mortality from World Health Organization (WHO), Global Burden Disease (GBD) and Global Cancer Observatory (GCO).MethodsLiver cancer mortality was extracted from WHO, GBD and GCO for 92 countries for the most recent year. Age‐standardized rate (ASR) was computed and used for current comparisons across the three data sources. Temporal trend for 75 countries was analysed and compared between WHO and GBD from 1990 to 2019 using joinpoint regression. Average annual percentage change for the most recent 10 years was used as indicator for change.ResultsThe estimates of ASR were quite consistent across the three data sources, but most similar estimates were found between WHO and GCO in both region and country levels. The differences in ASR were negatively correlated with completeness of cause‐of‐death registration, human development index and proportion of liver cancer because of alcohol consumption. Consistent trends of ASR were found from 35 countries between WHO and GBD in the most recent 10 years. However, opposite trends were found from 10 countries with five from Southern America, four from Europe and one from Asia. Of the 18 countries for projection, opposite trends between WHO and GBD were found from seven countries.ConclusionWhile the ASR of primary liver cancer mortality was comparable across the three data sources, most similar estimates were found between WHO and GCO. The opposite trends found from 10 countries between WHO and GBD raised concerns of true patterns in these countries.

Contrasting Trends of Primary Liver Cancer Mortality in Chinese Mongol and Non-Mongol.

Background:This study aims to investigate the temporal trend as well as the burden of primary liver cancer among Mongol and non-Mongol in China. Materials and Methods:The registered data from up to 20 monitoring points in the periods of 2008 to 2015 in Inner Mongolia were used to calculate and model the trend of liver cancer among Mongol and non-Mongol using log-linear regression. Logistic regression was used to characterise the risk of liver cancer by using hospitalization records from 2008 to 2017. Results:Over the study period, significant reduction of liver cancer mortality was found among non-Mongol population (4.8/100,000 from 23.7/100,000 to 18.9/100,000, p=0.04), while the increase of liver cancer mortality was observed among the Mongolian population (8.4/100,000 from 10.7/100,000 to 19.1/100,000, p=0.02), particularly the Mongol from East (25.5/100,000 from 11.2/100,000 to 36.7/100,000, p=0.005). Comparing to the non-Mongol patients with primary liver cancer, the Mongolian patients were more likely to be from East Inner Mongolia (aOR=3.65, 95% CI:2.75-4.87) and those residing in urban area (aOR=2.11, 95%CI: 1.55-2.91). In 2015, a total of 3056 primary liver cancer deaths could be converted if the four known risk factors (HBV, Hepatitis C Virus, alcohol consumption and smoking) could be prevented. HBV remained to be the leading risk factor of liver cancer (PAF=56%, contributing to 2616 deaths) with the highest among the Mongol from East (PAF=65.1%, contributing to 763 deaths). Conclusion:The continuing increase of primary liver cancer among Mongol suggested further interventions were needed to combat its burden.

The Mortality and Overall Survival Trends of Primary Liver Cancer in the United States.

Recent trends of hepatocellular carcinoma (HCC) mortality and outcome remain unknown in the United States. We investigated the recent trends of primary liver cancer (excluding intrahepatic cholangiocarcinoma) mortality and HCC stage, treatment, and overall survival (OS) in the United States. The National Center for Health Statistics Database was analyzed to investigate the trend of primary liver cancer mortality. We analyzed the Surveillance, Epidemiology, and End Results 18 Database to assess the temporal trend of tumor size, stage, treatment, and OS of HCC. We investigated the association between HCC diagnosis year and OS using Cox regression analysis. All statistical tests were 2-sided. During 2000-2018, liver cancer mortality rates increased until 2013, plateaued during 2013-2016 (annual percent change = 0.1%/y, 95% confidence interval [CI] = -2.1%/y to 2.4%/y, P = .92), and started to decline during 2016-2018 (annual percent change = -1.5%/y, 95% CI = -3.2%/y to 0.2%/y, P = .08). However, mortality continues to increase in American Indian and Alaska Native, individuals aged 65 years or older, and in 33 states. There was a 0.61% (95% CI = 0.53% to 0.69%, P < .001) increase in localized stage HCC and a 0.86-mm (95% CI = -1.10 to -0.62 mm, P < .001) decrease in median tumor size per year. The 1-year OS rate increased from 36.3% (95% CI = 34.3% to 38.3%) to 58.1% (95% CI = 56.9% to 59.4%) during 2000-2015, and the 5-year OS rate almost doubled from 11.7% (95% CI = 10.4% to 13.1%) to 21.3% (95% CI = 20.2% to 22.4%) during 2000-2011. Diagnosis year (per year) (adjusted hazard ratio = 0.96, 95% CI = 0.96 to 0.97) was independently associated with OS in multivariable analysis. Primary liver cancer mortality rates have started to decline in the United States with demographic and state-level variation. With an increasing detection of localized HCC, the OS of HCC has improved over the past decades.

Trends in Incidence and Mortality of Primary Liver Cancer in Lithuania 1998-2015.

Background: Recently, reports have suggested that rates of liver cancer have increased during the last decades in developed countries; increasing hepatocellular carcinoma and cholangiocarcinoma rates were reported. The aim of this study was to examine time trends in incidence and mortality rates of liver cancer for the period of 1998–2015 in Lithuania by sex, age, and histology. Methods: We examined the incidence of liver cancer from 1998 to 2015 using data from the Lithuanian Cancer Registry. Age-standardized incidence rates were calculated by sex, age, and histology. Trends were analyzed using the Joinpoint Regression Program to estimate the annual percent change. Results: A total of 3086 primary liver cancer cases were diagnosed, and 2923 patients died from liver cancer. The total number of liver cancer cases changed from 132 in 1998 to 239 in 2015. Liver cancer incidence rates changed during the study period from 5.02/100,000 in 1998 to 10.54/100,000 in 2015 in men and from 2.43/100,000 in 1998 to 6.25/100,000 in 2015 in women. Annual percentage changes (APCs) in the age-standardized rates over this period were 4.5% for incidence and 3.6% for mortality. Hepatocellular cancer incidence rates were stable from 1998 to 2005 (APC −5.9, p = 0.1) and later increased by 6.7% per year (p < 0.001). Intrahepatic ductal carcinoma incidence increased by 8.9% per year throughout the study period. The rise in incidence was observed in all age groups; however, in age groups < 50 and between 70 and 79 years, observed changes were not statistically significant. For mortality, the significant point of trend change was detected in 2001, where after stable mortality, rates started to increase by 2.4% per year. Conclusions: Primary liver cancer incidence and mortality increased in both sexes in Lithuania. The rise om incidence was observed in both sexes and main histology groups. The increasing incidence trend may be related to the prevalence of main risk factors (alcohol consumption, hepatitis B and C infections. and diabetes).

Combined use of transversus abdominis plane block and laryngeal mask airway during implementing ERAS programs for patients with primary liver cancer: a randomized controlled trial

The incidence and mortality of primary liver cancer are very high and resection of tumor is the most crucial treatment for it. We aimed to assess the efficacy and safety of combined use of transversus abdominis plane (TAP) block and laryngeal mask airway (LMA) during implementing Enhanced Recovery After Surgery (ERAS) programs for patients with primary liver cancer. This was a prospective, evaluator-blinded, randomized, controlled parallel-arm trial. A total of 96 patients were enrolled (48 in each group). Patients in the control group received general anesthesia with endotracheal intubation, while patients in the TAP + LMA group received general anesthesia with LMA and an ultrasound-guided subcostal TAP block. The primary end-point was postoperative time of readiness for discharge. The secondary end-points were postoperative pain intensity, time to first flatus, quality of recovery (QoR), complications and overall medical cost. Postoperative time of readiness for discharge in the TAP + LMA group [7 (5–11) days] was shorter than that of the control group [8 (5–13) days, P = 0.004]. The postoperative apioid requirement and time to first flatus was lower in the TAP + LMA group [(102.8 ± 12.4) µg, (32.7 ± 5.8) h, respectively] than the control group [(135.7 ± 20.1) µg, P = 0.000; (47.2 ± 7.6) h, P = 0.000; respectively]. The QoR scores were significantly higher in the TAP + LMA group than the control group. The total cost for treatment in the TAP + LMA group [(66,608.4 ± 6,268.4) CNY] was lower than that of the control group [(84,434.0 ± 9,436.2) CNY, P = 0.000]. There was no difference in complications between these two groups. The combined usage of a TAP block and LMA is a simple, safe anesthesia method during implementing ERAS programs for patients with primary liver cancer. It can alleviate surgical stress, accelerate recovery and reduce medical cost.

Descriptive epidemiology of incidence and mortality of primary liver cancer in 185 countries: evidence from GLOBOCAN 2018.

This study aims to examine the burden of primary liver cancer in 185 countries in 2018. The estimates of incidence, mortality and prevalence of primary liver cancer were procured from GLOBOCAN 2018. The development status of a country was measured using the human development index-a composite indicator of income per capita, education and life expectancy. Globally, primary liver cancer resulted in an estimated 781 631 deaths at age-standardized mortality rate of 8.5/100 000, and 841 080 cases were estimated to be diagnosed in 2018. Males accounted for 596 574 cases and 548 375 deaths, which is more than twice the burden of primary liver cancer in females (cases: 244 506; deaths: 233 456). The global age-standardized incidence rate was 9.3/100 000 in 2018, varying from Morocco (1.1/100 000) to Mongolia (93.7/100 000). There were remarkable variations in terms of age-standardized mortality rate, too, which ranged from 1/100 000 in Nepal to 75.4/100 000 in Mongolia. East Asia was the top region contributing 55.6% of global cases and 54.7% of global deaths. Since majority of the primary liver cancer burden pertains to hepatocellular carcinoma and screening approaches are yet to be fully proven, the policy focus must be on prevention approaches through the hepatitis-B vaccine, early detection of hepatitis-C infection, reduced alcohol consumption, obesity control, reduced aflatoxin exposure and containment of other modifiable risk factors.

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults.

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose-response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HRTertile 3 vs. 1 2.05; 95% confidence interval [CI] 1.23-3.41) and death from this disease (SHRTertile 3 vs. 1 1.97; 95% CI 1.13-3.41). Similar results were obtained for DII score from food only. A nonlinear dose-response pattern was identified for the aforementioned associations (all pnonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.

Magnesium intake and primary liver cancer incidence and mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1 : 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1 : 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.

Polyphyllin II inhibits liver cancer cell proliferation, migration and invasion through downregulated cofilin activity and the AKT/NF-κB pathway.

ABSTRACTThe morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anti-cancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkably suppress the proliferation of two liver cancer cell lines, HepG2 and BEL7402, resulting in significant cell death. Besides, low doses of PP2 have displayed properties that inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cell motility. Decreased expression of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway may also be also responsible for this process. Rescue experiments done with either non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of the AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we report a potential agent for liver cancer treatment and reveal its underlying mechanisms.

Mortality trends of liver diseases in mainland China over three decades: an age-period-cohort analysis

ObjectiveTo analyse mortality trends of liver diseases in China over the past 30 years.DesignAge-period-cohort analyses were applied to liver diseases data obtained from the Chinese Health Statistics Annual Report (1987–2001)...

Primary prevention by hepatitis B vaccine on liver cancer in high incidence area of China

Objective: Incidence of primary liver cancer (PLC) in China is mostly related to chronic infection of hepatitis B virus (HBV). Qidong was one of the endemic areas with high incidence of PLC in China before 2000. We conducted a series of studies regarding on PLC etiological prevention during the past decades to develop better primary prevention strategies for PLC. Methods: Qidong Hepatitis B Intervention Study was conducted in 1983-1990. A total of 41 182 newborns were randomly assigned to vaccination group and 40 211 (97.64%) of them completed the three-dose, 5 µg-plasma-derived hepatitis B (HB) vaccination series at age 0, 1, 6 month. Among them, 28 988 participants received one-dose 10 µg recombinant HB booster vaccination at age 10-14 years. A total of 41 730 newborns were randomly assigned to the control group. When they were at age 10-14 years, 23 368 participants received the catch-up vaccination with three-dose, 10 µg-recombinant HB vaccine. Two cross-sectional HBV serology surveys were conducted in 1996-2000 and 2008-2012. Information on PLC incidence and mortality of chronic liver diseases were collected through cancer registry and vital statistics until December 31, 2016. Cox proportional hazard models were employed to compute hazard ratio (HR) of PLC and other liver diseases for the participants with neonatal HB vaccination or catch-up vaccination, and the protective efficacy was also calculated. Results: During serologic survey in 1996-2000, a total of 22 689 participants in vaccination group and 12 395 participants in control group donated blood samples. The HBsAg seropositive rates in the vaccination group was 2.16% (491/22 689), which is significantly lower than that of control group (9.08%, 1 126/12 395) (χ2=896.61, P<0.001). During serologic survey in 2008-2012, a total of 17 386 participants in vaccination group and 18 060 participants in control group donated blood samples. The HBsAg seropositive rates in the vaccination group was 1.83% (319/17 386), which is still significantly lower than that of control group (6.77%,1 222/18 060) (χ2=518.05, P<0.001). By December 31, 2016, 4 cases of PLC in the vaccination group and 17 cases of PLC were identified in the vaccination and control group, respectively. The estimated efficacy of neonatal HB vaccination on HBsAg seroprevalence in childhood (at age 10-11 years), early adulthood (at age 19-28 years) and incidence rate of PLC at age below 33 years was 79% (95%CI: 76%-81%), 74% (95%CI: 71%-78%) and 79% (95%CI: 36%-93%), respectively. The estimated efficacy of three-dose, 10 µg-recombinant HB catch-up vaccination in early adulthood is 21% (95%CI: 11%-30%), which is significantly lower than that of neonatal HB vaccination. Conclusion: HB vaccination to neonates/infants is crucial against chronic HBV infection in childhood through young adulthood, and subsequently reduced the risk of PLC in young adults.

A 22-year-follow-up cohort study on primary liver cancer in Haimen city of Jiangsu province

Objective: A prospective cohort study was carried out to assess the mortality and potential risk factors for primary liver cancer (PLC) in Haimen city of Jiangsu province. Methods: The cohort involved 89 789 adult residents aged 25-69 years. Upon the entry of this project, each subject was asked to complete a questionnaire and to provide a blood sample of 10 ml. Surface antigen of hepatitis B virus (HBsAg) was tested by radioimmunoassay. All the subjects were followed-up every year for vital statistics and death certificate information until 2014. Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (95%CI) for PLC mortality associated with HBsAg status and other risk factors. Results: During the 1 299 611 person-years of follow-up, a total of 2 583 PLC cases were identified, including 2 149 men and 434 women. Mortality of the PLC for men and women were 247.80/100 000 person-years and 100.38/100 000 person-years, respectively. Among those who died of PLC, 73.87% had been tested HBsAg positive. HBV infection seemed the predominant risk factor for PLC and the HRs were 15.97 for men (95%CI: 14.29-17.85) and 21.63 for women (95%CI: 16.16-28.96) respectively. Ageing, cigarette smoking, previous history of hepatitis, and family history of HCC were factors associated with the increased risk for PLC. Conclusion: People living in Haimen city had a high risk on PLC. HBV infection appeared the most important risk factor for HCC mortality in this area.

Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride.

Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations

To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD. Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.

Abstract SY14-04: Global burden of liver cancer: Emerging needs in Asia.

Globally, driven by increased life expectancy, the overall incidence of cancer is expected to nearly double over the next 20 years. Nonetheless, the target organs where these diagnoses will occur will still vary widely from country to country because of divergent exposures and other etiologic factors (1). One cancer that currently illustrates this geographic disparity is primary liver cancer (PLC). Currently, PLC is the third leading cause of cancer mortality worldwide with an estimated 696,000 deaths in 2008. Half of these PLC deaths of those deaths occur in the People9s Republic of China. The major etiological factors associated with PLC in China, as established from prospective cohort studies, are chronic infection with hepatitis B virus (HBV) and extended exposure to high levels of aflatoxin in the diet, especially from corn and groundnuts (2). The largest study, comprising more than 18,000 men residing in Shanghai in the 1980s, examined HBV infection and aflatoxin exposure as independent and interactive risk factors for PLC (3). This nested case control study revealed a statistically significant increase in the relative risk (RR) of 7.3 for men who were chronically infected with HBV (HBsAg) but unexposed to aflatoxin. In men on whom urinary aflatoxin but not HBV biomarkers were detected, the RR was 3 (4). Furthermore, in men exhibiting both urinary aflatoxin biomarkers and positive HBsAg status, the RR was 59.4.3 A subsequent cohort study in Taiwan confirmed these results.4 In light of this synergistic interaction, programs to eliminate either factor, or both, should have substantial impact on the burden of PLC. Chronic infection with HBV has been long regarded as the major cause of PLC and initiatives have been undertaken to implement universal immunization programs. It is estimated that more than 90% of countries now routinely vaccinate newborns against HBV, and approximately 70% are now delivering 3 immunization doses. Newborns are targeted because HBV transmission is often vertical from mother to child at birth or during the perinatal period. In 1986, Taiwan became the first region to vaccinate all newborns against HBV. Since then, the number of HBV carriers in the juvenile population has declined dramatically. As of 2009, incidence of hepatocellular carcinoma was significantly lower among children aged 6-19 years in vaccinated compared with antecedent unvaccinated birth cohorts (5). For many years, we have been working with colleagues in Qidong, China, located at the mouth of the Yangtze River, an endemic area for liver cancer, where early age of onset and high mortality rates from PLC are reported (6). HBV vaccination of newborns in the rural townships was initiated during the 1980s but did not become universal until 2002. Crude rates of PLC per 100,000 residents of Qidong rose slightly from 1972 through 1990 at levels around 50/100,000 before increasing in the 1990s to a stable rate of about 75/100,000. Such data have led to the perception that Qidong remains an irrevocably high-risk region (7). However, the latter PLC mortality rate increase largely reflects a dramatically altered age distribution in the population rising from 17.0% over 50 years of age in 1973 to 22.7% in 1988 and 34.2% in 2003. Prognosis for survival from liver cancer following diagnosis remains poor: currently In order to accurately describe aflatoxin exposures over the past quarter century, frozen serum samples collected since 1989 were measured for aflatoxin-albumin adduct content (9–11). There has been a dramatic decline in levels of exposure from the 1980s to the present. Median levels of aflatoxin-albumin adducts from residents of the villages of Daxin and HeZuo declined from 19.3 pg/mg albumin in 1989, to 3.6 in 1995, to 2.3 in 1999, to 1.4 in 2003 and undetectable (i.e., Acknowledgments This work has been funded by the National Institutes of Health USA (P01 ES 006052) and the National Science and Technology Mega-Projects of China (No. 2008ZX10002-015, No. 2012ZX10002-008. Citation Format: John D. Groopman, Thomas W. Kensler. Global burden of liver cancer: Emerging needs in Asia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY14-04. doi:10.1158/1538-7445.AM2013-SY14-04

Incidence and survival condition of primary liver cancer among residents in Pudong district of Shanghai, from 2002 to 2011

To analyze the incidence and survival rates of primary liver cancer (PLC) among residents in Pudong district of Shanghai. Permanent residents of Pudong district, Shanghai were recruited in the study between 2002 and 2011, among whom 7981 PLC cases were diagnosed and 7233 death cases were certified. Both morbidity and mortality of PLC were calculated and standardized (ASR) by the world population of 1966, in order to analyze the survival condition of PLC patients on gender or address, to explore the prognosis of surgical excision treatment. Among the incident cases of PLC between 2002 and 2011, 5754 cases were males, with an average age of 60.27; while 2227 cases were females, with an average age of 68.26. The crude incidence rate for both sexes was 30.73 per 100 000 person-year, and was 44.30 per 100 000 person-year for males, higher than that in females, 17.16 per 100 000 person-year. The difference showed statistical significance (u = 3.46, P < 0.01). The ASR for incidence rates were 25.72 per 100 000 person-year in males and 8.22 per 100 000 person-year in females, respectively, with difference statistically significant (u = 3.00, P < 0.01). There were 7233 PLC death cases in total, including 5151 males and 2082 females, with the crude mortality rate as 27.85 per 100 000 person-year. Rate for males was 39.65 per 100 000 person-year, significantly different from 16.04 per 100 000 person-year in females, statistically (u = 3.16, P < 0.01). The ASRs for mortality were 22.77 per 100 000 person-year in males and 7.39 per 100 000 person-year in females, with statistically significant difference (u = 2.80, P < 0.01). Both incidence and mortality rates increased apparently for males aged over 35 and females aged over 45. The 1- to 5-year survival rates of PLC were 19.88%, 14.91%, 12.19%, 10.29% and 8.56%, respectively. There were statistically significant differences among urban, town and rural areas in the over-all survival rates (χ(2) = 8.711, P = 0.013); The differences in 1- to 5-year survival rates between surgical and non-surgical groups showed statistically significant differences (u = 10.8, 6.93, 4.75, 3.3 and 2.61, respectively, P < 0.01). The incidence and mortality rates in males were significantly higher than in females and the over-all survival in rural area was significantly lower than in other areas of Pudong district, suggesting that surgical treatment could improve the prognosis of PLC.