| BackgroundLiver cancer is one of the most common cancers in the world,with a particularly large geographical difference in incidence.About 86% of cases occur in developing countries,especially in east Asia,north Asia and South Asia,and sub-saharan Africa.The incidence of liver cancer ranks the sixth in all malignant tumors,and the mortality ranks the third.The mortality rate ranks the third among malignant tumors,and nearly 50% of liver cancer occurs in China.Liver cirrhosis is a common chronic disease in clinical practice.Viral hepatitis,alcoholic liver damage and autoimmune liver disease are common pathogenesis factors of liver cirrhosis.Decompensated cirrhosis will convert 1-8% of liver cancer every year,active compensatory cirrhosis will convert 6% of liver cancer every year,and inactive cirrhosis will convert 2% of liver cancer every year.Therefore,it is of great significance to understand the population distribution,regional and temporal changes,risk factors,and the correlation and hysteresis effect of viral hepatitis of liver cancer,liver cirrhosis and related diseases.The reported incidence of hepatitis B in Wuwei City of Gansu Province used to be the highest in China for a long time.From 2005 to 2009,the average reported incidence of hepatitis B in China was 85.26/100,000,the average in Gansu Province was230.28/100,000,and the average in Wuwei City was 743.63/100,000,which was at the higher level in China.Due to backward economy and lack of technical support and other reasons,it was not until 2006 that large-scale studies on the prevalence of hepatitis B and related risk factors were started.However,the impact of the prevalence of hepatitis B in local populations on the incidence of cirrhosis and liver cancer has not been assessed so far.In 2008,with the support of the major special project for prevention and control of infectious diseases of the Ministry of Science and Technology,our teaching and research office carried out intervention research on reducing the incidence and fatality of hepatitis B in Wuwei City,but the impact of hepatitis B related diseases in the local area has not been systematically evaluated.Therefore,it is of great significance for the prevention and treatment of local liver cancer,cirrhosis and related diseases to study the temporal and spatial distribution characteristics of local viral hepatitis,cirrhosis and liver cancer,and to explore the correlation and lag effect between viral hepatitis(type B and C),cirrhosis and liver cancer.PurposeTo explore the influence of general demographic characteristics and related disease history on the occurrence of liver cancer.To understand the time and spatial prevalence trend of hepatitis B,cirrhosis and liver cancer in Wuwei area,and to explore the spatiotemporal clustering with the help of mathematical model to find the high-incidence clustering areas.To analyze the correlation and lag effect among viral hepatitis,cirrhosis and liver cancer,and to estimate the latent effect of hepatitis B,cirrhosis and liver cancer and its spatio-temporal relationship,To provide a theoretical basis for the formulation of comprehensive prevention and treatment of liver cirrhosis and liver cancer in Wuwei City.Methods1.Medical record information collection: The inpatient medical records of liver cancer and cirrhosis meeting the requirements from January 1995 to December 2016 were collected from 12 Grade II,Grade A and above hospitals in Wuwei City.The relevant information needed for the research was collected,and the EQURY field epidemiology and public health investigation system was used to establish the data database,and the data needed for the research were uniformly recorded by the staff through mobile APP.The data of viral hepatitis were derived from the database of information report management system of China CDC and the statistical report system of infectious disease epidemic in all counties(districts)of Wuwei City from January 1990 to December 2016.2.The quality control:The staff of the project team unified the training content and requirements,and the staff recorded the required information one by one through the mobile APP.The double input method was adopted to improve the quality of the input data.The supervisor monitors the daily input data in real time through the background of the system,and compares the 10% input data with the original medical record PDF randomly selected by team members in hospitals at all levels every day to correct errors,so as to ensure the accuracy of the data.3.Data analysis method:SAS 9.0,Join Point 4.8,ArcGIS 10.2 and Sat Scan 9.4 software were used for data analysis to study the characteristics,temporal and spatial incidence trends and temporal and spatial clustering of liver cancer and cirrhosis in Wuwei City.To explore the influence of related factors on the occurrence of liver cirrhosis and liver cancer,and to analyze the correlation and lag effect among viral hepatitis,liver cirrhosis and liver cancer.SAS9.0(SAS Institute,Cary,NC,USA)software was used to analyze the general demographic characteristics,basic hospitalization,treatment and hospitalization expenses.Measurement data were described in the form of mean ± standard deviation,while counting data were described in the form of frequency,composition ratio and frequency.Comparison between the two groups was performed by 2 test or Fisher’s test,P<0.05 means the statistical difference is significant.Join Point software developed by the National Cancer Institute of the United States was used to analyze the incidence rate,standardized rate,age group rate and time trend of liver cancer(cirrhosis)at township level in Wuwei City from January 1995 to December2016.The crude incidence rate was normalized by the standard population composition of the 6th national census in 2010.By calculating Annual Percent Change(APC),Annual Average Change(AAPC)and its 95%CI value,the increase and decrease of disease incidence rate were estimated,and its Change trend was described.Determine the year in which the trend direction changed.Geographic information system(GIS)is applied to visualize the digitized information data.ArcGIS 10.2 software was applied to make the electronic map of Wuwei city as the basic map layer,longitude and latitude coordinates were added,and township administrative codes were added to draw the spatial distribution map of liver cancer and liver cirrhosis in Wuwei city.Different colors were filled in each area according to the incidence level,and the low-incidence and high-incidence areas of tumors were visually described.The spatial distribution maps of liver cancer and cirrhosis can be drawn continuously for 22 years,and the annual spatial distribution characteristics and the change trend of 22 years can be described.Spatial aggregation analysis USES SaTScan9.4 for spatio-temporal scanning to detect hot spots of disease,and to detect whether there is disease aggregation and its location in the study area.The degree of aggregation was judged based on the Log Likehood Ratio(LLR),and the difference was judged to be statistically significant based on the p-value,with the test level =0.05.SAS9.0 software was used to explore the influence of general demographic characteristics,related disease history and clinical symptoms on the occurrence of liver cancer by means of logistics regression analysis and correlation analysis,and the correlation and hysteresis effect among hepatitis B,cirrhosis and liver cancer were analyzed.Result1.Characteristics of liver cancer case data in Wuwei cityThere were 2271 patients with liver cancer who met the inclusion requirements,The average age was 58.73,with the largest number of people aged between 60 and 64(17.66%).Among them,there were 1,680 males(73.97%)and 591 females(26.02%),with more males than females.Trend Chi-square test showed that the difference in the proportion of male and female patients was statistically significant(2=3.82,P<0.05),indicating that the incidence of liver cancer in males was higher than that in females in Wuwei city in the past 22 years.The majority of the cases were Han(2238 cases,98.55%),followed by tibetans(1.18%).There were 1369 farmers(61.80%),270 workers(11.89%)and 230 cadres(10.13%).The Median(IQR)of patient hospitalization days is 10(5,17)days.The number of patients with liver cancer complicated with lung cancer was the largest,followed by gastric cancer,gallbladder cancer,pancreatic cancer,etc.2.1.Characteristics of liver cirrhosis case data in Wuwei cityThere were 3,308 patients with cirrhosis who met the inclusion requirements,with an average age of 55.34 years old,and the incidence was highest in the 50-54 age group.There were 2,176 males(65.78%)and 1,131 females(34.22%).According to the results of the trend chi-square test,the difference in the proportion of male and female patients was statistically significant(2=22.71,P<0.05),indicating that there were more cases of cirrhosis in males than females in Wuwei in the past 22 years.The majority of the patients were Han(3258 cases,98.49%),followed by 39 Tibetans(1.18%).There were 1795 farmers(54.26%),492 workers(14.87%)and 388 cadres(11.73%).The differences of occupational composition in different regions were statistically significant(P<0.05);According to trend chi-square test results(2=11.93,P<0.05),the proportion of workers in patients with cirrhosis was increasing over time;The hospitalization days of hospitalized cirrhotic patients with Median(IQR)were 12(7,19)days.There were 160(4.80%)patients with liver cancer(108 cases),stomach cancer(15 cases),gallbladder cancer(12 cases)and other 11 types of cancer.3.Surveillance data of viral hepatitis in Wuwei city from 1990 to 2016A total of 18564 cases of viral hepatitis were reported in Wuwei city,including 9489 cases of Viral hepatitis A,4560 cases of viral hepatitis B,3351 cases of viral hepatitis C,89 cases of viral hepatitis E and 1075 cases of unclassified hepatitis.The incidence of hepatitis B has been on the rise(average annual incidence of 281.00/100,000,P<0.01);The reported incidence of hepatitis C showed an annual upward trend(annual incidence of102.15/100,000,P<0.01)4.Time trend analysis of liver cancer and cirrhosis cases in wuwei cityThe results of the analysis using Joinpoint software showed that the standardized rate of liver cancer in the whole population increased at an average rate of 12.8% per year from 1995 to 2016,AAPC=12.8(95%CI: 9.5-16.7).There was a Joinpoint in 2009,APC=16.7(95%CI:12.3-21.3).APC=5.1(95%CI:-0.6-11.1)in 2009-2016.The standardized rate of liver cancer in men increased at an average rate of 12.4% per year,AAPC=12.4(95%CI: 9.2-15.7).APC=4.0(95%CI:-1.60-9.90)in 2009-2016.The standardized rate of liver cancer in women increased at an average rate of 12.3% per year,AAPC=12.3(95%CI: 9.8-14.9),and there was no Joinpoint change(APC=12.3(95%CI: 9.8-14.9)between1995 and 2016.The change of APC in this period was statistically significant.During 1995-2016,the standardized rate of liver cirrhosis in the whole population increased at an average rate of 16.7% per year.There was a Joinpoint in 2010 and APC=11.1 during 1995-2010.The change of APC during this period was statistically significant.There was also a Joinpoint in 2013,APC=66.5 in 2010-2013,and the change of APC in this period was statistically significant.APC for 2013-2016 was 4.4.The standardized rate of male cirrhosis increased at an average rate of 15.6% per year,AAPC=15.6.In 2013,there was also a Joinpoint.The APC of 2010-2013 was 60.7,and the change of APC in this period was statistically significant.APC was 2.4 in2013-2016.The standardized rate of female cirrhosis increased at an average rate of 22.1%per year.There were 3 Joinpoint points from 1995 to 2016,which were 2002,2009 and2012.From 1995 to 2002,APC was 25.70,and the change of APC in this period was statistically significant.From 2002 to 2009,the growth rate slowed down,and the APC was 0.30.From 2009 to 2012,the growth rate was significantly increased,and the APC was 92.20(95%CI: 20.5-206.6),the change of APC in this period was statistically significant.In 2016,the growth rate was a turning point of slowing down,and in2012-2016,the APC was 16.3,and the change of APC in this period was statistically significant.5.Spatial trend and temporal cluster analysis of liver cancer and cirrhosis cases in Wuwei CityGeographic distribution map was made with ArcGIS 10.2 software,and clustering area detection was conducted with SaTScan 9.4 software.The results showed that:The average annual incidence of liver cancer was the highest in hongshagang town of minqin county,and the incidence of liver cancer was lower in bahaobo township of gulang county and dongping township of tianzhu county.From 1995 to 2004,the incidence of liver cancer in wuwei city was generally low,and that in only a few towns was high.After 2005,the incidence of liver cancer in all towns and villages increased gradually,and the darker areas on the map continued to expand.From 1995 to 2016,there were five clusters of liver cancer in wuwei city.The first cluster covered 14 towns and villages.The aggregation time was 2009-2016,LLR=192.21,RR=3.16,P< 0.00.The second cluster is hongshagang town,minqin county.The aggregation time is from 2001 to 2015,LLR=78.07,RR=28.14,P< 0.00.The third cluster cover two towns,and the agglomeration time is from 2002 to2016,LLR=51.62,RR=3.23,P< 0.00.The fourth cluster covered nine towns,and the aggregation time was from 2014 to 2015,LLR=23.88,RR=2.57,P< 0.00.The five clusters cover 13 towns and villages,and the aggregation time is from 2011 to 2016.LLR=19.40,RR=1.92,P< 0.00.The results of the distribution of liver cirrhosis in towns and villages showed that the average annual incidence of liver cirrhosis was the highest in hongshagang town,minqin county.From 1995 to 2010,the general incidence was relatively low.After 2010,the incidence of liver cirrhosis in towns and villages gradually increased,and the darker areas on the map kept expanding.According to the spatio-temporal detection of the aggregation of liver cirrhosis in wuwei city,from 1995 to 2016,there were four aggregation areas of liver cirrhosis in wuwei city.The first cluster area covered 14 towns and villages,and the aggregation time was from 2012 to 2016.LLR= 671.69 RR=6.10,P< 0.00.The second cluster covers 14 towns and villages,and the aggregation time is from 2012 to 2016,LLR=279.56,RR=3.76,P< 0.00;The third cluster area covers 25 towns and villages,and the aggregation time is from 2011 to 2016.LLR=85.45,RR=2.23,P< 0.00.The fourth cluster covered 22 towns,and the aggregation time was from 2013 to 2016,LLR=44.57RR= 2.05,P<0.00.The results of spatial scanning and basic spatial distribution were basically consistent,and the results of clustering time and temporal trend analysis were basically consistent,suggesting that the incidence of cirrhosis in Wuwei City had obvious spatial and temporal clustering.At the same time,the aggregation area of liver cirrhosis and liver cancer overlaps spatially,and the aggregation area is larger than that of liver cancer,which further suggests the causal relationship between the two.6.Analysis of the hysteresis effect of viral hepatitis on liver cancer and cirrhosisThe correlation coefficient between liver cirrhosis and hepatocellular carcinoma was0.85(P<0.01),the correlation coefficient between hepatitis C virus and liver cancer was0.83(P<0.01).The correlation coefficient between hepatitis C and cirrhosis was 0.83(P<0.01).Hepatitis B was positively correlated with the incidence of liver cancer 4-6 years later.Hepatitis A was negatively correlated with liver cancer 1-8 years later and 17-19 years later.Hepatitis C was positively correlated with liver cancer 1-8 years later.Cirrhosis was positively correlated with liver cancer 1-20 years later.Hepatitis C was positively correlated with cirrhosis after 1-4 years.Viral hepatitis e was positively correlated with cirrhosis after 1-4 years.Conclusion1.From 1995 to 2016,the overall incidence of hepatitis B,liver cancer and cirrhosis in Wuwei still showed an increasing trend,but the growth rate slowed down since 2009;The incidence of liver cancer and cirrhosis in Wuwei city from 1995 to 2016 was non-random,with obvious spatial and temporal aggregation.2.The incidence of liver cancer and cirrhosis in Wuwei city from 1995 to 2016 was non-random,with obvious spatial and temporal aggregation.The aggregation area of liver cirrhosis overlaps with that of liver cancer in space,and the aggregation area is larger than that of liver cancer,which further suggests the causal relationship between the two.3.There is lag effect between viral hepatitis and liver cancer and cirrhosis.Between the onset of liver cancer,the latent effect of hepatitis B may last 4-6 years,hepatitis C may last 1-8 years,and cirrhosis may last 1-20 years.Latent effects of hepatitis C may persist for 1 to 4 years between the onset of cirrhosis. |
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