hepatocellular carcinoma ( hcc ) is the fifth and seventh most commonly diagnosed cancer in males and females , respectively , and the third leading cause of cancer mortality worldwide .
the incidence and mortality rates for hcc are similar because most hcc patients are diagnosed at an advanced stage , highlighting the importance of early hcc detection in the application of potentially curable treatment options .
hepatitis b virus ( hbv ) is the major risk factor for hcc and early detection of hcc through surveillance of high - risk populations improves hcc mortality .
therefore , national practice guidelines recommend regular hcc surveillance for high - risk hbv - infected persons . in korea ,
the korean association for the study of the liver and the national cancer center jointly developed guidelines for hcc screening in 2001 recommending that high - risk adults with hbv infection should undergo surveillance for hcc using ultrasonography and alpha - fetoprotein ( afp ) every 6 months . based on this recommendation ,
the korean government introduced nationwide hcc screening as a part of the organized national cancer screening program ( ncsp ) for lower income levels in 2003 .
the ncsp provides a biannual ultrasonography and afp test for males and females 40 years of age that were hepatitis b surface antigen ( hbsag)-positive , had hepatitis c infection , or liver cirrhosis . in the beginning ,
the ncsp supplied medicaid recipients and national health insurance ( nhi ) beneficiaries in the lower 30% income bracket with free hcc screening services . in 2006 , the ncsp provided participants in the lower 50% income bracket with hcc screening services free of charge .
in addition to these national hcc screening programs , ultrasonography and afp testing are performed in outpatient clinics or private health promotion centers across korea .
based on the advantages of early hcc detection , it is crucial to investigate the rate of adherence to hcc screening to understand how hcc surveillance tests are being implemented in high - risk groups in korea .
although a nationwide organized screening program has been provided in korea since 2003 , no study to date has investigated changes in adherence rates to hcc screening in practice .
this study used data from the second and fifth korea national health and nutrition examination surveys ( knhanes ) , which is a nationally representative , cross - sectional survey .
we analyzed screening rates for hcc among the hbv - infected korean population after the introduction of the nationwide hcc screening program and assessed factors related to hcc screening adherence .
this study used the second knhanes ( knhanes ii ) data collected during 2001 and fifth knhanes ( knhanes v ) data collected from 2010 to 2011 . the knhanes is a series of nationally representative , cross - sectional health and nutrition examination surveys conducted by the korean centers for disease control and prevention since 1998 .
it uses a complex , stratified , multistage probability sample representative of the korean population .
the procedures for selecting the sample and conducting the interviews and examinations have been described elsewhere .
consistent with current korea ncsp recommendations , we restricted the analysis to adults 40 years of age at the time of the interview
. there were 14,936 individuals who participated in knhanes ii and 9159 who participated in knhanes v who met the age criteria ; 3763 and 8145 , respectively , of these participants , were tested for hbsag . of these ,
176 and 285 participants in knhanes ii and v , respectively , were infected with hbv . among these populations ,
we excluded participants who reported a personal history of hcc ( n = 4 in knhanes v ) or did not answer questions on compliance to hcc screening tests ( n = 11 and 5 in knhanes ii and v , respectively ) . in the final analysis , we included 165 and 276 participants 40 years of age who were hbsag - positive from knhanes ii and v , respectively [ figure 1 ] .
all participants provided informed consent , and the protocol was approved by the institutional review board of the korea centers for disease control .
hbsag was measured using enzyme - linked immunosorbent assays in knhanes ii ( coda ; bio - rad , hercules , ca , usa ) , and an electrochemiluminescence immunoassay ( modular e-170 ; roche diagnostics , mannheim , germany ) in knhanes v. all other parameters were determined from the self - reported questionnaires .
ii , participants were asked ,  have you had a screening test for hcc within the last 2 years ?  ; possible responses were  yes ,   no ,  and  do not know .  in knhanes v ,
participants were asked ,  when was the last time you had hcc screening test ?  ; possible responses were  never ,  
> 2 years ago ,  and  do not know .  to standardize the major outcome variable , participants who had undergone hcc screening test within the previous 2 years were considered to have undergone recent hcc screening .
participants were also asked ,  have you ever been diagnosed with hbv infection by a doctor or a health professional ?  subjects who answered positively to this question were defined as those who were self - aware of hbv infection .
data were also collected on demographic and socioeconomic factors ( e.g. , age , gender , urbanity , marital status , education , household income , health insurance , smoking , and alcohol consumption ) relevant to hcc screening .
two categorical levels for education attainment were used based on the highest level of education achieved by the respondent : high school or higher , and less than high school .
household income was divided into four groups on the basis of monthly income quartile . with regard to health insurance
three categorical groups for alcohol amount were used : light drinking ( < 10 g / d for women , < 20 g / d for men ) , moderate drinking ( 1020 g / d for females , 2040 g / d for males ) , and heavy drinking ( 20 g / d for females , 40 g / d for males ) .
statistical analyses were performed using sas software ( version 9.3 , sas institute , cary , nc , usa ) , which incorporates sample weights and adjust the analyses for the complex sample design of the survey .
the survey sample weights , which were calculated taking into consideration the sampling rate , response rate , and age / gender proportion of the reference population ( 2000 and 2005 national census registry , respectively ) , were used in all analyses to produce estimates representative of the noninstitutionalized civilian korean population considering a complex , stratified , multistage probability sampling design . the prevalence and 95% confidence interval ( ci ) of hbv infection aged 40 years
the hcc screening rate within 2 years and 95% ci for each survey year were calculated using cross - tabulation .
differences in the proportion of participants who had hcc screening in each survey were analyzed using the chi - square test ( proc surveyfreq procedure ) . to identify risk factors for adherence to an hcc screening program ,
the crude and adjusted odds ratios ( ors ) were calculated using logistic regression ( proc surveylogistic procedure ) .
the covariates for the adjusted or calculation were household income , smoking status , awareness of hbv infection , and survey year .
this study used the second knhanes ( knhanes ii ) data collected during 2001 and fifth knhanes ( knhanes v ) data collected from 2010 to 2011 . the knhanes is a series of nationally representative , cross - sectional health and nutrition examination surveys conducted by the korean centers for disease control and prevention since 1998 .
it uses a complex , stratified , multistage probability sample representative of the korean population .
the procedures for selecting the sample and conducting the interviews and examinations have been described elsewhere .
consistent with current korea ncsp recommendations , we restricted the analysis to adults 40 years of age at the time of the interview
. there were 14,936 individuals who participated in knhanes ii and 9159 who participated in knhanes v who met the age criteria ; 3763 and 8145 , respectively , of these participants , were tested for hbsag . of these ,
176 and 285 participants in knhanes ii and v , respectively , were infected with hbv . among these populations ,
we excluded participants who reported a personal history of hcc ( n = 4 in knhanes v ) or did not answer questions on compliance to hcc screening tests ( n = 11 and 5 in knhanes ii and v , respectively ) . in the final analysis , we included 165 and 276 participants 40 years of age who were hbsag - positive from knhanes ii and v , respectively [ figure 1 ] .
all participants provided informed consent , and the protocol was approved by the institutional review board of the korea centers for disease control .
hbsag was measured using enzyme - linked immunosorbent assays in knhanes ii ( coda ; bio - rad , hercules , ca , usa ) , and an electrochemiluminescence immunoassay ( modular e-170 ; roche diagnostics , mannheim , germany ) in knhanes v. all other parameters were determined from the self - reported questionnaires .
ii , participants were asked ,  have you had a screening test for hcc within the last 2 years ?  ; possible responses were  yes ,   no ,  and  do not know .  in knhanes
v , participants were asked ,  when was the last time you had hcc screening test ?  ; possible responses were  never ,  
> 2 years ago ,  and  do not know .  to standardize the major outcome variable , participants who had undergone hcc screening test within the previous 2 years were considered to have undergone recent hcc screening .
participants were also asked ,  have you ever been diagnosed with hbv infection by a doctor or a health professional ?
 subjects who answered positively to this question were defined as those who were self - aware of hbv infection .
data were also collected on demographic and socioeconomic factors ( e.g. , age , gender , urbanity , marital status , education , household income , health insurance , smoking , and alcohol consumption ) relevant to hcc screening . two categorical levels for education attainment were used based on the highest level of education achieved by the respondent : high school or higher , and less than high school .
household income was divided into four groups on the basis of monthly income quartile . with regard to health insurance
three categorical groups for alcohol amount were used : light drinking ( < 10 g / d for women , < 20 g / d for men ) , moderate drinking ( 1020 g / d for females , 2040 g / d for males ) , and heavy drinking ( 20 g / d for females , 40 g / d for males ) .
statistical analyses were performed using sas software ( version 9.3 , sas institute , cary , nc , usa ) , which incorporates sample weights and adjust the analyses for the complex sample design of the survey .
the survey sample weights , which were calculated taking into consideration the sampling rate , response rate , and age / gender proportion of the reference population ( 2000 and 2005 national census registry , respectively ) , were used in all analyses to produce estimates representative of the noninstitutionalized civilian korean population considering a complex , stratified , multistage probability sampling design . the prevalence and 95% confidence interval ( ci ) of hbv infection aged 40 years
the hcc screening rate within 2 years and 95% ci for each survey year were calculated using cross - tabulation .
differences in the proportion of participants who had hcc screening in each survey were analyzed using the chi - square test ( proc surveyfreq procedure ) . to identify risk factors for adherence to an hcc screening program , the crude and adjusted odds ratios ( ors ) were calculated using logistic regression ( proc surveylogistic procedure ) .
the covariates for the adjusted or calculation were household income , smoking status , awareness of hbv infection , and survey year .
there were 165 and 276 participants 40 years of age infected with hbv in 2001 and 20102011 , respectively .
the weighted seroprevalence of hbv infection was 4.3% in 2001 , and 3.8% in 20102011 .
the baseline distribution of the study population was broadly similar between survey years , with the exception of educational attainment , household income , smoking status , and alcohol intake .
baseline characteristics of the participants 40 years of age with hepatitis b infection * based on weighted data . based on unweighted data .
p values are derived from rao - scott chi - square test ( proc surveyfreq procedure ) .
the proportion of study participants with hbv infection reporting an hcc screening test within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 20102011 ( p < 0.0001 ) .
an increased rate of hcc screening tests from 2001 to 20102011 was also observed in the entire study population .
rate of recent hepatocellular carcinoma screening within 2 years * based on weighted data ; based on unweighted data .
p values are derived from rao - scott chi - square test ( proc surveyfreq procedure ) .
the results of the multivariable logistic regression models for factors associated with the adherence to hcc screening tests are reported in table 3 . following adjustments for household income ,
smoking status , awareness of hbv infection , survey year , and individuals in higher income quartiles were more likely to have undergone recent hcc screening ( third quartile : adjusted or = 3.03 , 95% ci : 1.277.23 ; fourth quartile : adjusted or = 2.49 , 95% ci : 1.085.73 ) .
self - awareness of hbv infection was positively related to recent hcc screening ( adjusted or = 2.74 , 95% ci : 1.405.38 ) .
survey year 20102011 was associated with a significantly higher rate of recent hcc screening ( adjusted or = 3.37 , 95% ci : 1.955.81 ) .
regression models for adherence to hepatocellular carcinoma screening * based on weighted data ; based on unweighted data . crude and
adjusted ors ( 95% cis ) were calculated using logistic regression ( proc surveylogistic procedure ) . or : odds ratio ; ci : confidence interval ; knhanes : korea national health and nutrition examination surveys .
there were 165 and 276 participants 40 years of age infected with hbv in 2001 and 20102011 , respectively .
the weighted seroprevalence of hbv infection was 4.3% in 2001 , and 3.8% in 20102011 .
the baseline distribution of the study population was broadly similar between survey years , with the exception of educational attainment , household income , smoking status , and alcohol intake .
baseline characteristics of the participants 40 years of age with hepatitis b infection * based on weighted data . based on unweighted data .
p values are derived from rao - scott chi - square test ( proc surveyfreq procedure ) .
the proportion of study participants with hbv infection reporting an hcc screening test within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 20102011 ( p < 0.0001 ) .
an increased rate of hcc screening tests from 2001 to 20102011 was also observed in the entire study population .
rate of recent hepatocellular carcinoma screening within 2 years * based on weighted data ; based on unweighted data .
p values are derived from rao - scott chi - square test ( proc surveyfreq procedure ) .
the results of the multivariable logistic regression models for factors associated with the adherence to hcc screening tests are reported in table 3 . following adjustments for household income ,
smoking status , awareness of hbv infection , survey year , and individuals in higher income quartiles were more likely to have undergone recent hcc screening ( third quartile : adjusted or = 3.03 , 95% ci : 1.277.23 ; fourth quartile : adjusted or = 2.49 , 95% ci : 1.085.73 ) .
self - awareness of hbv infection was positively related to recent hcc screening ( adjusted or = 2.74 , 95% ci : 1.405.38 ) .
survey year 20102011 was associated with a significantly higher rate of recent hcc screening ( adjusted or = 3.37 , 95% ci : 1.955.81 ) .
regression models for adherence to hepatocellular carcinoma screening * based on weighted data ; based on unweighted data . crude and
adjusted ors ( 95% cis ) were calculated using logistic regression ( proc surveylogistic procedure ) . or : odds ratio ; ci : confidence interval ; knhanes : korea national health and nutrition examination surveys .
given the considerable burden and overall poor prognosis of hcc , early diagnosis through screening enables curative treatments , and , therefore , has the potential to reduce liver - related mortality .
it is important to investigate changes in the use of hcc screening to understand how screening is being conducted in practice following the introduction of a nationwide hcc screening program in korea .
this study revealed a significant increase in recent hcc screening from 2001 to 20102011 . in 2001 , only 17.5% of respondents had undergone hcc screening test ; however , 40.3% of hbv - infected participants had been screened for hcc within the preceding 2 years in 20102011 . this substantial increase in hcc screening
, the korean government has provided individuals at high - risk for developing hcc for free or with a 90% subsidy for hcc screening services .
however , no prominent increase in hcc screening among individuals with low household income was detected .
moreover , the participation rate of hcc screening in the low - income group remained low , even though screening services were offered free of charge by the ncsp .
hcc screening programs are different from those of other solid cancers , such as stomach , breast , cervical , or colorectal cancers , in that they target not a general population but a high - risk population .
therefore , omission from the target population might cause underuse of hcc screening tests among individuals in the low - income group . the target population for hcc screening in korea
first , the ncsp identifies the high - risk population for hcc among the lower 50% of nhi beneficiaries by screening a computerized medical claims database stored in the nhi corporation within the past 2 years .
the ncsp also analyzed serologic tests for hbsag and hcv antibody to identify the high - risk group among medicaid recipients .
therefore , individuals with hbv infection who had never undergone a health check - up might be missing from the target population group .
consequently , the opportunity to make use of free hcc screening services would have been lost in this missing population .
the lower participation rate among the low - income group may also have been due to their unawareness of hbv infection status , and lack of information regarding the nationwide cancer screening program and the benefits of hcc screening .
we also found that moderate - to - high household income , awareness of hbv infection status , and survey year were associated with increased use of recent hcc screening .
the association between household income and hcc screening in this study was similar to a previous report that participants with higher income were more likely to use hcc screening tests .
in general , individuals with higher household income are more likely to undergo screening for colorectal , gastric , breast , and cervical cancer . in addition , self - awareness of hbv infection
several reports have shown that awareness of hbv infection significantly affected participation in hcc screening programs . in this report ,
16.3% of hbv - infected participants aged 40 years were aware of their hbv infection status in 2001 .
however , the rate of infection awareness among hbv carriers 40 years of age was 21% in 20102011 , which was not significantly increased compared to that in 2001 .
these results imply that the identification of hbv - infected individuals among the general population group is important for hcc surveillance among hbv - infected persons .
therefore , to increase the low rate of hcc screening use , a national policy should encourage hbsag screening programs to identify hbv - infected persons , as well as improve patient adherence to hcc screening among hbv - infected individuals .
first , causal associations could not be examined due to the cross - sectional design .
second , this study defined recent hcc screening use as that performed within the previous 2 years to make uniform the measurement in the two survey periods .
the guidelines released jointly by the korean association for the study of the liver and the national cancer center recommended regular screening every 6 months on the basis of tumor doubling time .
therefore , the primary outcome in this study does not represent the recommended hcc screening criteria .
moreover , previous studies reported that the rate of participation in regular hcc screening ( every 6 months ) was lower compared to that of irregular or lifetime hcc screening .
nevertheless , this study that revealed relatively few participants had undergone recent hcc screening within the previous 2 years .
third , we relied on self - reported data to determine whether a subject had actually been screened and when the screening was performed .
therefore , this limitation does not seem to overstate our finding of underuse of hcc screening among the study population .
in korea , opportunistic screening is widely accessible , in addition to nationwide organized screening programs .
finally , other factors influencing hcc screening use , such as a family history of hcc , or replicative state of hbv , or other co - morbidities , were not investigated . despite these limitations , this study had several strengths .
first , it was the first to analyze changes in hcc screening rates following the implementation of organized , nationwide hcc screening programs among hbv - infected groups targeted for screening .
a substantial increase in hcc screening in hbv - infected individuals following implementation of the nationwide screening program provides lessons for government 's hcc screening policy in areas endemic for hbv .
second , we used data representative of the korean population . therefore , we could evaluate the nationwide change in the utilization of hcc screening .
third , we also identified potential factors related to underuse of screening . to improve the efficiency of national hcc screening program and
reduce socioeconomic disparities , identification of proper screening targets for active surveillance is a crucial step in hbv - endemic areas .
we anticipate that our results might bring about improvements in hcc screening of high - risk individuals . in conclusion ,
the rate of adherence to hcc screening within the past 2 years among hbv - infected korean people aged 40 years has more than doubled in 20102011 compared to 2001 . however , the hcc screening rate among the high - risk group remained suboptimal despite the implementation of a nationwide screening program .
household income and awareness of hbv infection were positively associated with hcc screening in this study population at high - risk for hcc .
these results suggest that multiple strategies , including encouragement for hbv - infected persons to attend hcc screening , as well as more efficient identification of hbv - infected subjects unaware of their infection , are urgently needed to maximize the advantages of hcc screening .
this study was supported by a research grant from the korean association for the study of the liver ( the research supporting program of the korean association for the study of the liver ) .
this study was supported by a research grant from the korean association for the study of the liver ( the research supporting program of the korean association for the study of the liver ) .
 background : evaluating a change in the screening rate for hepatocellular carcinoma ( hcc ) is critical for understanding screening implementation , and whether targeted population groups are receiving proper screening . 
 this study examined recent nationwide changes in hcc screening use among hepatitis b virus ( hbv)-infected populations after the introduction of the korean national cancer screening program and predictors of screening adherence.methods:we analyzed 165 and 276 participants 40 years of age who were hepatitis b surface antigen - positive from 2001 ( 14,936 participants ) to 20102011 ( 9159 participants ) korea national health and nutrition examination surveys , respectively . 
 demographic data , socioeconomic factors , and hcc screening use were collected by means of self - reported questionnaires.results:the rate of hcc screening within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 20102011 ( p < 0.0001 ) . 
 the rate of hcc screening use increased from 2001 to 20102011 in all study populations . 
 subjects who had a higher income status and were aware of their infection were more likely to have undergone recent hcc screening.conclusions:this study showed a substantial increase in hcc screening in high - risk hbv - infected subjects from 2001 to 20102011 . however , the hcc screening participation rate remained suboptimal despite the introduction of the nationwide screening program . 
 efforts should be made to identify high - risk individuals and increase attendance at hcc screening events among high - risk groups . 
I
M
Study population
Data collection
Statistical analysis
R
Baseline characteristics of the participants 40 years of age with hepatitis B virus infection
Rates of recent hepatocellular carcinoma screening tests within 2 years
Factor influencing hepatocellular carcinoma screening tests among hepatitis B virus-infected participants 40 years of age
D
Financial support and sponsorship
Conflicts of interest