hepatitis a is an infectious disease caused by the hepatitis a virus ( hav ) , which is transmitted by the fecal - to - oral route , and a one - time infection can provide lifelong immunity ( 1 ) . the disease typically presents as a mild disease with no overt clinical features in children , but the severity of disease increases with age . it tends to show more severe symptoms such as persistent jaundice and fulminant hepatitis in the elderly and patients with underlying liver diseases ( 23 ) . the distribution of hepatitis a is uneven according to geographical region and population group ; the epidemiology of hepatitis a is closely related to socioeconomic factors ( 4 ) . hav infection is more prevalent in low socioeconomic areas where a lack of sanitation and poor hygiene facilitate spread of the infection . improvements in sanitation and living standards are contributing to a change in the epidemiology of the viral disease ( 5 ) ; this is the case in korea . the decrease in hav infection in young children has resulted in the reduction in the seroprevalence of anti - hav igg , with a corresponding increase observed in the adult population ( 6 ) . as a result , since the 2000s , hepatitis a has taken over from hepatitis b as the leading cause of viral hepatitis in the adult population in korea ( 7 ) . in 2009 , the incidence of hepatitis a peaked and a total of 15,231 cases were reported to the korea centers for disease control and prevention ( kcdc ) . although the number of reported cases has decreased from 2010 onwards , considering the importance of hav infection to public health , the kcdc designated hav infection a national notifiable infectious disease and , for effective control , is going to add hepatitis a to the national vaccination program for children , beginning may 2015 . the aim of the present study was to describe the current status and regional differences in the incidence rate of hepatitis a in korea . hav was designated a national notifiable infectious disease in 2001 and a surveillance system based on sentinel hospitals was established . since 2011 , the surveillance system has been expanded to every hospital and all hav infection cases are mandatorily reported by physicians to the kcdc through the national infectious diseases surveillance ( nids ) system . these reported cases have the typical symptoms of acute hepatitis , which include the presence of anti - hav serum igm or a positive reverse - transcription polymerase chain reaction result . the data from the nids system includes demographic data such as gender , age , and residence of each patient ; disease onset ; and prognosis . we also used international classification of disease b15 ( icd ) data from the national health insurance review and assessment service ( hira ) to identify the trend of hav infection from 2002 to 2013 . in addition , we used national population data from statistics korea for estimating the incidence rates of hav infection according to age , gender , and administrative district , and investigating the demographic factors associated with regional differences in incidence . the incidence rate of hav was presented by : years and months ; patient age and gender ; and county level administrative districts . for estimating incidence rate , we used national statistical data , which stratified the total population by age , gender , and county level administrative districts . the incidence rates were imputed into the biogeographical information system software program diva - gis 7.5 to evaluate the distribution of hepatitis a by each county . a total of 251 county level administrative districts were used as the spatial unit of analysis . to assess the overall spatial correlation , moran 's index ( i ) was calculated for the distribution of hepatitis a incidence rate using the r statistical package ( institute for statistics and mathematics , vienna , austria , v3.1.2 moran 's i is a measure which enable the detection of the spatial autocorrelation for a county with its adjacent county . the values range from -1 ( indicating perfect dispersion ) to + 1 ( perfect correlation ) . cluster analysis was performed using the spatial and space - time scan statistic ( satscan ) software , version 9.0 ( martin kulldorff , boston , ma , usa ) , which uses a continuous poisson model to find hotspot of hav infection . satscan literally scans across the study region with varying sized candidate area ( scan window ) . for each window , the likelihood ( here based on poisson distribution for counts data ) is calculated and the candidate area with the maximum likelihood defines the most likely cluster and so on . hav was designated a national notifiable infectious disease in 2001 and a surveillance system based on sentinel hospitals was established . since 2011 , the surveillance system has been expanded to every hospital and all hav infection cases are mandatorily reported by physicians to the kcdc through the national infectious diseases surveillance ( nids ) system . these reported cases have the typical symptoms of acute hepatitis , which include the presence of anti - hav serum igm or a positive reverse - transcription polymerase chain reaction result . the data from the nids system includes demographic data such as gender , age , and residence of each patient ; disease onset ; and prognosis . we also used international classification of disease b15 ( icd ) data from the national health insurance review and assessment service ( hira ) to identify the trend of hav infection from 2002 to 2013 . in addition , we used national population data from statistics korea for estimating the incidence rates of hav infection according to age , gender , and administrative district , and investigating the demographic factors associated with regional differences in incidence . the incidence rate of hav was presented by : years and months ; patient age and gender ; and county level administrative districts . for estimating incidence rate , we used national statistical data , which stratified the total population by age , gender , and county level administrative districts . the incidence rates were imputed into the biogeographical information system software program diva - gis 7.5 to evaluate the distribution of hepatitis a by each county . a total of 251 county level administrative districts were used as the spatial unit of analysis . to assess the overall spatial correlation , moran 's index ( i ) was calculated for the distribution of hepatitis a incidence rate using the r statistical package ( institute for statistics and mathematics , vienna , austria , v3.1.2 , www.r-project.org ) . moran 's i is a measure which enable the detection of the spatial autocorrelation for a county with its adjacent county . the values range from -1 ( indicating perfect dispersion ) to + 1 ( perfect correlation ) . cluster analysis was performed using the spatial and space - time scan statistic ( satscan ) software , version 9.0 ( martin kulldorff , boston , ma , usa ) , which uses a continuous poisson model to find hotspot of hav infection . satscan literally scans across the study region with varying sized candidate area ( scan window ) . for each window , the likelihood ( here based on poisson distribution for counts data ) is calculated and the candidate area with the maximum likelihood defines the most likely cluster and so on . data from the hira service revealed that hepatitis a cases had increased from 2005 , reached a peak in 2009 , and had then decreased from 2010 over the next 4 yr . a similar pattern was found in data from the kcdc sentinel surveillance system between 2002 and 2010 . hepatitis a incidence have decreased continuously since 2011 , the year when the surveillance system was expanded to every hospital . a total of 7,585 cases of hav infection were reported through nids system between 2011 and 2013 ; 5,521(10.9 cases per 100,000 populations ) , 1,197 ( 2.3 cases per 100,000 populations ) , 867 ( 1.7 cases per 100,000 populations ) cases were reported in 2011 , 2012 , and 2013 respectively ( fig . fifty - eight patients were infected outside of the country and 7,527 patients represented autochthonous hav infection cases . autochthonous hav infection occurred more frequently among men than among women ( 4,619 cases , 6.1 cases per 100,000 population vs. 2,908 cases , 3.9 cases per 100,000 population ) . the incidence rate was highest in the 20 - 29 yr - old group ( 2,309 cases , 11.6 cases per 100,000 population ) and the 30 - 39 ( 3,306 cases , 13.6 cases per 100,000 population ) yr age groups ; they accounted for 88.6% ( 5,616/7,527 ) of total cases . higher incidence rate was shown in the metropolitan area compared to the non - metropolitan area ( 3,525 cases , 5.1 cases per 100,000 population vs. 4,002 cases , 4.9 cases per 100,000 population ) ( table 1 ) . autochthonous hepatitis a incidence reached a peak in march of each year ( 14.5% , 1,089/7,527 ) , and the majority of cases were reported from march to june of each year ( 53.6% , 4,038/7,527 ) ( fig . the incidence rates of hav infection in the various administrative districts of korea ranged from 0 to 21.9 cases per 100,000 residents . the incidence rates of hav infection for each administrative district and the results of the spatial scan statistics are shown in fig . 3 and fig . five clusters with higher risk for hav infection were found and the relative risks ( rr ) were determined as 3.90 in cluster 1 ( p<0.001 ) ; 1.43 in cluster 2 ( p=0.046 ) ; 2.88 in cluster 3 ( p<0.001 ) ; 1.25 in cluster 4 ( p=0.019 ) ; and 2.13 in cluster 5 ( p<0.001 ) . one cluster(cluster 6 ) was found in 2012 ( rr=2.35 , p<0.001 ) and two clusters ( cluster 7 and 8) were found in 2013 ( rr=6.40 , p<0.001 ; rr=1.86 , p<0.001 , respectively ) . geographic analyses revealed a consistently high relative risk of hav infection in mid - western regions ( clusters 4 , 6 , and 8) ( fig . data from the hira service revealed that hepatitis a cases had increased from 2005 , reached a peak in 2009 , and had then decreased from 2010 over the next 4 yr . a similar pattern was found in data from the kcdc sentinel surveillance system between 2002 and 2010 . hepatitis a incidence have decreased continuously since 2011 , the year when the surveillance system was expanded to every hospital . a total of 7,585 cases of hav infection were reported through nids system between 2011 and 2013 ; 5,521(10.9 cases per 100,000 populations ) , 1,197 ( 2.3 cases per 100,000 populations ) , 867 ( 1.7 cases per 100,000 populations ) cases were reported in 2011 , 2012 , and 2013 respectively ( fig . fifty - eight patients were infected outside of the country and 7,527 patients represented autochthonous hav infection cases . autochthonous hav infection occurred more frequently among men than among women ( 4,619 cases , 6.1 cases per 100,000 population vs. 2,908 cases , 3.9 cases per 100,000 population ) . the incidence rate was highest in the 20 - 29 yr - old group ( 2,309 cases , 11.6 cases per 100,000 population ) and the 30 - 39 ( 3,306 cases , 13.6 cases per 100,000 population ) yr age groups ; they accounted for 88.6% ( 5,616/7,527 ) of total cases . higher incidence rate was shown in the metropolitan area compared to the non - metropolitan area ( 3,525 cases , 5.1 cases per 100,000 population vs. 4,002 cases , 4.9 cases per 100,000 population ) ( table 1 ) . autochthonous hepatitis a incidence reached a peak in march of each year ( 14.5% , 1,089/7,527 ) , and the majority of cases were reported from march to june of each year ( 53.6% , 4,038/7,527 ) ( fig . the incidence rates of hav infection in the various administrative districts of korea ranged from 0 to 21.9 cases per 100,000 residents . the incidence rates of hav infection for each administrative district and the results of the spatial scan statistics are shown in fig . 3 and fig . five clusters with higher risk for hav infection were found and the relative risks ( rr ) were determined as 3.90 in cluster 1 ( p<0.001 ) ; 1.43 in cluster 2 ( p=0.046 ) ; 2.88 in cluster 3 ( p<0.001 ) ; 1.25 in cluster 4 ( p=0.019 ) ; and 2.13 in cluster 5 ( p<0.001 ) . one cluster(cluster 6 ) was found in 2012 ( rr=2.35 , p<0.001 ) and two clusters ( cluster 7 and 8) were found in 2013 ( rr=6.40 , p<0.001 ; rr=1.86 , p<0.001 , respectively ) . geographic analyses revealed a consistently high relative risk of hav infection in mid - western regions ( clusters 4 , 6 , and 8) ( fig . in this nationwide study of hav infection in korea , various analyses including spatial analyses , such as moran 's i and satscan , were applied to the nationwide data collected from 2011 to 2013 in order to determine the present epidemiologic status of hav infection . the data suggested that the prevalence of hepatitis a has been decreasing gradually since 2010 and the population group at risk for acquiring the disease was young males in their twenties or thirties who are living in cluster regions . through nids system , the kcdc has investigated the number of hepatitis a cases since 2001.the number of reported cases increased sharply until 2009 ; only 106 cases were reported in 2001 , followed by 2,081 cases in 2006 , 2,233 cases in 2007 , 7,895 cases in 2008 , and 15,231 cases in 2009 . in 2010 , the number of reported cases was 7,655 and with this , the hav infection incidence rate seemed to take a downward turn despite of the expansion of the surveillance into whole hospitals since 2011 . we also conduct additional analysis with the data from the hira in order to reconcile the trend of hav infection between 2002 and 2013 . according to the analysis of data from the hira , the number of hepatitis a patients increased continuously until 2009 and decreased rapidly since 2010 . however , in the present study , we can find much higher incidences in hira data than those in nids system . in the hira database , a reimbursement claim for hav diagnosis is made when an examination has been performed because the infection is suspected , and not definitely diagnosed . therefore , unlike data from nids system , data from the hira include many suspected cases that lack laboratory confirmation and the number of patients with hav infection may be overestimated . our study showed that young adults aged 20 - 40 yr old were the age group with the highest risk for symptomatic hav infection . previously , hepatitis a had been mostly detected in children under 10 yr of age in korea ( 389 ) . however , the number of infections in early age has decreased in accordance with socioeconomic development and this results in a low anti - hav antibody seroprevalence rate among young adults . other recent studies in korea have also shown that the age group most at risk for infection was the 20 - 40 yr - old age group ( 378910 ) . anti - hav antibody seroprevalence rates reflect vulnerability to hav infection in a certain population group ; therefore , epidemiologic change patterns can be predicted through the analysis of anti - hav antibody seroprevalence rate changes . in fact , the seroprevalence data of many asian countries that have experienced rapid socioeconomic progress coincide with epidemiologic shift patterns ( 11 ) . in korea , the rates of seropositivity for the period 1979 - 1981 were as follows : 46.6% for 1 - 9 yr - olds ; 86.4% for 10 - 19 yr - olds ; 96% for 20 - 29 yr - olds ; and 100% among people > 30 yr old ( 12 ) . in 1989 , lim et al . reported that the anti - hav seropositivity in koreans according to age was : 27% for 1 - 9 yr - olds ; 76% for 10 - 19 yr - olds ; and 95.3% for 20 - 29 yr - olds ( 13 ) . in 1997 , however , sohn et al . ( 6 ) reported that an anti - hav antibody seroprevalence rate of only 8% was observed among teenagers ( 10 - 19 yr old ) . a study conducted in the guri city from 2001 to 2013 revealed that the seroprevalence of igg anti - hav in the late 2000s had increased compared with the early 2000s : 66% for 1 - 9 yr - olds ; 34% for 10 - 19 yr - olds ; and 18% for 20 - 29 yr - olds ( 8) . considering the total sales of hav vaccine products and the high vaccination rate ( about 40% ) among children aged 1 - 2 yr in 2006 , the results of the guri city study seems to be the effect of the vaccination against hav which began in 1997 ( 10 ) . the higher prevalence in males has been reported in many of the previous studies not only in korea ( 389 ) , but also in many other countries ( 14151617 ) . however , the exact cause that leads to this difference in gender prevalence is still not known . the incidence rate of hepatitis a peaked during the months march to june , which is consistent with that reported by previous studies conducted in korea ( 79 ) . in hong kong , which is located near korea , a higher hepatitis a incidence was reported during spring to early summer ( 17 ) . in contrast to this , there were no seasonal differences reported in the studies conducted in greece and the united states ( 1819 ) . first , the analyzed data includes only patients who were diagnosed at health care institutions . second , the laboratory systems for detecting hav infection in each hospital were not standardized . the spatial disparity of incidence rate might be the result of differing reporting rates by areas . finally , this study uses population data , and it does not integrate personalized data . therefore , it does not take into account personal characteristics or dynamic factors such as population movement . fortunately , the kcdc is going to initiate a hepatitis a national vaccination program for children beginning may 2015 . however , the majority of young adults at present who have not yet experienced hav infection , and who did not receive a vaccination are still vulnerable to hepatitis a. therefore , effective hav control and prevention strategies for young adults , especially young males in their 20s and 30s who are living in cluster regions are also necessary .
the hepatitis a virus ( hav ) has been the leading cause of viral hepatitis in korea since the 2000s . 
 we aimed to describe the current status and regional differences in hepatitis a incidence . 
 we studied the total number of hepatitis a cases reported to the korea centers for disease control and prevention through the national infectious diseases surveillance system between 2011 and 2013 . additionally , national health insurance review and assessment service data and national population data from statistics korea were used . in total , 7,585 hepatitis a cases were reported ; 5,521 ( 10.9 cases per 100,000 populations ) , 1,197 ( 2.3 cases per 100,000 populations ) , and 867 ( 1.7 cases per 100,000 populations ) in 2011 , 2012 , and 2013 , respectively . 
 fifty - eight patients were infected outside of the country and 7,527 patients represented autochthonous hav infection cases . 
 autochthonous hav infection occurred more frequently among men than women ( 4,619 cases , 6.1 cases per 100,000 population vs. 2,908 cases , 3.9 cases per 100,000 population ) . 
 the incidence rate was higher in the 20 - 29 yr - old group ( 2,309 cases , 11.6 cases per 100,000 populations ) and 30 - 39 yr - old group ( 3,306 cases , 13.6 cases per 100,000 populations ) . 
 the majority of cases were reported from march to june ( 53.6% , 4,038/7,527 ) . 
 geographic analyses revealed a consistently high relative risk ( rr ) of hav infection in mid - western regions ( 2011 , rr , 1.25 , p=0.019 ; 2012 , rr , 2.53 , p<0.001 ; 2013 , rr , 1.86 , p<0.001 ) . in summary , we report that hepatitis a incidence has been decreasing gradually from 2011 to 2013 and that some regions show the highest prevalence rates of hav infection in korea .