INTRODUCTION
Hepatitis A virus (HAV) causes around 80% of acute hepatitis in South Korea and its clinical manifestation is mild in children but is severe in many adults.
1 The number of cases of hepatitis A reported to Korea Centers for Disease Control and Prevention increased sharply from 798, 2,081 and 2,233 in 2005, 2006 and 2007, respectively to 7,895 and 15,231 in 2008 and 2009, respectively.
2 These are data from surveillance reporting system, while the numbers of claims actually made to National Health Insurance Cooperation are at least 3-4 times higher than them. However, this increase of symptomatic hepatitis in adults does not mean the increase of infection rate of HAV around the nation. Before 1990, most Koreans were infected with HAV before they were in their 20s and over 90% of the public already had protective antibodies in their 20s, so the incidence rate of symptomatic hepatitis A in adult population was low. With the improvement of the sanitary condition associated with the current economic development, the nationwide infection of HAV was reduced significantly while young adults and adolescents aged less than 40 years became more vulnerable to the infection because most of them do not have the protective antibody following natural infection. As the clinical manifestation of hepatitis A tends to be mild in children but severe in about 80% cases of adults, the cases of severe symptomatic hepatitis A are felt to be raised in recent years.
The current epidemic of hepatitis A was observed mainly in Seoul, Gyeonggi and Incheon and it spreads around the nation.
1,
3 Although the patients are usually in their 20s and 30s, the number of symptomatic hepatitis patients aged over 40s has been increasing these days. Epidemiological studies on the prevalence of hepatitis A antibody (anti-HAV) have been conducted continuously since the late 1990, but most of them investigated limited areas, had a small number of subjects or were performed for a short period and there have not been sufficient researches examining the nationwide antibody positive rates by year and age. Therefore, the authors analyzed the results of 45,296 hepatitis A antibody tests from Seoul Clinical Laboratories (SCL) requested by 1,699 medical institutions around the nation for the last five years, to determine total anti-HAV positive rates by year, age and area. Moreover, it obtained age- and area-adjusted anti-HAV positive rates with the population in 2005 Census as a standard population.
DISCUSSION
This study investigated area- and age-adjusted anti-HAV positive rate from 2005 to 2009 by analyzing the results of totally 25,140 cases of anti-HAV test from one central laboratory requested by 1,699 medical institutions around the nation. Although the nationwide anti-HAV positive rates were not largely different from 62.5% in 2005 to 60.7% in 2009, the rates by area and age changed dynamically. The antibody positive rate of the young children aged less than 10 years increased sharply in the capital area for the recent five years, and the age which was the most vulnerable to hepatitis A infection was found to be 20s years with the seroprevalence rate of 11.9% which was followed by 10s years having the rate of 23.4%. The seropositive rates of the persons in their 30s and 40s were 48% and 89%, respectively, and particularly the rate of the persons in their 40s in Seoul was reduced to 80%.
In South Korea, anti-HAV positive rate had been over 50% in the persons in their 10s and it had reached nearly 100% in adults in the 1970s and the early 1980s, but it reduced remarkably from the 1990s by recording 54% in the personsaged 21-25 years in the late 1990s and 20-23% and 40-42% in the personsaged 10-24 years and 25-30 years, respectively in Seoul and Gyeonggi in the mid 2000s. The overall decrease of the antibody positive rate was found to move to older age.
4-
7 This tendency was observed in other countries such Spain, Greece and Israel.
8-
10 This epidemiological change could show a regional difference between urban and rural areas and the difference by income level was also reported. It was also found in developing countries including the Middle East, China and Central and South America and a study conducted in Bangladesh revealed that income level provoked the epidemiological difference.
11-
14 In South Korea, Song et al. reported that the anti-HAV positive rates of the persons in their 20s and 30s (25.6%) were significantly lower in Seoul than in other areas (55.6%) in 2007, but Kim et al. did not find any significance difference in the rate between Seoul and Gyeonggi in 2007.
5,
7 The study of Song et al. revealed that the positive rate of particularly Gangnam in Seoul was lower (20.0%) in the persons aged less than 40 years compared to the rate of other areas (55.6%). However, the number of the subjects in their study was not sufficient to compare the difference in the antibody positive rates by nationwide area and there has been no study on age- and area-adjusted rates based on Census in South Korea.
5
The subjects of this study were 25,140 patients out of 45,296 for whom anti-HAV test were done by 1,699 medical institutions around the nation by excluding 20,156 ones for whom total anti-HAV test was requested along with IgM anti-HAV test because some of them could be acute hepatitis A patients. However, on what purposes the 25,140 subjects underwent total anti-HAV could not be defined, which was a limitation of this study. Medical institutions having asked SCL to conduct the antibody tests consist of hospitals or higher institutions in 55%, clinics in 30% and public health centers and others in 15%. As the cases of hepatitis A went up dramatically in 2008 and 2009, the public interest in the disease also increased to raise cases requesting the test by year.
This study calculated nationwide area- and age-adjusted hepatitis A antibody positive rates with 2005 Census, the latest population survey as a standard. However, the number of cases of the test by area and year was not sufficient to obtain standardized positive rates by administrative districts, so the whole nation was arbitrarily divided into five areas- Seoul, Incheon/Gyeonggi/Gangwon, Chungcheong, Gyeongsang and Honam/Jeju. As the antibody positive rate by gender was not significantly different in each age group and in each area, adjustment by gender was not applied. In addition, because this study examined the antibody positive rate of patients visiting hospitals rather than general population, their positive rate was likely to be lower than that of the general population and that can be a limitation of this study.
According to the result of this study, the antibody positive rate of the young children aged less than 10 years around the nation doubled from 33% in 2005 to 70% in 2009 and especially the increase was the largest in the capital area including Seoul. Vaccination against hepatitis A focusing on children had been conducted from 1997 and then the vaccination mainly for infants have been done. When the imported dose of hepatitis A vaccine for the last five years was examined, the vaccines for young children increased from 290,000 doses in 2005 to 400,000 doses in 2007, and 880,000 doses in 2009, while vaccine dose for adults were raised from 10,000 doses in 2006 to 20,000 in 2008 and 620,000 doses in 2009. Even though some vaccines for children were administered to adults due to the insufficient supply of vaccines for adults following the rapid increase of incidences hepatitis A in adults for the last three years, the numbers of vaccines for children are considered to show a continuous increase. Because children conventionally play an important role in the transmission of HAV and the vaccination for children reduced the adult cases of hepatitis A outstandingly in the U.S., Israel and Chile, it is considered that universal vaccination against hepatitis A for children should be recommended in South Korea.
The persons in their 10s and 20s were found to be the most vulnerable to the infection of HAV with the lowest antibody positive rates from 2005 to 2009. In 2009, the positive rate of the persons in their 20s recorded the lowest level (12%) and it was followed by that of the persons in their 10s (23%), which was not significantly different by area. In the meantime, although the total antibody positive rate of the persons in their 30s was 48%, the rates by area were different significantly (39%, 69% and 48% in Seoul, Honam/Jeju and other areas, respectively).
In particular, the positive rate of the persons in their 40s was lower in Seoul than in other areas. Therefore, even in persons in their early 40s living in the capital area becomes at risk of HAV infection although they have been thought to be relatively safe from the risk. The mortality rate of hepatitis A becomes higher at older age and the mortality rates of the persons in their 30s, 40s, 50s and 60s are estimated to be 0.04-0.06%, 0.03-0.1%, 0.08-0.23% and 0.58%, respectively.
15 Moreover, Kim et al. reported that factors affecting the severity with 716 patients with hepatitis A were hepatitis B virus carriers, history of alcohol drinking and old age.
16
In the U.S., around 200,000 cases of hepatitis A occurred to the mid 1990s and the cyclic epidemic with a cycle of 10-15 years, but an active vaccination for children from 1996 reduced its incidences considerably.
17 However, in South Korea the vaccination rate against hepatitis A for children reaches 50-70%, which suggests the possibility of food-born transmission rather than children as a major source of infection. So, catch-up vaccination for the persons aged 10-29 years with a low antibody positive rate needs to be considered. The outstanding increase of vaccines for adults as well as those for children during recent years seems to be closely related with the decreased incidences of hepatitis A since 2010. Saab et al. insisted that if hepatitis A antibody positive rate was over 35% and anti-HAV test cost less than 25 U.S. dollars, vaccination without testing the antibody was cost-effective than vaccination after testing.
18 Therefore, it is reasonable that persons aged less than 30 years undergo HAV vaccination without the antibody test while those aged over 30 years do after the test, but there have not been sufficient studies on the cost-effectiveness. Moreover, as this study found that the antibody positive rates were different by area and the seroprevalence rates of the persons in their 30s varied by area from 39% to 69%, the vaccination and the test should be conducted by considering the regional difference.
In conclusion, the hepatitis A antibody positive rate has changed rapidly in Korea for the last five years, and to prevent the nationwide spread of the hepatitis A, universal vaccination for children should be adapted and continuous monitoring and epidemiological studies are necessary.