Epidemiology of hepatitis B and hepatitis
C in Hong Kong
(adopted from Surveillance of Viral Hepatitis in Hong Kong
- Update report 2008)
CME : 1 point / CNE : 1 point / PEM : 1 point (Not direct midwifery-related
activity)
Similar to many other places worldwide, viral hepatitis is a notifiable disease in Hong Kong. Locally, voluntary reporting was started in as early as 1966 and, since 1974, the disease has become notifiable. It was not until 1988 that the reported cases are classified by viral aetiology, namely hepatitis A, hepatitis B, non-A non-B hepatitis and unclassified hepatitis. Since 1996, non-A non-B hepatitis is further categorized into hepatitis C, hepatitis E and hepatitis (not elsewhere classified). Under the current reporting system maintained by the Department of Health (DH), hepatitis A and B are defined by the presence of IgM anti-HAV and IgM anti-HBc respectively, whereas hepatitis C and E are diagnosed by positive tests for anti-HCV and anti-HEV.
Expectedly, virtually all of the notified cases were acute viral hepatitis. While the figures captured under the local system could be a good reflection of the acute disease burden of viral hepatitis, the extent of chronic infections resulting from some hepatitis, notably hepatitis B and C, has to be determined by other mechanisms. Insight of the epidemiology of various forms of hepatitis in Hong Kong can be gained by an analytical interpretation of regular statistics collected by health care or other institutions, and the information generated from designated studies. An annual viral hepatitis surveillance report attempts to present the latest findings from collation and analysis of viral hepatitis data obtained from the disease notification system, service statistics, seroprevalence studies and other research findings, notwithstanding the limitations posed by the nature and availability of data amongst others. This article extracts the situation of hepatitis B and C as gauged in the 2008 update report.
Parenterally-transmitted viral hepatitis B resulting in chronic infection state is endemic in Hong Kong. Nevertheless, the number of reported hepatitis B virus (HBV) infections has remained relatively stable over the last decade, with an apparent drop to 74 and 82 cases reported in 2007 and 2008 respectively, from about 150 a decade ago. Demographically, acute HBV infection is more common in male than female, and is most prevalent in the age range of 25-44 years old.
Determining the seroprevalence of HBV sheds light on how common the infection is in different communities, as well as informing its chronic disease burden. The various adult communities can be categorized into 3 groups according to their risk of contracting HBV: those (a) without apparent risk, (b) with undetermined risk, and (c) with apparent risk. Groups without apparent risk for which data in 2008 was available include blood donors, university students/staff, pre-marital screening attendees, antenatal women, police officers, new health care workers (HCW). Clients seeking post-exposure management and tuberculosis patients are those with undetermined risk. Drug users, HIV/AIDS patients and female sex workers are at apparent risk of contracting HBV related to risk behaviours.
A majority of the available seroprevalence data in different populations were limited to overall positivity rate of HBV markers. Still, temporal trend can be discerned as most have yearly data for the past decade or so. For groups with some demographic characteristics available, such as age and gender, further analyses have been made per the aggregate data. Several features on the current pattern of HBV could be observed from the serologic investigations, namely (a) chronic HBV infection is in a general declining trend, (b) HBV prevalence increases with increasing age, and (c) chronic HBV infection is commoner in male than female. A word of caution in the interpretation of data though, is that HBV testings had been performed for a variety of reasons in different communities, with heterogeneous mix of population characteristics which could certainly affect the findings.
The temporal decline of hepatitis B markers in most community groups without apparent risk was especially obvious in new blood donors. Its HBsAg prevalence follows a continual falling trend since early 1990s, to a record low of 1.8 % in year 2007 and 2008. There is also a falling trend over the years, albeit less prominent, in antenatal women. The HBsAg prevalence in antenatal mothers is confounded by the place of birth. A study of 2480 pregnant women attending the Maternal and Child Health Centre (MCHC) of DH in 1996 found a 13.1% in those born in Mainland China as compared to 8.4% in local mothers [1]. More recent data from Virus Unit, Department of Health also showed a higher prevalence of 12.5% and 13.8% in the subset of non-resident expectant mothers versus the overall positivity rate of 8.5% and 8.6% in 2004 and 2005 respectively. The HBsAg rates in university students/staff remains low (0 - 1.2%) in 2008. The prevalence in pre-marital package service users had increased slightly since 2001, to 6.4% in 2008. The prevalence in antenatal women however remained stable at 8.4 -9.2% since 2001. The demographic and geographic backgrounds of the clients in the community groups could have contributed to the difference in HBV prevalence elucidated. The prevalence in newly recruited health care workers as determined at pre-HBV vaccination screening showed a stable level in the last 3 years, at around 4-5%.
Of 3,485 tuberculosis patients who attended TB & Chest Clinics, Department of Health between March and May during 2006 to 2008, 341 (9.8%) were detected HBsAg positive, with the highest prevalence rate in the middle age group (40-59 years old; 14.6%) followed by the more elderly group (>= 60 years old; 8.7%). The HBsAg positivity rate was also found to be higher in male clients (11.4%) than in female (6.9%). Both the age and gender pattern were consistently observed in the last three years. Among clients attended for post exposure management, HBsAg rate was higher in non-health care workers than in health care workers, which may be partly explained by the success of pre-employment vaccination programme for health care workers. HBsAg prevalence in female sex workers attending the clinic of Action for REACH OUT, a non-governmental organization serving female sex workers in the last two years was 9.0 -10.4%, which is higher than the 6.8% found in the Social Hygiene Service survey a decade ago.
Compared with aforementioned groups, a higher HBsAg prevalence was generally noted in drug users and HIV-infected patients, underscoring their infection risk. Furthermore, due to the underlying immunosuppression, HIV/AIDS patients are more prone to becoming chronically infected with HBV after acute infection. Except for wide fluctuation in isolated years, HBsAg was present at 10-16% in these two groups of clients for the last decade, which was substantially higher than the 2-10% in other clients. However, caution is needed in interpreting the data in drug users for the last few years as its number tested for HBV markers dropped substantially since 2003 to only 7 in 2008.
For some groups, evidence supports age as an important correlate of HBV infection, with a higher proportion of the older population having viral markers or being chronically infected. From the 1996 to 2006 data in police officers, the HBsAg rate progressively increased with each 10-year age group, being 4.7% in <=20 years old and 9.1% in 51-60 years old subjects. Similarly, HBsAg positivity appears to be lower in antenatal women aged <19 years but not too different among older subjects.
The age effect was also evident in a screening of convenient samples among persons who underwent virologic investigations in 2001. HBsAg was absent in those below 10 years old, but was found to be >10% in those over 20 years old. Yet, anti-HBc was present, at a rate of 1.3% in subjects 1-4 years of age and rose to 7% in those 5-9 years old. In a similar testing of 573 sera left over from persons up to 19 years old after virologic investigation in 2004, HBsAg rate was found to be 0.5% (1-<5 years old), 0% (5-9 years old), 0% (10-14 years old) and 8% (15-19 years old). Convenient sample testing was repeated in 2006. Of 896 sera left over after virologic investigation, HBsAg rate among persons over 20 years old (n = 300; 14% tested positive in subjects of 20-24 years old, 10% in 25-29 years old, 12% in 30-34 years old, 8% in 35-39 years old, 5% in >39 years old) was found to be substantially higher than persons under 19 years (n = 596; 0-1%). HBsAg rate was consistently low among different age groups below age 20, i.e. 1% (1-4 years old), 0% (5-9 years old), 1% (10 -14 years old) and 1% (15-19 years old). The decrease in HBsAg rate for persons under 20 years old is likely attributed to the success of newborn HBV vaccination programme launched in 1988. A recently published study conducted in Tuen Mun Hospital provided added further evidence in this regard. Of 121 infants born to HBsAg positive mothers from November 2000 to June 2001 at TMH, only three (2.5%) became chronic HBV carriers at 12 months of age. One (0.8%) was suspected to be infected by the S-mutant [2].
Male had a higher HBV prevalence than female, again observed in several groups. In 2008, the HBsAg positivity rate among new blood donors was 2.3% in male and 1.5 % in female. From 1996 - 2006, the HBsAg rate in male police officer (6.6%) was higher than female police officer (4.0%). The 2001 community research programme on viral hepatitis (CRPVH) household study also showed that a higher overall HBsAg rate in male at 10.4% vs 7.7% in female.
Occurrence of new HBV infection is dependent on the interplay of multiple factors, including size of HBV pool, proportion of susceptible population and chance of exposure to the virus. It is likely that the circulating pool of HBV has reduced over the years in Hong Kong, thereby lessening the risk of exposure which can lead to acute infection. The reduced HBV pool in the community might have resulted from the universal vaccination programme for newborns, increased vaccination coverage in adults, practice of universal precaution in health care settings, predonation blood screening and promotion of safer sex [3].
A 16-year follow up study of 1112 neonates born to HBV carrier mothers who received HBV vaccine and hepatitis B immunoglobulin at different schedules demonstrated the long term protective efficacy of immunization [4]. Upon completion of the vaccination schedules, 92.6% developed antibody against surface antigen (anti-HBs) seroconversion. Only 39 (3.5%) babies were tested positive for HBsAg and had become chronic carriers, 35 of which occurred before one year of age. At the end of the 16th year, 610 subjects (54.9%) returned for blood test evaluation. Although the anti-HBs seroconversion rate dropped to 33.3% at the 16th year and a total of 96 (8.9%) vaccinees developed anti-HBc seroconversion, none was found to have breakthrough infection. Two hundred seventy-eight (25%) vaccinees were subsequently followed up at the 25th year [unpublished data]. The anti-HBs seroconversion rate was maintained at 37.1% at the 25th year. Although two and three subjects developed anti-HBc seroconversion at the 21st and 25th year respectively, no new HBsAg positive subject was detected. This finding suggests that the protective efficacy of immunization can be as long as at least 25 years. In another study of 2/3-doses HBV vaccine regimen without boosters to 318 HBV negative children recruited at age 3 months to 11 years and followed up annually, no subjects became HBsAg up to 18 years of follow up (88 subjects). A total of 88 anamnestic responses with significant increase in anti-HBs titers were documented in 70 subjects; 3 subjects had benign breakthrough HBV infection with isolated anti-HBc seroconversion [5].
Universal neonatal HBV vaccination programme has been in place in Hong Kong since 1988, and a supplementary Primary 6 vaccination programme was introduced in 1998. From the statistics collected and maintained by Family Health Services, DH, the coverage rate for first dose HBV vaccine was consistently above 99% over the years. However there is generally a drop of coverage rate in the second or the third dose. The drop in known post-first HBV vaccination coverage rate may be related to the fact that more local-births have returned to Mainland after delivery and did not attend MCHC for services, and also more babies received combined vaccine by private doctors and were not known to MCHC.
A community-based cross-sectional survey on immunization coverage was conducted by DH in year 2001 for 4746 children aged 2 to 5 recruited from 16 kindergartens and 8 child care centres, 99.2% of locally born children (3669, 88.67% of all) versus 95.2% of Mainland China born children (273, 6.6%) received a full course of HBV vaccination. A follow up survey using similar methodology was conducted by DH in year 2003 for 3345 children aged 2 to 5 recruited from 19 kindergartens and 8 child care centres [6]. The estimated full-course completion of HBV vaccine in yearly cohorts of local-born children (1997-2000) was 99.7-100%, as compared to 96.3-100% in the corresponding yearly cohorts of Mainland-born children. The survey on immunization coverage was repeated in 2006 with a larger number of participants [7]. Of 6720 children included in the final analysis, 89% were born in Hong Kong and 8% were born in the Mainland. These children were aged 2 to 5 at year 2006. Similar to previous survey result, very high HBV immunization coverage was recorded in both local-born and the Mainland-born children. The completion of 3-doses HBV vaccination among local-born children (who were born between 2000 and 2003) were 99.7 -100% versus 98.1 -100% of Mainland-born children who were born in the corresponding years.
In the last 10 years, the first dose coverage of the Primary 6 mop-up programme was consistently over 99.5% while that for the third dose is >98%. In the CRPVH 2001 study, about 16% of the telephone-interviewed subjects reported a history of HBV vaccination, with a higher frequency in persons below 50 years of age. Some 83% of them reported having completed the vaccination course. Over 99% had the cost paid by them or borne by their employers. Nonetheless, the persistent high HBsAg prevalence, though declining, means a significant disease burden in the years to come. Continued tracking of the trends of new infections and prevalent cases could inform more of the changing HBV situation in our locality.
Although HCV shares similar transmission routes with hepatitis B, the two infections may not be of equal prevalence in a locality, as what epidemiological data points to in Hong Kong. While HBV is still prevalent in many populations in Hong Kong, HCV prevails only in isolated communities from available evidence. Conceivably related to the different epidemiology, HCV has been of relatively less public health significance regarding chronic liver diseases when compared to HBV in Hong Kong. In a local study published in 1992, while 80% of 424 consecutive HCC patients attending a single centre were tested positive for HBsAg, only 7.3% were found to be anti-HCV positive [8]; the figure included 3.5% from HBV-HCV coinfection and 3.8% with HCV infection alone. Among 76 liver transplants done in Queen Mary Hospital due to cirrhosis from 1999 to 2000, 7 and 51 were related to hepatitis B and C respectively [9]. From 1996-2008, only 13 hepatitis C cases were reported to DH under the statutory notification system; four of which were reported in 2002, two and three cases in 2007 and 2008 respectively.
Data from new blood donors who were mostly adolescents and young adults in the last decade suggested that HCV infection is around 0.1% locally, with the figure in 2008 being 0.11% (95% confidence interval 0.078% - 0.144%). This is much lower than the known prevalence of HAV, HBV and HEV. Among new blood donors, anti-HCV was most commonly detected in the middle-age group (30-39 year-old group or > 49 year-old group in male; >49 year-old group in female). Findings of the household study of the entire spectrum of adult age groups conducted in 2001 further supported the uncommon scene of HCV infection among general population in Hong Kong; the overall positive rate was 0.3% in 936 subjects (95% confidence interval, 0.07%-0.94%). From 1999 to 2007, 3 of 700 (0.43%) clients who attended the Therapeutic Prevention Clinic (TPC) at Integrated Treatment Centre (ITC) of CHP, DH for post-exposure management were tested positive for anti-HCV at 6 months. All 3 cases were non-HCW and already HCV infected at time of injury upon retrospective testing of baseline specimens.
Experience of clinicians and virologists has previously confirmed that HCV was common in injecting drug users (IDU, 66.8%), haemophilia (56%), haemodialysis (4.6%) and other patients requiring frequent blood/blood product transfusions but not persons at risk through sexual contact [10]. Another early 1990s study conducted for 51 haemodialysis patients found that 8 (16%) were positive for anti-HCV by second generation enzyme immunoassay and 1 (2%) for HCV RNA alone, giving an overall infection rate of 18% [11]. This study also found a new infection rate of 4.9% per patient-year upon longitudinal follow up of 19 months. Results of testing non-random samples from drug users under treatment showed a HCV positive rate of 74% in 1988/1989 and 46% in 2000/2001. A more recent HCV seroprevalence study conducted in methadone clinics targeting injecting drug users echoed the high prevalence rate of HCV in this community [12]. Of 567 IDU recruited in 2006, 84% were male and 98% were ethnic Chinese. The median age was 49 years and median injection duration was 17 years. Two-thirds (62%) admitted ever sharing injecting equipments. Prevalence of anti-HCV was 85% (95% confidence interval 82.5 - 88.3%). Injection duration, recent injection, ever sharing injecting equipments and concomitant use of other drugs were independent factors associated with HCV infection.
HIV/AIDS patients, with a proportion being IDU, is another group with consistent data showing a comparatively high HCV prevalence. From 2000 to 2008, HCV-HIV coinfection among new patients attending ITC ranged from 8% to 26%. The prevalence rate appears to be higher in male than female patients, likely related to the differential risk of parenteral and blood product exposure. While HCV infection is present in 1.5 - 6 % of HIV/AIDS patients infected due to sexual contact, HCV was nearly universal in patients infected through drug injection. The higher HCV prevalence, coupled with the hastened liver disease progression in HIV-infected patients [13], would no doubt result in a unique HCV/HIV co-infection that demands attention.
Limited genotypic studies in Hong Kong has identified that 1b and 6a were the prevalent HCV genotypes locally, a scenario different from that in western countries where 1a predominated [14]. In an early study of 212 blood donors tested anti-HCV positive from 1991 to 1994, the commonest genotype found was 1b (58.8%), followed by 6a (27.0%) [15]. A significantly greater number of donors infected with type 6a reported a history of drug abuse than those infected with type 1b. In a study of hospitalized patients with HCV testing for clinical indications, similar to the blood donors study, 1b was the commonest type in chronic liver diseases and chronic renal failure patients [16]. Yet, the commonest genotype in intravenous drug users was 6. A retrospective analysis of 106 intravenous drug users and 949 non-drug users with samples collected between December 1998 and May 2004 also confirmed the significant high prevalence of genotype 6a in drug users (58.5%) followed by 1b (33.0%), in contrast to 63.6% for 1b and 23.6% for 6a in non-drug users [17]. Besides intravenous drug use, age and sex were independent factors associated with HCV genotypes in this study. In the methadone clinic-based study in 2006, of 273 IDUs, 52% had genotype 6a, 38% had 1b and 5% 3a while others had genotypes 2a, 3b and 6h [18]. Another local study of renal failure patients and non-renal failure controls also showed the predominance of genotype 1b, followed by 1a and 6a [19].
Since 2003, a surveillance project has been piloted to enhance understanding of the HCV situation in Hong Kong, with the participation of the laboratories of Hong Kong Red Cross Blood Transfusion Service (HKRCBTS) and Princess Margaret Hospital Department of Microbiology. Prince of Wales Hospital joined the project in 2005. Some 180,000-210,000 new and repeat blood donors of HKRCBTS were tested for anti-HCV each year; the prevalence was consistent at 0.018% in 2006, 0.020% in 2007 and 0.025% in 2008. The overall anti-HCV prevalence detected in hospital patients tested over the last six years was 3.8%. The highest anti-HCV rate was in drug users, of which 44.3% were found positive. This was followed by patients with history of blood transfusion at about 9.8%, and patients done for clinical indication (4.5%) not falling under the standardised categorisation of screening. Overall, the male-to-female ratio of HCV positive subjects was about 2 to 1, with a mean age of 47.7 years old.
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