Background

The World Health Organization estimated that about 3% (170 million) of the global population is infected with hepatitis C.¹ Every year, there are three to four million new infections. Hepatitis C is caused by hepatitis C virus (HCV), a small (40 to 60 nanometers in diameter), enveloped, single-stranded RNA virus of the family Flaviviridae and genus Hepacivirus. There are at least six major genotypes and more than 50 subtypes of HCV. The different genotypes have different geographic distributions.²

Hepatitis C is a major cause of chronic liver disease, including cirrhosis and liver cancer. Injecting drug use has been found to be the most common risk factor for contracting HCV after the introduction of screening for HCV for blood donation in many countries and regions including Hong Kong. The Centers for Disease Control and Prevention (CDC) of the United States (US) estimated that injecting drug use is the risk factor in 60% of patients with HCV infection, followed by sexual contact (15%), transfusion before donor screening (10%), others, viz haemodialysis, health care work and perinatal transmission (5%), and unknown (10%).³ The incubation period of HCV infection ranges from 15 to 150 days. In acute infection, the most common symptoms are fatigue and jaundice. Less than 30% of acute infection is symptomatic⁴ and about 80% of the cases will progress to chronic infection, which is substantially higher than that of hepatitis B infection.⁵ However, HCV is of relatively less significance regarding chronic liver disease when compared to hepatitis B virus (HBV) in Hong Kong. In a local study, 7% of hepatocellular carcinoma patients were found to be anti-HCV positive.⁶ The figure included 3% from HBV-HCV coinfection and 4% with HCV infection alone.

Local Epidemiology

From 1996 to 2004, only five hepatitis C cases were reported to the Department of Health (DH) under the statutory notification system, four of which were reported in 2002 and one case in 2004. The five Chinese patients (2 males and 3 females) aged between seven to 62 years. While one patient had a history of injecting drug use, the route of transmission could not be established in the remaining four patients.

One early study in 1988 reported a prevalence of hepatitis C of 0.5% in 382 individuals who attended a health exhibition.⁷ Amongst clinical subjects recruited from an outpatient liver clinic, sexually transmitted disease clinics, dialysis centres and drug rehabilitation centres, prevalence of hepatitis C was highest in parenteral drug abusers (66.8%), followed by haemophilia patients (56%) and haemodialysis patients (4.6%). None of the persons at high sexual risk and partners of HCV patients were tested positive. The study concluded that parenteral and blood product exposures were the two main risk factors for hepatitis C in Hong Kong.

From 1991 to 2004, the annual HCV prevalence in new donors as detected by the Hong Kong Red Cross Blood Transfusion Service (HKRCBTS) ranged from 0.035% to 0.1%, with no definite temporal trend. However, knowingly the donor population is biased towards young, healthy adults who are free from known blood-borne diseases. Another study conducted in 2001 recruited Chinese adults aged 18 years or above through a household telephone survey also showed the low prevalence of HCV infection in the community.⁸ Of 936 subjects recruited and consented for blood screening for hepatitis C, only three of them (0.3%, 95% confidence interval: 0.07%-0.94%) were confirmed anti-HCV positive.

Studies on drug users recruited from methadone clinics of the DH and other drug treatment centres found a prevalence of 46%-74% of HCV infection among the group in the period of 1988-2001. HIV/AIDS patients, with a proportion being injecting drug users, are another group with data showing a comparatively high HCV prevalence. From 2001 to 2004, about 8-18% of new HIV/AIDS patients attending Integrated Treatment Centre of the DH each year were HCV infected (Table 1). It appears that the prevalence is higher in male than female patients, which may be related to the differential risk of injecting drug use.

Table 1 Anti-HCV Prevalence in New HIV/AIDS Patients, 2001 - 2004

Year	Male		Female		Total
	No. tested	Anti-HCV + (%)	No. tested	Anti-HCV + (%)	No. tested	Anti-HCV + (%)
2001	71	7 ( 9.9%)	23	1 ( 4.3%)	94	8 ( 8.5%)
2002	118	10 ( 8.5%)	22	1 ( 4.5%)	140	11 ( 7.9%)
2003	87	14 (16.1%)	13	0 ( 0.0%)	100	14 (14.0%)
2004	107	20 (18.7%)	21	3 (14.3%)	128	23 (18.0%)

Limited genotypic studies in Hong Kong have identified that 1b, 6a and 1a are the prevalent HCV genotypes locally, a scenario different from that in western countries.⁹ In a study of 212 blood donors tested anti-HCV positive from 1991 to 1994, the commonest genotype was 1b (58.8%), followed by 6a (27.0%).¹⁰ A significantly greater number of donors infected with genotype 6a reported a history of drug use, compared with those infected with genotype 1b. A comparison of the distribution of genotypes from this study¹⁰ and a US study⁹ is at Table 2.

Table 2 HCV Genotypes in Hong Kong and United States

Genotype of HCV	Hong Kong10	United States9
1a	6.2%	56.7%
1b	58.8%	17.0%
2a	1.4%	3.5%
2b	1.4%	11.4%
3a	1.9%	7.4%
4	0.0%	0.9%
6	27.0% (6a)	3.2%

Another local study on renal failure patients and non-renal failure controls also showed the predominance of genotype 1b, followed by 1a and 6a.¹¹

Laboratory Diagnosis

HCV infection can be identified by anti-HCV testing, which comprises antibody screening assay like enzyme immunosorbent assays (EIA), and supplemental or confirmatory tests such as recombinant immunoblot assay (RIBA). EIA can detect more than 95% of chronically infected HCV infections, but can detect only 50-75% of acute infections. In Hong Kong, laboratory screening for HCV infection is carried out in several hospitals and private laboratories, generally using EIA. Blood donors are confirmed positive by RIBA. The Government Virus Unit of the Public Health Laboratory Services Branch of the DH uses a combination of EIA to confirm the test results. Polymerase chain reaction (PCR) may be performed on some occasions to supplement EIA results.

Enhancing Laboratory Surveillance

In Hong Kong, while statutory notification has covered hepatitis C, effective surveillance is difficult because of firstly, a poorly defined acute stage, and secondly, the absence of a good laboratory marker. In 2001, the then Scientific Working Group on Viral Hepatitis Prevention recognized the public health significance of hepatitis C infection in Hong Kong and recommended to strengthen the surveillance mechanism to monitor its clinical and epidemiological patterns.¹² Since 2003, a surveillance project has been piloted to enhance understanding of the HCV situation in Hong Kong. Key components of the proposed HCV surveillance system include:

(a) reporting of newly diagnosed HCV cases by laboratories and clinical units;
(b) establishment of a central repository for the collected data;
(c) regular collation and synthesis of data with report generation.

Two laboratories, namely, HKRCBTS and Department of Microbiology of Princess Margaret Hospital (PMH) reported newly diagnosed anti-HCV positive cases to a central repository maintained by Special Preventive Programme (SPP) of the DH on a quarterly basis. Testing for anti-HCV was performed on 180 000-200 000 blood donations of HKRCBTS each year; and the prevalence was found to be 0.016% in 2003 and 0.021% in 2004. As for the PMH Laboratory, 1 629 and 2 288 samples were tested in 2003 and 2004 respectively and the overall anti-HCV prevalence was 8.55%. Understandably, there was a much higher proportion of subjects tested positive at PMH than HKRCTS, as the former were tested for clinical indications while the latter had routine pre-donation blood screening. The highest anti-HCV rate was found among drug users, of which about half were positive (as shown in Table 3). This was followed by patients with history of blood transfusion (11.1%), and patients with test done for clinical indication not falling under the standardized categorisation of screening (6.7%).

Table 3 Prevalence of Anti-HCV Categorised per Indication of HCV Testing

Category		2003			2004			Overall
		No. tested	HCV +ve		No. tested	HCV +ve		No. tested	HCV +ve
			No.	%		No.	%		No.	%
1.	Test done by Hong Kong Red Cross Blood Transfusion Service (HKRCBTS)	178 188	28	0.016	197 423	41	0.021	375 614	69	0.018
2.	Test done by Department of Microbiology of Princess Margaret Hospital (PMH)	1 629	138	8.47	2 288	197	8.61	3 917	335	8.55
	Screening	935	98	10.48	1 008	122	12.10	1 943	220	11.32
	- Drug use	167	87	52.10	202	100	49.50	369	187	50.68
	- History of blood transfusion	35	2	5.71	46	7	15.22	81	9	11.11
	- Dialysis	508	5	0.98	463	13	2.81	971	18	1.85
	- Transplant	43	2	4.65	68	0	0.00	111	2	1.80
	- Pre-chemotherapy	91	1	1.10	99	1	1.01	190	2	1.05
	- Needlestick injuries	90	1	1.11	130	1	0.77	220	2	0.91
	- Pre-vaccination	1	0	0.00	0	0	0.00	1	0	0.00
	Clinical indication	501	30	5.99	710	51	7.18	1 211	81	6.69
	Others or unknown	193	10	5.18	570	24	4.21	763	34	4.46
TOTAL (1 + 2)		179 817	166	0.09	199 711	238	0.12	379 531	404	0.11

A total of 404 clients was found anti-HCV positive in the two years at HKRCBTS and PMH laboratory. More than 80% came from PMH. Overall, the male-to-female ratio was about 2 to 1 (Table 4). The mean age was 43 years old (range 11-86). Nearly half of the cases tested positive at PMH were drug users, followed by those with clinical indications (20%), those with others or unknown reason (8.2%) and dialysis patients (4.5%).

Table 4 Characteristics of Anti-HCV Positive Patients from HKRCBTS and PMH Laboratory

		2003		2004		Overall
		(n=166)		(n=238)		(n=404)
		No.	(%)	No.	(%)	No.	(%)
Laboratory	Hong Kong Red Cross Blood Transfusion Service (HKRCBTS)	28	(16.9)	41	(17.2)	69	(17.1)
	Princess Margaret Hospital (PMH)	138	(83.1)	197	(82.8)	335	(82.9)
Sex	Male	115	(69.3)	157	(66.0)	272	(67.3)
	Female	51	(30.7)	81	(34.0)	132	(32.7)
Age at diagnosis	Mean	41.6		44		43
	Standard deviation	14.6		14.7		14.7
	Range	17 - 83		11 - 86		11 - 86
Category	Drug use	87	(52.4)	100	(42.0)	187	(46.3)
	Clinical indication	30	(18.1)	51	(21.4)	81	(20.0)
	Blood donation	28	(16.9)	42	(17.6)	70	(17.3)
	Dialysis	5	(3.0)	13	(5.5)	18	(4.5)
	History of blood transfusion	2	(1.2)	7	(2.9)	9	(2.2)
	Pre-chemotherapy	1	(0.6)	1	(0.4)	2	(0.5)
	Transplant	2	(1.2)	0	(0.0)	2	(0.5)
	Needlestick injuries	1	(0.6)	1	(0.4)	2	(0.5)
	Others or unknown	10	(6.0)	23	(9.7)	33	(8.2)

Discussion

HCV shares similar routes of transmission with HBV. Nevertheless, while HBV is prevalent across the whole society in Hong Kong, HCV appears to prevail only in isolated communities from the limited epidemiological data. Experience of clinicians and virologists 15 years back was that HCV was rare in the general population but common in injecting drug users, haemophiliacs and other patients requiring frequent blood/ blood product transfusions. The situation has remained the same currently. Screening of drug users showed a prevalence of HCV of about 50% in the last few years, although the representativeness of the tested people was unknown. Besides this group, high HCV prevalence is found mainly in patients with frequent blood transfusion as well as HIV/AIDS patients, which is similar to overseas observations. Data from new blood donors in the last decade showed a local prevalence of below 0.1% in adults. Taking into consideration of the available data, the prevalence of HCV infection is low in the general population.

Initially, under the enhanced surveillance mechanism, clinical units were included to report newly diagnosed HCV cases. However, the number of reports from clinical sources was small and regularity of its reporting could not be guaranteed. The laboratory reporting turns out to be the more successful part of the HCV surveillance system. Regular statistics have been assured from the two participating laboratories and classification of testing samples is based on well-defined categories of clinical indications. In 2005, Prince of Wales Hospital Microbiology Laboratory joined the HCV laboratory surveillance system. Continued tracking and reporting of the data could establish the temporal trend of changes of HCV prevalence as per different clinical indication. Representativeness of the data will be enhanced if reporting can be further extended to other laboratories. Collaboration of the stakeholders is the key element for successful implementation of HCV laboratory surveillance.

There is no vaccine for the prevention and control of hepatitis C. Prevention has to be targeted towards the different transmission routes and their relative importance. From a public health perspective, injecting drug use fuels the rapid spread of injection-related diseases such as HIV infection and hepatitis. Prevention programmes for injecting drug users help reduce HIV and hepatitis transmission by reducing risky behaviours. It is necessary to advise drug users not to share needles, syringes, solution, cotton wool balls and other drug paraphernalia. The use of methadone is one well-recognised harm reduction measure which effectively reduces blood-borne diseases, including HIV infection and hepatitis, among heroin drug users.¹³ The HKRCBTS strives to safeguard blood safety by its donor deferral and screening procedures. Transmission of HCV in health care settings can be reduced by adhering to standard precautions. Although the risk of spread of hepatitis C from sexual transmission is relatively low, practice of safer sex serves to protect from other sexually transmitted diseases as well.

Acknowledgements

The authors would like to thank collaborators who have contributed data to the understanding of HCV situation in Hong Kong, in particular the Hong Kong Red Cross Blood Transfusion Service and the Department of Microbiology, Princess Margaret Hospital.

¹Senior Medical and Health Officer   ²Research Assistant   ³Consultant Medical Microbiologist   ⁴Consultant

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