Hepatitis C has surfaced worldwide as a formidable concern to public health. Recent developments have sharpened methods of serological detectability, epidemiological study and patient treatment. In the light of the global situation, this article briefly presents known local epidemiology about hepatitis C derived from routine data and personal communication from some key workers. The occurrence of a serious, potentially progressive, transmissible condition in a young population will incur high-costs to patients, contacts and care services. The article concludes by highlighting the areas offering greatest scope to check this condition through prevention and patient management.peer-reviewe

Falzon, Dennis

Gauci, Charmaine

Mallia Azzopardi, Charles

Portelli, Alfred V.

English

OAR@UM

19 ---, Maltese Medical Journal. 1997; 9 (I): 19 All rights reserved Hepatitis C: an emerging concern D. Falzon*, A. Portelli**, C. Mallia Azzopardi***, C. Gauci* ABSTRACT: Hepatitis C has surfaced worldwide as a formidable concern to public health. Recent developments have sharpened methods of serological detectability, epidemiological study and patient treatment. In the light of the global situation, this article briefly presents known local epidemiology about hepatitis C derived from routine data and personal communication from some key workers. The occurrence of a serious, potentially progressive, transmissible condition in a young population will incur high-costs to patients, contacts and care services. The article concludes by highlighting the areas offering greatest scope to check this condition through prevention and patient management. * Department of Public Health, 15 Merchants Str, Yalletta, ** Department of Pathology, St Luke's Hospital, Gwardamangia *** Department of Medicine, St Luke's Hospital, Gwardamangia Correspondence: 	 D. Falzon, Department of Public Health, 15 Merchants Street, Valletta. [Email: dennis.falzon@magnet.mt] Keywords: blood transfusion. epidemiology, hepatitis C, intravenous drug use (IDU), prison, screening A global overview After many years of doubt about non-A, non-B hepatitis (NANBH), these last eight years have seen major advances in the characterisation of the hepatitis C virus (HCY) and substantial progress in the methodology of detection and disease management. Recent developments have underlined the main areas of risk associated with transmission of blood borne viruses. The recent history of hepatitis C has overlapped with that of hepatitis B virus and HIY, with which it shares several characteristics. Hepatitis C is a cosmopolitan infection, varying in frequency by region (Table I )1,2. Many HCY -infected individuals in the West are either intravenous drug users (lDUs), or recipients of blood products which, in the past, had not been screened for anti-HCy3. Before the introduction of blood donor screening and virus inacti vation methods for plasma products, infection of haemophiliacs was widespread owing to contamination of pooled clotting factor concentrates4. Other parenteral risks include tattooing, and needle­stick injuries among health care workers. Needle-stick InJunes from HCY -viraemic patients lead to transmission in 3-10% of cases, a risk lying between that for hepatitis B virus and HIy3. Care workers acquiring bloodborne viruses may subsequently pose a risk of infecting patients. At least one episode of carer-to­patient transmiSSIOn of hepatitis C infection is documented to have followed cardiac surgery in UK in 19945. The first known transmission of HCY from tattooing occurred in 19896• Some cases of hepatitis C, without evident history of previous parenteral exposure, may have resulted from use of improperly sterilised surgical instruments, or by blood admixture in folk medicine3. Table1 - Inter-country comparison of anti-HCV seroprevalence in blood donors Country 	 % donors Year ELISA-1 publishrd positive Taiwan 0.28% 1991 Turkey 0.31% 1991 Australia 0.45% 1992 USA 0.5% 1990 Finland 0.51% 1992 UK 0.6% 1992 Netherlands 0.7% 1990 Cuba 0.8% 1992 Guadeloupe 0.8% 1992 Malta* 1.01% 1993 Italy (South) 1.37% 1989 Spain 1.5% 1990 * ELISA-2 screening; confirmed 0.04% Intrafamilial spread by social contact has not been proven, but mother-to-infant transmission occurs in some 10% of seropositive mothers, commonly when the mother is co-infected with HIY, and when HCY titres are high 7.8. Sexual transmission is probably negligible or rare (Table 2): two studies in low prevalence areas showed no evidence of transmission9.10. Diagnosis and screening As serological tests for hepatitis A and hepatitis B I D. Falzon, et al. 20 Table 2 - Co-prevalence of anti-HCV jn spouses of HCV-positive cases' Country 	 HCV-positive Year of spouses / index publication USA Spain Finland USA (muiticentre) Japan Taiwan Italy USA/ltaly/ Australia Netherlands case 0/40 1990 5/71 1990 0/30 1991 5/194 1991 14/176 1992 5/25 1992 13/83 1992 3/106 1992 0/50 1993 became commercially available by the mid-seventies I I , non-A non-B hepatitis remained essentially a diagnosis of exclusion until 1990 when the first specific test for anti-HCV antibodies (ELISA-l) was introduced l2 . With time, test sensitivity II and specificity l3 were improved, and supplementary tests using recombinant immunoblot assay technology were developed 11. The move from ELISA-l to ELISA-2 shifted detectibility for anti-HCV from 90% to close to 100%14. The first reports on alpha interferon treatment for NANBH appeared in 1986 15 , and the RNA genome of hepatitis C first described in 1989 16. Hepatitis C virus is associated with 90% of non­A non-B hepatitis3. The Maltese perspective As in the rest of the world, commercial blood testing for hepatitis C only became available in Malta in the early nineteen-nineties. Epidemiological description has been problematic due to the high frequency of asymptomatic infections, and practical difficulties in investigating infection with connotations of socially undesirable acti vi ty. Data collection The term 'serum hepatitis' used in statutory notification of hepatitis in Malta17 does not distinguish between hepatitis B and C. Time trends derived from official figures of notified disease l8 (Table 3) may suffer from substantial artefactual variation due to inconsistent notification practices amongst clinicians over the years. While anonymity may encourage more persons at risk to test, it limits the possibility for epidemiological surveillance. The codification used for anonymous testing is non-standard and so repeat testing cannot be easily differentiated from fresh testing by surveying laboratory records alone. Virology laboratory, St. Luke's Hospital Diagnostic anti-HCV testing became available at the Malta state health services in 1992 19. The tests employed recombinant antigens which overcame initial problems of low sensitivity and specificity of earlier tests. ELISA-3 has been introduced very recently at the Virology Laboratory. Supplemental tests, including recombinant immunoblot assays (RIBA), are also performed. Common reasons for testing include IDU, sexual exposure, investigation of jaundice, deranged liver function, post-transfusion and pre-dialysis. From January 1994 to April 1997, 431 individuals are known to have reacted positive for HCV at Virology Laboratory, SLH. 80% were males and the main identified risk factor is IDUI9. Blood transfusion & organ donation In Malta, ELISA-2 is used by the Blood Transfusion Department for anti-HCV screening: initial positives are subjected to 3-8 further tests to minimise false positives2. Anti-HCV screening of blood products started in March 1992. HCV antibodies were detected in 2.9-4.7 per 10,000 donations over the period 1992-1994. As blood is nowadays fractioned into several products, screening for hepatitis C helped avert an estimated 4 to 24 primary infections per year over this period. Intravenous drug use The size of the local IDU population is undetermined. A total of 1074 users have been registered with the Detoxification Unit, SLH20. IDUs started being screened for anti-HCV in December 1993. 316 were tested by August 1996: 48% were anti-HCV positive. 65% of 104 users testing through the anti-drug NGO CARIT AS were also anti-HCV positive21 . In contrast, only 3% of newly admitted drug addicts tested at Detoxification Centre, Malta over 1992-93 were HBsAg positive22 . Users of formal drug rehabilitation programmes are almost certainly a non-representative fraction of the underlying IDU population: grapevine reports hint at unreached pockets of users, circumscribed by age, location (eg. newly built areas) and social status (both extremes)23. Anecdotal reports (to the author) indicate HCV transmISSIOn in Malta going back at least to the mid­1980s, and occurring as recent as 1996, and presumably extending also to the present. Prisons Prisoners may be at risk of hepatitis through injecting drugs, skin piercing and sexual activity. Prison Table 3 - Notified cases of serum hepatitis and AIDS, Maltese residents, 1988-96 1988 1989 1990 1991 1992 1993 1994 1995 1996 NANBH 3 3 I 1 6 7 5 2 HBV 10 9 10 18 13 14 8 5 2 AIDS 8 o I 7 4 3 5 3 4 21 Hepatitis C: an emerging concern authorities worldwide differ in their efforts to prevent hepatitis which present with classical features in the bloodborne infections, but in most countries, persons in acute or subacute stage. prison are afforded less protection against infection than Following current recommendations, in Malta, patients those outside24 (Table 4). with deranged liver function and histological proof of active hepatitis are considered for alphaTable 4 - Prison health policies in Malta and around the world 24,25 Australia England France\ Germany ! India Israel Malta Methadone treatment t/ t/ t/ t/ n/a t/ t/ Netherlands t/ Scotland t/ Thailand )( US t/ Condom Needle provision exchange •t/ )( t/ t/ )( )( )( t/ )( )( t/ t/ Yes/Some )( No )( )( n/a )( )( )( •t/ )( )( n/a • Cleaning facilities in some Alpha interferon treatment has its interferon treatment. Treatment guidelines have been formulated and are, at present, Voluntary being piloted, Apart from disease criteria, Education Segregation for inclusion, patients with a history ofofHIV+ves testing drug use have to be clean of abuse for at t/ )( t/ least six months before start of treatment.t/ )( t/ The regimen currently adopted locally uses n/a )( t/ three mega Units of alpha interferon byt/ t/ t/ sub-cutaneous injection three times at/ t/ )( week. Duration of treatment is generallyt/ t/ t/ t/ n/a t/ 12 months: however this may be extended, as recent studies suggest that outcomes can t/ n/a t/ t/ )( t/ improve with regimens spread out n/a t/ t/ longer27. Optimisation stands to be t/ n/a t/ determined. Quantitative measurement of HCV RNA, though costly, is a useful tool Notapplicable/available in determining prognosis or evaluating response to therapy 14. Anti-HCV testing was introduced in Malta's Corradino Correctional Facilities in 1994. Testing is voluntary and coupled with incentives of free basic routine immunisation and inclusion in drug rehabilitation programmes25 . In February 1997, 46% of 251 inmates were anti-HCV positive26. The raised HCV seroprevalence noted in this setting is confounded by a high proportion of inmates with past or concurrent history of IOU. Other risk areas There is no data available on occupational and iatrogenic transmission of hepatitis C in Malta. Ad hoc studies in this area are not prioritised given no standard eradicative treatment as yet for asymptomatic carriage. There is also risk of infection from skin instrumentation at tattooing, cosmesis, electrolysis, bodypiercing and acupuncture. Skin instrumentation has not been independently linked to HCV infection in Maltese seropositives. Although mother-to-child transmiSSIOn has yet to be documented in Maim, the likelihood of its occurrence may increase as more of our females with a history of intravenous drug use bear children, mirroring the experience in vertical HIV -1 transmission in countries where IOU is an important component of HIV transmission . Local experience in paediatric hepatitis C is limited. Clinical perspective In Malta, patients with hepatitis C coming to treatment are picked up largely through screening of IDUs and prison inmates, or from follow-up investigations for abnormal liver function tests. Most are asymptomatic with only minimally raised transarninases indicative of ongoing hepatitis. This is in contrast with other forms of drawbacks: apart from the cost (thrice weekly injection for 12 months tops Lm 1,000 in medicinal costs alone28), adverse effects are quite common. These include flu­like symptoms, depression and neutropenia29 , A full evaluation of response to treatment (which would include key quality of life measures) is in order for patients undergoing care. Conclusion In conclusion, a case is made for prioritising hepatitis C in Malta as a formidable emerging concern, which will have a significant impact on health resources. The following summary recommendations are being made based on greatest scope for action. 1. Safe practices at transfusion and organ donation. It is essential to ring-fence this priority area given that: • efficiency of infection via this route is high • fractioning of blood products means one infected donation can affect several recipients • infection acquired post-donation has become highly unacceptable more so for conditions which can be detected 2. Preventive action in other risk areas. Efforts should be directed at educating IDUs on safe practice, and risks of needle sharing. The policy of distributing syringes freely should be upheld, The management of correctional facilities will increasingly have to face in-prison transmission of bloodborne conditions, and pressures to stream inmates by crime category or serostatus. Preventive action is labour-intensive, involving contact tracing, pre- and post-test counselling, testing and referral. Given the occurrence of associated risk locally (IOU, sexual exposure), there is sufficient scope to customise services towards preventive action coupled with AIDS education, and in conjunction with other sectors outside the formal health services. 1 22 D. Falzon, et at. Regulatory functions remain necessary to uphold sterile practice in areas like dentistry, other surgery, tattooing and beauty therapy. 3. Occupational risk management Workers occupationally exposed to blood and blood products may be at increased risk of acquiring hepatitis through their work. An infected worker can then transmit infection to patients treated. If the litiginous setting stands to intensify , this would have to be addressed. Infected workers will have to be suspended from performing interventions with high risk of viral transmiSSIOn, with attendant loss of hard-gained expertise. Universal precautions in risky patient-worker interactions remains important. 4. Epidemiological survey and analysis There is clear scope for focusing studies in specific risk areas. Such might include seroprevalence surveys of those multiply-transfused in the pre-screening era and offspring of women at risk or with confirmed HeV. Known associated conditions which may be of local relevance and amenable to study include subjects with thalassaemia, haemophilia, and on dialysisl4. Serial testing of comparable populations over time (eg blood donors, IDUs or antenatal females) could be a useful indicator of extension of infection over time. Unlinked anonymous studies would help estimate seroprevalence in various at-risk subgroups not generally in contact with the health services. 5. Patient care Dedicating care services through a centralised liver clinic is expected to concentrate expertise, ensure better adherence to evaluated protocols and enhance academic pursuit. This should promote uniform eligibility and management modalities based on evidence rather than idiosyncrasy and routine habit. The possible stigma connotations of a 'liver clinic' have to be recognised. Therapy with new and expensive chemotherapy has also to be viewed in the light of its 'transplant-sparing' effect, as these interventions incur very high costs to patients and services. References 1. 	 Van der Poel CL. Hepatitis C virus: epidemiology, transmission and prevention. In Reesink HW ed. Current series in Haematology and Blood transfusion: hepatitis C virus. Basle: Karger 1994. 2. 	 Schembri-Wismayer R. National Blood Transfusion Services, Malta. Personal communication. 3. 	 Van der Poe1 CL, Cuypers HT, Reesink HW. Hepatitis C virus six years on. Lancet 1994; 344:1475-79. 4. 	 Makris M, Garson lA, Ring CIA, et al. Hepatitis C viral RNA in clotting factor concentrates and the development of hepatitis in recipients. Blood 1993; 81: 1898-902. 5. 	 Health worker infects patient with hepatitis e. BMJ 1995; 311:8. 6. 	 Abildgaard N. Peterslund NA. Hepatitis C virus transmitted by tattooing needle . Lancet 1991; 338:460. 7. 	 Weintrub PS, Vecreman-Wauters G. Cowan MJ. et al. Hepatitis C virus infection in infants whose mothers took street drugs intravenously. J Peds 1991: 119:869-74. 8. 	 Ohto H, Terazawa S. Sasaki N. et al. Transmission of hepatitis C virus from mothers to infants . N Engl J Med 1994: 330:744-50. 9. 	 Bresters D. Mauser-Bunschoten EP, Reesink HW, et al. Sexual transmission of hepatitis C virus. Lancet 1993: 342:210-11. 10. 	 Gordon Se. Patel AH. Kulesza GW, et al. Lack of evidence for the heterosexual transmission of hepatitis e. Am J Gastroenterology 1992: 87 : 1849-5 I. 11. 	 Bader TF. Viral hepatitis: practical evaluation and treatment. Hogrefe & Huber, USA 1995: 9. 12. 	 Alter HJ. New kit on the block:evaluation of second generation assays for detection of antibody to hepatitis C virus. Hepatol1992: 15:350:53. 13 . Simmonds P, Alberti A, Alter HJ, et al. A proposed system for the nomenclature of hepatitis C viral genomes. Hepatology 1994: 19:1321-24. 14. 	 Fishman LN, Jonas MM, Lavine JE. Update on viral hepatitis in children. Pediatric Clinics of North America. February 1996: 43(\):65-69. 15. 	 Hoofnagle JH. Mullen KO. Jones DB et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 1986; 315(25):1575-78. 16. 	 Choo QL, Riclunan KH, Han JH. et al. Genetic organisation and diversity of the hepatitis C virus. Proc Nat! Acad Sci USA 1991: 88:2451-55. 17. 	 Prevention of Disease Ordinance. Cap 36, Sect 10. Malta. 18. 	 Notifiable Infectious Diseases in the Maltese Islands. Department of Health Information , Health Division, Malta. Annual Reports 1988-96. 19. 	 Barbara e. Virology Department. SLH, Malta. Personal communication. 20. 	 Detoxification Unit, SLH, Malta. 1996. Unpublished data. 21. 	 Gatt J. CARITAS, Malta. Personal communication. 22. 	 Attard Montalto E, Portelli A, Mamo J. Hepatitis B prevalence in two Maltese subpopulations. MMJ 1996; 8(1 ):25-27. 23. 	 Grech G. SEDQA, Malta. Personal communication. 24. 	 Connor S, Christie B, Zinn C et al. Prison policies put inmates at risk. BMJ 1995: 310:278. 25. 	 Zammit Montebello J. Corradino Corrective Facilities. Personal communication. 26. 	 Muscat e. Corradino Corrective Facilities . Personal communication. 27. 	 Terrault N, Wright T. Interferon and hepatitis C virus infection.(ed). New Engl J Med 1995: 332:22: 1509-11. 28. 	 Government Pharmaceutical Services, Guardamangia. 1996. Unpublished data. 29. 	 Interferons. Adverse effects and treatment. Martindale, The Extra Pharmacoepia 30th ed 1993; 550-551 The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

Corradino Corrective Facilities .

Corradino Corrective Facilities.

Genetic organisation and diversity of the hepatitis C virus. Proc Nat! Acad Sci USA

Health worker infects patient with hepatitis e.

Hepatitis B prevalence in two Maltese subpopulations. MMJ

Hepatitis C viral RNA in clotting factor concentrates and the development of hepatitis in recipients. Blood

Hepatitis C virus infection in infants whose mothers took street drugs intravenously.

Hepatitis C virus transmitted by tattooing needle . Lancet

Hepatitis C virus: epidemiology, transmission and prevention.

Interferon and hepatitis C virus infection.(ed).

Lack of evidence for the heterosexual transmission of hepatitis e.

National Blood Transfusion Services,

New kit on the block:evaluation of second generation assays for detection of antibody to hepatitis C virus.

Prevention of Disease Ordinance.

Prison policies put inmates at risk. BMJ

Reesink HW. Hepatitis C virus six years on. Lancet

Sexual transmission of hepatitis C virus. Lancet

Transmission of hepatitis C virus from mothers to infants .

Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report.

Update on viral hepatitis in children. Pediatric Clinics of North America.

Viral hepatitis: practical evaluation and treatment. Hogrefe & Huber,

Hepatitis C : an emerging concern

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Hepatitis C : an emerging concern

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