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  • Volume 377 1719 (2011)
  • May 21, 2011

Hepatitis C: A real cause for concern in Pakistan

Hepatitis is an insidious disease, to such an extent that a carrier’s mild symptoms might go unrecognised, let alone confident identification of the type of Hepatitis virus causing the disease. It is only through a high index of suspicion along with recognition of high-risk groups and frequent screening campaigns, that people infected with Hepatitis C can be identified. Furthermore, in Pakistan, diagnosed patients seem more concerned over the cost of polymerase chain reaction (PCR) tests for the confirmatory detection of Hepatitis C [1] as well as the added cost and timeframe of interferon therapy, than of the implications of the actual diagnosis.

In a study that we are currently conducting in the Mayo Hospital Outdoorpatients’ Department, Lahore, Pakistan, funded by the Students’ Patients’ Welfare Society of King Edward Medical University,* we have been looking at the reaction of patients upon being diagnosed with Hepatitis B or C by serological tests for HBsAg and Anti-HCV. Patients neither twitch nor switch their facial expressions upon being labelled as positive, quite surprisingly, even though we, as medical students, are extremely careful that we inform our patients in simple terms about the sensitivity and specificity issues of serological testing, and the significant requirement for a PCR test and therapy, if confirmed. Patients seem far more concerned about the cost of the PCR test rather than their carrier status and consider it an added burden even though our serological testing is offered free of cost. As medical students, we are often asked in a very casual tone as to why Hepatitis infection renders their blood inept for donation!

We find such observations to be truly peculiar and surprising considering that other diseases -especially AIDS – can elicit a far more serious and concerned reaction from patients. Although this may appear to be a controversial statement to undermine AIDS, the statistics suggest something else. The prevalence of AIDS in Pakistan has been found to vary between 0% and 0.0064% in 1998![2] The total number of actual studies documenting this prevalence are limited, however, so further conclusions can not be made.

Prevalence of Hepatitis C

Even though our study is still in its infancy and our sample sizes relatively small, the results strongly suggest a prevalence rate of Hepatitis C in excess of 10%. There is only small adjustment of these values when allowance is given for the sensitivity and specificity of Anti-HCV (99.8% and 99.9%, respectively) [3] and the fact that this test only detects the presence of antibodies to HCV.

In well documented studies, Hepatitis C seropositivity is varied. It is reported as 16% for Anti-HCV and 28% for HCV RNA by PCR in Faisalabad [4]. In another study, 26% is the reported rate in Lahore for individuals in the general public older than 20 years of age, and 34% for individuals in the general public of Gujranwala [5]. In comparison, the prevalence rate of Hepatitis C in Japan amongst blood donors was estimated at 0.49% [6] and in the USA it was estimated at 1.8% [7]. In India, 1.85% was the reported rate in healthy blood donors [8].

As is evident from these studies, only the general public has been used for classifying the true prevalence rate and not samples from hospital settings or elsewhere. As such epidemiological studies in Pakistan are generally lacking, we were not aware of the Hepatitis C prevalence rate. We began to understand the seriousness of Hepatitis C in Pakistan once we started detecting cases ourselves, being careful to exclude patients with liver disease.

Why is Hepatitis C so prevalent in Pakistan?

Instead of quickly jumping to the idea that lack of awareness is the cause for prevalence of Hepatitis C in Pakistan, some other factors need to be examined. Most important is the fact that no vaccine for Hepatitis C exists because of its viral complexity [9]. This naturally implies that a vaccination programme similar to Hepatitis B cannot exist [ 10].

The initial symptoms are mild and extremely non-specific, such as fatigue, nausea, mild tenderness, poor appetite, etc [1]. It is extremely difficult to identify the possibility of Hepatitis C in such cases as these symptoms are merely passed off by the Pakistani community. Coupled with the lack of regular screening campaigns and actual epidemiological studies, this problem goes unaddressed. Also chronic infection develops in 70–80% of cases and is typically silent [11]. In 20% of patients with chronic infection, cirrhosis develops within about 20 years [11]. Hepatocellular Carcinoma (HCC) develops in 1–4% of patients with cirrhosis each year after an average of 30 years [11]. Individuals infected with Hepatitis C realise their diagnosis after suffering from HCC and cirrhosis, rather than being diagnosed via opportunistic screening.

The question still remains: why is the prevalence rate so high? One possible explanation links the vaccination of smallpox and simultaneous Hepatitis C infections, which explains why its prevalence rate is so high in the population greater than 20 years of age compared with younger individuals [5]. However this factor has never been further examined. It’s obvious, however, that it is hinting towards an important risk factor: sharing of needles and needle stick injuries.

There have been only small studies examining the risk factors associated with Hepatitis C. Identification of risk factors is critical because it would alter the way new prevention strategies are devised and advertised. In our study of this issue, needle stick injuries are very frequent, especially among women who sew clothes at home and may share the same needle. Exposure via dental treatment has also been significant: among local clinics there is no way to confirm whether dentists employ good sanitation measures (autoclaving of equipment, etc.) . However, even with proper disinfection, contaminating material may still be present in the internal areas of the equipment [12]. Gynaecological history has been significant with regards to home births: so-called trained professionals that assist in the births have no knowledge of aseptic measures, often using the same set of instruments on multiple patients without sterilisation. Of special note here is the current maternal mortality ratio in Pakistan – the estimated maternal mortality ratios per 100 000 livebirths ranges from a low of 281 in Karachi to a high of 673 in Khuzdar [Balochistan] [13]. Haemorrhage (52.9%), puerperal sepsis (16.3%), and eclampsia (14.4%) are the leading causes for direct maternal deaths [13]. The frequency of deaths from both haemorrhage and puerperal sepsis may indicate the use unsterilised equipment. This repetitive use of unsterilised equipment also pertains to barber shops and establishments where body piercing is performed. In a study, patients with Hepatitis C analysed by Anti-HCV ELISA were more likely to have daily face shaves (adjusted OR=5.1, 95% CI: 1.5–17.0) and armpit shaves (adjusted OR=2.9, 95% CI: 1.3–6.5) by a barber [14]. Multiple therapeutic injections in Pakistan have also been pointed as culprits in at least two studies [14,15]. In one such study, cases were more likely to have received therapeutic injections in the past 10 years (1–10 vs. 0 therapeutic injections; adjusted OR=2.8, 95% CI: 1.1–7.1; > 10 vs. 0 therapeutic injections; adjusted OR=3.1, 95% CI: 1.2–7.9) [14]. This study identifies injected drug use, blood transfusion, pricked with a needle, re-use of syringes, and even being over the age of 35 years as separate independent risk factors for HCV infection from amongst blood samples of apparently healthy people of the province of Punjab, Pakistan [16].

Role of the government and various organisations in addressing HCV

The government of Pakistan is, at present, trying to address this situation by partnering with the World Health Organization (WHO) to empower and strengthen the national programme for prevention and control of Hepatitis for early detection, and encouraging research in cost effective treatment. They are also in the process of setting diagnosis and counselling centres throughout the country for the treatment of Hepatitis, as announced by the national programme manager on the national channel Pakistan Television [17]. The Sindh government has planned to vaccinate 1.4 million newborns and 245 000 adults against Hepatitis B and provide treatment to about 16 600 patients of Hepatitis C under the “Chief Minister’s initiative for Hepatitis-free Sindh” [18]. However, no follow up report has been published in any leading newspaper.

The Hepatitis C trust, London, has taken up the initiative to create awareness for people of Pakistan about Hepatitis C, as published in its 2006 end of year update report in which they described their awareness raising initiative [19]. Human Development Promotion Group (HDPG) in association with Glaxo Smith Kline (A multinational pharmaceutical company) undertook a one-month awareness campaign (June-July, 2002) against Hepatitis B & C in the district Charsadda. HDPG survey data from the area showed that people were unaware about the basic information about this disease. The campaign concentrated on creating awareness by involving student communities, politicians, and youths. Numerous activities including gatherings, walks, placards, banners, and visiting schools were inculcated in their campaign. HDPG claim to have been successful in creating awareness in a sizeable population of Charsadda [20].

Role of media

Beginning 10 years ago, the media initiated a huge campaign to increase awareness about AIDS, focusing largely on the fact that it is incurable. In Pakistan, it would be more relevant and appropriate, however, to raise awareness about Hepatitis C, as the prevalence rate is much greater than that of AIDS. The way AIDS progresses is also not much different from Hepatitis C, with non-specific symptoms at first followed by a latent phase and then full blown immunodeficiency [21]. Although it has significantly reduced some similar risk factors, especially the continuous use of the same blade on everyone by the barber, the attention of the general public has however diverted more in favour of AIDS.

Various channels do address other healthcare issues. There is usually a limited amount of coverage on healthcare issues on Dawn News and Geo News channels. Maternal and child healthcare constitute most of these messages. Pakistan Television also offers some coverage of maternal and child healthcare issues [22]. Regular news and reports do frequently mention the situation of healthcare in Pakistan and the associated factors as evidenced by the videos [23,24]. There are also infrequent debates and discussions regarding the healthcare system of Pakistan [25]. The Dawn Newspaper has a section “Letter to the Editor” that may infrequently publish health-related messages expressed in the form of “Letters” [26].

Of peculiar interest is the regular and frequent publications in leading Urdu newspapers, such as Jang and Nawai-Waqt, of homoeopathic treatment options, not only for diseases that can be potentially cured by allopathic medications such as Hepatitis C, but also for diseases that are virtually incurable such as AIDS and diabetes mellitus. The degree of confidence offered is usually 100%. These can take the shape of advertisements on television as well as painted on the sides of buses, wagons, and rickshaws. These have a major effect on the attitude of the public because a major attractive factor in this business is the promise of a 100% cure for diseases otherwise deemed incurable by current medical knowledge and research [27].

This warrants the existence of regulatory bodies to keep track of the flow of not only this information, but also of potentially misleading advertisements such as those by Safeguard Soap, which claim to guard against every known bacterial and viral disease (including Swine Flu) known to mankind (interestingly, superficial fungal and parasitic infections never get a mention) [28].

The pursuit of a vaccine

A vaccine is an obvious development that can significantly decrease the incidence of Hepatitis C infection. Given the viral complexity and extreme genetic heterogeneity of the Hepatitis virus, there is no vaccine available as yet [29]. However various novel techniques are being considered in pursuit of the development. In 2005, Chen and Li attempted to express immunogenicity in mice by using Hepatitis B Core antigen (HBcAg) as the immuno-carrier to express HCV T epitope. Their results were encouraging, having induced strong non-specific lymphocyte proliferation in the group of mice receiving the vaccine [30]. Genotype-specific vaccines are also being sought [31]. However, the vaccine that can end the drought once and for all may be the IC41 peptide vaccine developed by the company Intercell. Studies into this new vaccine have yielded very encouraging results. IC41 is a synthetic peptide vaccine containing seven relevant Hepatitis C virus (HCV) T-cell epitopes. It has been shown to be safe, well tolerated, and induces HCV specific TH1 immune response [32]. Studies into the immunogenic capability and safety of different injection routes of IC41 have also taken place, yielding very encouraging results [33]. The safety of IC41 is permitting evaluation of further clinical trials in HCV infected individuals.

Conclusion

Given such an alarming situation, it is imperative that the Pakistani government starts nationwide campaigns against Hepatitis C, the same way it did against AIDS about 10 years ago. Case control, cohort, and cross-sectional studies should all be conducted and all the risk factors must be identified in great detail. This should then be used as a criterion for making new policies concentrating on prevention of Hepatitis C. It cannot be stressed enough just how significant random screening campaigns are for identification of positive cases.

Public attitude must be altered and the best way to approach the public in today’s world is through media. Public-health messages, preventive measures, and treatment options available must all be advertised on air and through newspapers. Funds should also be allocated to offer PCR and therapy free of cost to people who have been detected as positive. Every media channel should be used to air as many public-health messages as possible in order to address the entire population of Pakistan.

Only through a nationwide government-supported campaign can the prevalence rate of Hepatitis C and its transmission in Pakistan be significantly reduced.

Ayaz Mahmood Khawaja
King Edward Medical University (Lahore, Pakistan), Final year medical student
dr.ayazmk(a)yahoo.com

Ubaid ur Rehman
Allama Iqbal Medical College (Lahore, Pakistan), Final year medical student
drubaid(a)live.com

Mehmood ul haque
Allama Iqbal Medical College (Lahore, Pakistan), Final year medical student sunny_pakistani(a)hotmail.com

References

1. Information acquired from http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/ accessed 5th March 2010.

2. A A Hyder, O. A. Khan (1998). “HIV/AIDS in Pakistan: the context and magnitude of an emerging threat.” Journal of Epidemiology and Community Medicine 52: 579-585.

3. Description in Accu-Chek pamphlet and product description at http://www.tootoo.com/d-p8336137-HCV_test/

4. AHMAD Nasir, ASGHAR Muhammed, SHAFIQUE Muhammad, QURESHI Javedanver. (2007). “An evidence of high prevalence of Hepatitis C virus in Faisalabad, Pakistan.” Saudi medical journal 28: 390-395.

5. Aslam, M. M. D. A., Junaid (2001). “Seroprevalence of the Antibody to Hepatitis C in Select Groups in the Punjab Region of Pakistan.” Journal of Clinical Gastroenterology 33(5): 407-411.

6. Junko Tanaka, J. K., Keiko Katayama, Yutaka Komiya, Masaaki Mizui, Retsuji Yamanaka, Kou Suzuki, Yuzo Miyakawad, Hiroshi Yoshizawa (2004). “Sex- and Age-Specific Carriers of Hepatitis B and C Viruses in Japan Estimated by the Prevalence in the 3,485,648 First-Time Blood Donors during 1995-2000.” Intervirology 47(1): 32-40.

7. Miriam J. Alter, P. D., Deanna Kruszon-Moran, M.S., Omana V. Nainan, Ph.D., Geraldine M. McQuillan, Ph.D., Fengxiang Gao, M.D., Linda A. Moyer, B.S., Richard A. Kaslow, M.D., M.P.H., and Harold S. Margolis, M.D. (1999). “The Prevalence of Hepatitis C Virus Infection in the United States, 1988 through 1994.” The New England Journal of Medicine 341: 556-562.

8. Aswini K. Panigrahi, S. K. P., Rajesh K. Dixit, Kanury V. S. Rao, Subrat K. Acharya, Srinivasan Dasarathy, Ambika Nanu (1997). “Magnitude of Hepatitis C virus infection in India: Prevalence in healthy blood donors, acute and chronic liver diseases.” Journal of Medical Virology 51(3): 167-174.

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11. Hepatitis C: http://emedicine.medscape.com/article/177792-followup

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17. Information acquired from http://www.dawn.com/wps/wcm/connect/dawn-content-library/dawn/the-newspaper/local/lahore/lahore-who-wants-pakistan-to-update-medical-syllabus-030, accessed 30th April 2010.

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29. Randal, J. (1999). “Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical Restraints.” J. Natl. Cancer Inst. 91(11): 906-908.

30. Chen, J. and F. Li (2006). “Development of Hepatitis C virus vaccine using Hepatitis B core antigen as immuno-carrier.” WORLD JOURNAL OF GASTROENTEROLOGY 12(48): 7774.

31. Yusim, K., W. Fischer, et al. (2010). “Genotype 1 and Global Hepatitis C T-cell Vaccines Designed to Optimize Coverage of Genetic Diversity.” Journal of General Virology.

32. Klade, C. S., H. Wedemeyer, et al. (2008). “Therapeutic Vaccination of Chronic Hepatitis C Nonresponder Patients With the Peptide Vaccine IC41.” Gastroenterology 134(5): 1385-1395.e1381.

33. Firbas, C., T. Boehm, et al. (2010). “Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.” Vaccine 28(12): 2397-2407.

* SPWS is a non-profit organization run solely by undergraduate medical students, funded by dedicated donors, at King Edward Medical University, Lahore, Pakistan. http://www.spwske.com/

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