Hepatitis C, A Mega Menace: A Pakistani Perspective

 The World Health Organization (WHO) had estimated that 180 million people are infected with Hepatitis C virus in 2009. Three to four million people get newly infected each year. Two third of these newly infected cases develop chronic liver disease [1]. HCV infection is responsible for 60-70% of all liver cancer cases and is the commonest cause of liver transplant all over the worldwide [1]. Liver cirrhosis is the 18^th commonest cause of mortality [2]. HCV related liver cancer is the 8^th common cancer worldwide. HCV infection prevalence varies from country to country. The global prevalence of HCV infection is 2.2 to 3% [3]. In the US and European countries, prevalence is 1.6 to 1.8% and 1 to 2.3%, respectively [4]. Pakistan is the 6^th most populous country in the world with an estimated population of 16,094,3000. Prevalence of HCV infection reported in various studies by the Pakistani authors ranges from 2.2-14% [5]. Accordingly, approximately 10 million people in Pakistan are infected with HCV [6]. Within Pakistan, the HCV prevalence rate varies between the four provinces; prevalence rate reported in Punjab is 6.7%, in Sindh 5%, in Baluchistan 1.5%, and in Khyber Pakhtunkhwa 1.1%. The prevalence of the HCV antibody positivity high risk groups (such as patients on chronic hemodialysis, health care workers, and thalassemia or hemophilia patients) is 38% to 55%. The comparison of prevalence and anti-HCV positive cases with neighboring countries of Pakistan is demonstrated in Table 1.

Injudicious use of injections had been reported as a major risk factor for HCV infection in Pakistan [9]. Luby et al reported in their study from Hafizabad, Punjab that HCV infected patients had received five or more injections in the past 10 years compared to non-infected persons [10]. In another study, Pasha et al reported that the household members who had more than 4 injections per year were 11.9 times more likely to get HCV infection than others [11]. Shazi L et al in 2006 reported injection use as a major mode of transmission of Hepatitis C [12]. Injection drug users (IDUs) were even at high

risk of acquiring HCV infection. In studies conducted by Kuo et al in Lahore and Quetta in 2003, HCV prevalence rate was 93% and 75% in IDUs. Other risk factors for the transmission of HCV infection were injections given by health care workers, sex workers as well as household contacts. In health care workers, HCV prevalence rate was 5.5-6%, which is less than the community [11]. In Pakistan, a large segment of rural population goes to barbers for facial shave. Quite often barbers use razors that are not disposable, possibly contaminated, and often reused for shaving without proper disinfection. Janjua et al reported that only 13% people knew that hepatitis can be transmitted by contaminated razors. There is no cohort study to prove the exact risk of transmission of HCV infection with contaminated razors, scissors and other instruments used by salon workers. Transmission of HCV in household contacts as well as within families is not well documented in Pakistan. A study by Portic et al showed that the prevalence of HCV in household contacts of HCV families was 2.5 times that of the general population [12].

In Pakistan, major cause of liver disease is HCV infection. As HCV infection has high chronicity rate, it leads to an increase burden of chronic liver disease with its complications. About 10 million people harboring HCV infection are at risk of developing some form of complication, such as cirrhosis, hepatic encephalopathy, variceal bleed, hepatocellular carcinoma or liver

related death. There is no formal registration of hepatitis patients in Pakistan. However, hospital based data has shown that every 4th patient admitted in medical ward has liver related disorders. HCV related liver disease is one of the commonest cause of death in Pakistan. A study published from our department showed that out of 21999 patients admitted in medical department  past 9 years (1998-2008), 6053 (27.51%) patients were with liver disease. Average patients admitted per year were 2205±725. 3655 patients died (16.61% of total admissions in 9 years); 24.43% (n=993) of these were liver related deaths. 893 liver related deaths were noted annually [13]. Approximately half of these liver related deaths can be attributed to HCV, but keeping in mind the limitations of the study as PCR or RIBA was not done to confirm the HCV status.

In Pakistan, the commonest genotype is 3a.15 Genotype 2 and 3 are considered easy to treat as compared to genotype 1. Being cheap, standard interferon plus ribavirin combination therapy is to be considered the first line treatment for chronic hepatitis C patients.9 This combination has been used in Pakistan since 1998. Different authors have reported different treatment responses from different centers. Details of end-of-treatment response (ETR) and sustained viral response (SVR) are shown in Table 5. SVR in patients treated with conventional interferon and ribavirin ranges from 50 to 81%. One limitation of these studies was that all the viral responses were not checked uniformly. Secondly, the data analysis methods were not clearly defined; either the treatment responses were analyzed as intention to treat (ITT) analysis or per-protocol (PP) analysis. This resulted in great variation particularly in SVR. That is one possible explanation in varying of SVR from 50 to 81% in different national studies shown in Table 5. Regarding pegylated interferon, limited data is reported. One study of 73 patients by Khan et al showed an SVR of 85% from Lahore [18]. We analyzed data of 300 patients at our department (Liver Research Clinic, Holy Family Hospital, Rawalpindi, Pakistan) treated with conventional interferon and ribavirin as PP analysis. The results showed a rapid virological response (RVR) 68.9%, early virological response (EVR) 77.6%, ETR 70.9% and SVR 63.2%. Similarly, analysis of 227 patients from our department treated with pegylated interferon and ribavirin showed RVR 68%, EVR 75.8%, ETR 76.6% and SVR 60.5%. We conclude two important points from our data analysis. One being that the treatment responses in patients treated with pegylated interferon and ribavirin are  comparable to patients treated with conventional interferon and ribavirin. Secondly, the SVR achieved in patients treated with pegylated interferon and ribavirin even in genotype 2 and 3 is much lower than that reported in international studies [19,20] Based on our data and other national studies,   Pakistan Society of Gastroenterology and GI Endoscopy recommended that in Pakistan, the first line therapy for genotypes 2 and 3 patients should be conventional interferon and ribavirin and only non-responders and relapsers to conventional interferon and ribavirin should be treated with pegylated interferon and ribavirin [15]. This will be the cost effective approach.

There is no reimbursement or health insurance system in Pakistan. Mostly patients and their family pay for the treatment. Six months treatment with standard interferon and ribavirn cost about US$500 for drugs and US$200 for the follow-up and investigations. Treatment with pegylated interferon and ribavirin costs around US$4000. Considering the emerging data of equal response rates in genotypes 2 and 3, Pakistan Society of Gastroenterology and GI Endoscopy and Pakistan Society of Hepatology National Consensus Guidelines 2009 had recommended standard interferon and ribavirin as the first line therapy for HCV genotypes 2 and 3 patients in Pakistan.¹⁵ Pegylated interferon and ribavirin should be reserved for non-responders and relapsers of standard interferon and ribavirin therapy as well as in individualized cases.

The tables in this article have been reproduced after permission from Pakistan’s Journal of Gastroenterology and Journal of College of Physicians and Surgeons Pakistan. A proof of the permission is available for review of the editorial board of JPMS.

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