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      Recent HCV genotype changing pattern in the Khyber Pakhtunkhwa province of Pakistan; is it pointing out a forthcoming problem?

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          Abstract

          Dear Editor, A recent article by Gul et al. 1 highlights an important issue of Hepatitis C Virus (HCV) subtypes sero-prevalence in the Khyber Pakhtunkhwa (KPK) province of Pakistan. It is the first report of its kind on the changing epidemiological pattern of HCV genotypes in the province. The results of the study showed an increase in mixed HCV subtypes (22.9%) and genotype 1a (11.6%) and decrease in 3a genotype (45.5%). 1 The outcome of interferon plus ribavirin therapy is viral genotype specific, some genotypes/subtypes being good responders while others are not. Keeping in view the importance of sero-prevalent viral genotype regarding the management of patients, we analyzed the previous reports (26 published studies) from Pakistan on prevalence of HCV genotypes. The existing data showed that genotype 3a (57.37) is the most common genotype in the country while the prevalence of 1b subtype is only 1.985% and 1a is 5.93% (Fig. 1a), which support the study by Gul et al. 1 The analysis of previous published results regarding province wise distribution of the viral genotypes showed that 3a is the major circulating viral genotype in all four provinces of the country but the distribution of other viral clades is differential (Fig. 1b). By comparing the previously published results with the current report by Gul et al. it is evident that the pattern of HCV subtypes is changing in the region. Fig. 1 Relative frequency distribution of HCV subtypes in Pakistan. * Subtype not defined (a) and province-wise distribution pattern of major HCV genotypes (b). Due to the error prone nature of viral polymerase, HCV has many genotypes and subtypes. The interferon therapy response is genotype dependent and different viral genotypes showed varied level of sustained virological response (SVR). Among all viral genotypes 3a has shown to be a good responder to interferon therapy. 2 Pakistan is a resource constrained country with very low per capita income and considerably low expenditure on health by the Government (just 2.7% of GDP). 3 It ranked second in the world in terms of HCV infection with more than 10 million infections. 3 As the data indicates that 3a, supposedly to be a good responder to therapy, is the most prevalent genotype in the country most of the treated individuals with interferon therapy should attain SVR. Accordingly, a most recent report (2014) from Pakistan regarding response of different HCV genotypes to interferon therapy showed 95% SVR in 3a infections in contrast to only 34% of 1b infections. 4 The current shift in the circulating viral genotype enlighten an important upcoming danger. Health care workers may face problems to successfully treat patients as it will be more difficult for patients to achieve SVR. For achieving higher rates of SVR antiviral therapy will have to be extended thus increasing the economic burden on society and psychology trauma on the patients and their families. SVR rates are greatly increased with direct acting antivirals (DAA) therapy but the high cost is a major obstacle. 5 In Pakistan, the allocated budget for health is already pretty low and the country is also endemic for other viral infections like polio and dengue which would result in shifting of priorities. By viewing the forthcoming giant of HCV therapy resistance, it is needed to properly monitor the pattern of HCV genotypes in the country. A well developed surveillance system is highly needed to timely tackle the upcoming problem. Role of the funding source There is no role of any funding agency in this study. Conflicts of interest The authors declare no conflicts of interest.

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          Response of different HCV genotypes to interferon therapy in different age groups of chronic hepatitis-C patients.

          Although new Pegylated Interferon is available, yet the conventional Interferon with the combination of Ribavirin is still the therapy of choice to treat the Hepatitis C patients. This study was conducted to investigate the response of different HCV genotypes in different age groups of chronic Hepatitis C patients treated with conventional Interferonα-2b (IFNα-2b) plus Ribavirin (RBV).
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            Diagnostically untypable hepatitis C virus variants: it is time to resolve the problem.

            Pakistan is a low income country with more than 10 million hepatitis C virus (HCV) infections and the burden is on continuous raise. Accurate viral genotyping is very critical for proper treatment of the infected individuals as the sustained virological response of the standard antiviral interferon therapy is genotype dependent. We observed at our diagnostic center that 15.6% of HCV patient's samples were not genotype-able by using Ohno et al method. The genotyped samples showed that 3a (68.3%) is the major prevalent genotype in Pakistan followed by 2a (10.3%), 3b (2.6%), 1b (1.5%), 2b (1.2%) and 1a (0.5%). Presence of large number of untypable HCV variants in the current study highlights an important issue of health care setup in Pakistan. Untypable HCV cases create difficulties in treatment of these patients. The problem of routine diagnostics setup of Pakistan should be addressed on priority basis to facilitate the medical professionals in patient's treatment and to help in achieving the maximum sustained virological response.
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              Effect of Functional Interleukin-10 Polymorphism on Pegylated Interferon-α Plus Ribavirin Therapy Response in Chronic Hepatitis C Virus Patients Infected With 3a Genotype in Pakistani Population

              Dear Editor, Pakistan is a low socio economic country having more than 10 million people infected with hepatitis C Virus (HCV) with a major genotype of 3a (GT 3a) (1). Due to high rate of resistance to standard Interferon plus Ribavirin therapy, it is highly needed to identify new marker for response prediction to therapy. Interleukin 10 (IL-10) is a key member of Cytokine, which regulates Th1/Th2 Cytokine balance, a major part of immune system against infection (2). IL-10 production varies inter individually based on functional polymorphism (-1082 G/A, -819 C/T and -592 C/A) in its promoter region. Previously we have shown that IL-10 polymorphic variants play important role in HCV susceptibility/prevention (2). Recently we conducted a study to analyze the impact of functionally important IL-10 polymorphism on outcomes of standard Interferon-α plus Ribavirin therapy. The results of current study strengthen previous findings that IL-10 polymorphism effect disease susceptibility in Pakistan (2-4). Our results showed that high IL-10 producing -1082 GG genotype (P = 0.02; OR = 0.4; 95% CI = 0.2-0.8) and GTA haplotype (P = 0.03; OR = 0.55; 95% CI = 0.3-1) were significantly higher in HCV patients as compared to healthy subjects, while IL-10 -1082 GA genotype (P = 0.03; OR = 1.95; 95% CI = 1.1-3.4) showed protective effect against HCV infection. The current data failed to show any significant corelation between IL-10 polymorphism inheritance and standard therapy response in HCV patients. Age and pretreatment viral load are the parameters which influence therapy response; Patients with sustained virological response (SVR) were younger and had lower pretreatment HCV RNA levels. No gender-based statistical difference was found between chronic hepatitis C patients who achieved SVR or failed to respond. To our knowledge this is the first report from Pakistan to evaluate the role of IL-10 polymorphism on the outcomes of standard antiviral therapy. We are unable to find any corelation between IL-10 polymorphic variants and interferon therapy outcomes, may be due to small number of subjects. This study is a preliminary and is on small scale. We believe that our effort may stimulate some additional personal genetic makeup based studies on larger scale using these and new multi-locus analysis approaches for a deeper analysis of the epistatic interaction of the pro- and anti -inflammatory molecules toward hepatitis C progression. Better understanding of genetic factors that have effect on hepatitis C progression and pathogeneses will provide scientific basis for the development of new immunomodulatory treatments for chronic hepatitis C patients and will also help health care workers about the standard therapy effectiveness.
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                Author and article information

                Contributors
                Journal
                Braz J Infect Dis
                Braz J Infect Dis
                The Brazilian Journal of Infectious Diseases
                Elsevier
                1413-8670
                1678-4391
                08 March 2016
                May-Jun 2016
                08 March 2016
                : 20
                : 3
                : 312-313
                Affiliations
                [a ]Department of Chemistry, School of Science, University of Management and Technology (UMT), Lahore, Pakistan
                [b ]Department of Physics, School of Science, University of Management and Technology (UMT), Lahore, Pakistan
                [c ]Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
                Author notes
                [* ] Corresponding author. sohail.ncvi@ 123456gmail.com
                Article
                S1413-8670(16)30033-2
                10.1016/j.bjid.2015.12.011
                9425352
                26963150
                28dcea31-1f61-4ebd-a1b5-b4eb75c8be4c
                © 2016 Elsevier Editora Ltda.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 December 2015
                : 28 December 2015
                Categories
                Letter to the Editor

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