Abstract
Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD with the cost of a liver transplant approximately $200 000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole.
Keywords: :
Introduction
Hepatitis C is a transmissible liver disease that results from infection with Hepatitis C Virus (HCV). It has diverse implications ranging from no symptoms to fatality. It was discovered in the late 1980s but remained in the dark for many years and thought to be of be little importance. In 2010, the World Health Assembly recognized viral hepatitis as a global public health Problem.Citation1 Hence, there is a need for widespread active interventions for its prevention and control. In June 2013, WHO launched the Global Hepatitis Network one of its aims was to support countries with planning and implementation of viral hepatitis plans and programmes. On World Hepatitis Day, WHO urged governments to act against the five hepatitis viruses that can cause severe liver infections and lead to 1.4 million deaths every year.Citation2
The HCV infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.Citation3,Citation4 Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer.Citation5-Citation7 Among those chronically infected, the risk of cirrhosis after 20 y varies between studies but has been estimated at ~10–15% for men and ~1–5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing hepatocellular carcinoma is ~1–4% per year.Citation8
HCV is most commonly transmitted through exposure to infectious blood. This can occur through receipt of contaminated blood transfusions, blood products, and organ transplants; injections given with contaminated syringes and needle-stick injuries in health-care settings; injection drug use; being born to a hepatitis C-infected mother. Hepatitis C may be transmitted through sex with an infected person or sharing personal items contaminated with infectious blood, but these are less common. It is not spread through breast milk, food or water or by casual contact such as hugging, kissing, and sharing food or drinks with an infected person.Citation9 The primary route of transmission in the developed world is intravenous drug use (IDU), while in the developing world the main methods are blood transfusions and unsafe medical procedures.Citation10 The vertical transmission rate has been estimated to be 3–5% but higher rates have also been reported (18%, 6–36%, and 41%).Citation11,Citation12 Heavy alcohol consumption, age, and HCV/human immunodeficiency virus (HIV) co-infection may be associated with more rapid progression of HCV liver disease, especially fibrosis.Citation13
Global Overview
HCV has been shown to have a worldwide distribution, occurring among persons of all ages, genders, races, and regions of the world. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases.Citation9 Globally the prevalence and number of people with HCV infection has increased from 2.3% to 2.8% and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australia, and Central, Eastern, and Western Europe have moderate prevalence (1.5–3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). The prevalence of hepatitis C is even higher in some areas, reaching levels of up to 10%.Citation14 Worldwide the prevalence of HCV infection among pregnant women and children has been estimated to 1–8% and 0.05–5% respectively.Citation15 About 30% of the 33 million persons infected with HIV also are infected with HCV.Citation16
Need for Vaccine
A hepatitis C vaccine will be like winning the battle for preventive as well as therapeutic world of medicine. Due to the six different genotypes, easily mutability of the virus bringing technical difficulties, there has been a delay in getting to the gold but good progress have been made in developing an effective and affordable vaccine.Citation17
The gold standard treatment for HCV infection is a weekly subcutaneous injections of pegylated interferon (PEG-IFN) combined with daily oral ribavirin for a period of 24 weeks for genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. This gold treatment is not so shiny, it has significant side effects and leads to a Sustained Virological response (SVR; patients are negative for the virus by reverse transcription PCR 6 mo after finishing therapy) in approximately 40–50% of patients with genotype 1 infection, 65–70% with genotype 3 and 80% of those with genotype 2.Citation18
Recently hepatitis medicines are included in the WHO Essential Medicines List, which member states are encouraged to adopt.Citation9 But, for low income or middle income countries, to include these costly drugs for affordable cost will definitely be a tedious task requiring rigorous budgeting and planning. Two new therapeutic agents, telaprevir and boceprevir which are protease inhibitors, have recently been licensed in some countries.Citation9 Because these drugs will be used together with PEG-IFN/ribavirin, the cost of treatment will rise further and additional side effects, in particular skin rashes, can be anticipated more over they are currently only effective against genotype 1.Citation18
In course of progress of a nation, hepatitis C poses a great financial burden. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD in 2003Citation19 with the cost of a liver transplant as of 2011 costing approximately $200 000 USD.Citation20 PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries.Citation21
Even though results for the treatment of new infections have been promising, there still remains the problem of treating the ~170 million chronically infected patients worldwide, many of whom have not responded to IFN/Ribavirin treatment in the past.Citation17 Despite the remarkable achievements in development of treatment against HCV, and the recent advances in new prevention technologies, the rate of new HCV infections continue to outpace efforts on HCV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of HCV remains a global public health priority.
Vaccines for HCV are expected to give answers to all the questions. HCV vaccines can be divided into vaccines designed to induce T-cell responses, targeting non-structural proteins or those primarily designed to induce neutralizing antibody responses, targeting the envelope region of the virus.Citation17 The four main strategies have been investigated in clinical trials namely recombinant protein vaccines, epitope vaccines, DNA vaccines, and vector vaccines.Citation22
Only a small fraction of animal HCV vaccine studies have progressed to human trials. The majority of these trials have evaluated potential therapeutic vaccines in HCV infected patients.Citation17 HCV vaccine research to date has mostly focused on one area of the virus (the NS3/4A proteins) to induce T-cell responses. A vaccine named ChronVac-C developed by Inovia Pharmaceuticals has successfully completed its phase II clinical trial.Citation23 Another vaccine named INO 8000 also developed by Inovia Pharmaceuticals is expected to soon enter phase I/IIa clinical trial. It is a synthetic multi-antigen DNA vaccine covering HCV genotypes 1a and 1b and targeting the antigens NS3/4A, which includes HCV non-structural proteins 3 (NS3) and 4A (NS4A), as well as NS4B and NS5A proteins.Citation24 It is one of the milestones that have been achieved and hope further research will soon give the relief which has been eyed for so long.
To conclude, hepatitis C not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
References
- World Health Organization. Sixty-third World Health Assembly. Viral hepatitis: WHA 63.18. Geneva,Switzerland:WHO;2010. Available from: http://apps.who.int/iris/bitstream/10665/85397/1/9789241564632_eng.pdf [Accessed on 10 October 2013]
- World Health Organization. WHO urges governments to act on hepatitis threat. World Hepatitis Day 2013. Geneva,Switzerland:WHO;2013. Available from: http://www.who.int/mediacentre/news/releases/2013/hepatitis_threat_20130724/en/. [Accessed on 12 October 2013]
- Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005; 5:558 - 67; http://dx.doi.org/10.1016/S1473-3099(05)70216-4; PMID: 16122679
- Chen YD, Liu MY, Yu WL, Li JQ, Peng M, Dai Q, Liu X, Zhou ZQ. Hepatitis C virus infections and genotypes in China. Hepatobiliary Pancreat Dis Int 2002; 1:194 - 201; PMID: 14607738
- Lauer GM, Walker BD. Hepatitis C virus infection. [Accessed on 10 October 2013] N Engl J Med 2001; 345:41 - 52; http://lcbaxterlibrary.tripod.com/ereserves/internal_medicine_core_readings/nejm_345_41.pdf http://dx.doi.org/10.1056/NEJM200107053450107; PMID: 11439948
- Afdhal NH. The natural history of hepatitis C. Semin Liver Dis 2004; 24:Suppl 2 3 - 8; http://dx.doi.org/10.1055/s-2004-832922; PMID: 15346240
- Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332:1463 - 6; http://dx.doi.org/10.1056/NEJM199506013322202; PMID: 7739682
- Yu ML, Chuang WL. Treatment of chronic hepatitis C in Asia: when East meets West. J Gastroenterol Hepatol 2009; 24:336 - 45; http://dx.doi.org/10.1111/j.1440-1746.2009.05789.x; PMID: 19335784
- Sheet F. Hepatitis C. Geneva, Switzerland: World Health Organization; 2013. Available from: http://www.who.int/mediacentre/factsheets/fs164/en/ [Accessed on 14 Oct 2013]
- Maheshwari A, Thuluvath PJ. Management of acute hepatitis C. Clin Liver Dis 2010; 14:169 - 76, x; http://dx.doi.org/10.1016/j.cld.2009.11.007; PMID: 20123448
- Hunt CM, Carson KL, Sharara AI. Hepatitis C in pregnancy. Obstet Gynecol 1997; 89:883 - 90; http://dx.doi.org/10.1016/S0029-7844(97)81434-2; PMID: 9166361
- Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ. A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection. Int J Epidemiol 1998; 27:108 - 17; http://dx.doi.org/10.1093/ije/27.1.108; PMID: 9563703
- Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier MH, Myers RP, Muntenau M, Ratziu V, Manns M, et al, PANFIBROSIS Group. A comparison of fibrosis progression in chronic liver diseases. J Hepatol 2003; 38:257 - 65; http://dx.doi.org/10.1016/S0168-8278(02)00413-0; PMID: 12586290
- Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57:1333 - 42; http://dx.doi.org/10.1002/hep.26141; PMID: 23172780
- Arshad M, El-Kamary SS, Jhaveri R. Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment?. J Viral Hepat 2011; 18:229 - 36; http://dx.doi.org/10.1111/j.1365-2893.2010.01413.x; PMID: 21392169
- Price JC, Thio CL. Liver disease in the HIV-infected individual. Clin Gastroenterol Hepatol 2010; 8:1002 - 12; http://dx.doi.org/10.1016/j.cgh.2010.08.024; PMID: 20851211
- Major ME. Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives. Viruses 2009; 1:144 - 65; http://dx.doi.org/10.3390/v1020144; PMID: 21994543
- Halliday J, Klenerman P, Barnes E. Vaccination for hepatitis C virus: closing in on an evasive target. Expert Rev Vaccines 2011; 10:659 - 72; http://dx.doi.org/10.1586/erv.11.55; PMID: 21604986
- Wong JB. Hepatitis C: cost of illness and considerations for the economic evaluation of antiviral therapies. Pharmacoeconomics 2006; 24:661 - 72; http://dx.doi.org/10.2165/00019053-200624070-00005; PMID: 16802842
- El Khoury AC, Klimack WK, Wallace C, Razavi H. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hepat 2012; 19:153 - 60; http://dx.doi.org/10.1111/j.1365-2893.2011.01563.x; PMID: 22329369
- Grieve R, Roberts J, Wright M, Sweeting M, DeAngelis D, Rosenberg W, Bassendine M, Main J, Thomas H. Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C. Gut 2006; 55:1332 - 8; http://dx.doi.org/10.1136/gut.2005.064774; PMID: 15994216
- Yu CI, Chiang BL. A new insight into hepatitis C vaccine development. J Biomed Biotechnol 2010; 2010:548280; http://dx.doi.org/10.1155/2010/548280; PMID: 20625493
- Pharmaceuticals I. Inovio collaborator ChronTech Reports Interim Phase II Clinical Study Results from ChronVac-C Vaccine for Hepatitis C infection. Inovio Pharmaceuticals; 2013 April 2. Available from: http://ir.inovio.com/2013-04-02-Inovio-Collaborator-ChronTech-Reports-Interim-Phase-II-Clinical-Study-Results-from-ChronVac-C-Vaccine-for-Hepatitis-C-Infection [Accessed on 15 Oct 2013]
- Pharmaceuticals I. Inovio Pharmaceuticals to Initiate Clinical Trial for its Hepatitis C Therapeutic Vaccine (INO-8000) Later this Year. Inovio Pharmaceuticals; 2013 Jan 9. Available from: http://www.inovio.com/products/infectious-disease vaccines/hepatitis/ino8000HCV/ [Accessed on 15 Oct 2013]