Hepatitis C

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.

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.¹ 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.²

The HCV infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.^3,4 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.^5-7 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.⁸

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.⁹ 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.¹⁰ The vertical transmission rate has been estimated to be 3–5% but higher rates have also been reported (18%, 6–36%, and 41%).^11,12 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.¹³

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.⁹ 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%.¹⁴ Worldwide the prevalence of HCV infection among pregnant women and children has been estimated to 1–8% and 0.05–5% respectively.¹⁵ About 30% of the 33 million persons infected with HIV also are infected with HCV.¹⁶

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.¹⁷

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 2.¹⁸

Recently hepatitis medicines are included in the WHO Essential Medicines List, which member states are encouraged to adopt.⁹ 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.⁹ 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 1.¹⁸

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 2003¹⁹ with the cost of a liver transplant as of 2011 costing approximately $200 000 USD.²⁰ 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.²¹

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.¹⁷ 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.¹⁷ The four main strategies have been investigated in clinical trials namely recombinant protein vaccines, epitope vaccines, DNA vaccines, and vector vaccines.²²

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.¹⁷ 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.²³ 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.²⁴ 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.

10.4161/hv.26970