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 Table of Contents  
EDITORIAL
Year : 2019  |  Volume : 6  |  Issue : 1  |  Page : 1-2

Hepatitis C: A success story in the making


Director, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Submission24-May-2019
Date of Acceptance24-May-2019
Date of Web Publication10-Jul-2019

Correspondence Address:
Prof. Rakesh Aggarwal
Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAMR.IJAMR_68_19

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How to cite this article:
Aggarwal R. Hepatitis C: A success story in the making. Int J Adv Med Health Res 2019;6:1-2

How to cite this URL:
Aggarwal R. Hepatitis C: A success story in the making. Int J Adv Med Health Res [serial online] 2019 [cited 2019 Dec 16];6:1-2. Available from: http://www.ijamhrjournal.org/text.asp?2019/6/1/1/262494



Hepatitis C is a major cause of liver disease in most parts of the world. The causative agent, hepatitis C virus (HCV), consists of 55–65 nm, enveloped virions that contain a positive- and single-stranded RNA genome.[1],[2] These virions infect and multiply in hepatocytes, from where these are released into blood circulation. The virus is not excreted into most of the body fluids, except semen and vaginal secretions. The predominant route of its spread therefore is through blood, with small contributions from sexual and mother-to-child transmission. Nosocomial transmission is possible, and unsafe healthcare practices are associated with an increased risk. Some groups such as injecting drug users, recipients of blood and blood products, and persons on maintenance hemodialysis are at a particularly high risk, as are those engaging in ritual scarification, tattooing, and acupuncture. The virus can cause infection only in humans; thus, there is no zoonotic reservoir. It has at least six known genotypes; these have largely similar routes of transmission and clinicopathological consequences, but differ in their geographic distribution and in response to some drugs.

Around 30%–50% of those infected develop a chronic infection, defined as persistence of HCV in a person's body beyond 6 months. Even those who clear the virus do not develop any protection against reinfection. Chronic infection incites a host immune response, albeit too feeble to clear the virus. However, the consequent continuing liver inflammation results in progressive liver inflammation and fibrosis, culminating in cirrhosis and liver cancer in a proportion of those infected.

Discovery of HCV was relatively recent, and its existence was not even suspected till the 1970s. Though transmission of hepatitis through blood products was known before that, all such cases were believed to be caused by hepatitis B, as distinct from hepatitis A which had fecal–oral transmission. Once specific tests for hepatitis A and B viruses were developed, it was found that some cases of blood-borne hepatitis were not related to these viruses, raising the specter of existence of another virus – which was then provisionally named as hepatitis C. The proof came in 1989 with the isolation and cloning of a specific nucleic acid sequence belonging to HCV.[3]

Attempts to treat HCV infection began even before the virus had been definitively identified. It was found that combination therapy with pegylated interferon and ribavirin was effective in a subset of patients, and this became the standard of care in the early 2000s.[4] However, this treatment was costly, frequently caused adverse effects, needed injections, had success rate of only ~50%, and was contraindicated in patients with advanced liver disease or prior organ transplantation.

Discovery of HCV and research into its biology however changed the scene, with the identification of three viral proteins – HCV protease (also known as nonstructural 3a or NS3a protein), viral RNA-dependent RNA polymerase (NS5b), and viral replication complex (NS5a) – as potential drug targets. This was soon followed by development of specific inhibitors for each of these proteins. These compounds, referred to collectively as “direct-acting anti-viral agents” (DAAs), have revolutionized the treatment of HCV infection. The first drug in this group, sofosbuvir – an NS5b inhibitor – was released in 2014,[5] and several other drugs have been released since then.

Several regimens containing either two (NS3a + NS5b inhibitors) or three (NS3a + NS5a + NS5b inhibitors) DAAs have been tried and have proven to be highly efficacious. The rates of sustained virological response, defined as absence of detectable virus in a person's body 6 months after stopping treatment and implying lasting cure, have exceeded 95% in most patients with HCV infection.[6] These excellent trial results also have been replicated in real-life situations, with less stringent patient selection criteria and lower rates of compliance. The DAA regimens have also worked well in difficult-to-treat HCV-infected groups, such as those with renal failure, HIV coinfection, or those receiving immunosuppressive drugs, for example, organ transplant recipients. Thus, we now have the ability to cure a large majority of HCV-infected persons. More recently, even shorter treatment regimens (of 6–8 weeks) have been found to have comparable efficacy,[7] and studies on even shorter regimens are currently underway.

In India, HCV infection affects about 0.4%–0.7% of the population and is responsible for 20%–40% of cases with cirrhosis.[8] Data on transmission are scanty, but it appears that a majority of cases are related either to transfusion of blood and blood products prior to introduction of screening for HCV in blood banks or to unsafe infection control practices, such as reuse of injection equipment. Four DAAs including an NS5B inhibitor (sofosbuvir) and three NS5A inhibitors (ledipasvir, daclatasvir, and velpatasvir) are currently available in the Indian market. A redeeming feature of the Indian HCV scenario is the extremely low price of DAAs, with the cost of treating one patient being much below 100 US dollars, compared to upward of US dollars 30,000 in high-income countries. Using a mathematical modeling technique, we have shown that HCV treatment at this cost is not only cost-effective but actually cost-saving.[9] This implies that the savings in future healthcare costs (through prevention of cirrhosis and liver cancer) would far exceed the money spent on treating HCV infection, thus leading to an overall monetary saving while improving survival, a win-win situation.

Given this happy trade-off, governments of some states, in particular Punjab, have started programs for free HCV treatment for all those eligible.[10] More recently, Government of India has launched a national viral hepatitis control program.[11] This program has been able to procure anti-HCV drugs at prices even far below the market prices indicated above (of the order of US$ 40 for 3-month regimen for treating one person). Thus, the country is on the cusp of a large hepatitis C treatment program.

The main challenge thus lies in our ability to identify HCV-infected persons so that they may be treated. HCV infection is largely asymptomatic. Hence, most of the infected persons are unaware of their HCV status. Thus, we will need to set up a large-scale HCV screening program, beginning with those who have identifiable risk factors for HCV infection, and later covering the general population. In India, blood transfusion before 2000, when HCV screening of donated blood became mandatory, is possibly the best such identifier. The success of treatment program will also depend on availability of adequate health workforce to treat the nearly 7 million HCV-infected Indians. This is possible only through a major task shift in the healthcare sector, with the diagnosis and treatment of HCV infection moving from the hands of hepatologists into those of internists and finally of non-specialist doctors.

The availability of highly efficacious and safe treatments has led to a major change in our thinking about HCV. Thus, the World Health Assembly, in 2016, endorsed a Global Health Sector Strategy on Viral Hepatitis. This strategy envisages elimination of hepatitis C,[12] which is defined as: (i) 90% reduction in new cases of HCV; (ii) detection of HCV infection in 90% of those infected; and (iii) treatment and cure of HCV infection in 80% of persons eligible for current treatments. Successful achievement of these targets is estimated to reduce the mortality due to hepatitis C worldwide by 65% by the year 2030. This could not have even been imagined a decade ago, but now appears achievable.[13] Several countries such as Egypt, Georgia, and Mongolia have already started on this path, by launching large HCV screening and treatment programs, and several other countries are contemplating doing so. India too has started action on this front. Overall, the future looks very optimistic and bright.



 
  References Top

1.
Webster DP, Klenerman P, Dusheiko GM. Hepatitis C. Lancet 2015;385:1124-35.  Back to cited text no. 1
    
2.
Kim A. Hepatitis C virus. Ann Int Med 2016;165:ITC33-48.  Back to cited text no. 2
    
3.
Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989;244:359-62.  Back to cited text no. 3
    
4.
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet 2001;358:958-65.  Back to cited text no. 4
    
5.
Koff RS. Review article: The efficacy and safety of sofosbuvir, a novel, oral nucleotide NS5B polymerase inhibitor, in the treatment of chronic hepatitis C virus infection. Aliment Pharmacol Ther 2014;39:478-87.  Back to cited text no. 5
    
6.
Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral direct-acting agent therapy for hepatitis C virus infection: A systematic review. Ann Intern Med 2017;166:637-48.  Back to cited text no. 6
    
7.
Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med 2014;370:222-32.  Back to cited text no. 7
    
8.
Goel A, Seguy N, Aggarwal R. Burden of hepatitis C virus infection in India: A systematic review and meta-analysis. J Gastroenterol Hepatol 2019;34:321-9.  Back to cited text no. 8
    
9.
Aggarwal R, Chen Q, Goel A, Seguy N, Pendse R, Ayer T, et al. Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India. PLoS One 2017;12:e0176503.  Back to cited text no. 9
    
10.
Dhiman RK, Satsangi S, Grover GS, Puri P. Tackling the hepatitis C disease burden in Punjab, India. J Clin Exp Hepatol 2016;6:224-32.  Back to cited text no. 10
    
11.
Ministry of Health and Family Welfare, Government of India. National Action Plan Combating Viral Hepatitis in India. Available from: https://mohfw.gov.in/sites/default/files/National%20Action%20Plan_Lowress_Reference%20file.pdf. [Last accessed on 2019 May 20].  Back to cited text no. 11
    
12.
World Health Organization. Global Health Sector Strategy on Viral Hepatitis 2016±2021. World Health Organization; 2016. Available from: http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en. [Last accessed on 2019 May 20].  Back to cited text no. 12
    
13.
Thomas DL. Global elimination of chronic hepatitis. N Engl J Med 2019;380:2041-50.  Back to cited text no. 13
    




 

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