Are we close to curing hepatitis C? (With new research for #WorldHepatitisDay)

A Hepatitis C expert writes about what’s being done to tackle the disease

Giuseppe Ippolitto, MD, is Scientific Director of of the National Institute for Infectious Diseases "Lazzaro  Spallanzani" in Rome an and author of one of the articles in the collection featured at the end of this story.Hepatitis is caused by viruses – hepatitis A, B, C, D and E – and like all viral diseases, they are transmitted from person to person. Infection can lead to liver inflammation, cirrhosis and liver cancer; around 1 in 4 liver cancer deaths are caused by hepatitis B and C infection. However, the progression of infection does not always lead to disease or death, and progression is slow. The problem is that the disease is very widespread and can be severe or fatal.

The World Health Organization set up World Hepatitis Day to raise awareness of these diseases, reduce infection rates and improve survival. But what is needed if we want to eradicate hepatitis and is it even possible?

Here, Dr. Giuseppe Ippolitto, Scientific Director of the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, writes about his expertise on Hepatitis C. An article he authored for the International Journal of Antimicrobial Agents leads off the collection of research at the end.

Hepatitis C: a widespread public health concern

Hepatitis C is a significant public health problem globally. The Hepatitis C virus was identified around 25 years ago and now infects about 3 percent of the population, causing more than 350,000 deaths every year.

A computer-generated model of hepatitis C virus, the cause of hepatitis C liver disease. The virion has a symmetrical protein coat or capsid (blue), from which project surface protein molecules (orange) that help the virus attach to its target cell. The capsid contains strands of RNA (ribonucleic acid, not seen), the virus' genetic material. Hepatitis C is most commonly spread by blood contact, through blood transfusions or the sharing of infected needles. It causes inflammation of the liver with slowly progressing diseases. There is currently no vaccine for hepatitis C. (Source: Russell Kightley/Science Photo Library)At the National Institute for Infectious Diseases (INMI) Lazzaro Spallanzani, we work on the pathogenesis, epidemiology, treatment and public health aspects of hepatitis C. A patient can come to INMI for care from first diagnosis to liver transplant; we have 162 ward beds, 12 intensive care beds and outpatient services to help patients at all stages of disease. It’s also vital to continue to research the virus and develop new treatments and prevention strategies. We focus on several aspects, including molecular pathways, viral evolution and immunity.

Traditionally, hepatitis C infections were treated using a combination of two drugs – interferon and ribavirin – with a success rate of around 50 percent. These drugs have serious side effects and as a result are not ideal for widespread use.

The recent introduction of new compounds that directly block the virus from replicating has changed the face of hepatitis C treatment. Direct-acting antivirals (DAAs) appear to be safer than traditional treatments and are much more effective, having a sustained effect in 80-100 percent of patients.

Although this is a promising development for the disease, costs are prohibitive. The price of DAAs is so high that most patients cannot afford the treatment, and most public health departments cannot pay for it, which means that a limited number of patients may benefit from the treatment. Despite this, companies are reluctant to reduce the price of the drugs. So even though DAAs could have a significant effect on disease progression and improve the lives of millions of patients, the high cost means they are not currently a viable option on a large, long-term scale.

Is eradication possible?

Eradication is a big word when it comes to hepatitis C. Currently, people believe the best way to eradicate the disease in an individual patient is to stop virus replication for long enough that the virus disappears from every infected cell. This is very difficult to confirm, since tiny amounts of viral RNA can go undetected in tests, giving the false impression that the virus has been eliminated.

Eradication at the population level is an even bigger challenge. There are models for eradication, but these depend on the number of patients and the effectiveness of drugs; there are millions of hepatitis C patients, including a large proportion who are unaware they are infected, and the treatments widely used until today are not fully effective. One of the big problems the World Health Organization faces with hepatitis is this lack of ability to eradicate the disease immediately, therefore a step-by-step approach is needed.

World Hepatitis Day

World Hepatitis Day logoViral hepatitis affects hundreds of millions of people globally, killing 1.4 million people every year: almost 4,000 deaths a day. Many of these deaths could be avoided by preventing infection, and the World Health Organization (WHO) established World Hepatitis Day to raise awareness of the disease for this purpose. On World Hepatitis Day 2015 – July 28 – WHO and partners will urge policymakers, health workers and the public to act to prevent infection and death from hepatitis. The official hashtags are #PreventHepatitis and #WorldHepatitisDay.

For more information, visit the websites of WHO and the World Hepatitis Alliance.

Related resource

The American Journal of Medicine has an online Hepatitis C Resource Center.

The two steps to take first are to reduce the impact of the disease and reduce HCV circulation. When it comes to reducing impact, it is important to consider disease progression. Because of the cost of treatment, patients in advanced stages of disease are prioritized, leaving the large reservoir of people at different stages of infection untreated. Many of these people may not know about their infection.

Targeted screening has been suggested as a way to address this reservoir, but it has also been a topic of debate, since there have been no studies to suggest that widespread screening is beneficial. Several organizations and indirectly pharmaceutical companies are keen to support screening, since it would increase the number of patients eligible for treatment. In any case, it should be noted that knowing the presence of  infection is useful to prevent other cases.

However, if screening was to identify a large proportion of infected people, healthcare systems may not be able to cope: in Italy we would have 1 million patients to treat. Some countries are experimenting with different approaches to this. In Spain they are treating patients with the most advanced disease – grade 4 – first, then moving on to grade 3 and so on.

So for eradication to be a realistic possibility, we would need cheap and accurate tools to monitor virus elimination from infected individuals, the cost of drugs would need to be manageable for public health authorities and sustainable in the long term, and people with advanced disease would need immediate care first.

Raising awareness to reduce infection

One approach to reducing the incidence of hepatitis C is to increase awareness of the infection risk; this is one role of World Hepatitis Day. Hepatitis viruses are transmitted through two different routes: oral-fecal and via blood: for example, through sharing syringes or during medical procedures. Hepatitis B and C are transmitted via the second route, so prevention is possible by avoiding the exchange of syringes and ensuring medical devices are properly sterilized.

For people with hepatitis, this is an important day, but we must remember that people live with the disease the whole year. It’s an opportunity to reflect on the great work that is being done, and address some of the challenges that still stand in the way of disease reduction.

We need to try to increase awareness and sensitivity, particularly among politicians, about the problems associated with hepatitis. We also need to negotiate with companies a sustainable approach to treatment. We need to continue to research and understand the virus and disease progression in more detail, and look for public health approaches that enable us to tackle hepatitis in a long-term, sustainable way.

Free access to new new research on hepatitis

This virtual collection of articles has been collated to support the WHO in its efforts to raise awareness about viral hepatitis and to call for access to treatment, better prevention programs and government action. You can read these articles for free until 30 November 2015.

International Journal of Antimicrobial Agents

Is hepatitis C virus eradication around the corner only 25 years after its discovery?Ippolito G., Capobianchi M.R., Lanini S., Antonelli G.
International Journal of Antimicrobial Agents, volume 45, issue 2, Pages 111-112

Clinical Microbiology and Infection

Current knowledge and future perspectives on acute hepatitis C infection
Hullegie, S.J., Arends, J.E., Rijnders, B.J.A., Irving, W.L., Salmon, D., Prins, M., Wensing, A.M., Klenerman, P., Leblebicioglu, H., Boesecke, C., Rockstroh, J.K., Hoepelman, A.I.M.
Clinical Microbiology and Infection, Available online 16 April 2015

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort
Postorino, M.C., Prosperi, M., Quiros-Roldan, E., Maggiolo, F.,
Clinical Microbiology and Infection, Volume 21, Issue 4, April 2015, Pages 386.e1–386.e9

Journal of Infection

Exploratory trial of ombitasvir and ABT-450/r with or without ribavirin for HCV genotype 1, 2, and 3 infectionEric Lawitz,  Greg Sullivan, Maribel Rodriguez-Torres, Michael Bennett, Fred Poordad, Mudra Kapoor, Prajakta Badri, Andrew Campbell, Lino Rodrigues Jr., Yiran Hu, Tami Pilot-Matias, Regis A. Vilchez
Journal of Infection
, Volume 70, Issue 2, February 2015, Pages 197–205

Differences in serum microRNA profiles in hepatitis B and C virus infectionSakura Akamatsu, C. Nelson Hayes, Masataka Tsuge, Daiki Miki, Rie Akiyama, Hiromi Abe, Hidenori Ochi, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, Hiroshi Aikata, Tomokazu Kawaoka, Yoshiiku Kawakami, Waka Ohishi, Kazuaki Chayama
Journal of Infection, Volume 70, Issue 3, March 2015, Pages 273–287

International Journal of Infectious Diseases

Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C
Wang J.-H., Jiang D., Rao H.-Y., Zhao J.-M., Wang Y., Wei L.
International Journal of Infectious Diseases, Volume 30, January 2015, Pages 52-56

An albumin, collagen IV, and longitudinal diameter of spleen scoring system superior to APRI for assessing liver fibrosis in chronic hepatitis B patients
Huang Z.-L., Chen X.-P., Zhao Q.-Y., Zheng Y.-B., Peng L., Gao Z.-L., Zhao Z.-X.
International Journal of Infectious Diseases, Volume 31, February 2015, Pages 18-22

Diagnostic Microbiology and Infectious Disease

Can serum level of HBsAg differentiate HBeAg-negative chronic hepatitis B from inactive carrier state?
Shahnaz Sali, Heidar Sharafi, Seyede Hoda Alavian, Seyed Moayed Alavian, Faranak Etesam, Shima Salimi, Muayad A. Merza, Maryam Keshvari
Diagnostic Microbiology and Infectious Disease, Volume 82, Issue 2, June 2015, Pages 114-119

Clinical Immunology

Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C
Li-Yuan Wu, Shuhong Liu, Yuan Liu, Chaonan Guo, Hanwei Li, Wenshu Li, Xueyuan Jin, Keming Zhang, Ping Zhao, Lai Wei, Jingmin Zhao
Clinical Immunology, Volume 158, Issue 1, May 2015, Pages 77–87

Human Immunology

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia
Piotr Kuśnierczyk, Iwona Mozer-Lisewska, Katarzyna Zwolińska, Arleta Elżbieta Kowala-Piaskowska, Maciej Bura, Iwona Bereszyńska, Anna Pauli, Jan Żeromski
Human Immunology, Volume 76, Issues 2–3, March 2015, Pages 102–108

Immunology Letters

Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway
Yi Chen, Si Chen, Li-Yuan Liua, Zhuo-Lin Zoua, Yi-Jing Caia, Jin-Guo Wang, Bi Chen,
Lan-Man Xu, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
Immunology Letters, Volume 162, Issue 2, Part B, December 2014, Pages 222–228

Journal of Hepatology

Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases
Francesco Negro
Journal of Hepatology, Volume 61, Issue 1, Supplement, November 2014, Pages S69–S78

Elsevier Connect Contributor

Dr. Giuseppe Ippolito Scientific Director of the National Institute for Infectious Diseases (INMI) "Lazzaro Spallanzani" in Rome, Italy.

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