How far are we from global viral hepatitis elimination?

Worldwide, over 300 million people around the world are living with viral hepatitis. However, 80 % of infected people lack access to prevention, testing and treatment. Here, we summarise the current information about the different types of viral hepatitis and therapeutic options.

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By definition, hepatitis is an inflammation of the liver which can be due to different possible causes, including toxic substances, such as alcohol or certain drugs and autoimmune diseases. However, viral infections are the most common cause of hepatitis around the world.

Over 300 million people (roughly 4% of the world's population) are living with viral hepatitis resulting in approximately 1.3 million deaths per year1. However, the real public health dimensions and the impact of hepatitis epidemics are poorly understood in many countries, being the contribution of chronic hepatitis to global morbidity and mortality generally underestimated.

Viral hepatitis is a leading cause of death and disability worldwide, killing more people than either HIV or malaria and having a devastating impact on communities worldwide. Most viral hepatitis deaths were due to chronic liver disease and primary liver cancer. Until few years ago, it was a hidden epidemic with little hope for a treatment or cure. However, with recent improvements in vaccines and treatments against viral hepatitis, that is no longer the case.

During World Hepatitis Day 2019 campaign, WHO is urging all countries and partners to promote the theme “Invest in eliminating hepatitis” to achieve globally agreed hepatitis elimination goals by 2030. Here, we summarise the current information about the different types of viral hepatitis and therapeutic options.

There are five main hepatitis viruses, which are responsible for most cases of viral hepatitis, referred to as types A, B, C, D and E. All the different hepatitis viruses can cause acute hepatitis. However, only hepatitis B, C and D viruses are responsible of causing chronic hepatitis, which can lead to fibrosis, cirrhosis and/or hepatocellular carcinoma.

Symptoms of hepatitis can include: fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-coloured stools, joint pain, and jaundice. However, many people with hepatitis do not have symptoms and do not know they are infected for many years.

Hepatitis A (HAV):

HAV is a non-enveloped, positive sense, single stranded RNA virus that can cause mild to severe illness. Most people make a full recovery after which they develop life-long protection from future infection. However, if the infection progresses, symptoms can be severe and life-threatening.

Transmission: The virus mainly spreads by the faecal–oral route and is transmitted through ingestion of contaminated food and water or through direct contact with an infectious person. The disease is often endemic in countries with a lack of safe drinking water and poor sanitation.

Treatment and prevention: There are no specific drugs to cure HAV infection but safe and effective vaccines that protect against HAV infection have been developed.

World hepatitis day 2019: campaign material (WHO)

Hepatitis B (HBV):

HBV is an enveloped DNA virus which is a major global health problem that can cause both acute and chronic infections. Most people recover in 6 months. However, in a long-term infection could put people at high risk of death from cirrhosis and liver cancer.

Transmission: HBV spreads mainly through contact with blood from an infected person but also by contact with other body fluids such as vaginal secretions, or semen.

Treatment and prevention: Currently there is no cure for hepatitis B infection but some antiviral drugs can help keep the virus under control and, most importantly, greatly reduce the risk of life-threatening complications. Nowadays, treatment for HBV infection is based on pegylated interferon (IFN) alpha and reverse transcriptase inhibitors, or combinations resulting in viral rebound if treatment is interrupted. Entry inhibitors and encapsidation inhibitors are also being developed to increase the chance of reaching the functional cure of HBV.

An early win in the global response to viral hepatitis was achieved through the effective scaling up of safe and effective hepatitis B vaccines.

Hepatitis C (HCV):

Hepatitis C is the most common type of viral hepatitis and is caused by an enveloped, positive-sense single-stranded RNA virus. HCV is found worldwide, being central and east Asia and north and west Africa the most affected regions.

About 15 to 25 % of people with the virus clear it without treatment. However, chronic hepatitis C infection can lead to permanent liver damage by developing cirrhosis and/or hepatocellular carcinoma.

Transmission: Hepatitis C is transmitted through direct contact with infected body fluids, mainly through blood-to-blood contact, and typically through injection drug use and sexual contact.

Treatment and prevention: Currently there is no vaccination for hepatitis C. However, new treatments based of direct-acting antiviral drugs are available and can cure over 95 % of people who take them. Current treatments are provided generally between 8 to 12 weeks with fewer side effects compared to previously used treatments including other drugs such as IFN alpha and ribavirin.

Hepatitis D (HDV):

HDV is a small enveloped, single-stranded, negative sense RNA satellite virus that requires of a co-infection with HBV to assemble new virion particles and to infect liver cells due to the necessity of the envelope proteins of HBV.

Transmission: Hepatitis D is transmitted through contact with infected blood. Patients who already have chronic hepatitis B infection can acquire hepatitis D virus infection at the same time as they acquire the hepatitis B infection, or at a later time.

Treatment and prevention: As mentioned above, hepatitis D only occurs in people who are already infected with HBV. Therefore, hepatitis D infection can be prevented through hepatitis B virus vaccination. Treatment available for hepatitis D infection are not very effective and the antiviral drugs being used are shared with HBV.

World hepatitis day 2019: campaign material (WHO)

Hepatitis E (HEV):

HEV is a non-enveloped, positive-sense, single-stranded RNA virus similar to hepatitis A in terms of disease progression. HEV is found worldwide, but mainly in countries with limited access to essential sanitation and health services.

Most people with hepatitis E usually recover by themselves and rarely develops into a very severe disease. However, infection with hepatitis E virus can be very dangerous for anyone with weak immune systems, including elderly people and pregnant women.

Transmission: HEV is mainly transmitted via faecal–oral route through eating contaminated food or drinking contaminated water.

Treatment and prevention: Currently there is no standard treatment or global available vaccine for HEV but people usually recover by themselves. Treatment with IFN alpha and ribavirin is sometimes provided to immunosuppressed hosts.

In summary, the public health goal is to further reduce the global mortality and morbidity related to viral hepatitis. There are good evidence that eliminating viral hepatitis is technically feasible, by extensively applying the hepatitis B vaccine and the recent development of highly effective treatments against HCV, which are responsible for 96% of all hepatitis mortality.

However, as access to affordable hepatitis testing is limited, millions of people worldwide are undiagnosed carriers of hepatitis B or C virus infections, which can remain asymptomatic for decades, leading to life-threatening diseases.

World hepatitis day 2019: campaign material (WHO)

Therefore, despite research in the field of viral hepatitis has been highly active, to complete the set of tools available to eliminate viral hepatitis infections, investment in resources to increase the proportion of those infected who are diagnosed represent a major challenge. In addition, finding of a functional cure for those already chronically infected with HBV and a vaccine against HCV infection would dramatically increase the options to achieve the global elimination of viral hepatitis in the future.

Jose M. Jimenez-Guardeño and Ana M. Ortega-Prieto

Images: World hepatitis day 2019: campaign material (WHO)

References and further reading:

World Health Organization (WHO)

http://www.worldhepatitisday.org/

https://www.cdc.gov/hepatitis/abc/index.htm

https://bescienced.com/

http://www.worldhepatitisalliance.org

1          Waheed, Y., Siddiq, M., Jamil, Z. & Najmi, M. H. Hepatitis elimination by 2030: Progress and challenges. World J Gastroenterol 24, 4959-4961 (2018).

Jose M. Jimenez-Guardeño

Research Fellow, King's College London

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