A new serious pediatric hepatitis of unknown origin has recently set off alarms around the world. But you’re not alone: there are at least five known viruses that cause hepatitis (A, B, C, D and E). The viral hepatitis they cause are among the four major causes of mortality worldwide and are responsible for 1.4 million deaths each year. That far exceeds deaths due to tuberculosis, malaria or AIDS.
Specifically, in 2019 it was estimated that around 296 million people worldwide had chronic hepatitis B infection and it is currently estimated that 58 million have chronic hepatitis C.
How many types of hepatitis are there?
In essence, hepatitis is inflammation of the liver when it has been injured or infected. This means that its causes can be varied: hereditary, autoimmune if it is cells of the immune system that attack the liver, viral, bacterial, etc. But also a consequence of a high consumption of alcohol or the abuse of certain medications, such as an overdose with paracetamol.
Viral hepatitis is due to infection of liver cells (hepatocytes) with one of the five hepatitis viruses: A, B, C, D or E. They are diagnosed with specific antibodies (serological tests) or by PCR (molecular tests ).
Viral hepatitis begins as an acute illness with flu-like symptoms, including poor appetite, nausea, vomiting, and malaise. If they become chronic, because the immune system cannot get rid of the virus after six months, other problems appear such as jaundice (yellowing of the skin, mucous membranes or eyes), hepatomegaly (exaggerated size of the liver), ascites (accumulation of fluid in the abdomen) and dark urine.
Furthermore, over time, chronic hepatitis can lead to fibrosis of the liver parenchyma and develop into liver cancer, that is, hepatocellular carcinoma.
Are viral hepatitis serious? As we have said before, they are among the four highest causes of mortality worldwide. While the number of annual deaths from hepatitis C is decreasing globally, the number of deaths from hepatitis B or D is increasing.
Variability of hepatitis viruses and their treatment
Why does each viral hepatitis behave differently? What is the reason for these number dances between the different viral hepatitis? Basically, each hepatitis virus belongs to a different family.
1. Hepatitis A.
Hepatitis A is always acute, caused by an RNA virus, and does not require treatment because the immune system eliminates it in about six months. Its transmission is oral-faecal, by the consumption of contaminated water or food, and the areas of greatest incidence are the majority of developing countries where sanitary and hygiene measures regarding drinking water are deficient.
The most common is to get the hepatitis A while traveling to high-incidence areas or while having sex or caring for an infected person. Drug use is also a risk factor.
2. Hepatitis B.
It is caused by the HBV virus, which is a DNA virus that can integrate into the genome of the cell it infects. It is transmitted through blood, semen and other body fluids and from mother to child (vertical transmission). It generates both acute and chronic hepatitis. It is the latter that require treatment.
Its most important antigen is the HBsAg antigen on its surface, the point of entry to hepatocytes and used in diagnosis and for vaccination. It shares risk factors with hepatitis A but, in addition, health workers in contact with needles, blood or body fluids, and people with some immunosuppression, including HIV patients, are at high risk of contracting HBV.
3. Hepatitis C.
Due to the HCV virus, which is a single-stranded RNA virus. Like HBV, it is spread through contact with the blood of an infected person or through mother-to-child transmission. Hepatitis C is the leading cause of cirrhosis, hepatocarcinoma, and liver transplants.
It shares risk factors with the HAV and HBV viruses, but hemophiliacs, dialysis patients and people with tattoos are added.
4. Hepatitis D.
Caused by a single-stranded, circular RNA virus that is considered defective as it requires double infection with the HBV virus and its HBsAg antigen. Without it, it could not even generate new viruses, as its envelope did not form.
This double infection is the most characteristic of this virus, because it is only found in people already infected with HBV. The virus causes both acute and chronic hepatitis, the latter so severe that it is the leading cause of liver transplants in Europe. The areas of greatest risk of contracting hepatitis D They are Eastern Europe, the Mediterranean region, the Middle East, Asia, Central Africa, and the Amazon region of South America.
5. Hepatitis E.
It originates from another single-stranded RNA virus. In developing countries, it is usual to contract it from contaminated water, affecting adolescents and young people above all. In developed countries, it is spread through undercooked pork or wild game, with the elderly being the most vulnerable. This virus normally generates an acute hepatitis that the immune system manages to contain and in a few weeks it disappears.
Antivirals that stop the virus and antivirals that eliminate it
Hepatitis caused by HBV is treated with classic antivirals, or virostatics, that is, they do not eliminate the virus but rather stop its replication. The most used are entecavir or tenofovir. A new antiviral has recently been approved in Europe, bulevirtide, which mimics its HBAgs surface antigen. This same drug has begun to be used to treat chronic HDV hepatitis.
For chronic HCV hepatitis, classical antivirals such as ribavirin were first used, but currently there are new direct-acting antivirals that achieve total cure. The most used are sofosbuvir, glecaprevir or velpatasvir.
So deaths from chronic hepatitis C are decliningwhile deaths from chronic hepatitis B and D increase, indicating that the different antivirals are not successful in reactivating infections.
As the immune response of patients with chronic hepatitis is also unable to control these viruses naturally, in order to lower the global incidence of chronic hepatitis we should develop more preventive tools.
One of the biggest problems in the treatment of all chronic hepatitis is that the antiviral medication lasts the entire life of the patient. In addition to the high cost it entails for the health system, it gives rise to the appearance of resistance and toxicities. Without forgetting how uncomfortable it is for the patient to be treated for life. Therefore, the new antivirals in experimentation are ultra-long-acting (XLA-antivirals), so they are given only once a year, have a semi-preventive character and are one of the great bets in antivirals. Also, treatment might be adequate for hepatitis B and D.
Vaccines are only available for hepatitis A and B
Regarding the development of preventive vaccines against the different viral hepatitis, we have two vaccines for the hepatitis A virus (HAV) with inactivated virus. They are HAVRIX, from the GlaxoSmithKline company, and VAQTA, from the MERCK company. Both generate a good production of antibodies and confer long lasting protection.
The hepatitis B virus (VHB) It also has a recombinant vaccine, with the HbAgs surface antigen. It is safe, effective and capable of preventing infection. It is offered in the Spanish vaccine calendar to newborns, and for adults over 18 years of age, a form of this recombinant vaccine has recently been approved together with an immunomodulator, Heplisav-B.
For hepatitis C, D and E viruses there are no vaccines available today. The good news is that the experimental approaches used against SARS-CoV-2 could be applied to develop vaccines for these orphan hepatitis of preventive tools. This would make it possible to reduce the global incidence and mortality figures, in addition to protecting those most exposed: children, the elderly and people with weak immune systems, mainly.