You’ve probably heard of hepatitis before. Maybe you’ve even been immunised against it. But the term “hepatitis” doesn’t just refer to one disease, it’s actually an umbrella term for a whole range of diseases, ranging from relatively mild and short-lived to chronic disease, resulting in liver failure and death. As today is World Hepatitis Day, let’s take a look at the different types of hepatitis and what diagnosis with them can mean.
Hepatitis simply means ‘inflammation of the liver’, and is most commonly caused by five different viruses – handily named hepatitis A, B, C, D and E. There are other causes of hepatitis, such as long-term alcohol abuse, autoimmune conditions, and misuse of certain drugs such as paracetamol. However, since my expertise lies in virology and immunology, we’re going to focus the viral types today.
For millennia, hepatitis-like diseases have been recorded. In fact, the earliest known description of a hepatitis-like disease dates back to Ancient Sumeria, around 3000 BC, a disease named Ahhazu that attacked the liver and killed patients within 11 days. One of the main symptoms of hepatitis, jaundice – a yellowing of the skin and eyes - was also described as a symptom of an epidemic by the Greeks and Romans, however, it wasn’t until the 20th-century that the different types of viral hepatitis were differentiated and the virus was discovered. The need for research into infectious hepatitis was highlighted initially during World War II due to outbreaks of hepatitis occurring in recipients of blood and plasma transfusions, and in recipients of the yellow fever vaccine – a vaccine made up of donor plasma. These outbreaks of hepatitis decimated troops around the world. A number of ‘volunteer’ studies at the time resulted in the identification of two different types of hepatitis, varying in incubation, symptoms and epidemiology (the frequency, distribution, and possible control of diseases) – ‘infectious hepatitis’ and ‘serum hepatitis’, later named hepatitis A and B respectively. The definitive confirmation of this came between 1964-1967, in a series of studies at the Willowbrook School in New York State, which suffered from successive outbreaks of hepatitis. Patients from this school for developmentally disabled children were involved in a trial in which they were deliberately inoculated with serum from hepatitis infected patients in order to monitor incubation, symptoms and outcome, and conclusively outline the differences between hepatitis A and B. To us now, this sounds barbaric and completely unethical. Human studies were far more commonplace and relaxed in the early-mid 20th-century, so these inoculations were not out of the ordinary at the time. These days thankfully, any studies in humans are carefully monitored and subject to strict ethical guidelines, and this kind of experiment would certainly not be allowed to go ahead.
The more we know about hepatitis A and B, the more differences we can see between the two diseases, despite them both affecting the liver. Hepatitis A is usually transmitted via the faecal-oral route, and infected patients shed high loads of virus in their faeces for several weeks before showing symptoms. This leads to extremely high infection rates in areas of poor infrastructure and sanitation, particularly as the virus can survive for long periods of time in food and water at room temperatures. In some countries, up to 90% of children have had hepatitis A before their 10th birthday, many without any symptoms. Once the virus has been ingested via contaminated food or water, it travels to the liver where it begins to replicate. This causes symptoms such as fever, hives and abdominal pain, progressing to jaundice, swelling of the stomach and potentially liver failure. Most people however, do make a full recovery in a few months and without any specific treatment; deaths are very rare and account for only 0.5% of all viral hepatitis deaths annually. Hepatitis E, discovered only 40 years ago in India, is very similar to hepatitis A in that it causes a mostly mild, short lasting disease and is transmitted by contaminated water.
In comparison, Hepatitis B is most commonly transmitted from mother to child during birth, though it can also be transmitted by exposure to infected blood, for example in contaminated blood transfusions or sexual contact. Hepatitis B patients often do not show symptoms when they’re first infected, but 20-30% of adults and up to 90% of children can develop a chronic, long term infection and liver failure. The good news is that cheap, low-side effect treatment is available for hepatitis B, which can minimise long term complications such as liver cancer. However, these anti-virals cannot cure the disease, so people must take them for life. Although a vaccine is available, the WHO estimates that as of 2015 there are around 257 million people living with chronic hepatitis B, with 887,000 deaths per year resulting from disease complications. Part of the reason for this is that due to lack of early symptoms, many people are not diagnosed until after severe liver damage has already occurred.
Just like hepatitis B, hepatitis C is also transmitted by infected blood, through infected needles, sexual contact and contaminated blood products. While successful vaccines are available for hepatitis A and B, hepatitis C can only be prevented by eliminating exposure to the virus, through methods such as needle exchange, protected sex and proper screening of blood products. Just like hepatitis B, people infected with hepatitis C don’t tend to show any symptoms after infection, and often are not diagnosed until complications such as cirrhosis of the liver and a cancer called hepatocellular carcinoma, occur. Hepatitis C can be cured however, with drugs called DAAs. Though these drugs started out very expensive, making them inaccessible in poorer areas, generic versions have now been developed, dropping the price and making them more accessible. Unfortunately, these won’t make a real difference in hepatitis C deaths – around 400,000 people per year worldwide – until access to early diagnosis is improved and more funding and energy is poured into preventative measures.
Of all the hepatitis viruses, hepatitis D is the most unique, with a structure completely different to hepatitis A, B and C. When first discovered in 1977 in the liver cells of patients infected with hepatitis B, the examining doctor - Italian, Mario Rizzetto - initially thought the hepatitis D virus was a new hepatitis B protein, and called it the delta antigen. It wasn’t until further research was performed in chimpanzees that scientists discovered that this delta protein was actually derived from a completely new virus. Hepatitis D infection is totally dependent on the patient already having a hepatitis B infection, as it cannot grow in the liver without help from hepatitis B. There is no specific treatment for hepatitis D, but its severity depends on when infection occurs in relation to hepatitis B infection. If both hepatitis B and D are contracted at the same time, this is known as a “co-infection”, and the overall infection will usually be short, and the infection cleared by the immune system. If a patient already has a hepatitis B infection then later catches hepatitis D, this is known as a “super-infection” and can be extremely severe, causing neurological symptoms such as personality changes, insomnia and coma as well as chronic liver damage. The mortality rate for this kind of super-infection can be as high as 80%.
Of the five different hepatitis viruses, vaccines exist for only two: hepatitis A and B, though the B vaccine also indirectly protects against hepatitis D, due to D’s dependency on the other virus. The first hepatitis B vaccine was developed shortly after the identification of hepatitis B, a vaccine derived from the blood of infected patients, which purified the key surface proteins out from the samples. However, this was replaced in 1981 by the very first recombinant vaccine. The protein that coats the outside of hepatitis B – known as the surface antigen, or HBsAg – is the main target of the immune system and key in producing an effective immune response. The recombinant vaccine was created by inserting the gene for this protein into yeast cells, which can then be easily grown to extremely high volumes. The protein is purified out, and creates empty structures which are still able to trigger a good immune response, without the danger of the virus replicating. This vaccine was ground-breaking in its time and is credited for contributing significantly to the understanding of not only hepatitis B, but all the hepatitis viruses.
Hepatitis viruses continue to be an insidious, chronic public health issue worldwide. Though combinations of vaccines, treatments and preventative measures exist for almost all the hepatitis viruses, they continue to proliferate and cause hundreds of thousands of deaths and millions of infections every year. The main reason for this is simply lack of access, whether it be to diagnosis, prophylaxis (treatment given or action taken to prevent disease) or drugs. Until we can spread this access to every corner of the globe, hepatitis will remain as a significant disease of humanity.
You can find out more about World Hepatitis Day here.
