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Next Lesson - Human Immunodeficiency Virus
Core
Hepatitis simply means inflammation of the liver and is by no means limited to viral infection. Other causes include:
- Viral hepatitis - the focus of this article.
- Alcoholic hepatitis - excessive consumption of alcohol resulting in an alcohol-related liver disease, which involves inflammatory changes.
- Autoimmune hepatitis - where the body attacks its own liver. This requires immunosuppression treatment. The cause of autoimmune hepatitis is unknown.
Hepatitis caused by viruses can be from two causes;
- Inflammation of the liver could simply be collateral damage from a viral disease process e.g. Epstein Barr Virus, Cytomegalovirus and Varicella zoster virus
- Inflammation of the liver is caused directly by viruses replicating inside hepatocytes leading to damage. This is classically referred to as viral hepatitis and is the main focus of this article.
There are five main types of viral hepatitis (A to E) which multiply in the hepatocytes to cause damage. Types A,D and E are easily cleared by the body in weeks whereas B and C have the potential to develop into chronic infections and are the main focus of this article.
Hepatitis B and Hepatitis C are the more common causes of viral hepatitis. Approximately 240 million people worldwide are infected with hepatitis B (acute or chronic) and it is the leading cause globally of liver cirrhosis.
Looking at the UK, the British Liver Trust website estimates that 180,000 people are living with a chronic hepatitis B infection and in certain areas, 1 in 60 pregnant women may be affected (figures from https://www.britishlivertrust.org.uk/liver-information/liver-conditions/hepatitis-b/)
An article updated in February 2018 said that the World Health Organisation (WHO) estimates that 71 million people are infected with hepatitis C worldwide and is responsible or 399,000 deaths each year. The NHS website states that 215,000 people in the UK are currently infected with hepatitis C.
Hepatitis B virus (HBV) is a double-stranded enveloped DNA virus. Transmission of HBV is via blood, sexual intercourse and vertical transmission. Once an individual has been infected with HBV, it can take 6 weeks to 6 months for the virus to incubate and begin to cause damage the individual’s liver.
Up to 50% of people with HBV infections will have vague symptoms or be asymptomatic, but those that do experience symptoms will most likely have jaundice, fever, nausea, vomiting and arthralgia (joint pain).
50% of adults will clear the infection themselves within around 6 months without symptoms. Of the remaining symptomatic 50%, 10% will progress from an acute to a chronic infection. In countries such as China and parts of Asia, there is a high infancy HBV infection rate and 90% of these cases will progress to a chronic infection.
The most important test for hepatitis B is serology. This is the analysis of blood serum (cells or clotting factors) to see what immune response has occurred and look for the presence of extra substances. The serology of hepatitis B involves three antigens and three antibodies.
The first antigen detectable is HBsAg which is the hepatitis B (HB) surface (s) antigen (Ag). The matching antibody produced is HBsAb, hepatitis B (HB) surface (s) antibody (Ab). This can be detected in the blood and is an indication of a current hepatitis B infection. It is normally found in the blood after around 6 weeks.
The second antigen is HBeAg and its matching antibody, HBeAb. Here the “e” stands for envelope. This can be detected in the blood and indicates that there is active viral replication i.e. the patient is infectious and the virus can spread to other people.
The third antigen is HBcAg and its matching antibody, HBcAb (although only the Ab is detected). Here the “c” stands for core. IgM is the first antibody ecountered unless the patient has had a previous HBV infection in which case it is IgG.
Although the antigens appear in the order above, the antibodies actually appear in the reverse order. So, for a patient that hasn’t had a hepatitis B infection before, their timeline would look like:
- Contract the virus through unprotected sex on a holiday in sub-Saharan Africa
- After 6 weeks the HBsAg is detectable in blood serum and there is a corresponding rise in ALT on liver function tests. They would now be considered infected
- Symptoms start to appear at this point
- HBeAg appears and the patient is now infectious
- HBcAg is present in the blood but not detectable by serology
- HBcAb appears in the form of IgM (as it is an acute infection)
- HBeAb appears and after HBeAg has been cleared the person is no longer infectious
- HBsAb appears and the virus is completely cleared from the body
- IgM then converts to IgG and persists in the body
Diagram: Shows the structure of HBV
Creative commons source by TimVickers [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]
Another test that can be done is a HBV DNA PCR test to see how much viral DNA is in the body.
If HBV infection doesn't resolve, then a patient can develop a chronic HBV infection. Chronic HBV is a lifelong chronic infection that is defined by HBsAg staying in the body for longer than 6 months. Of the chronically infected patients, 25% will go on to develop cirrhosis and 5% will develop hepatocellular carcinoma.
Chronic HBV cannot be cured so those infected will spend the rest of their life taking antivirals to try and suppress viral replication. Acute HBV infections cannot be treated either, though antivirals like tenofovir and entecavir can be used to suppress HBV replication.
There is a vaccine for HBV. It involves injecting the patient with a genetically engineered surface antigen for HBV (HBsAg) that is harmless and allows the body to develop HBsAb so it can fight off a HBV infection. The target for long term protection is if the patient has more than 100 surface antibodies. There are three doses and any boosters, which is effective for most people. The WHO recommends that all babies are vaccinated preferably within 24 hours of birth (the NHS offers it as part of their vaccination schedule at 8, 12 and 16 weeks old).
Hepatitis C virus (HCV) is a single-stranded RNA virus that is enveloped and icosahedral in shape. Transmission of HCV is through sex and blood. Those at most risk of HCV are those that come in contact with needles including; intravenous drug users and healthcare workers (needlestick injury). Others at risk include infants born to HCV positive mothers and those who had blood transfusions before 1991. Incubation is much faster with HCV compared to HBV at around 6 to 12 weeks.
Around 80% of acute HCV infections are asymptomatic. When symptoms present, they include fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark coloured urine, grey faeces, arthralgia and jaundice. The WHO estimates between 15-45% of adults can clear the HCV infection within about 6 months. 80% of HCV patients will develop a chronic infection.
Testing and detecting HCV is different to HBV. The only serological test is for the anti-hepatitis C antibody which will detect whether people have been infected by HCV or if they have been infected before. This antibody is not protective and is only really of diagnostic value.
As the anti-hepatitis C antibody remains after clearance, the next step is to do a viral PCR to look for HCV RNA to confirm if the patient has a chronic infection. For those that can clear HCV, they will still be positive for anti-hepatitis C antibody. Once a patient is confirmed to have a chronic infection, the degree of cirrhosis and variation of HCV needs to be ascertained to guide the patient’s treatment will be.
HCV does not have a vaccine so to prevent infection so prevention is limited to exposure limitation. However, an antiviral combination can be used to treat and cure HCV. The combination is 95% effective. The treatment of HCV lasts about 8-12 weeks and costs between £20,000 to £60,000.
Needlestick injuries aren’t as common as they used to be, but they do still happen. The incidence of contracting something from a needlestick injury are:
- HIV = 1 in 300
- Hepatitis B = 1 in 3
- Hepatitis C = 1 in 30
If a healthcare worker receives a needlestick injury from a patient with one of these conditions, then antivirals should be started no later than 72 hours afterwards. Research has shown that post-exposure prophylaxis (PEP) is not very effective for hepatitis C .
- The PEP treatment for HIV consists of 3 different antivirals (ARVs) for 28 days and then re-tests at 1 and 3 months.
- The hepatitis B vaccine is very effective as post-exposure prophylaxis for a potential needlestick injury.
- If the individual tests are negative for HBsAg and positive for HBsAb then you do not need to give a booster, otherwise give the booster or start the vaccination if they haven’t had it already.
If someone has received a needlestick injury, they must immediately bleed, wash and cover the wound and report to occupational health as soon as possible. After this, they should be referred from counselling and advised to use condoms until they have received the all clear.
Edited by: Dr. Thomas Burnell and Dr. Ben Appleby
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