Hepatitis B virus (often known as HBV) is an infection that can cause severe and even fatal damage to your liver.

It is a very common infection around the world, particularly in Africa and the Indian sub-continent. At some London HIV clinics, as many as 6% of gay men, are co-infected with both hepatitis B and HIV. It is also common in people who have shared equipment for injecting drugs.

 

Transmission

The reason why so many people with HIV also have hepatitis B is because it can be spread in a similar way to HIV, particularly by contact with bodily fluids like blood, semen and vaginal fluid, and from a mother to her baby whilst pregnant. Hepatitis B is many times more infectious than HIV. Although small amounts of hepatitis B virus can be found in saliva, saliva is not likely to spread hepatitis B, unless saliva from an infected person gets into a cut or sore, for example, following a bite.

In richer countries, such as the UK, hepatitis B has mainly affected gay and bisexual men, injecting drug users, and people with haemophilia. Increasing numbers of cases are being seen in people from Africa and India.

It is very important that people with HIV are vaccinated against hepatitis B. Using a condom for anal, vaginal and oral sex reduces the chances of hepatitis B being passed on during sex. Similarly, you should never share needles or other injecting drug equipment.

Bloods products in the UK are routinely screened for hepatitis B.

 

Symptoms

The majority of adults who are infected with hepatitis B have no symptoms to suggest that they have the infection, and it is often only diagnosed by routine blood tests. Even if you have no symptoms at all, you can still pass on the virus to others.

However, if symptoms do occur, you may experience a yellowing of the skin and whites of the eyes (jaundice), loss of appetite, pain in the stomach, nausea and vomiting, a high temperature, joint and muscle aches and feeling generally unwell.

These symptoms can be very severe and in some very rare cases can even cause death.

 

 

Stages of infection

There are four stages of hepatitis B infection.

·       Stage 1 - Immune tolerance:  At this stage hepatitis B is able to reproduce freely in the body but does not cause any symptoms or liver damage. In adults, this stage tends to last for several weeks after infection with hepatitis B. In infants it can last for several years after infection.

·       Stage 2 - Immune response: During this stage the body’s natural defences, the immune system, attacks the hepatitis B-infected cells in the liver and starts to clear the infection from the body. In some people who have been recently infected with hepatitis B, this phase may last for no more than a few weeks. However, in people who cannot clear the infection, it can last for years.  Because the immune system attacks liver cells with hepatitis B virus this causes liver damage and many people develop symptoms and become unwell at this time.

·       Stage 3 - Viral clearance:  This is often also known as ‘seroconversion’ because the body produces antibodies in response to a substance on the surface of the hepatitis B virus called the ‘e’ antigen. During this stage, hepatitis B stops reproducing itself.

·       Stage 4 - Immunity to hepatitis B:  This is when the immune system produces a full antibody response to hepatitis B, and clears the body of hepatitis B virus. Hepatitis B genetic material (DNA) usually disappears from the body.

 

Most adults infected with the hepatitis B virus fully recover and develop life-long immunity. However, up to 10% of individuals infected as adults do not enter stages two and three described above and so will become chronic carriers of the virus. This means that they will continue to be infectious to others and can develop chronic liver damage. Infected children, especially new-born babies, are much more likely to become chronic carriers.

Infection with the hepatitis B virus that lasts for several years could lead to the following complications:

·         Chronic hepatitis.

·         Liver cirrhosis.

·         Liver cancer.

 

Monitoring

There are a number of tests to see if you are infected with hepatitis B, or if you have been infected and have managed to clear the infection.

If the tests find fragments of hepatitis B virus called surface antigens, for more than six months, then you are a chronic carrier of hepatitis B and continue to be potentially infectious to other people.

People who are test positive for these antigens have higher rates of replication of hepatitis B and are also more likely to be infectious.

If you have antibodies but no antigen after six months of infection, then your immune system has cleared hepatitis B infection.

You are also likely to have regular tests to see if your liver has been affected by hepatitis B. These are called liver function tests and they look at levels of certain chemicals, proteins and enzymes which give an indication of how much ongoing damage there is to the liver and how well your liver is working. They should be performed at least every six months.

Ultrasound examinations are also used, particularly if your liver is damaged. In some cases it may be necessary to perform a liver biopsy, when a tiny sample of tissue from the liver is extracted using a hollow needle for examination under a microscope.

 

Treatments

Treatments are available if you do not clear infection with hepatitis B. There current treatments for hepatitis B are alpha interferon, pegylated alpha interferon, the anti-HIV drug 3TC (lamivudine, Epivir, but Zeffix when used to treat hepatitis B without HIV therapy), adefovir (Hepsera) and entecavir (Baraclude).

Tenofovir (Viread)and FTC (emtricitabine, Emtriva) both have good activity against hepatitis B virus and many HIV physicians will use them to treat both HIV and HBV in patients infected with both viruses.

The aims of hepatitis B treatment are to reduce liver inflammation, reduce the amount of hepatitis B DNA, and ideally, to eradicate hepatitis B antigens from the body and produce antibodies that reduce the risk of progression to cirrhosis and liver damage.

These treatments usually eradicate hepatitis B in about a third of the people who take them.

Alpha-interferon

Alpha interferon is recommended as an option for the initial treatment of adults with chronic hepatitis B. It is given by injection, usually three times a week (every other day) for four to six months, and leads to clearance of detectable hepatitis B in between 20 - 40% of people with hepatitis B infection alone. However, it works less well in men, people who have had hepatitis B for a long time, people who have large amounts of hepatitis B DNA, and people who are also infected with HIV.

Alpha interferon can cause unpleasant side-effects, including flu-like symptoms, aches and pains, and bone marrow suppression.

Severe psychological effects, particularly depression, suicidal ideation and attempted suicide have also been observed in a small number of patients during therapy. This can also occur after treatment has been stopped, mainly during the 6-month follow-up period. Some patients have also reported acute hypersensitivity reactions to the drug.

Pegylated alpha interferon is a modified version of standard interferon alpha that results in 'longer-action' and has been associated with an improved response rate compared with conventional interferon.  The usual course for pegylated alpha interferon is 48 weeks.

3TC

3TC is better known as a potent anti-HIV drug (lamivudine, Epivir), but also works against hepatitis B and so is licensed for the treatment of both infections (with the brand name Zeffix for the treatment of hepatitis B). The dose of 3TC for hepatitis B treatment is 100mg taken orally once daily. This is lower than the twice-daily 150mg dose of 3TC used when the drug is included in anti-HIV drug combinations. 3TC should never be given as monotherapy (the only drug) to people who have hepatitis B and HIV coinfection if they have a detectable HIV viral load as the low dose could lead to 3TC resistance developing in the HIV virus.

It is not known how long it is necessary to take 3TC for, and although studies have generally looked at people taking the drug for a year or two, lifelong therapy with the drug may be needed.  One of the major problems with using 3TC as the only anti-HBV drug is the development of resistance in the HBV.  This may occur in 90% of patients on this drug alone after three years.

Some people may be allergic to 3TC and should report the following symptoms immediately: chest pain or tightening, swelling of eyelids, face or lips, skin rash or hives on the body.

Adefovir

Adefovir (Hespera) is used as a treatment for hepatitis B in Europe and the US, usually if treatment with alpha-interferon has failed. The standard dose is 10mg and the drug is effective against hepatitis B virus that is resistant to 3TC. Side-effects include headache, stomach pain, feeling sick, and diarrhoea. Adefovir has previously been tested as an anti-HIV drug at 60mg and 120mg doses, but was not licensed because at high doses the risk of kidney toxicity was too great.

You should inform your doctor if you have previously experienced kidney disease or abnormalities identified from your blood or urine tests indicating problems with your kidneys. This is particularly important if you are taking other medicines which may damage your kidneys, such as vancomycin and aminoglycosides (for bacterial infections), amphotericin B (for fungal infections), foscarnet (for viral infections) and pentamidine (for infections) or medicines which may interact with adefovir such as cidofovir (for viral infections), or  tenofovir (Viread) or tenofovir-containing treatments (tenofovir and emtricitabine, Truvada) as part of your HIV therapy. 

Entecavir

Entecavir (Baraclude) is approved for use in adults with chronic hepatitis B infection with compensated liver disease and evidence of active viral replication, evidence of persistent elevations of the blood levels of aminotransferases (a marker for liver disease) and active liver disease as determined by biopsy. It is a particularly potent anti-HBV agent, although a higher dose is required in patients who have previously used 3TC, since it may be less effective in such patients. Entecavir has recently been shown to have some activity against HIV, and it should not be used if you are not taking anti-HIV treatment as this could lead to the development of drug-resistant HIV.

Hepatitis B and HIV

It was generally thought that having hepatitis B did not increase HIV disease progression and severity. However, because the introduction of effective anti-HIV drugs has extended life expectancy and decreased illness due to HIV itself, hepatitis B or C have emerged as a significant cause of illness and death in people with HIV. 

Anti-HIV treatment and hepatitis B

Potent anti-HIV treatment can be used safely and effectively if you have hepatitis B.

However, when some people infected with HIV and hepatitis B (coinfected) start taking anti-HIV treatment, they may experience a short-term flare-up of hepatitis B. This is usually the consequence of the anti-HIV treatment restoring the immune system, which then becomes better at responding to infections such as hepatitis B. This improved immune response can lead to active hepatitis B disease.

To try and prevent these flares happening, many doctors recommend that people with chronic hepatitis B infection who are starting anti-HIV treatment should start treatment for hepatitis B infection at the same time.

People with hepatitis B appear to be at greater risk of experiencing the increases in liver enzymes which some anti-HIV drugs can cause. The drugs particularly associated with liver side-effects are ritonavir, indinavir, nevirapine, AZT and ddI, as well as some drugs used to treat other infections to which people with HIV can be vulnerable, including pentamidine, some sulphur-based antibiotics, and ketaconazole.

 

Hepatitis B treatment if you have HIV

The British HIV Association, the organisation that sets UK guidelines for the treatment of HIV, recommends that if a person with hepatitis B virus is taking antiretroviral treatment, then this should include an anti-HIV drug that is also effective against hepatitis B. These are 3TC or FTC, and tenofovir. Anti-HIV drugs (and entecavir) should not be used for the treatment of hepatitis B if a person is not taking antiretroviral therapy.