Hepatitis C virus (or HCV) was first identified in 1989 and can affect the liver and lymphatic system. It is not related to hepatitis B, even though it often causes similar symptoms. Over 0.4% of the UK population are chronically infected, representing over 200 000 patients living with hepatitis C. The majority of those infected with hepatitis C are undiagnosed.

In recent years an epidemic of hepatitis C has emerged amongst HIV-positive gay men, and a small study recently found hepatitis C transmission in HIV-negative gay men.

Transmission

Hepatitis C is transmitted mainly via direct blood-to-blood contact. The most common route of transmission in the UK is by sharing equipment for injecting drug use, mainly via blood contaminated needles and syringes. Many people also contracted hepatitis C from blood products before screening and sterilisation was introduced.

Sexual transmission of hepatitis C is thought to be unusual, but probably does occasionally occur. Increasing numbers of gay men testing positive for hepatitis C and most of these are HIV-positive and some reported unprotected sex as their only risk activity. The most recent evidence seems to suggest that the hepatitis C virus is found more frequently in the semen of men who are coinfected with HIV, than in the semen of men who are only infected with hepatitis C. This could be one factor contributing to the rise in infections. Some doctors and researchers think that fisting is the sexual activity that involves the biggest risk of hepatitis C transmission. Cases of hepatitis C transmission from vaginal sex remain rare. Doctors are unsure whether the infection that occurs between heterosexual partners is because of sexual exposure or because of other reasons, for example, sharing personal items which may have traces of blood on them.

Sharing household items that may have tiny amounts of blood on them, such as razors, toothbrushes and nail scissors, should be avoided.

Mother-to-baby transmission of hepatitis C is thought to be uncommon, but the risk is increased if the mother is also infected with HIV. A high hepatitis C viral load also increases the chance that a mother will pass on hepatitis C to her baby. As with HIV, a caesarean delivery reduces the chance of mother-to-child transmission of hepatitis C.

Some studies have found a risk from breastfeeding, but the evidence is inconclusive. However, in the UK and other countries where safe alternatives are available, mothers with HIV should avoid breastfeeding.

Symptoms

Less than 5% of people experience symptoms when they are first infected with hepatitis C. When they do occur, symptoms can include jaundice, diarrhoea, and feeling sick. Even without the presence of symptoms, the virus can still be passed on to others.

In the longer term, about half of people with hepatitis C will experience some symptoms. The most common ones are feeling generally unwell, extreme tiredness, weight loss, intolerance of alcohol and fatty food, and depression.

Disease progression

Current evidence suggests that only about 20% of individuals who have been infected with the hepatitis C virus appear to clear the virus naturally from the blood, whilst about 80% will develop chronic hepatitis C. Those with chronic infection will continue to be infections and can pass on the virus to others. If a person continues to be infected over a number of years with the hepatitis C virus, they could develop the following complications:

• Chronic hepatitis.
• Liver cirrhosis.
• Liver cancer.

Patterns of disease vary from person to person. Some people never experience any of these complications but about a third of those with chronic infection will develop serious liver disease after 15 to 25 years of infection.

The severity of disease can be affected by a number of factors. It is thought that it may take between 30 and 40 years for hepatitis C to cause cirrhosis - serious scarring to the liver. But men, people who drink alcohol, older people, and people who also have HIV, seem to have faster hepatitis C disease progression.

Diagnosing and monitoring hepatitis C

A blood test can tell if you have been exposed to hepatitis C and have antibodies to it. The British HIV Association recommend that those with HIV are tested for hepatitis C at least once a year, and have more frequent tests if you are at risk of hepatitis C.

A test is also available to measure hepatitis C viral load (PCR). This can show if you are one of the small numbers of people who clear hepatitis C from the body naturally. Unlike HIV viral load testing, a hepatitis C viral load is not an indicator of when to start treatment. However, it can be used to show how long you should continue to take treatment against hepatitis C. If you have a very high hepatitis C viral load (above 2 million copies) you may require a longer course of treatment.

Tests on levels of enzymes produced by your liver, called ‘liver function tests’, can give an indication of whether or not hepatitis C has damaged your liver. However, some people with hepatitis C can have normal liver function tests, even though they have suffered significant liver damage.

If the degree of liver damage you have suffered is unclear, then you may need to have a liver biopsy. This involves using a hollow needle to remove a small sample of the liver, which is checked under the microscope for signs of liver damage.

Liver biopsies can also be used to help decide what kind of hepatitis C treatment you need and how long it should last for. However, liver biopsies can be uncomfortable for some patients and very rarely can cause bleeding. If you have haemophilia you may need to receive extra clotting factor before and after the biopsy, and a very small number of people with haemophilia may not be able to have a biopsy at all because of very low clotting factor levels.

Because of these issues, some doctors are exploring the possibility of using a number of different blood tests that, viewed together, can give an accurate impression of liver function and damage, rather than using biopsies.  Another method for assessing liver damage is ‘elastography’ or fibroscan which is a measure of liver stiffness assessed by a vibration probe.  This is a test very much like an ultrasound scan of the liver.  Many centres are now offering this as an alternative or an adjunct to the liver biopsy for accurate and frequent monitoring for liver damage. 

How does HIV affect hepatitis C?

In the past few years several studies have confirmed the link between HIV and hepatitis C co-infection and faster progression of liver disease. It seems that people coinfected with HIV and hepatitis C are more likely to develop liver disease than people infected only with hepatitis C. This seems to be the case even if you have a high CD4 count. More severe liver damage is seen in people who have advanced HIV.

The effect of hepatitis C on HIV

In countries like the UK, where potent anti-HIV treatment is widely available and people are living longer, healthier lives with HIV, liver disease is now a major cause of hospital admission and death among HIV-infected people because of hepatitis B and C liver-related problems.

Hepatitis C does not appear to significantly alter your chances of becoming ill due to HIV, developing AIDS, dying of an AIDS-defining illness, or responding poorly to anti-HIV treatments.

Anti-HIV treatment if you have HIV and hepatitis C

Potent anti-HIV treatment can be used safely and effectively if you are coinfected with HIV and hepatitis C. However, you may be at greater risk of side-effects affecting the liver, which some anti-HIV drugs can cause.

For instance, research indicates that coinfected patients should use the anti-HIV drugs ddI (didanosine, Videx) and d4T (stavudine, Zerit) with caution, due to the increased risk of developing hepatic steatosis, or fatty liver – which is the accumulation of fat in the liver.

You may also be at greater risk of developing some of the metabolic disorders that can be a side-effect of potent anti-HIV treatment, such as insulin resistance and diabetes.

You and your doctor should bear these factors in mind when selecting which anti-HIV drugs you are going to take, and careful monitoring of your liver after you start taking anti-HIV treatment is strongly recommended. More information on HIV and hepatitis C treatment interactions can be found later in this booklet.

Your decision when to start anti-HIV treatment should be based on your CD4 cell count and HIV viral load, as it is in people who have HIV alone.

Some people with hepatitis C have a lower CD4 count rise on anti-HIV treatment than those without hepatitis C.

Treatments for hepatitis C

Treatments are available for hepatitis C.

The British HIV Association recommends that before you start treatment for hepatitis C, doctors who are expert in the treatment of hepatitis C and HIV assess you.

Before treatment is started it is important to have a test to show which strain, or genotype, of hepatitis C you have been infected with, as hepatitis C genotype can predict your response to treatment. There are at least six type of hepatitis C genotype. Type 1 is the most common in the UK and Europe. Unfortunately, type 1 responds least well to the currently available treatments for hepatitis C. Those with genotypes 2 or 3 respond better to treatment.

Factors such as age, gender, duration of infection, degree of liver damage and whether cirrhosis has developed are also important in deciding if treatment is likely to be effective.

Unlike antiretroviral therapy, treatment for hepatitis C is not indefinite. It consists of a 24 or 48 week course of treatment, and the length of treatment you receive is dependent upon the genotype you are infected with and your response to treatment. A test after 12 weeks can predict if you are not going to respond to treatment.

The current treatments for hepatitis C are ribavirin, alpha interferon, and pegylated interferon or peg-interferon (Pegasys, PegIntron, ViraferonPeg).

Alpha interferon can be used by itself or in combination with ribavirin. Pegylated interferon can also be used either by itself or in combination with ribavirin. While a combination of drugs improves response rates, for the few people unable to tolerate combination therapy, alpha interferon on its own is sometimes beneficial. Ribavirin should never be used as a treatment for hepatitis C by itself. Improved response rates are also seen when ribavirin is dosed according to a patient’s weight and some studies suggest that renal function should also be considered.

Treatment with pegylated interferon and ribavirin is now the standard of care recommended by the British HIV Association. It is recommended that patients receive regular eye checks as it is thought that treatment can cause serious eye problems, such as retinal haemorrhage, cotton wool spots and decreased colour vision, in some patients.

Some people with chronic hepatitis C virus (HCV) infection do not clear the virus with their first attempt at treatment, whilst others relapse after an initial response. This is especially true if originally treated with the older conventional interferon or if their regimens did not include adequate doses of ribavirin.

A second attempt at treatment may be advised and studies have shown that some HIV/HCV co-infected patients responded well to this.  On occasion treatment may need to be prolonged to 72 weeks to achieve viral clearance.

Aims of hepatitis C treatment

The aim of treatment should be to eradicate hepatitis C completely. Although 50-80% of non HIV-positive individuals respond to treatment with pegylated interferon and ribavirin, the response rate in people coinfected with HIV and hepatitis C is much lower.

If clearance of hepatitis C is not possible, then treatment should have the aim of normalising liver function, reducing the inflammation in your liver caused by hepatitis C, and the prevention of further damage to the liver.

If you have very advanced HIV disease the aim of hepatitis C treatment is likely to be different and focus on improving your tolerance of anti-HIV drugs, improving liver function, reducing your risk of death from liver problems, and improving your quality of life.

Side-effects of hepatitis C treatment

The side-effects of hepatitis C treatment can be very severe, though they tend to lessen as treatment goes on.

Side-effects include high temperatures, joint pain, weight loss, feeling sick, and depression. Depression is particularly common in people taking alpha or pegylated interferon and you may be offered antidepressants if you are taking this drug.

Other major side-effects of alpha interferon include blood abnormalities such as low haemoglobin (anaemia), a low white blood cell (neutropenia), and/or a low platelet count (thrombocytopenia).

Anaemia is a common side-effect and can lead to fatigue and shortness of breath.  Doctors will often use injections of erythropoietin (EPO) to increase red cells and haemoglobin to counter this.  Injections of G-CSF (filgastrim) can also be used to increase white cell counts.

Most HIV-positive patients will experience a slight decrease in there CD4counts whilst on treatment with interferon.  This is an interferon effect rather than a HIV effect.  Once treatment is complete the CD4 counts will return to the level they were when anti-hepatitis C treatment was started.

Ribivarin must not be given to pregnant women because it is possible that this could lead to the loss of the baby, the birth of a malformed baby or to problems in the baby after birth. Ribavirin can enter the sperm. It is important that sperm that contains ribavirin is not allowed to start a pregnancy and that ribavirin is not allowed to reach an unborn child.  Couples who have been treated with ribavirin should avoid pregnancy for at least six months after the completion of treatment.

Which infection to treat first – HIV or hepatitis C?

The British HIV Association recommends that the infection that is the greatest threat to your health should be treated first.

If you have a good CD4 cell count and are not becoming ill because of HIV, then you should be offered the choice of receiving treatment for hepatitis C before you start anti-HIV treatments.

However, if your CD4 cell count is low (below 200), falling rapidly, or are becoming ill because of HIV, then you should start antiretroviral therapy first.

Hepatitis C drugs in the pipeline

Many doctors are optimistic that much better drugs will be available for hepatitis C in the future. These include hepatitis C protease inhibitors and polymerase inhibitors. However, it could be a few years before these drugs are available.

If you are going to take treatment for hepatitis C, then you might want to consider joining a clinical trial, if there’s one available. This means that you will be monitored more frequently and may receive newer treatments as and when they become available on clinical trial.