Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). Over time, HCV can cause serious liver damage including cirrhosis (scarring), liver cancer, and life-threatening liver failure.

Because both HIV and HCV can be spread by contact with infected blood, many people are infected with both viruses. This is called co-infection. About one in four people living with HIV (HIV+) in the US are co-infected with HCV. Co-infection is even more common among HIV+ injection drug users, of whom about 80 percent also have HCV.

HCV can progress more rapidly and lead to serious liver damage more often in HIV+ people. According to the Centers for Disease Control and Prevention (CDC), having HIV more than triples the risk of liver disease, liver failure, and liver-related death due to HCV. Co-infection with HCV may also make HIV treatment more challenging. Therefore, it is important for HIV+ people to know whether they have HCV. The CDC recommends that all HIV+ people be screened for both hepatitis B and hepatitis C. Some experts recommend that HIV+ people at risk for HCV be screened every year.

Treatment of HIV/HCV co-infection is complicated. It is important to have a health care provider who is familiar with HIV and HCV to get the best treatment for both diseases. The good news is that HCV can be treated successfully, even in HIV+ people.

There are many things to consider when deciding if and when to begin treatment for HCV. Talk to your health care provider about all your options before deciding. If you are at risk for HCV disease progression and liver damage, you may want to consider starting HCV treatment sooner rather than later since research shows that earlier treatment has a better outcome.

Not everyone who has HCV needs treatment. Among those who develop chronic HCV, many will not develop serious liver damage. Research shows, however, that HIV+ people are more likely to develop HCV-related liver damage and develop it faster than HIV-negative people.

Health care providers look at a variety of tests and health-related factors when deciding whether or not to recommend HCV treatment. Treatment decisions are not based on symptoms alone, since the early stages of liver damage do not always cause symptoms or abnormal lab test results. Instead, health care providers consider any symptoms, your overall health, the results of liver enzyme tests, and the results of tests that determine the extent of any liver damage.

Tests for HCV include:

• HCV viral load
  

This blood test cannot tell if or when someone with HCV will develop liver damage. However, the HCV viral load (amount of HCV in the blood) can help predict how well someone will respond to HCV treatment. Generally, the lower the HCV viral load, the better the chances that treatment will work well. Decisions about HCV treatment are not based on specific viral load levels; however, people with undetectable HCV viral load do not need treatment.

• Liver enzyme (or liver function) tests

Liver enzyme tests are blood tests that look at levels of liver enzymes. Because levels of liver enzymes can tell us how well the liver is working, liver enzyme tests are often referred to as liver function tests. Liver enzyme tests measure several things that the liver produces, including ALT, AST, bilirubin, albumin, and some indicators of your blood’s ability to clot. Elevated liver enzymes may indicate liver damage. However, some people with HCV have normal liver enzymes, even in very advanced disease.

• Genotype tests

Worldwide, there are six different types of HCV called genotypes. These genotypes differ in their regional distribution and can predict how well treatment will work. Genotype 1 is the most common globally (60 percent of all infections) and is also the most common in the US. Genotypes 2 and 3 are less common in the US. Genotype 3 is very common in Southeast Asia, while genotype 4 is found mostly in the Middle East and central Africa. Genotype 5 is located almost entirely in South Africa, and genotype 6 is found in Asia.

HCV genotype 1 is less likely to respond to treatment than HCV genotypes 2 and 3. Before you begin treatment, you should have a genotype test to find out which genotype you have. This will help you and your health care provider make decisions about which treatments to use and how long to use them.

• Liver biopsy

A liver biopsy (inserting a needle through the skin and into the liver to obtain a small sample that is examined under a microscope) is the most reliable way to determine how much damage has been done to your liver. It can also help you and your health care provider figure out when to start HCV treatment. However, a liver biopsy is not necessary in order to start treatment.

• FibroSURE™ (or FibroTest)

FibroSURE™ is a blood test that looks at six markers of liver activity to measure liver damage. It is often used as a non-invasive alternative to liver biopsy. This test is good at identifying either no liver damage or advanced liver damage. However, if the damage is somewhere between none and advanced, it does not give very helpful information. A liver biopsy gives more detailed information about all levels of liver damage.

• FibroScan

FibroScan is a new non-invasive test currently used in Europe but not available in the US. It is similar to an ultrasound, and is done in the office or clinic by your provider. The scan uses a dull probe that presses against the skin over the liver.

In general, health care providers are more likely to suggest treatment if you:

• want and are motivated to be treated
• have a liver biopsy or FibroSURE™ test that shows liver damage (inflammation, and particularly fibrosis)
• have early cirrhosis (scarring of the liver) but are not ill
• have HIV in addition to HCV
• are otherwise in good health or with well controlled other medical problems
• have acute hepatitis C (infected within the last 6 months)

There are also several factors to consider that have been shown to be associated with faster disease progression in HCV-infected people. Some of these factors include:

• Being older than 50
• Being male (most women with HCV do not develop liver damage as quickly as men)
• Alcohol use
• Co-infection with HBV or HIV

Treatment options for HCV have improved a great deal in recent years. Today, the standard treatment is a combination of two medications:

• Pegylated interferon (Pegasys or Peg-Intron)
• Ribavirin (Rebetol, Copegus)

The length of HCV treatment depends on the type of HCV a person has and whether they are co-infected with HIV. There are several different types of HCV, called genotypes. Genotypes 2 and 3 are easier to treat and treatment usually lasts six months for HIV-negative people. Genotype 1 - the most common in the US - is harder to treat, so treatment usually lasts 12 months for HIV-negative people. One year of HCV treatment is recommended for people with both HIV and HCV.

Last year, the US Food and Drug Administration (FDA) approved two new drugs for hepatitis C treatment: Victrelis (boceprevir) and Incivek (telaprevir.) Both drugs are HCV protease inhibitors; they work by interrupting HCV’s ability to multiply or replicate. They are both meant to be taken in addition to the standard treatment combination of pegylated interferon plus ribavirin. Recent studies have shown that people with HCV only who took either Victrelis or Incivek in addition to pegylated interferon and ribavirin had higher cure rates than those taking pegylated interferon and ribavirin alone. Studies directly comparing Victrelis to Incivek have not yet been done.

People infected with HIV and HCV face some special treatment issues. Basically, significant liver damage makes it harder to tolerate HIV drugs. At the same time, some HIV drugs can cause liver issues. Therefore, it is important for you and your provider to monitor your liver enzymes closely when taking either or both treatments.

The HIV treatment guidelines published by the US Department of Health and Human Services (DHHS) recommend that antiretroviral therapy for HIV be given to most co-infected people, regardless of their CD4 count. The DHHS suggests that the benefits of HIV drugs outweigh concerns about potential damage to the liver caused by the drugs.

Research studies on the new HCV protease inhibitors are still ongoing for people co-infected with HIV and HCV, and the FDA has not yet approved the use of Incivek or Victrelis for this group. However, early research results for both Incivek and Victrelis are promising. Small studies have shown that HIV/HCV co-infected people taking either Incivek or Victrelis combined with pegylated interferon and ribavirin have better cure rates than those taking pegylated interferon and ribavirin alone.

These same studies have also shown significant drug interactions between Victrelis or Incivek and some HIV drugs. Recent research has shown that Victrelis interacts with Norvir (ritonavir)-boosted protease inhibitors (boosted PIs). Because Victrelis and Norvir-boosted protease inhibitors are processed by the body in the same way, the two types of drugs can interact, or get in the way of one another. As a result, the HIV drugs may be less effective. The DHHS suggests that Victrelis not be used with boosted PIs; it adds that Victrelis should not be used with Sustiva (efavirenz).

Research on Incivek suggests that it can be given with Norvir-boosted Reyataz (atazanavir), unlike Victrelis. Incivek can also be given with Sustiva, but should be given at an increased dose when both are taken at the same time. Either Victrelis or Incivek can be given with Isentress (raltegravir).

If you are co-infected, it is important for you to work closely with your health care providers to monitor the status of your liver as well as your HIV and HCV disease. There may be certain drugs you need to avoid taking together or taking at all, and it may be more beneficial to treat just one disease at a time.

Unlike HIV, successful treatment can cure HCV. Treatment success is measured in different ways. End-of-treatment virological response means HCV is undetectable in the blood at the end of treatment. Sustained virological response, or SVR, means HCV is still undetectable six months after the end of treatment. After this, the virus rarely comes back, and people are considered cured.

For HIV-negative people, combination treatment with pegylated interferon plus ribavirin cures HCV in about 80 percent of those with genotype 2 or 3, and about 45 percent of those with genotype 1. HCV treatment is less effective for co-infected people. SVR rates are about 20 to 30 percent with genotype 1 and 45 to 75 percent with genotypes 2 or 3. It is important to use pegylated interferon and ribavirin together, as neither drug is effective enough when it is used alone.

People receiving HCV treatment should have their liver function tests and HCV viral load levels monitored regularly, since this can show how well treatment is working. If your HCV level has not started to drop after 12 weeks of treatment, it is unlikely that the treatment is working, and your health care provider will probably advise you to stop taking the drugs.

Sometimes a second round of treatment can lead to a cure even if the first attempt was unsuccessful. This is especially true if the first attempt used the older form of interferon or interferon without ribavirin. Different types of interferon and new drugs that directly attack HCV are currently in clinical trials for people infected only with HCV and those who are co-infected with HCV and HIV.

For people infected with both HIV and HCV, a recent study among several hundred US veterans showed that high levels of adherence to both pegylated interferon and ribavirin predicted the best chances of SVR, or cure from HCV. Adherence to HIV drugs is very important in keeping viral loads low, avoiding resistance, and maintaining good immune system health. We now know that adherence to HCV drugs is similarly important for the successful treatment and cure of hepatitis C.

Like most medications, the drugs used to treat HCV can cause side effects. The most common side effects of pegylated interferon include:

• Flu-like symptoms (fever, nausea, muscle aches)
• Depression
• Anxiety or irritability
• Low white blood cell count (neutropenia)

While women tend to do better on HCV therapy than men, studies show that depression is more likely to affect women taking interferon. It is very important to speak to your health care provider about any side effects you are experiencing so he or she can help you manage them properly.

The most serious side effect of ribavirin is anemia, or a reduced number of red blood cells that carry oxygen throughout the body. This side effect can often be managed using a drug called Procrit or Epogen (erythropoietin or EPO).

Ribavirin can also cause serious birth defects. Do not take ribavirin if you are pregnant or planning to become pregnant, and stop taking ribavirin at least six months before becoming pregnant. Women and their male partners must use effective birth control while taking ribavirin. Many providers will recommend that women use two forms of birth control to prevent pregnancy while taking ribavirin. Additionally, men taking ribavirin who have female partners are encouraged to use two forms of birth control since sperm exposed to ribavirin can cause birth defects.

Both of the new drugs – Incivek and Victrelis – commonly cause fatigue and nausea. Many people who took Incivek in research studies also reported having a rash. For most people, the rash was mild and did not lead them to stop taking Incivek. However, in a very few cases, the rashes were severe and life-threatening due to an immune reaction known as Stevens Johnson Syndrome.

Incivek and Victrelis can also cause anemia. This is especially concerning because ribavirin can also cause anemia, and because anemia is already a common problem among HIV+ people.

While treatment for HCV can be challenging, it may help to know in advance what side effects to expect. Various medications can help manage these side effects. Peer support groups can also help you get through treatment. And remember, unlike HIV therapy, HCV treatment usually lasts no more than six to 18 months.

There is some debate about whether to start HIV or HCV treatment first. Effective HIV treatment may reduce the risk of liver damage, so you may be less likely to need HCV treatment. On the other hand, treating HCV first seems to make it easier to tolerate drugs for HIV. HCV treatment does not work well for co-infected people with CD4 cell counts below 200 and is not recommended.

The decision about which to treat first depends on many individual factors, including HIV viral load, CD4 cell count, and amount of existing liver damage. For this reason, it is important to see a health care provider familiar with both diseases whenever possible.

In addition to medical treatment, there are steps you can take to keep your liver healthy, including:

• Eating a healthy diet
• Avoiding alcohol and street drugs
• Getting regular physical activity
• Getting vaccinated against hepatitis A and hepatitis B

Some herbs may help your liver, but others can cause serious liver damage. Be sure to tell your health care provider about any products you are taking, including over-the-counter or prescription medications, street drugs, herbal remedies, or nutritional supplements.