Viral Hepatitis and HIV
What Is Hepatitis C and How Is It Transmitted?
Hepatitis C is caused by the hepatitis C virus (HCV). The virus can cause lifelong infection, cirrhosis of the liver, liver cancer, liver failure, and death. There is no vaccine to protect against HCV, and as many as five million people have been infected with the virus in the United States.
HCV infection is common among people with HIV, and liver failure as a result of HCV infection is now a leading cause of death among people with HIV. Between one-quarter (25%) and one-third (33%) of all people with HIV in the United States are infected with HCV. This means that as many as 350,000 Americans are coinfected with HIV and hepatitis C.
HCV infection can cause liver disease to develop faster in people who are also infected with HIV and can make it more difficult to treat HIV. This is why the United States Public Health Service and the Infectious Disease Society of America consider hepatitis C to be an AIDS-related opportunistic infection in people with HIV (although having HCV does not necessarily mean that a person with HIV has an AIDS diagnosis).
Injection drug users (IDUs) who share needles and other drug paraphernalia are at the highest risk of being infected with HCV. Between 50% and 90% of all IDUs with HIV are also infected with HCV. This is because both viruses can be transmitted easily through blood-to-blood contact. HCV can pass from the blood of an infected person into the blood of another person through means such as:
Sharing paraphernalia (needles, syringes, cookers, cotton, water) used to inject drugs;
Open wounds or mucous membranes (e.g., inside the mouth, vagina, or anus) that are exposed to infected blood; and
Blood products or blood transfusion (before 1992).
Unlike HIV, it is generally believed that HCV cannot be transmitted through semen or other genital fluids unless blood is present. Thus, the risk of becoming infected with HCV through unprotected sexual intercourse is low. But it is still possible, especially if sexually transmitted infections such as herpes are present or the sexual act increases the risk of mucous membrane tearing and blood-to-blood contact (fisting, anal sex, etc.). It is recommended that people with HCV practice safer sex using a condom or other barrier to protect their partners.
Women with HCV have a less than 6% chance of transmitting the virus to their babies during pregnancy or delivery, although the risk increases if the woman's HCV viral load (the amount of HCV in the blood) is high. It is unlikely that HCV can be transmitted through breastfeeding or breast milk.
If you have not been tested for HCV, or don't know whether you've been tested, you may want to discuss this with your healthcare provider. HCV testing is strongly recommended for anyone who is HIV-positive.
Does HCV Infection Affect Everyone the Same?
No. Simply because someone is infected with HCV does not necessarily mean that liver disease will occur. It's also important to note that it can take many years -- more than 20 or 30 years, in many cases -- for HCV to cause life-threatening liver disease if it does occur.
Only a relatively small number of people (25% at most) experience symptoms when they are first infected (acute infection). Symptoms of acute hepatitis C infection (if they occur) are similar to those of hepatitis A and hepatitis B -- fatigue, decreased appetite, nausea, and jaundice. More than half of people infected with HCV will have an increase in their ALT levels (an enzyme produced by the liver), but they will not "feel" this as a symptom. Many people may have normal ALT levels and still have liver disease.
About 20% of people infected with HCV clear the virus from their bodies, usually within six months. However, the majority of people (80%) who are infected with HCV develop chronic hepatitis C, and the infection will likely stay with them for the rest of their lives or until treatment clears the virus from their bodies. In other words, if 100 people are infected with HCV tomorrow, 20 of them will clear the virus from their bodies within six months, and 80 will remain infected with the virus.
Of the 80 people with chronic hepatitis C, approximately 28 (35%) of them will remain healthy. This means that their liver enzymes will remain normal and they will not go on to experience liver disease because of the infection. However, the virus can still be detected in the liver and bloodstream, which means that the infection can still be transmitted to others. The remaining 52 people (65%) with chronic hepatitis C will have some symptoms of liver disease, usually within 15 years. About 16 people (20%) with chronic hepatitis C will develop cirrhosis -- scarring of the liver resulting from widespread fibrosis (an extreme overgrowth of the liver's connective tissue) -- within 20 years after first becoming infected.
Although cirrhosis is not immediately life-threatening, it can seriously affect the liver's ability to work properly and increases the risk of liver cancer. Of the 16 people with HCV who develop cirrhosis, four (25%) of them will likely experience liver failure or liver cancer within 25 years after becoming infected with the virus. These numbers refer to people who are infected only with HCV. Coinfection with HIV (see below), hepatitis B virus, or alcohol use severely affect the progression of HCV disease.
How Is Hepatitis C Different for People With HIV?
A number of studies have shown that HIV can have a negative effect on the way HCV acts in the body. For starters, HIV can increase the chance that someone with chronic HCV infection will develop cirrhosis of the liver. Between 20 and 25 of every 80 people with healthy immune systems who have chronic HCV infection will go on to develop cirrhosis within 20 years. But if HIV is also present, between 30 and 35 of every 80 people are likely to develop cirrhosis.
HIV infection can also speed up the rate at which HCV infection causes cirrhosis. In one study, people infected with both HIV and HCV were twice as likely to have cirrhosis after 13 years than people only infected with HCV (15% vs. 6%). Similar results have been seen in other studies.
People with both HIV and HCV are also more likely to experience liver failure -- which is often fatal unless a transplant is performed -- than people infected only with HCV. In one study, people with hemophilia who were infected with both viruses were 21 times more likely to die of liver failure than those only infected with HCV.
Another issue to consider is liver health and anti-HIV medications. Many anti-HIV drugs, including protease inhibitors and non-nucleoside reverse transcriptase inhibitors, are broken down (metabolized) by the liver. This can cause problems for people who have both HIV and HCV. First, the liver needs to be healthy in order to break down these drugs efficiently. If HCV damages the liver, it might not be possible to take anti-HIV therapy. Also, some of the drugs used to treat HIV can cause liver damage, even in people who aren't infected with HCV. In turn, some anti-HIV drugs might worsen or speed up HCV-related liver disease.
What Are the Symptoms of Hepatitis C?
As discussed above, only about one out of four people experience any symptoms when they're first infected. Many people with chronic hepatitis C have no symptoms of liver disease either. That is, they don't feel or look sick. If symptoms are present, they're usually mild, not very specific, tend to come and go, and are similar to those seen in acute hepatitis C.
If HCV infection causes serious liver damage and/or cirrhosis, symptoms usually occur or become worse. In addition to fatigue, these may include poor appetite, nausea, headache, fever, vomiting, jaundice, weight loss, itching, depression, mood swings, mental confusion, muscle and joint pain, fluid retention, abdominal swelling, abdominal pain, and ankle swelling.
What Laboratory Tests Do I Need to Know About?
There are laboratory tests to diagnose HCV infection and laboratory tests to monitor the health of people with HCV.
HCV Antibody Testing: Diagnosing HCV infection begins with an antibody test, similar to the one used to diagnose HIV infection. Antibodies to HCV can usually be detected in the blood within six or seven weeks after the virus enters the body, although it can take as long as three months or more for some people to develop detectable antibodies. If the HCV antibody test is positive, a second test is usually performed to confirm the result -- either another antibody test or a PCR test.
If a person is positive for HCV antibodies, he or she has been exposed to the virus in the past. Since approximately 20% of people infected with HCV clear the virus from their bodies, usually within six months of exposure, the next step is to look for the actual virus in the bloodstream.
HCV Viral Load Testing: To look for HCV, a healthcare provider can request a qualitative PCR test to determine whether or not the virus is in a person's bloodstream. A healthcare provider can also order a quantitative PCR test -- very similar to that used in HIV -- to check for the presence of HCV and to figure out the person's HCV viral load (the amount of HCV in a measurement of blood).
The quantitative HCV viral load is a very important lab test. Unlike viral load testing for HIV, which can help predict how quickly someone may progress to an AIDS diagnosis, the HCV viral load test cannot determine if or when someone with hepatitis C will develop cirrhosis or liver failure. However, the HCV viral load can help determine how likely it is that someone will respond to treatment. As a rule of thumb, the lower the HCV viral load, the better someone's chances that he or she will respond to anti-HCV treatment. HCV viral load testing is also used during treatment to determine if therapy is working.
It is very important to be aware that HCV viral load results are usually much higher than HIV viral load results. This can be confusing. While a low HIV viral load is considered to be less than 5,000 to 10,000 copies/mL, a low HCV viral load is considered to be anything less than two million copies/mL. HCV viral loads are now usually reported in International Units (IUs). There is no standard way to convert from copies/mL to IU/mL. Each quantitative viral load test is different, so it is important to use the same laboratory and the same test whenever you have your viral load measured. Results are generally reported only as low or high:
Low -- less than 2 million copies/mL (600,000-800,000 IU/mL)
High -- over 2 million copies/mL (600,000-800,000 IU/mL)
Genotypic Testing: Not all hepatitis C viruses are the same. There are at least six different "genotypes" of HCV -- meaning that their genetic structures differ somewhat from each other. What's more, some of these genotypes can be divided into subtypes. For example, HCV genotype 1 is divided into subtypes "a" and "b."
In the United States, HCV genotypes 1, 2, and 3 are the most common. The other genotypes are found mostly in the Middle East, Africa, and Asia.
HCV genotype does not predict the likelihood that someone with hepatitis C will develop cirrhosis or liver failure, nor does it affect the speed by which these problems can occur. In other words, the HCV genotype does not seem to affect disease progression. But HCV genotype can predict how effective treatment may be -- HCV genotypes 1 and 4 are the most difficult to treat, whereas HCV genotypes 2 and 3 are much more likely to respond well to treatment, usually in a shorter period of time. Unfortunately, HCV genotype 1 is the most common among people with HIV in the United States, accounting for as many as 75% of all hepatitis C infections.
Knowing your HCV genotype can help you and your healthcare provider determine how best to approach treatment if and when the time comes. This might include decisions about which treatment to use as well as the length of your treatment.
Liver Enzyme Tests: As with hepatitis A and hepatitis B, the most important liver enzymes to monitor are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In approximately two-thirds of people with chronic hepatitis C, ALT levels are always elevated, reflecting ongoing damage to liver cells. But for one-third of people with chronic hepatitis C, ALT levels remain normal. Many of these people will live with HCV infection without any liver-related problems, but others with normal or even low ALT levels may be experiencing progressive liver damage. AST levels are also often high in people with chronic hepatitis C. However, AST levels are usually lower than ALT levels. If cirrhosis develops, AST levels can rise above ALT levels -- a sign that damage to the liver is worsening.
Liver Biopsy: HCV viral load and liver enzymes are very useful tests. However, they cannot determine if -- and how much -- damage has been done to the liver by HCV infection. In order to figure this out, a liver biopsy is often necessary, especially in terms of deciding when or whether to begin treatment. Information about the liver biopsy procedure is reviewed in the discussion of hepatitis B.
How Is Hepatitis C Treated?
When it comes to treating hepatitis C, the first question is: how do I know when it's time to start?
Generally speaking, the National Institutes of Health recommend that treatment be started before cirrhosis occurs (this can be determined through a liver biopsy), but only for people who are considered to be at a "high risk" of developing cirrhosis in the future. This includes people who have all of the following:
Elevated ALT levels;
HCV that is detectable by viral load testing;
A liver biopsy that shows moderate to severe signs of fibrosis, inflammation, and necrosis (cell death); and
No safety concerns to indicate that treatment shouldn't be offered.
If these criteria are met, a patient should be offered treatment, regardless of the presence or absence of symptoms, the route of HCV infection, HCV genotype, or HCV viral load.
Circumstances in which healthcare providers should make a decision about starting treatment on an individual basis after talking with the patient include:
Normal ALT levels, even if HCV is detectable by PCR (treatment may not yet be necessary);
A prior liver transplant;
Active substance use, including alcohol;
A history of problems that might interfere with the safety or effectiveness of therapy, such as severe untreated depression (which can be made worse by the use of interferon-alfa, the standard treatment for hepatitis C).
Treatment is contraindicated (shouldn't be used) under the following circumstances:
Severe liver disease such as decompensated cirrhosis, when the liver is no longer able to compensate for the damage that it has suffered (a liver transplant may be the best option for these patients);
Prior kidney or heart transplant;
Women who are pregnant;
Women who are unable or unwilling to use birth control (hepatitis C therapies can cause severe birth defects).
For people coinfected with HIV and HCV, there are additional factors to consider when figuring out if and when to begin HCV treatment. It's very important that people with both viruses thoroughly discuss their options with their healthcare provider. Issues to consider include:
People with HIV and HCV may develop cirrhosis or liver failure faster than people singly infected with HCV. In turn, some liver experts recommend treatment, even if a biopsy reveals mild signs of fibrosis, inflammation, and necrosis (as opposed to moderate to severe signs in people with only hepatitis C).
HCV may increase the risk of liver damage, which can prevent certain anti-HIV medications from being broken down in the body properly. Someone coinfected with HIV and HCV is more likely to benefit from HCV treatment when the immune system is strong (when the CD4 cell count is high and HIV viral load is low, for example). For these reasons, some liver experts recommend early treatment for HCV, before anti-HIV treatment is needed.
Anti-HIV medications may cause side effects in the liver that can worsen a person's hepatitis C. Some experts recommend HCV treatment to reduce the chance that hepatitis C will cause (more) damage to the liver once anti-HIV drugs are started.
Above all, deciding if and when to start treatment is a personal decision. Regardless of what "official" guidelines do or don't say, it is up to you and your healthcare provider to figure out what's best for you, based on your own thoughts, concerns, and circumstances.
Can Hepatitis C Be Cured?
It all depends who you ask.
As a general rule, the success of treatment is determined at two time points: just as the course of treatment is completed, referred to as the end-of-treatment response (ETR); and six months after treatment is completed, referred to as the sustained response (SR). The tests that are most important at these time points are the liver enzyme tests and the HCV viral load. If a person's liver enzyme levels are back to normal and HCV viral load is undetectable at the end of treatment, the person is said to have an effective ETR. If a person's liver enzyme levels remain normal and the HCV viral load is still undetectable six months after completing treatment, he or she is said to have an effective SR.
If someone is no longer on hepatitis C treatment and his or her liver enzymes are normal and no HCV virus is present in the blood, wouldn't this be considered a cure? Some liver experts say yes, this is a cure -- the vast majority of people who achieve a sustained response as a result of treatment maintain healthy livers for many years. However, some experts point out that most patients who achieve a SR still have traces of HCV in their liver that could, over time, become active again.
Only time will tell what a SR really means. Because HCV was only identified in 1988, our knowledge of how treatments work and what we can expect out of them is still young. However, an ETR is considered a good response to treatment and a SR an excellent outcome. Both translate into liver-health improvements that are life-saving and life-enhancing.
But what about people with hepatitis C who don't achieve either an ETR or a SR as a result of treatment? According to some recent studies, treatment has a great deal to offer people with hepatitis C who don't achieve either. Even if you experience only mild improvements in your liver enzyme tests or moderate improvements in your HCV viral load -- or see your lab results worsen after an initial good response during therapy -- this usually translates into some long-term benefits to the liver. Researchers are conducting studies to determine what these benefits mean in terms of people with hepatitis C living longer, healthier lives.
What Treatments Are Available for Hepatitis C?
Until 1998, the only treatment available for chronic hepatitis C was interferon-alfa, a synthetic version of a naturally occurring hormone that has antiviral and immune-boosting properties. The drug was only moderately effective in terms of end-of-treatment response (ETR) and sustained response (SR) and was associated with a significant number of often debilitating side effects.
While interferon is still sometimes used today, improved versions of the drug are now available. Pegylated interferon (Pegasys, PEG-Intron) contains microscopic particles (polyethylene glycol) linked to an interferon molecule that keeps the drug in the bloodstream for longer. This allows for once-weekly injections (standard interferon required daily or three-times-a-week injections). What's more, with pegylated interferon, drug levels in the bloodstream are higher and last longer than standard interferon, making the drug more effective against HCV. Although the side effects of pegylated interferon are similar to those of standard interferon, the benefit of treatment is more pronounced.
A second antiviral drug was approved by the Food and Drug Administration for use in combination with interferon for the treatment of hepatitis C. Ribavirin (Rebetol, Copegus) increases the chance of achieving an ETR and SR when it is combined with either standard or pegylated interferon. Combination therapy with ribavirin and pegylated interferon is now the preferred HCV treatment.
Here's a look at the treatments available for chronic hepatitis C:
Interferon-Alfa (Roferon-A, Intron A): If used alone, without ribavirin (not generally recommended), the usual dose is 3 million units (MU), three times a week, injected subcutaneously (under the skin). Therapy is continued for one year.
Only 10% to 20% of people using interferon-alfa alone achieve a SR -- undetectable HCV viral loads six months after stopping treatment. Results have been similar in both HIV-positive and HIV-negative patients with hepatitis C.
Side effects of interferon-alfa are common, although their severity varies from one individual to the next. They occur with both standard and pegylated versions of the drug and can include:
These side effects tend to be worse during the first few weeks of treatment, especially after the first injection, but usually diminish over time. Nighttime injections of interferon may lessen the side effects since they will occur during sleep. Ibuprofen (Advil, Motrin, etc.) can lessen some of the flu-like side effects, and antidepressants can help control persistent depression.
Pegylated Interferon (Pegasys, PEG-Intron): If used alone, treatment is generally recommended for one year. The dose depends on the brand used. The dose of PEG-Intron varies according to body weight, whereas the Pegasys dose is the same regardless of weight. Pegylated interferon is injected subcutaneously (under the skin) once a week.
Using pegylated interferon alone, 25% to 40% of people with chronic hepatitis C (but not HIV) have an effective SR. Liver enzyme tests and HCV viral loads have improved in some patients with decompensated cirrhosis -- an advanced form of liver disease that is usually not treated with standard interferon-alfa. There have also been studies demonstrating that pegylated interferon is equally effective in people with HIV and chronic hepatitis C. The side effects of pegylated interferon are similar to those of standard interferon-alfa, and the same methods may help to alleviate them.
Ribavirin (Rebetol, Copegus): Ribavirin must be used in combination with either standard interferon-alfa or pegylated interferon (it is not effective against hepatitis C if it is used by itself). Ribavirin is taken orally twice a day, and the dose ranges from 800 mg to 1,200 mg a day depending on HCV genotype and body weight.
In addition to the side effects associated with interferon, ribavirin can cause anemia (low red blood cell counts), itching, skin rash, nasal stuffiness, and cough. The anemia can be severe and is sometimes treated with injections of erythropoetin (Procrit or Epogen), which stimulates the bone marrow to produce more red blood cells. Ribavirin can also cause serious birth defects. Women should be careful not to become pregnant while they or their sexual partner are taking ribavirin and for six months after stopping the drug. Both men and women should use birth control while taking ribavirin and for six months afterwards. If possible, ribavirin should not be taken with Videx (ddI) and, to a lesser extent, with Zerit (d4T) -- two medications used in the treatment of HIV. Certain side effects of these drugs are more likely to occur when they are combined with ribavirin.
From studies in people with HCV (but not HIV), the length of combination treatment with interferon and ribavirin depends on a person's HCV genotype. With genotypes 2 or 3, therapy usually lasts six months. With genotype 1, it usually lasts a year. Unfortunately, with little information from clinical trials involving people with both HIV and HCV, it's difficult to say if this also holds true for them. Therefore, many liver experts feel it's best to treat people infected with both viruses for at least a year, regardless of genotype.
We also know from studies involving people living with HCV (but not HIV) that the effectiveness of therapy combining ribavirin and interferon depends on the type of interferon-alfa used and the HCV genotype being treated. Using standard interferon with ribavirin, 35% to 45% of people achieve a SR. Using pegylated interferon with ribavirin, overall sustained response rates in excess of 50% were seen in two important studies involving people with HCV (but not HIV). Between 42% and 46% of people in these studies with HCV genotype 1 had sustained responses. And between 76% and 82% of people with HCV genotypes 2 or 3 were sustained responders.
Early results from studies involving people with both HCV and HIV indicate that response rates to interferon (both standard and pegylated) combined with ribavirin are lower and that the side effects are often worse. To increase the likelihood of a SR in people with both HIV and HCV -- particularly those with HCV genotype 1 -- some healthcare providers continue interferon/ribavirin treatment for 18 months (sometimes longer).
Using standard interferon-alfa with ribavirin, usually no more than 20% of coinfected people achieve a sustained response. Using pegylated interferon with ribavirin, the overall sustained response rates were between 27% and 40% in three clinical trials that have been reported (the U.S. study ACTG A5071, the international APRICOT study, and the French RIBAVIC study).
Sustained response rates differed, depending on the HCV genotype being treated. In these same studies of pegylated interferon plus ribavirin, 44% to 73% of people with HIV and HCV genotypes 2 or 3 had a sustained response, compared to only 14% to 29% of those with genotype 1.
A more complete list of factors that may influence a successful response to treatment (based on studies involving people with HCV, but not HIV) includes:
genotype 2 or 3
low HCV viral load when starting treatment (less than two million copies/mL or 600,000-800,000 IU/mL)
age under 40
low body mass index (BMI)
It's unclear how these somewhat predictive factors apply to people with HIV/HCV coinfection.
Many people are evaluated after three months on treatment. If their HCV viral load hasn't dropped significantly, treatment is often stopped since this indicates that they're unlikely to achieve a sustained response. Some people go through treatment more than once if they don't achieve a sustained response the first time. While the likelihood of treatment working a second or third time is relatively low, re-treatment definitely works for some people. And some people use low-dose interferon as "maintenance therapy" following a course of treatment.
There are many experimental medications being developed for the treatment of chronic hepatitis C. These include medications that prevent HCV from binding to liver cells, drugs that attack viral enzymes that help HCV to reproduce, and treatments to strengthen the body's own immune response to HCV.
Because depression before and while on HCV treatment is common, people who are considering interferon therapy may find the help they need to see them through if they have a support network in place beforehand, including a mental health professional and/or a support group.
How Can Hepatitis C Be Prevented?
With no hepatitis C vaccine, the best way to prevent infection is to reduce the risk of coming into contact with another person's blood. This also applies to people who are already infected with HCV to prevent transmitting the virus to somebody else. And even if you're one of the lucky people whose immune system cleared the virus after infection or had a successful response to HCV treatment, you can be infected again with HCV. Unlike the antibodies to hepatitis A and hepatitis B, HCV antibodies do not protect from future HCV infection.
Stopping injection drug use would eliminate the most common route of HCV transmission, but stopping isn't a realistic possibility for everyone. If you inject drugs, always use a new, sterile syringe, cotton, cooker, and fresh water every time you inject -- never reuse or share syringes, needles, water, or other drug preparation equipment. If you're splitting drugs, split them when they're dry (in powder form) or use a new, sterile syringe to split them. Don't backload into someone else's syringe, and be sure to clean the injection site and avoid contact with blood.
Don't share toothbrushes, razors, nail clippers, or other items that may have blood on them. If you're considering a tattoo or body piercing, be sure that the procedures are performed by reputable, licensed experts and that strict hygienic measures are in place, including sterile equipment and ink.
Although HCV is not transmitted efficiently through sexual activity, it is best to use barrier protection (condoms, latex gloves, etc.) to reduce the risk of transmitting HIV, HCV, and other sexually transmitted diseases.