Viral Hepatitis and HIV
What Is Hepatitis B and How Is It Transmitted?Hepatitis B is caused by the hepatitis B virus (HBV). HBV is a noncytopathic virus, meaning that it does not cause direct damage to liver cells. Instead, it is the immune system's aggressive response to the virus that usually leads to inflammation and damage to the liver.
As with hepatitis A virus (HAV), people can be vaccinated against HBV to prevent infection. HBV is very similar to HIV in the ways it is transmitted. HBV is present in blood, semen, and vaginal fluids and is transmitted through sexual activity, sharing injection drug equipment (including needles, cookers, tourniquets) and, possibly, sharing cocaine straws and crack pipes. Pregnant women who have hepatitis B can also transmit the virus to their babies, most likely during birth. Blood levels of HBV are much higher than for HIV or the hepatitis C virus, making it much easier to transmit in certain situations (from mother to child during delivery, for example).
The number of new hepatitis B infections in the U.S. has declined from about 260,000 a year in the 1980s to about 78,000 in 2001, with the greatest decline occurring in children and adolescents due to routine HBV vaccination.
Like hepatitis A, hepatitis B can cause acute, symptomatic hepatitis. But unlike hepatitis A, hepatitis B can become a chronic infection. This means that the immune system is not able to get rid of the virus within six months after infection. In other words, the virus continues to reproduce in the liver for several months or years after infection. This increases the risk of liver damage and liver cancer. What's more, someone with chronic HBV infection can transmit the virus to others.
Less than 10% of adults infected with HBV go on to experience chronic HBV infection. Approximately 90% of babies infected with HBV around the time of birth go on to experience chronic HBV infection. Medication can be given to the baby after birth to help prevent hepatitis B. Young children who are infected with HBV have a 25% to 50% risk of developing chronic hepatitis B.
With adults, the risk of developing chronic HBV infection depends on the health of the immune system. For example, people with weakened immune responses because they are recovering from organ transplants, undergoing dialysis for kidney problems or chemotherapy, receiving steroid therapy to suppress the immune system, or are HIV-positive are more likely to develop chronic HBV infection than people with strong immune responses.
Approximately 1.25 million people in the U.S. have chronic hepatitis B, and between 4,000 and 5,000 people die each year as a result of HBV-related liver disease. Studies suggest that more than 90% of all people with HIV have been infected with HBV at some point in their lives and that 15% are chronically infected with the virus.
What Are the Symptoms of Hepatitis B?Not everyone who is infected with HBV experiences symptoms of acute hepatitis. Between 30% and 40% of people infected with the virus do not experience any noticeable symptoms. If symptoms do occur, they usually do so within four to six weeks after infection and can last anywhere from a couple of weeks to several months. Symptoms of acute hepatitis B are similar to those of HAV infection (see symptoms of hepatitis A). Some people who experience symptoms of acute hepatitis B feel so sick and run down that they're unable to do anything for weeks or months. As with HAV, less than 1% of people infected with HBV may experience a quick and severe (fulminant) infection, which -- very rarely -- can lead to liver failure and death.
If the immune system is not able to control HBV infection within six months, symptoms of chronic hepatitis B may appear. Not everyone with chronic hepatitis B will have symptoms. Some people experience occasional symptoms, while others have symptoms that never seem to go away.
Symptoms of chronic hepatitis B can be similar to those seen in acute hepatitis B. They tend to be mild to moderate in intensity and typically come and go. Additional symptoms can occur, particularly in people who have been dealing with chronic hepatitis B for many years. These include rash, hives (urticaria), arthritis, and burning/tingling in the arms and legs (polyneuropathy).
Symptoms of hepatitis, whether acute or chronic, should always be brought to the attention of a healthcare provider.
What Laboratory Tests Do I Need to Know About?There are laboratory tests to diagnose HBV infection and laboratory tests to monitor people with chronic hepatitis B.
Hepatitis B is first diagnosed using a blood test that looks for certain antigens (fragments of the hepatitis B virus) and antibodies (produced by the immune system in response to HBV). Initial blood tests to diagnose HBV infection look for one antigen -- HBsAg (the hepatitis B surface antigen) and two antibodies -- anti-HBs (antibodies to the HBV surface antigen) and anti-HBc (antibodies to the HBV core antigen). There are actually two types of anti-HBc antibodies produced: IgM antibodies and IgG antibodies.
The blood test used to check for HBV infection can be quite confusing, given that a number of different combinations of antigens and antibodies are possible and can mean different things. Here's a look at the most important test results to know and what they mean:
If you have chronic hepatitis B, your healthcare provider will usually order additional tests to determine if the infection is active and the extent of liver damage:
HBeAg and Anti-HBe: HBeAg is the hepatitis B envelope antigen, and anti-HBe are the antibodies produced against this antigen. If HBeAg is detectable in a blood sample, this means that the virus is still active in the liver (and can be transmitted to others). If HBeAg is negative and anti-HBe is positive, this generally means that the virus is inactive. However, this is not always the case. Some people with chronic hepatitis B are infected with what is known as a "precore mutant" of HBV. This can cause HBeAg to be negative and anti-HBe to be positive, even though the virus is still active in the liver.
HBV Viral Load: Similar to the technology used to measure the amount of HIV in the blood, viral load testing can determine if HBV is reproducing in the liver. An HBV viral load greater than 100,000 copies/mL indicates that the virus is active and has the greatest potential to cause damage to the liver. When the viral load is above 100,000 copies/mL, especially if liver enzymes are elevated, treatment is recommended. A viral load below 100,000 copies/mL, particularly when HBeAg is negative and anti-HBe is positive, suggests that the virus is being controlled by the immune system. However, even if this is the case, the virus can still be transmitted to others.
Liver Enzyme Tests: Levels of liver enzymes -- called alanine aminotransferase (ALT) and aspartate aminotransferase (AST) -- are measured by a liver enzyme test. Elevated enzyme levels indicate that the liver is not functioning properly and that there may be a risk of permanent liver damage. During acute hepatitis B infection, liver enzyme levels can be temporarily elevated, but this rarely leads to long-term liver problems. In chronic hepatitis B, these levels, particularly ALT levels, can either be periodically or consistently elevated, indicating a higher risk of long-term liver damage.
Alpha-Fetoprotein (AFP): This test looks for high levels of AFP, a protein that is produced by cancerous liver cells. Because people with chronic hepatitis B are at an increased risk of liver cancer, this test is often ordered by healthcare providers every six to 12 months. Using AFP levels to determine the presence of tumors can be misleading, so this test may be most useful for people with cirrhosis since they have a greater chance of developing liver cancer (hepatocellular carcinoma or HCC).
Ultrasound: Many liver experts also recommend ultrasound or "echo" machine to watch out for liver cancer in people with chronic hepatitis B since this procedure is more sensitive than AFP testing at detecting tumors. It is also much more expensive. Ultrasound uses a wand, called a transducer, which is placed on the upper abdomen and moved back and forth to examine the shape, size, and appearance of the liver. Ultrasound is painless and usually takes no more than ten or 15 minutes to conduct. Some experts recommend an abdominal ultrasound every six to 12 months although, as with monitoring AFP levels, it may be most useful for people with cirrhosis.
Liver Biopsy: Unfortunately, blood tests do not tell the whole story regarding the health of the liver. Measuring HBV viral load, liver enzyme levels, and AFP in the blood cannot determine if -- and how much -- liver damage exists. For this, a liver biopsy is needed. Liver biopsies are only recommended for patients who have a high HBV viral load (above 100,000 copies/mL) and elevated liver enzymes.
A liver biopsy is usually performed on an outpatient basis in a hospital. Sometimes, a trained healthcare provider -- such as a hepatologist or a gastroenterologist -- can perform a liver biopsy in his or her office. An ultrasound is sometimes used to identify the best location for the biopsy. You lie on your back or slightly to the left side. The area of the skin where the biopsy will be done is carefully cleaned. Then, a local anesthetic agent is used to numb the skin and tissue below. A specially designed thin needle is inserted through the skin. At this point, the physician will instruct you to take a deep breath in and out and hold it for about five seconds. The needle is inserted into and out of the liver. This takes only one or two seconds. A slender piece of liver tissue is removed with the needle and is then processed in a laboratory. The entire procedure from start to finish lasts only 15 to 20 minutes. You then have to lie still for several hours to avoid the possibility of internal bleeding. There may be some discomfort in the chest or shoulder, but this is almost always temporary.
People have different responses to a biopsy -- some find it painful, while most are surprised at how little pain they experience. Many people describe the procedure mostly as boring because of all that time laying still afterwards.
The results of the biopsy are usually available within a week and then explained to you by your healthcare provider.
How Is Hepatitis B Different for People With HIV?Although healthy adults who are infected with HBV have a less than 10% chance of seeing the infection develop into chronic hepatitis B, when an HIV-positive adult is infected, this risk jumps to almost 25%. In other words, people with HIV are more likely to develop chronic hepatitis B as a result of HBV infection than HIV-negative people with strong immune systems.
A number of reports also suggest that, as HIV disease progresses, the body's immune response to HBV gradually decreases or is sometimes lost. This can cause the hepatitis B virus to become active again after being inactive, which can increase the risk of liver damage.
It is not entirely understood what impact HIV has on the severity of chronic HBV infection. There have been a number of reports showing that people infected with both viruses have higher HBV viral loads and more cirrhosis, regardless of the health of the immune system. There are also data from studies suggesting that people with HIV and chronic hepatitis B are more than twice as likely as their HIV-negative counterparts to experience liver failure, which means considering a liver transplant. It is not yet known if people with HIV and chronic hepatitis B are at a higher risk of liver cancer than their HIV-negative peers, but given the strong link between HBV and liver cancer, this seems likely.
As discussed below, people coinfected with HIV and chronic hepatitis B need to be particularly careful when choosing treatments for both infections.
How Is Hepatitis B Treated?People with acute hepatitis B do not require treatment. Bed rest, drinking lots of fluids, and over-the-counter pain relievers such as ibuprofen (Motrin, Advil, etc.) are usually all that is needed for someone who is experiencing symptoms of acute hepatitis B.
Treatment is only recommended for people with chronic hepatitis B. The goal of therapy is to reduce HBV viral load to undetectable levels and to return liver enzymes to normal levels, with the intent of getting rid of both HBeAg and HBsAg. If these antigens are cleared from the bloodstream, the virus is less likely to rebound once treatment is stopped.
The best time to begin anti-HBV therapy is when the HBV viral load is above 100,000 copies/mL and ALT levels are at least two times their normal levels. Starting therapy when the ALT levels are normal or only slightly elevated isn't likely to be as effective.
There are three treatments approved for the management of chronic hepatitis B:
When used alone by people without HIV, interferon-alfa can clear HBeAg in up to 40% of otherwise healthy people and clear HBsAg in up to 15%.
For reasons that aren't fully understood, interferon-alfa is less effective when used by people with HIV and chronic hepatitis B. Given the low likelihood of benefit, interferon should probably not be used to treat HBV in people with HIV.
Pegylated interferon (Pegasys, PEG-Intron), a drug that contains microscopic particles (polyethylene glycol) linked to an interferon molecule, is being studied for the treatment of chronic HBV. It only needs to be injected once a week, and early clinical trial results suggest that it is more effective than standard interferon-alfa. Additional clinical trials are under way to determine how safe and effective pegylated interferon really is for the treatment of chronic hepatitis B.
Lamivudine (Epivir, Epivir-HBV): After being approved for the treatment of HIV, lamivudine was also approved for the treatment of chronic hepatitis B. People who are infected only with HBV (and not HIV) take one 100-mg lamivudine tablet every day. People who are coinfected with HBV and HIV should take the dose typically used for the treatment of HIV -- 300 mg a day.
In clinical trials of lamivudine using the 100-mg daily dose, treatment was associated with a loss of HBeAg after a year of therapy in 17% to 33% of people with chronic hepatitis B. Decreased scarring (fibrosis) of the liver was also observed in patients who received lamivudine.
As in HIV, HBV resistance to lamivudine can and does occur. When lamivudine is used alone without other anti-HBV treatments, approximately 14-32% of people develop HBV resistance to the drug within one year. After four years of lamivudine use, approximately 66% have HBV strains resistant to the drug, and this percentage is even higher in people who have both HBV and HIV. While this suggests that using lamivudine alone to treat HBV is somewhat limited, it also suggests that lamivudine resistance develops much more slowly with HBV than it does with HIV. And even when HBV resistance to lamivudine does occur, the drug still appears to help keep HBV viral load low and slow the progression of HBV-related liver disease.
People with HIV who use lamivudine to treat both their HIV and chronic hepatitis B should be aware that, even if their HIV becomes resistant to lamivudine, it might be necessary to continue taking the drug to treat their HBV. If lamivudine is stopped too quickly, it can cause the amount of HBV in the body to increase sharply, resulting in symptoms (called "flares"). These "flares" -- sometimes severe -- can also occur if your HBV develops resistance to lamivudine. In addition to being used under the brand name, Epivir, as a single-drug component of anti-HIV combination therapy, lamivudine is part of the combination pills Combivir and Trizivir.
Adefovir Dipivoxil (Hepsera): Originally studied as a potential treatment for HIV, the dose of adefovir needed to treat HIV was associated with kidney problems. For the treatment of HBV, the dose is much lower -- one 10-mg tablet every day -- and carries a much lower risk of kidney-related side effects. In clinical trials, adefovir was found to be an effective treatment for people with chronic hepatitis B starting therapy for the first time and for people whose HBV had developed resistance to lamivudine.
In two major studies conducted by the manufacturer, adefovir was more likely to reduce liver inflammation, improve fibrosis, decrease HBV viral load, and normalize liver enzymes after almost a year of treatment than a placebo. Promisingly, no one with hepatitis B who took adefovir for a year developed resistance to the drug.
It is not clear if people with HIV and HBV should be treated with adefovir. Adefovir is very similar to tenofovir (Viread), a drug that is approved for the treatment of HIV and is also active against HBV. If an HIV-positive person's regimen includes Viread, there is no need to add adefovir. One possibility is to use adefovir to treat HBV before combination anti-HIV therapy -- which should include Epivir and/or Viread -- is necessary (if the person's CD4 count is high and viral load is low, for instance). However, this approach has not been studied in clinical trials.
Although Viread is active against HBV, it has not been well studied in clinical trials and is not yet approved to treat HBV. The same is true of Emtriva (emtricitabine), an anti-HIV drug which is very similar to lamivudine.
In the future, it is likely that we will hear a lot more about combination therapy for the treatment of hepatitis B. Just as a combination of drugs helps to keep HIV viral load undetectable and delays drug resistance, it's likely that a combination of anti-HBV drugs will help increase the effect of therapy for HBV and reduce the development of resistance.
How Can Hepatitis B Be Prevented?The best way to prevent hepatitis B is to be vaccinated. Two HBV vaccines are available: Recombivax HB and Energix-B. Both vaccines require three injections administered over a six-month period. Side effects, if any occur, are usually mild and may include soreness at the injection site and mild flu-like symptoms. There is also a combined HAV and HBV vaccine available (Twinrix), which offers the added advantage of providing protection against both viral infections.
The HBV vaccine is effective for more than 90% of adults and children who receive all three doses. But some research suggests that people with HIV are less likely to develop immunity to HBV through vaccination, especially if they have compromised immune systems. So it's best for people with HIV to receive the hepatitis B vaccine when their CD4 cell counts are within healthy ranges.
If you don't think you were ever infected with hepatitis B, talk to your healthcare provider. Because people with HIV have a greater chance of developing chronic hepatitis B and a healthy liver is necessary to break down anti-HIV medications properly, the hepatitis B vaccine is strongly recommended for people with HIV. Getting vaccinated is especially important for people with HIV and hepatitis C or any other liver disease.
If you haven't been vaccinated against hepatitis B, there are still things you can do to prevent HBV infection. These include using a condom or other type of latex barrier while having sex. If you are an injection drug user and share equipment, cleaning your syringes with bleach will not help you avoid hepatitis B -- use new needles to prevent the risk of HBV infection. Also, don't share items that may have been contaminated with someone else's blood such as toothbrushes, razors, and needles used for body piercing, tattooing, or acupuncture.
If you haven't been vaccinated against hepatitis B and fear that you were recently exposed to HBV -- for example, after being poked with a used hypodermic needle or having sexual contact with someone with hepatitis B -- it's possible to receive an injection of hepatitis B immune globulin (HBIG). HBIG is recommended after exposure to hepatitis B virus because it provides immediate, short-term protection against the virus. A dose of the hepatitis B vaccine is given at the same time. Over time, two additional doses of hepatitis B vaccine are given to complete the series and ensure long-term protection.
This article was provided by AIDS Community Research Initiative of America. Visit ACRIA's website to find out more about their activities, publications and services.