Hepatitis B is caused by the hepatitis B virus (HBV). HBV is a noncytopathic virus. This means that the virus itself 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 (hepatitis). However, HBV can cause damage to the genetic material inside liver cells. This can lead to liver cancer which, like hepatitis, can also be fatal.
People who have not been infected with HBV can be vaccinated against the virus to prevent infection.
HBV is very similar to HIV in the ways it is transmitted: through direct blood-to-blood contact and through sexual activity. However, blood levels of HBV are much higher than for HIV or the hepatitis C virus, making this virus much easier to transmit in certain situations (e.g., from mother to child during delivery).
HBV is present in blood, semen, and vaginal fluids and is transmitted primarily through sexual activity. Another major transmission route is sharing injection drug equipment (including needles, cookers, tourniquets) and, to a lesser extent, non-injection drugs (cocaine straws and crack pipes) due to the possibility of exposure to blood. Pregnant women who have hepatitis B can also transmit the virus to their babies, most likely during birth.
The number of new hepatitis B infections in the U.S. has declined from about 260,000 a year in the 1980s to about 73,000 in 2003, with the greatest decline occurring in children and adolescents due to routine HBV vaccination.
What happens when someone is infected with HBV?
Soon after HBV enters the body, it infects cells in the liver called hepatocytes. In response to this infection, the immune system targets the virus and targets the hepatocytes already infected with the virus. This causes inflammation of the liver (hepatitis).
HBV can cause acute hepatitis, meaning short-term inflammation of the liver, until the immune system is able to clear the virus from the body, usually within six months of becoming infected with the virus. However, HBV 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 person's liver for several months or years after infection. This can increase 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 percent of adults infected with HBV go on to experience chronic HBV infection. Babies infected with HBV around the time of birth go on to experience chronic HBV infection approximately 90 percent of the time, which is why it is important that pregnant women know whether or not they are infected with the virus before giving birth. Medication can be given to the baby after birth to help prevent hepatitis B. Young children who are infected with HBV have a 25 percent to 50 percent 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, patients with impaired immune responses who are recovering from organ transplants, undergoing chemotherapy, undergoing dialysis for kidney problems, receiving steroid therapy to suppress the immune system, or are HIV-positive are more likely to develop chronic HBV infection than patients with normal immune responses. In other words, HIV-positive people are more likely to develop chronic HBV infection after being infected with the virus than HIV-negative people (with healthy immune systems).
What are the symptoms?
Not everyone who is infected with HBV will experience symptoms of acute hepatitis—between 30 percent and 40 percent 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 being infected and can last anywhere from one or two weeks to several months.
The symptoms of acute hepatitis B can include:
- Yellowing of the skin, whites of the eyes, and under the fingernails (jaundice)
- Dark urine and/or pale stool
- Feeling tired and rundown (fatigue)
- Abdominal pain
- Loss of appetite
- Joint pain
If the immune system is not able to control acute HBV infection within six months, symptoms of chronic hepatitis B are possible. Not everyone with chronic hepatitis B experiences symptoms. Some people with chronic hepatitis B experience occasional symptoms, while others experience symptoms that never seem to go away.
Symptoms of chronic hepatitis B can include those typically seen in acute hepatitis B. They tend to be mild to moderate in intensity and typically come and go. Other symptoms can occur, particularly in people who have been dealing with chronic hepatitis B for many years. Additional symptoms include rash, hives (urticaria), arthritis, and burning/tingling in the arms and legs (polyneuropathy).
Less than 1 percent of people infected with HBV may experience a quick and severe (fulminant) infection, which, very rarely, can lead to liver failure and death. Symptoms of hepatitis, whether acute or chronic, should always be brought to the attention of a healthcare provider.
How is it diagnosed?
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 HBV) 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. IgM antibodies are produced early in the course of infection. IgG antibodies are produced later in the course of infection and replace IgM 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:
|Hepatitis B status||HBsAg||Anti-HBc (total)||Anti-HBc (IgM)||Anti-HBs|
|Never infected with the virus (consider getting the vaccine).||Negative||Negative||Negative||Negative|
|Infection likely took place over the last six months and is still active.||Positive||Positive||Positive||Negative|
|Infection likely took place over the past six months and is in the process of clearing. A false-positive is another possibly (HIV-positive people with this particular test result should have their HBV viral load checked).||Negative||Negative||Positive||Negative|
|Infection likely took place more than six months ago and has been successfully controlled by the immune system.||Negative||Positive||Negative||Positive|
|The vaccine was successfully given to prevent HBV infection.||Negative||Negative||Negative||Positive|
|Chronic HBV infection.||Positive||Positive||Negative||Negative|
Depending on these results, additional diagnostic tests may be necessary. Somebody who has never been infected with HBV or has been vaccinated against the virus does not require any additional testing. Someone who was recently infected with HBV and has acute hepatitis B may want to get another blood test after six months have passed to make sure that the necessary immune response has occurred. People with chronic HBV infection require additional testing to learn more about their hepatitis B.
If you have chronic hepatitis B, your healthcare provider will usually order additional tests to determine if the infection is active:
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—especially those who have been infected with HBV for many years—may have 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 bloodstream, viral load testing can determine if HBV is reproducing in the liver. In a person with detectable HBeAg, an HBV viral load greater than 100,000 indicates that the virus is active and has the greatest potential to cause damage to the liver. Similarly, in a person with an HBV precore mutant, an HBV viral load of greater than 10,000 indicates that the virus is active and has the potential to cause damage to the liver. Generally speaking, if the HBV viral load is above these numbers, treatment is considered necessary. However, some experts believe that hepatitis B should be treated at any viral load, given that there is a risk of liver cancer developing even when the HBV viral load is low.
Liver Function Tests: One of the most important liver enzymes to look for is alanine aminotransferase (ALT), sometimes called SGPT on lab reports. An elevated ALT level indicates that the liver is not functioning properly and that there is a risk of permanent liver damage. During acute hepatitis B infection, ALT levels can be temporarily elevated, but this rarely leads to long-term liver problems. In chronic hepatitis B, ALT levels can either be periodically or consistently increased, indicating a higher risk of long-term liver damage.
HBV Genotype: There are actually eight different types—or "genotypes"—in the world. The differences between the eight genotypes are based on differences in HBV's genetic structure. HBV genotypes B and C are common in Asia, whereas genotypes A and D occur frequently in Europe. Genotypes F and H are found in Central and South America. In the United States, we see genotypes A, B, C, and D. There is still some debate regarding whether it is important to know a patient's HBV genotype. However, studies have demonstrated that patients with HBV genotypes A or B are likely to have better responses to some treatments than patients with genotypes C or D. In turn, finding out the HBV genotype may have some value when choosing treatments for hepatitis B.
Imaging: Magnetic resonance imaging (MRI) and "triple-phase" computed tomography (CT or CAT) scans are becoming more common, painless tests to look for changes in the liver, most notably liver cancer tumors. Some experts suggest that triple-phase CT and MRI are the best way to look for tumors in people who have cirrhosis of the liver.
Ultrasound: Like MRI and CT scans, ultrasound can be used to look for liver cancer tumors. Some experts suggest that ultrasound is an effective screening tool in people who do not have cirrhosis of the liver.
Alpha-fetoprotein (AFP): This test looks for high levels of AFP, a protein that is produced by cancerous liver cells. AFP is not a very sensitive test. In turn, it is often used if imaging or ultrasound suggests that liver cancer tumors are present.
Liver biopsy: Unfortunately, blood tests and imaging do not tell the whole story regarding the health of the liver. In turn, a liver biopsy may be needed to look for evidence of cirrhosis and liver cancer.
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 to make the biopsy. The patient lies on his or her 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 the patient to take a deep breath in and out, and to 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. The patient then has 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.
There is still some debate regarding the value of liver biopsies. Some experts argue that they can be useful in figuring out how best to treat hepatitis B, whereas others argue that treatment decisions (including when to start and which medications to use) can be made using blood tests.
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 have also suggested that as HIV progresses, the body's immune response to HBV gradually decreases or is sometimes lost. This can cause the virus to become active again after being inactive, which can once again 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 immune system status. There are also data from studies suggesting that people with HIV with chronic hepatitis B are more than twice as likely as their HIV-negative counterparts to experience liver failure, thus requiring consideration of a liver transplant. It is not yet known if people with HIV with 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 would seem to be likely.
People co-infected with HIV and chronic hepatitis B need to be careful when choosing treatments for both infections.
How is it treated?
People with acute hepatitis B do not require treatment. Bed rest, drinking lots of fluids, and over-the-counter pain relievers (products containing ibuprofen, such as Motrin and Advil, are considered to be safer than products containing acetaminophen, such as Tylenol, in people with acute hepatitis) are usually all that is needed for someone who is experiencing symptoms because 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.
There is still some debate regarding the best time to begin anti-HBV treatment. Many experts argue that treatment should be started when the HBV viral load is high or ALT levels are increased. Other experts argue that it doesn't matter what the HBV viral load is—if it's detectable it should be treated, given that any sign of active viral replication can mean an increased risk of liver cancer.
Treatments for Chronic Hepatitis B Infection
Interferon-alfa: Interferon-alfa mimics naturally occurring interferon-alfa, the body's own antiviral. Standard versions of interferon-alfa (Roferon A, Intron A) have been approved for several years for the treatment of chronic hepatitis B. Pegylated interferon-alfa—a drug that contains microscopic waxy particles (polyethylene glycol) linked to an interferon molecule—is now the preferred version of interferon-alfa for the treatment of hepatitis B. Genentech's Pegasys has been approved for the treatment of chronic HBV and Merck's Peg-Intron is currently being studied as a treatment for hepatitis B.
Studies of Pegasys indicated that pegylated interferon-alfa is more effective than standard interferon-alfa for treating HBeAg-positive HBV infection. Studies have demonstrated that pegylated interferon may not be as effective in people with HIV and HBV infection—it is best used while the T-cell count is above 350. Studies have also shown that HBV genotypes A and B respond better to interferon treatment than HBV genotypes C and D. In turn, if interferon-alfa is selected as a treatment for HBV infection, it is recommended that the patient's HBV genotype be checked first.
The Pegasys dose is 180 micrograms, injected subcutaneously (directly under the skin) once a week for a total of 48 weeks. Side effects of interferon-alfa are common and can include: fatigue, joint and muscle aches, low-grade fever and/or chills, headache, nausea and vomiting, skin irritation at the injection site, weight loss, low white and red blood cells, mild hair loss, irritability, depression, and/or suicidal thoughts (rare). These side effects are generally worse during the first few weeks of treatment, especially after the first injection, but usually diminish over time.
Lamivudine (Epivir, Epivir-HBV): After being approved for the treatment of HIV, the nucleoside analogue lamivudine was also approved for the treatment of chronic hepatitis B. People who are infected only with HBV (and not HIV) take one 100mg lamivudine tablet every day. People who are infected with both HBV and HIV should use the dose typically used for the treatment of HIV: one 300mg tablet (or two 150mg tablets) once a day.
As in HIV, HBV resistance to lamivudine can and does occur. When lamivudine is used alone without other anti-HBV treatments (monotherapy), approximately 25% of people with HIV/HBV develop HBV resistance to the drug within one year. After four years of lamivudine monotherapy use, approximately 90% have HBV strains resistant to the drug. (The percentage developing lamivudine resistance is somewhat lower in people infected with HBV but not HIV.)
Emtricitabine (Emtriva) is very similar to lamivudine and is known to be active against HBV. Because emtricitabine is also approved for the treatment of HIV, some healthcare providers use it instead of lamivudine to treat both infections at the same time. If an HIV-positive person's regimen contains emtricitabine, there is no need to add lamivudine.
Adefovir dipivoxil (Hepsera): Adefovir is a nucleotide analogue, which differs slightly in its chemical structure than the nucleoside analogues (lamivudine and entecavir). 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 10mg 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 who have tried and failed lamivudine in the past. Adefovir is active against HBV strains that are resistant to lamivudine.
HBV can develop resistance to adefovir, but not as quickly as HBV develops resistance to lamivudine. After four years of HBV monotherapy treatment, approximately 18% of people develop HBV resistance to the drug. After five years of adefovir monotherapy treatment, HBV resistance occurs in approximately 29%. Rates of resistance are likely higher in people who become resistant to lamivudine and then switch to adefovir monotherapy.
It is not clear if people living with HIV and HBV should be treated with adefovir. Adefovir is very similar to tenofovir (Viread, Truvada and Atripla), a drug that is approved for the treatment of HIV and is also active against HBV. If an HIV-positive person's regimen contains tenofovir, there is no need to add adefovir. In fact, trials have now confirmed that tenofovir is superior to adefovir and it is approved as a first-line treatment for HBV. Truvada, a once-daily tablet that contains Viread and Emtriva (see above), is frequently prescribed for people living with both HIV and HBV, always in combination with another HIV medication.
Because the adefovir dose used to treat HBV is considered too low to be active against HIV, it has been suggested that adefovir monotherapy can be used by people infected with both viruses to treat HBV before combination antiretroviral therapy is necessary. However, experts caution that this may be a risky choice—it is still possible that there will be a low-level effect of adefovir on HIV, when used as monotherapy for hepatitis B, which may cause HIV to become resistant to adefovir and similar HIV medications (e.g., tenofovir).
Entecavir (Baraclude): Entecavir is a nucleoside analogue like lamivudine. It was approved in March 2005 for the treatment of chronic hepatitis B. The dose of entecavir will depend on a person's hepatitis B treatment history. For example, if the person is starting a nucleoside analogue for the first time, the entecavir dose is one 0.5-mg tablet per day. If the person has taken Epivir or Emtriva in the past—and has HBV that is resistant to either of these drugs—the correct entecavir dose is one 1-mg tablet per day.
Very little is known about entecavir's resistance profile. After two years of entecavir monotherapy, no cases of HBV resistance to the drug have been reported. However, long-term follow-up data is needed from studies to better understand if, and how quickly, HBV develops resistance to entecavir.
While entecavir is not specifically approved for people with HIV/HBV coinfection, it has been studied in a trial involving people infected with both viruses. Entecavir was found to be effective, including against HBV resistant to lamivudine.
When entecavir was first approved, it was believed to have no effect on HIV replication. In turn, some experts suggested that it be used, as monotherapy, to treat HBV before combination therapy is prescribed for HIV, without the risk of HIV becoming resistant to the drug (and, in turn, cross resistant to other HIV medications). In early 2007, reports emerged showing that entecavir does have HIV activity and caused HIV drug resistance in some patients. In turn, experts and the U.S. Food and Drug Administration are urging caution if entecavir monotherapy is being considered for the treatment of HBV in HIV-positive patients.
Telbivudine (Tyzeka): Tyzeka is a once-daily anti-HBV treatment approved by the FDA in October 2006. Tyzeka was studied in a year-long international clinical trial involving 1,367 patients with chronic HBV. Three-quarters of the trial participants were male, and all were 16 years of age or older. The trial produced evidence of antiviral effectiveness, including the suppression of HBV, and improvement in liver inflammation comparable to Epivir.
It is not known how well Tyzeka works in people infected with HIV and HBV, nor is it known how well the drug works in people with HBV resistance to other available medications.
Telbivudine is not believed to have any activity against HIV. In turn, some healthcare providers may prescribe it, as monotherapy, to treat HBV before combination therapy is considered necessary for HIV, without the risk of HIV becoming resistant to the drug (and, in turn, cross resistant to other HIV medications). However, due to the emergence of data indicating that entecavir has anti-HIV activity, some experts are urging caution regarding the use of telbivudine as monotherapy in HIV/HBV-coinfected patients until additional studies exploring the effects of the drug on HIV are conducted and completed.
The U.S. Department of Health and Human Services has discussed how best to treat chronic HBV in people who are infected with HIV. These recommendations first appeared in the May 2006 publication of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. The Guidelines list a number of important general recommendations, including being vaccinated against the hepatitis A virus (if not already immune to the virus), avoiding alcohol, and learning about methods to prevent the transmission of HBV to others.
While there is some overlap between the drugs used to treat HIV and HBV (this can make things much easier), it is sometimes necessary to carefully consider which medications to use if it is necessary to treat one infection but not the other. For example, someone may have a very high HBV viral load and elevated liver enzymes, but a healthy T-cell count and low HIV viral load. In other words, this person may need treatment for his HBV but not his HIV. To help patients and doctors figure out what to do in situations like this, the DHHS makes the following recommendations:
Need to treat HIV, but not HBV
Use tenofovir (Viread) plus lamivudine (Epivir) or tenofovir plus emtricitabine (Truvada) in the anti-HIV drug regimen. Do not use tenofovir without lamivudine or emtricitabine (or vice versa), as this may lead to HBV drug resistance.
Need to treat HBV, but not HIV
The combination of tenofovir plus lamivudine or emtricitabine should be included in the first anti-HIV drug regimen. Another option might be entecavir (Baraclude) plus either tenofovir, lamivudine, or emtricitabine. Do not use only one drug with anti-HBV activity in an anti-HIV drug combination.
Need to treat HIV and HBV
Pegylated interferon monotherapy is an option. It does not lead to the development of drug-resistant HIV or HBV. Given recent HIV treatment guidelines changes toward earlier HIV treatment, many experts now recommend that people coinfected with both HBV and HIV start a full HIV regimen right away regardless of their CD4 count.
It is very important that people with chronic hepatitis B take their medications exactly as prescribed. Missing doses can cause HBV to become resistant to HBV medications. Prematurely stopping HBV medications can also cause HBV viral load and liver enzymes to quickly increase, which can damage the liver and cause severe symptoms. This can also happen in people who have HBV that develops resistance to the medications they are using. In turn, for people with chronic hepatitis B who are receiving treatment, it is very important to be monitored frequently and carefully by a healthcare provider.
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 Engerix-B. Both of these vaccines require three injections administered over a six-month period. The side effects of the hepatitis B vaccine are usually mild and may include soreness at the injection site and mild flu-like symptoms. There is also a combined hepatitis A (HAV) and HBV vaccine available (Twinrix), which also requires three injections administered over a six-month period but offers the added advantage of providing protection against both viral infections.
The HBV vaccine is generally effective for more than 90 percent of adults and children who receive all three doses. However, 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 is best for people with HIV to receive the hepatitis B vaccine when T4 cell counts are within healthy ranges. There is evidence that adding additional doses to the standard vaccine course might decrease the chance that a person will fail to benefit from the vaccine, but there are no official recommendations in this regard.
If you do not think you were ever infected with hepatitis B, talk to your healthcare provider. The vaccine is recommended for:
- People with HIV
- Men who have sex with other men
- Injection drug users
- People with chronic hepatitis C virus
- Heterosexual adults with more than one sex partner in the last six months or a history of sexually transmitted disease
- People who work in places where there is a risk of infection (such as hospitals and doctors' offices)
- Hemodialysis patients
- People who share living quarters with someone with chronic hepatitis B
- Increasingly, universal vaccination against HBV is being recommended for all children.
If you have not been vaccinated against hepatitis B, there are still things you can do to prevent HBV infection. These include using a condom or another 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. It's always best to 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 have not been vaccinated against hepatitis B and fear that you were recently exposed to HBV, it is possible to receive a single injection of hepatitis B immune globulin (HBIG). HBIG is recommended following 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. Two additional doses of hepatitis B vaccine are given to complete the series and ensure long-term protection.
Last Revised: February 14, 2016