Patient information: Hepatitis B

HEPATITIS B OVERVIEW

The liver is an organ that is located in the right upper abdomen, beneath the rib cage (figure 1). It performs many functions that are essential to life.

The term "hepatitis" is used to describe a common form of liver injury. Hepatitis simply means "inflammation of the liver" (the suffix "itis" means inflammation and "hepa" means liver). Hepatitis B is a specific type of hepatitis that is caused by a virus.

It is estimated that there are more than 300 million carriers of the hepatitis B virus in the world, with over 500,000 dying annually from hepatitis B-related liver disease.

Fortunately, treatments for chronic hepatitis B are available, and many new treatments are in development. Vaccines have been developed that can prevent hepatitis B infection, and are now given routinely to newborns and children in the United States and in many other countries. (See "Patient information: Adult immunizations".)

HOW DID I BECOME INFECTED WITH HEPATITIS B?

The hepatitis B virus can be spread in from one person to another in several ways.

• In the United States, the virus is most commonly spread by needle sharing during injection drug use or by unprotected sexual intercourse.
• In regions of the world where hepatitis B is more common, the virus is most commonly passed from mother to infant during pregnancy or delivery.

Contaminated needles — Any activity that transfers blood or body fluids beneath the skin can transmit the hepatitis B virus. This includes tattooing, acupuncture, and ear piercing (if these procedures are performed with contaminated instruments). Needle sharing among injection drug users is another potential cause of transmission.

Sexual intercourse — Transmission by unprotected sexual intercourse is the most common type of transmission of hepatitis B in developed countries.

Mother to infant — Perinatal transmission refers to transmission from a mother to her baby near the time of birth. Transmission usually occurs during or shortly after delivery. There is no evidence that a cesarean delivery prevents maternal-infant transmission, and breast-feeding does not appear to increase the risk of transmission.

During pregnancy, all women should have a blood test for a marker of hepatitis B virus, called hepatitis B surface antigen (HBsAg). This marker is produced by the hepatitis B virus and indicates that the woman is currently or has previously been infected with hepatitis B. (See 'Hepatitis markers' below.)

If the mother's HBsAg test is positive, the infant should receive an injection of hepatitis B immunoglobulin (HBIG) soon after birth. HBIG temporarily helps to protect the infant from infection. The infant should also receive the hepatitis B vaccine at birth, at 1 to 2 months, and at 6 months. The infant should have a blood test for hepatitis B infection at 9 to 18 months of age; if the test is negative, a fourth dose of the vaccine should be given at that time.

Close contact — Hepatitis B can be spread through close personal contact. Infection most likely occurs when body fluids containing the virus enter tiny breaks in the skin or the mucous membranes of the eyes and mouth. This type of transmission can occur between children. Because the virus can survive outside the body for long periods of time, transmission can also occur by sharing household items that carry the virus, including toys, toothbrushes, and razors.

Blood transfusion — Blood transfusion is now an uncommon route for the transmission of hepatitis B virus. Blood donors are carefully screened, and all donated blood is tested for markers of hepatitis infection. These procedures detect most contaminated units of blood, although a very small percentage of these units go undetected. As a result, people who require many blood transfusions during their lifetime (for conditions such as hemophilia or thalassemia) have an increased risk of hepatitis B. (See "Patient information: Blood donation and transfusion".)

In the hospital — In the hospital setting, hepatitis B virus can be transmitted from patient to patient or from patient to health care provider through contaminated needles or instruments. Transmission from a health care provider to patient is extremely rare. Measures to reduce this risk include using gloves, eye protection, a face mask, and hand washing.

Organ transplantation — Hepatitis B virus can be transmitted in donated livers and other organs. However, organ donors are routinely screened for hepatitis, which usually prevents this type of transmission.

HEPATITIS B SYMPTOMS

The symptoms of hepatitis B differ during acute (new) hepatitis and chronic (long-standing) hepatitis. Within these categories, the symptoms also vary widely from person to person.

Most infected people have no specific symptoms of hepatitis B for many years. However, the absence of symptoms does not necessarily mean that the infection is under control. Everyone with chronic hepatitis B is at increased risk of developing complications, including liver scarring (called cirrhosis when the scarring is severe) and liver cancer. (See "Patient information: Cirrhosis".)

Acute hepatitis B — Acute is the medical term for sudden onset. Symptoms of acute hepatitis B usually appear one to four months after becomeing infected. The first symptoms may be non-specific, including fever, skin rash, and joint pain and inflammation. Other symptoms may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain in the upper right abdomen (where the liver is located). Some people have no symptoms at all.

Acute hepatitis can be severe, with symptoms lasting for many weeks or months. Less commonly, acute hepatitis is life-threatening or "fulminant," in which the liver is so badly damaged that it can no longer function. The only treatment for fulminant hepatitis is liver transplantation.

The symptoms of acute hepatitis B usually resolve within three months as the body eliminates the virus or brings the virus under control. People with acute hepatitis rarely experience complications in other organs and tissues, and a very small percentage of people (0.1 to 0.5 percent) develop severe liver failure.

Most people with acute hepatitis B recover uneventfully. However, in about 5 percent of adults (1 in 20) the virus makes itself at home in the liver, where it continues to make copies of itself for many years. People who continue to harbor the virus are referred to as "carriers". Liver damage associated with longstanding infection is referred to as "chronic hepatitis."

Chronic hepatitis B — Chronic hepatitis B develops more commonly in people who are infected with the virus at an early age, such as at birth. Unfortunately, this is a common event in some parts of the world such as in southeast Asia, China, and sub-Saharan Africa, where as many as 1 in 10 people have chronic hepatitis B infection.

The symptoms of chronic hepatitis B can vary widely and can last for many years. Many people who carry the virus have no symptoms at all; other people have symptoms of ongoing liver inflammation, such as fatigue and loss of appetite. Some people with chronic hepatitis B experience sudden, temporary worsening of symptoms.

About 10 to 20 percent of people with chronic hepatitis B develop complications in other organs and tissues outside the liver; inflammation of blood vessels and kidney disease are the two most common complications. People with chronic hepatitis B who develop cirrhosis or liver cancer may experience symptoms such as fatigue, weight loss, fluid accumulation in the abdomen and legs, bleeding, mental confusion, and abdominal pain.

HEPATITIS B DIAGNOSIS

The diagnosis of hepatitis B is based upon a person's medical history, physical examination, and the results of diagnostic tests.

Liver tests — Liver tests are blood tests that provide information about the presence and severity of liver damage.

• Alanine and aspartate aminotransferases — During acute hepatitis B, blood levels of two liver enzymes, alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT), are usually elevated. High levels of these enzymes signal ongoing liver inflammation.

In most people with acute hepatitis, liver enzyme levels return to normal within one to four months. If ALT levels remain high after six months, this suggests that the person is developing chronic hepatitis. Liver enzyme levels may fluctuate during the course of chronic infection.

• Bilirubin — Bilirubin is a substance produced mostly from red blood cells and metabolized by the liver. A high bilirubin level can be a sign of severe liver damage. High bilirubin levels lead to jaundice, which is yellowing of the skin and eyes and darkening of the urine.
• Albumin — Low blood levels of albumin, a protein synthesized by the liver, often signal chronic liver damage.
• Prothrombin time — Prothrombin time is a measure of the time required for blood clotting. An abnormally long prothrombin time or high international normalized ratio (INR, another way of reporting prothrombin time) suggests more severe liver damage.

Hepatitis markers — Hepatitis B markers are substances produced by the hepatitis B virus (called antigens) and substances produced by the immune system to control and eliminate the virus (called antibodies). Levels of hepatitis markers in the blood can help to diagnose hepatitis B infection and differentiate acute from chronic hepatitis B infection.

The diagnosis of acute hepatitis B is based upon the presence of the hepatitis B surface antigen (HBsAg) and hepatitis B core IgM antibody. The diagnosis of chronic hepatitis B is based on the presence of the HBsAg marker for at least six months; hepatitis B core IgM antibody is usually negative.

• Hepatitis B surface antigen — In acute hepatitis, HBsAg can be detected soon after infection; falling levels of this marker and the appearance of hepatitis B surface antibodies (HBsAb or anti-HBs) signal recovery. In chronic hepatitis, HBsAg can be detected for many years, and HBsAb may never appear.
• Hepatitis B e antigen — Hepatitis B e antigen (HBeAg) is present when the hepatitis B virus is actively multiplying. In acute hepatitis, HBeAg can be detected soon after infection; falling levels of this marker and the appearance of hepatitis B e antibodies (HBeAb or anti-HBe) signal recovery.

In most patients with chronic hepatitis, HBeAg can be detected for many years. With time, the immune system may suppress the virus to such low levels that HBeAg is no longer detected and HBeAb is present. Loss of HBeAg and appearance of HBeAb (also called HBeAg seroconversion) is usually an indication that the virus is suppressed and the liver disease becomes inactive. However, some HBV mutants cannot make HBeAg (called precore mutants). In this case, patients may be HBeAg negative but still have high levels of virus and elevated liver enzymes (AST and ALT).

• Hepatitis B virus DNA — Detection of hepatitis B virus DNA in a blood sample signals that the virus is actively multiplying. In acute hepatitis, HBV DNA can be detected soon after infection; falling levels of HBV DNA signal recovery, and levels usually become undetectable over time.

In chronic hepatitis, levels of HBV DNA often remain high for many years and then decrease as the immune system gains control over the virus. In some patients, HBV DNA levels fluctuate due to alterations in balance between the immune system and the virus.

• Antibodies to hepatitis B core antigen — Antibodies to Hepatitis B surface antibody (anti-HBs) is a marker of immunity or protection. People who develop immunity to hepatitis B after vaccination have anti-HBs only while those who develop immunity after recovery from acute hepatitis B have anti-HBs and a specific class of antibodies (IgM) directed against the hepatitis B core antigen (anti-HBc). There are two classes of this antibody (core IgG and core IgM). The IgM class appears first during the acute phase of hepatitis and then gradually switches to the IgG type.

Liver biopsy — During a liver biopsy, a small sample of liver tissue is collected for microscopic examination. A liver biopsy is not routinely needed to diagnose hepatitis B. Liver biopsy is used for monitoring the progression of liver damage in people with chronic hepatitis, helping to decide if treatment is needed, and for detecting cirrhosis or liver cancer. (See "Patient information: Liver biopsy".)

WILL I DEVELOP CHRONIC HEPATITIS B?

The likelihood of a person with acute hepatitis progressing to chronic hepatitis largely depends on the person's age at the time of infection. Chronic infection develops in about 90 percent of children who are infected at birth, in 20 to 50 percent of children who are infected between the ages of 1 and 5 years, and in less than 5 percent of people infected with hepatitis B during adulthood.

The risk of developing complications of chronic hepatitis B is influenced by how rapidly the virus multiplies and the immune system's ability to control the infection. Other factors that appear to worsen the course of hepatitis include continued alcohol use and infection with other hepatitis viruses (hepatitis A or C). A vaccination to prevent infection with hepatitis A is available. (See "Patient information: Adult immunizations".)

HEPATITIS B TREATMENT

There is no specific treatment for acute hepatitis B; in 95 percent of adults, the immune system controls the infection and eliminates the virus within about six months. Treatmentn with an antiviral medication may be considered in the rare patient with severe acute or prolonged acute hepatitis B.

In people who develop chronic hepatitis, an antiviral medication may be recommended to stop the virus from multiplying (to reduce or reverse liver damage), to prevent the spread of infection to others, and to prevent long-term complications of hepatitis B.

Antiviral therapy — Several drugs are available to slow or stop the hepatitis B virus from multiplying: lamivudine, adefovir, entecavir, telbivudine, interferon (standard and pegylated), and tenofovir (in countries in which it is approved).

Not all people with hepatitis B will benefit from these treatments. You and your physician should discuss all available treatment options. If treatment is not begun immediately, periodic monitoring may be recommended to determine when hepatitis becomes more active (indicating that antiviral treatment should begin).

If treatment is needed, regular monitoring will be done during treatment to determine if the treatment is effective, if there are side effects or drug resistance, and to determine if/when relapse occurs after treatment is stopped.

Lamivudine — Lamivudine (Epivir-HBV®) is effective in decreasing hepatitis B virus activity and ongoing liver inflammation. It is safe in patients with liver failure and long-term treatment can decrease the risk of liver failure and liver cancer.

Lamivudine is taken by mouth, usually at a dosage of 100 mg/day. The major problem with lamivudine is that a resistant form of hepatitis B virus (referred to as a YMDD mutant) frequently develops in people who take lamivudine for long-term treatment. Lamivudine is used less commonly in people who require long-term treatment because new drugs are available that are less likely to cause resistance.

Adefovir — Adefovir (Hepsera®) is an alternative initial choice for people who have detectable hepatitis B virus activity and ongoing liver inflammation. An advantage of adefovir compared to lamivudine is that resistance to adefovir is less likely to develop. In addition, adefovir can suppress lamivudine-resistant HBV.

Adefovir has been associated with kidney problems when used in high doses or for long durations, so kidney function needs to be monitored before and during treatment. Adefovir acts slowly in some patients; additional treatment may be needed in those with little or no decrease in hepatitis B DNA levels after six months of treatment.

Adefovir is taken by mouth, at a dosage of 10 mg/day, for at least one year. Most patients will need long-term treatment to maintain control of the hepatitis B virus.

Entecavir — Entecavir (Baraclude®) is generally more potent than lamivudine and adefovir. Resistance to entecavir is uncommon in people who have never been treated with antivirals, but occurs in up to 50 percent of people who have used lamivudine.

A disadvantage of entecavir is its higher cost relative to the other oral hepatitis B drugs.

Entecavir is taken by mouth, at a dosage of 0.5 mg daily for patients who have no prior treatment and 1.0 mg daily for patients who have resistance to lamivudine, for at least one year. Most patients will need long-term treatment to maintain control of the hepatitis B virus.

Interferon-alpha — Interferon-alpha is an appropriate treatment for people with chronic hepatitis B infection who have detectable virus activity, ongoing liver inflammation, and no cirrhosis. Both conventional interferon (which is given by injection daily or three times a week) and pegylated interferon are approved in the United States.

Interferon-alpha may be considered in young patients who do not have advanced liver disease and do not wish to be on long-term treatment. Interferon-alpha is not appropriate for people with cirrhosis who have liver failure or for people who have a recurrence of hepatitis after liver transplantation.

Interferon is given for a finite duration (4 to 12 months). This is in contrast to the oral HBV drugs, which are given for many years until a desired response is achieved. Drug resistance to interferon has not been reported.

The disadvantages of interferon-alpha are that it must be taken by injection and it can cause many side effects. The drug triggers a flare of hepatitis in 30 to 50 percent of people who are HBeAg positive, although flares are uncommon in those who are HBeAg negative. These flares usually do not cause symptoms; in rare cases, usually in patients with cirrhosis, the flare can be fatal.

Telbivudine — Telbivudine (Tyzeka®) is similar (but slightly more potent) than lamivudine. Unfortunately, it is associated with a high rate of resistance, similar to lamivudine.

Tenofovir — Tenofovir (Viread®) is more potent than adefovir and is effective as a first line treatment in people who have not been treated with any antiviral drug and in patients who have lamivudine, telbivudine or entecavir-resistant hepatitis B virus. Tenofovir is not as effective in patients with adefovir-resistant hepatitis B. Resistance to tenofovir has not been seen after one year of treatment; results after longer duration treatment are not yet available.

Liver transplantation — Liver transplantation may be the only option for people who have developed advanced cirrhosis. The liver transplantation process is elaborate, involving an extensive screening process to ensure that a person is a good candidate. Thus, not all patients with cirrhosis are eligible, and only those with the most advanced cirrhosis and otherwise good medical and social conditions will be put on the transplant waiting list.

TIPS TO MAINTAIN LIVER HEALTH

As discussed above, the majority of people with acute hepatitis B spontaneously clear the infection. Those who develop chronic infection should be evaluated by a physician with expertise in liver disease (usually a gastroenterologist or hepatologist) who can discuss treatment options.

Vaccinations — Everyone with chronic hepatitis B should be vaccinated against hepatitis A unless they are known to be immune. Pneumococcal vaccine is recommended when HBV is diagnosed, and again at age 65. Influenza vaccination is recommended once per year, usually in the fall. Patients with liver disease should also receive standard immunizations, including a diphtheria and tetanus booster, every ten years. (See "Patient information: Adult immunizations".)

Liver cancer screening — Regular screening for liver cancer is also recommended, particularly for older individuals, those with cirrhosis, and patients with a family history of liver cancer. In general, this includes a yearly or every other year ultrasound examination of the liver and blood test for the alpha fetoprotein (AFP) level (a protein produced by some liver tumors, which is detectable in blood). However, the best approach to screening for liver cancer has not been determined.

Diet — No specific diet has been shown to improve the outcome in people with hepatitis B. The best advice is to eat a normal healthy and balanced diet.

Alcohol — Alcohol should be avoided since it can worsen liver damage. All types of alcoholic beverages can be harmful to the liver. People with hepatitis B may develop complications even with small amounts of alcohol.

Exercise — Exercise is good for overall health and is encouraged, but it has no effect on the hepatitis B virus.

Prescription and nonprescription drugs — Many medications are broken down by the liver. Thus, it is always best to check with a healthcare provider or pharmacist before starting a new medication.

As a general rule, unless the liver is already scarred, most drugs are safe for people with hepatitis B. An important possible exception is acetaminophen (Tylenol®); the maximum recommended dose in people with liver disease is no more than 2 grams (2000 mg) in 24 hours. Most acetaminophen tabs or capsules contain 325 or 500 mg.

Herbal medications — No herbal treatment has been proven to improve outcomes in patients with hepatitis B, and some can cause serious liver toxicity. Herbal or vitamin treatments are not recommended for anyone with hepatitis B.

Support — Sharing concerns with others infected with hepatitis B can provide support. A number of organizations are available around the world. (See 'Where to get more information' below.)

PREVENT INFECTION OF FAMILY

Acute and chronic hepatitis B are contagious. Thus, people with hepatitis B should discuss measures to reduce the risk of infecting close contacts. This includes the following:

• Discuss the infection with any sexual partners and use a latex condom with every sexual encounter.
• Do not share razors, toothbrushes, or anything that has blood on it.
• Cover open sores and cuts with a bandage.
• Do not donate blood, body organs, other tissues, or sperm.
• Immediate family and household members should have testing for hepatitis B. Anyone who is at risk of hepatitis B infection should be vaccinated, if not done previously. (See "Patient information: Adult immunizations".)
• Do not share any injection drug equipment (needles, syringes).
• Clean blood spills with a mixture of 1 part household bleach to 9 parts water.

Hepatitis B cannot be spread by:

• Hugging or kissing
• Sharing eating utensils or cups
• Sneezing or coughing
• Breastfeeding

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Adult immunizations
Patient information: Blood donation and transfusion
Patient information: Cirrhosis
Patient information: Liver biopsy

Professional Level Information:
Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection
Characteristics of the hepatitis B virus and pathogenesis of infection
Clinical manifestations and natural history of hepatitis B virus infection
Clinical significance and molecular characteristics of common hepatitis B virus variants
Clinical significance of hepatitis B virus genotypes
Combination therapy for chronic hepatitis B virus infection
Epidemiology, transmission and prevention of hepatitis B virus infection
Hepatitis B virus vaccination
Immunizations for patients with chronic liver disease
Lamivudine monotherapy for chronic hepatitis B virus infection
Newer treatments of chronic hepatitis B virus infection
Overview of the management of chronic hepatitis B and case examples
Serologic diagnosis of hepatitis B virus infection
Standard and pegylated interferon for chronic hepatitis B virus infection
Telbivudine in the treatment of chronic hepatitis B virus infection
Treatment and prevention of hepatitis B in the HIV-infected patient

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• Centers for Disease Control

      (www.cdc.gov/ncidod/diseases/hepatitis/index.htm)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov)

• National Institute of Allergy and Infectious Diseases

      (www.niaid.nih.gov/)

• National Foundation for Infectious Diseases

      (www.nfid.org)

• American Association for Study of Liver Diseases

      (www.aasld.org)

• American Gastroenterological Association

      (www.gastro.org)

• American Liver Foundation

      (www.liverfoundation.org)

• The Hepatitis B Foundation

      (www.hepb.org)

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