Medical Author: Mohamad El Mortada, MD and Mary Nettleman, MD, MS
Medical Editor: Jay W. Marks, MD
- What is hepatitis?
- How is the hepatitis B virus spread (transmitted)?
- What are the symptoms of acute hepatitis B infection?
- What are the symptoms of chronic hepatitis B infection?
- How is hepatitis B diagnosed?
- What is the role of a liver biopsy in chronic hepatitis B?
- What is the natural course of chronic hepatitis B?
- What medications are used to treat hepatitis B?
- What are the effects of alcohol on hepatitis B?
- What are the effects of immunosuppressive medications on hepatitis B?
- What is delta hepatitis?
- What about co-infection with hepatitis B virus and hepatitis C virus?
- What happens in co-infection with hepatitis B virus and human immunodeficiency virus?
- What is the role of liver transplantation in hepatitis B?
- What can be done to prevent hepatitis B?
- What is new in the treatment of hepatitis B?
- Hepatitis B At A Glance
- Patient Discussions: Hepatitis B - Describe Your Experience
What is hepatitis?
The term 'hepatitis' simply means inflammation of the liver. Hepatitis may be caused by a virus or a toxin such as alcohol. Other viruses that can cause injury to liver cells include the hepatitis A and hepatitis C viruses. These viruses are not related to each other or to hepatitis B virus and differ in their structure, the ways they are spread among individuals, the severity of symptoms they can cause, the way they are treated, and the outcome of the infection.
What is the scope of the problem?
Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV). It is estimated that 350 million individuals worldwide are infected with the virus, which causes 620,000 deaths worldwide each year. According to the Centers for Disease Control (CDC), approximately 46,000 new cases of hepatitis B occurred in the United States in 2006.
In the United States, rates of new infection were highest among people aged 25 to 44 years (3.1 cases per 100,000 population) and lowest among those younger than 15 years of age (0.02 per 100,000). This reflects the major modes of transmission of hepatitis B (sexual transmission, illicit drug use, exposure to infected blood) and the effect of universal vaccination of infants. In the United States, there has been a 75% decrease in newly diagnosed cases of hepatitis B during the past decade. This decrease is attributed to increased vaccination and to heightened public awareness of HIV/AIDS and the resulting safer sexual practices.
When a person first gets hepatitis B, they are said to have an 'acute' infection. Most people are able to eliminate the virus and are cured of the infection. Some are not able to clear the virus and have 'chronic' infection with hepatitis B that is usually life-long (see below). In the United States an estimated 800,000 to 1.4 million people are chronically infected with hepatitis B.
Hepatitis B is found throughout the world. Some countries have much higher rates of infection than the United States; for example, in Southeast Asia and Sub-Saharan Africa, as many as 15% to 20% of adults are chronically infected with hepatitis B.
What kind of a virus is hepatitis B?
The hepatitis B virus is a DNA virus, meaning that its genetic material is made up of deoxyribonucleic acids. It belongs to a family of viruses known as Hepadnaviridae. The virus is primarily found in the liver but is also present in the blood and certain body fluids.
Hepatitis B virus consists of a core particle (central portion) and a surrounding envelope (outer coat). The core is made up of DNA and the core antigen (HBcAg). The envelope contains the surface antigen (HBsAg). These antigens are present in the blood and are markers that are used in the diagnosis and evaluation of patients with suspected viral hepatitis.
How does hepatitis B virus cause liver injury?
The hepatitis B virus reproduces in liver cells, but the virus itself is not the direct cause of damage to the liver. Rather, the presence of the virus triggers an immune response from the body as the body tries to eliminate the virus and recover from the infection. This immune response causes inflammation and may seriously injure liver calls. Therefore, there is a balance between the protective and destructive effects of the immune response to the hepatitis B virus.
How is the hepatitis B virus spread (transmitted)?
Hepatitis B is spread mainly by exposure to infected blood or body secretions. In infected individuals, the virus can be found in the blood, semen, vaginal discharge, breast milk, and saliva. Hepatitis B is not spread through food, water, or by casual contact.
In the United States, sexual contact is the most common means of transmission, followed by using contaminated needles for injecting illicit drugs, tattooing, body piercing, or acupuncture. Additionally, hepatitis B can be transmitted through sharing toothbrushes and razors contaminated with infected fluids or blood.
Hepatitis B also may be spread from infected mothers to their babies at birth (so-called 'vertical' transmission). This is the most prevalent means of transmission in regions of the world where hepatitis B rates are high. The rate of transmission of hepatitis B from mother to newborn is very high, and almost all infected infants will develop chronic hepatitis B. Fortunately, transmission can be significantly reduced through immunoprophylaxis (see below).
Rarely, hepatitis B can be transmitted through transfused blood products, donated livers and other organs. However, blood and organ donors are routinely screened for hepatitis which typically prevents this type of transmission.
What are the symptoms of acute hepatitis B?
Acute hepatitis B is the period of illness that occurs during the first one to four months after acquiring the virus. Only 30% to 50% of adults develop significant symptoms during acute infection. Early symptoms may be non-specific, including fever, a flu-like illness, and joint pains. Symptoms of acute hepatitis may include:
- fatigue,
- loss of appetite,
- nausea,
- jaundice (yellowing of the skin and eyes), and
- pain in the upper right abdomen (due to the inflamed liver).
Rarely, acute hepatitis damages the liver so badly it can no longer function. This life-threatening condition is called "fulminant hepatitis." Patients with fulminant hepatitis are at risk of developing bleeding problems and coma resulting from the failure of the liver. Patients with fulminant hepatitis should be evaluated for liver transplantation. Small studies suggest that the drug lamivudine (Epivir), may be of limited assistance in these cases (see below)
What determines the outcome of acute hepatitis B?
The body's immune response is the major determinant of the outcome in acute hepatitis B. Individuals who develop a strong immune response to the infection are more likely to clear the virus and recover. However, these patients also are more likely to develop more severe liver injury and symptoms due to the strong immune response that is trying to eliminate the virus. On the other hand, a weaker immune response results in less liver injury and fewer symptoms but a higher risk of developing chronic hepatitis B. People who recover and eliminate the virus will develop life-long immunity, that is, protection from subsequent infection from hepatitis B.
Most infants and children who acquire acute hepatitis B viral infection have no symptoms. In these individuals, the immune system fails to mount a vigorous response to the virus. Consequently, the risk of an infected infant developing chronic hepatitis B is greater than 95%. In contrast, only 5% of adults who have acute hepatitis B develop chronic hepatitis B.
What are the symptoms of chronic hepatitis B?
The liver is a vital organ that has many functions. These include a role in the immune system, production of clotting factors, producing bile for digestion, and breaking down toxic substances, etc. Patients with chronic hepatitis B develop symptoms in proportion to the degree of abnormalities in these functions. The signs and symptoms of chronic hepatitis B vary widely depending on the severity of the liver damage. They range from few and relatively mild signs and symptoms to signs and symptoms of severe liver disease such as cirrhosis or liver failure.
Most individuals with chronic hepatitis B remain symptom free for many years or decades. During this time, the patient's blood tests usually are normal or only mildly abnormal. Some patients may deteriorate and develop inflammation or symptoms, putting them at risk for developing cirrhosis.
Cirrhosis of the liver due to hepatitis B
Inflammation from chronic hepatitis B can progress to cirrhosis (severe scarring) of the liver. Significant amounts of scarring and cirrhosis lead to liver dysfunction.
Symptoms may include:
- weakness,
- fatigue,
- loss of appetite,
- weight loss,
- breast enlargement in men,
- a rash on the palms,
- difficulty with blood clotting, and
- spider-like blood vessels on the skin.
Decreased absorption of vitamins A and D can cause impaired vision at night and thinning of bones (osteoporosis). Patients with liver cirrhosis also are at risk of infections because the liver plays an important role in the immune system.
Advanced cirrhosis of the liver due to hepatitis B
In patients with advanced cirrhosis, the liver begins to fail. This is life-threatening condition.
Several complications occur in advanced cirrhosis:
- Confusion and even coma (encephalopathy) results from the inability of the liver to detoxify certain toxic substances.
- Increased pressure in the blood vessels of the liver (portal hypertension) causes fluid to build up in the abdominal cavity (ascites) and may result in engorged veins in the swallowing tube (esophageal varices) that tear easily and may cause massive bleeding.
- Portal hypertension can also cause kidney failure or an enlarged spleen resulting in a decrease of blood cells and the development of anemia, increased risk of infection and bleeding.
- In advanced cirrhosis, liver failure also results in decreased production of clotting factors. This causes abnormalities in blood clotting and sometimes spontaneous bleeding.
- Patients with advanced cirrhosis often develop jaundice because the damaged liver is unable to eliminate a yellow compound, called bilirubin.
Hepatitis B virus and primary liver cancer (hepatocellular carcinoma)
Patients with chronic hepatitis B are at risk of developing liver cancer. The way in which the cancer develops is not fully understood. Symptoms of liver cancer are nonspecific. Patients may have no symptoms, or they may experience abdominal pain and swelling, an enlarged liver, weight loss, and fever. The most useful diagnostic screening tests for liver cancer are a blood test for a protein produced by the cancer called alpha-fetoprotein and an ultrasound imaging study of the liver. These two tests are used to screen patients with chronic hepatitis B, especially if they have cirrhosis or a family history of liver cancer.
Hepatitis B virus involvement of organs outside of the liver (extra-hepatic)
Rarely, chronic hepatitis B infection can lead to disorders that affect organs other than the liver. These conditions are caused when the normal immune response to hepatitis B mistakenly attacks uninfected organs.
Among these conditions are:
- Polyarteritis nodosa: a disease characterized by inflammation of the small blood vessels throughout the body. This condition can cause a wide range of symptoms, including muscle weakness, nerve damage, deep skin ulcers, kidney problems, high blood pressure, unexplained fevers, and abdominal pain.
- Glomerulonephritis: another rare condition, which is inflammation of the small filtering units of the kidney.
How is hepatitis B diagnosed?
Infection with hepatitis B is suspected when the medical history and the physical examination reveal risk factors for the infection or symptoms and signs that are suggestive of hepatitis B. Abnormalities in the liver tests (blood tests) also can raise suspicion; however, abnormal liver tests can result from many conditions that affect the liver. The diagnosis of hepatitis B can be made only with specific hepatitis B virus blood tests. These tests are known as hepatitis 'markers' or 'serology.'
Markers found in the blood can confirm hepatitis B infection and differentiate acute from chronic infection. These markers are substances produced by the hepatitis B virus (antigens) and antibodies produced by the immune system to fight the virus. Hepatitis B virus has three antigens for which there are commonly-used tests - the surface antigen (HBsAg), the core antigen (HBcAg) and the e antigen (HBeAg).
HBsAg and anti-HBs
The presence of hepatitis B surface antigen (HBsAg) in the blood indicates that the patient is currently infected with the virus. HBsAg appears an average of four weeks after initial exposure to the virus. Individuals who recover from acute hepatitis B infections clear the blood of HBsAg within approximately four months after the onset of symptoms. These individuals develop antibodies to HBsAg (anti-HBs). Anti-HBs provides complete immunity to subsequent hepatitis B viral infection. Similarly, individuals who are successfully vaccinated against hepatitis B produce anti-HBs in the blood.
Patients who fail to clear the virus during an acute episode develop chronic hepatitis B. The diagnosis of chronic hepatitis B is made when the HBsAg is present in the blood for at least six months. In chronic hepatitis B, HBsAg can be detected for many years, and anti-HBs does not appear
Anti-HBc
In acute hepatitis, a specific class of early antibodies (IgM) appears that is directed against the hepatitis B core antigen (anti-HBc IgM). Later, another class of antibody, anti-HBc IgG, develops and persists for life, regardless of whether the individual recovers or develops chronic infection. Only anti-HBc IgM can be used to diagnose an acute hepatitis B infection.
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