Viral Hepatitis

What is viral hepatitis?
Hepatitis means inflammation of the liver. Many illnesses and conditions can cause inflammation of the liver, for example, drugs, alcohol, chemicals, and autoimmune diseases. Many viruses, for example, the virus of mononucleosis and the cytomegalovirus can inflame the liver. Most viruses, however, do not primarily attack the liver; the liver is just one of several organs that the viruses affect. When doctors speak of viral hepatitis, they usually are referring to hepatitis caused by a few specific viruses that primarily attack the liver. There are several hepatitis viruses; they have been named types A, B, C, D, E, F (not confirmed), and G. As our knowledge of hepatitis viruses grows, it is likely that this alphabetical list will become longer. The most common hepatitis viruses are types A, B, and C.
The liver is located in the upper right hand side of the abdomen, mostly behind the rib cage. The liver of an adult normally weighs close to three pounds. The liver performs the following vital functions:

1. The liver helps purify the blood by changing harmful chemicals into harmless ones. The source of these chemicals can be external, such as medications or alcohol, or internal, such as ammonia or bilirubin. Typically, these harmful chemicals are broken down into smaller chemicals or attached to other chemicals that then are eliminated from the body in the urine or stool.
2. The liver produces many important substances, especially proteins that are necessary for good health. For example, it produces albumin, the protein building block of the body, as well as the proteins that cause blood to clot properly.
3. The liver stores many sugars, fats and vitamins until they are needed elsewhere in the body.
4. The liver builds smaller chemicals into larger, more complicated chemicals that are needed elsewhere in the body. An example of this type of function is the manufacture of cholesterol.

When the liver is inflamed, it does not perform these functions well, which brings about many of the symptoms, signs, and problems associated with hepatitis.

What are the common types of viral hepatitis?
Hepatitis A
Viral hepatitis A (HAV) accounts for about 150,000 of the 500,000-600,000 new cases of viral hepatitis that occur each year in the United States. The hepatitis caused by HAV is an acute illness (acute viral hepatitis) that never becomes chronic. At one time, hepatitis A was referred to as "infectious hepatitis" because it could be spread from person to person like other viral infections. Infection with hepatitis A virus can be spread through the ingestion of food or water, especially where unsanitary conditions allow water or food to become contaminated by human waste containing hepatitis A (the fecal-oral mode of transmission). Hepatitis A typically is spread among household members and close contacts through the passage of oral secretions (intimate kissing) or stool (poor hand washing). It also is common to have infection spread to customers in restaurants and among children and workers in day care centers if hand washing and sanitary precautions are not observed.
Hepatitis B
There are 200,000-300,000 new cases of viral hepatitis B (HBV) infection each year in the United States. Type B hepatitis was at one time referred to as "serum hepatitis," because it was thought that the only way hepatitis B virus (HBV) could spread was through blood or serum (the liquid portion of blood) containing the virus. It is now known that hepatitis B can spread by sexual contact, the transfer of blood or serum through shared needles in drug abusers, accidental needle sticks with needles contaminated with infected blood, blood transfusions, hemodialysis, and by infected mothers to their newborns. The infection also can be spread by tattooing, body piercing, and sharing razors and toothbrushes (if there is contamination with infected blood). About 6-10% of patients with hepatitis B develop chronic HBV infection (infection lasting at least six months and often years to decades) and can infect others as long as they remain infected. Patients with chronic hepatitis B infection also are at risk of developing cirrhosis, liver failure and liver cancer. It is estimated that there are 1.2 million people in the United States and 200-300 million people world-wide who suffer with chronic hepatitis B infection. article.
Hepatitis C
There are about 150,000 new cases of hepatitis C each year. Type C hepatitis was previously referred to as "non-A, non-B hepatitis," because the causative virus had not been identified, but it was known to be neither hepatitis A nor hepatitis B. The hepatitis C virus (HCV) usually is spread by shared needles among drug abusers, blood transfusion, hemodialysis, and needle sticks. Approximately 90% of transfusion-associated hepatitis is caused by hepatitis C. Transmission of the virus by sexual contact has been reported, but is considered rare. An estimated 50-70% of patients with acute hepatitis C infection develop chronic HCV infection. Patients with chronic hepatitis C infection can continue to infect others. Patients with chronic hepatitis C infection are at risk for developing cirrhosis, liver failure, and liver cancer. It is estimated that there are about 3.5 million people with chronic hepatitis C infection in the United States.
Types D, E, F, and G Hepatitis
There also are viral hepatitis types D, E, F (not confirmed yet), and G. The most important of these at present is the hepatitis D virus (HDV), also known as the delta virus or agent. It is a small virus that requires concomitant infection with hepatitis B to survive. HDV cannot survive on its own because it requires a protein that the hepatitis B virus makes (the envelope protein, also called surface antigen) to enable it to infect liver cells. The ways in which hepatitis D is spread are by shared needles among drug abusers, contaminated blood, and by sexual contact, essentially the same ways as for hepatitis B.
Patients who already have chronic hepatitis B infection can acquire delta virus infection at the same time as they acquire the hepatitis B infection or, alternatively, on top of a chronic hepatitis B infection. Patients with chronic hepatitis due to hepatitis B and hepatitis D viruses develop cirrhosis (severe liver scarring) rapidly. Moreover, the combination of delta and B virus infection is very difficult to treat.

Who is at risk for viral hepatitis?
People who are most at risk for developing viral hepatitis are workers in the health care professions, people with multiple sexual partners, intravenous drug users, and hemophiliacs who receive blood clotting factors. Blood transfusion, once a common means of spreading viral hepatitis, now is a rare cause of hepatitis. Viral hepatitis is generally thought to be as much as ten times more common among lower socioeconomic and poorly educated individuals. About one third of all cases of hepatitis come from an unknown or unidentifiable source. This means that you don't have to be in a high risk group in order to be infected with a hepatitis virus.
What are the symptoms and signs of viral hepatitis?
The period of time between exposure to hepatitis and the onset of the illness is called the incubation period. The incubation period varies depending on the specific hepatitis virus. Hepatitis A has an incubation period of about 15-45 days; hepatitis B from 45-160 days, and hepatitis C from 2 weeks to 6 months.
Many patients infected with hepatitis A, B, and C have few or no symptoms of illness. For those who do develop symptoms of viral hepatitis, the most common are flu- like symptoms including:

• loss of appetite
• nausea
• vomiting
• fever
• weakness
• tiredness
• aching in the abdomen

Less common symptoms include:

• dark urine
• light-colored stools
• fever
• jaundice (a yellow appearance to the skin and white portion of the eyes)

What is the prognosis of viral hepatitis?
The prognosis of viral hepatitis for most patients is good. Symptoms of viral hepatitis such as fatigue, poor appetite, nausea, and jaundice usually subside in several weeks to months, without any specific treatment. In fact, virtually all patients with acute infection with hepatitis A and most adults (greater than 95%) with acute hepatitis B recover completely. Complete recovery from viral hepatitis means

1. the hepatitis virus has been completely eliminated from the liver by the body's immune system,
2. the inflammation in the liver subsides,
3. the patient develops immunity to future infection with the same virus, and
4. the patient cannot transmit the infection to others.

Unfortunately, not all patients with viral hepatitis infections recover completely. Five percent of patients with acute hepatitis B infection and 80% of patients with acute hepatitis C infection develop chronic hepatitis.
Acute viral hepatitis needs no specific treatment. Patients who develop chronic infection have chronic viral hepatitis and often need treatment to prevent further liver damage.
What is acute fulminant hepatitis?
Rarely, individuals with acute infections with hepatitis A and hepatitis B develop severe inflammation, and the liver fails (acute fulminant hepatitis). These patients are extremely ill with the symptoms of acute hepatitis already described and the additional problems of confusion or coma (due to the liver's failure to detoxify chemicals) and bruising or bleeding (due to a lack of blood clotting factors). In fact, up to 80% of people with acute fulminant hepatitis can die within days to weeks; therefore, it is fortunate that acute fulminant hepatitis is rare. For example, less than 0.5% of adults with acute infection with hepatitis B will develop acute fulminant hepatitis.

What is chronic viral hepatitis?
Patients infected with hepatitis B and hepatitis C can develop chronic hepatitis. Doctors define chronic hepatitis as hepatitis that lasts longer than 6 months. In chronic hepatitis, the viruses live and multiply in the liver for years or decades. For unknown reasons, these patients' immune systems are unable to eradicate the viruses. The viruses cause chronic inflammation of the liver. Chronic hepatitis can lead to the development over time of extensive liver scarring (cirrhosis), liver failure, and liver cancer. Liver failure from chronic hepatitis C infection is the most common reason for liver transplantation in the United States. Patients with chronic viral hepatitis can transmit the infection to others.
How is viral hepatitis diagnosed?
Diagnosis of viral hepatitis is based on symptoms, physical findings as well as blood tests for liver enzymes, viral antibodies, and viral genetic materials.
Symptoms and physical findings
Diagnosis of acute viral hepatitis often is easy, but diagnosis of chronic hepatitis can be difficult. When a patient reports symptoms of fatigue, nausea, abdominal pain, darkening of urine, and then develops jaundice, the diagnosis of acute viral hepatitis is likely and can be confirmed by blood tests. On the other hand, patients with chronic hepatitis due to hepatitis B and hepatitis C often have no symptoms or only mild nonspecific symptoms such as chronic fatigue. Typically, these patients do not have jaundice until the liver damage is far advanced. Therefore, these patients can remain undiagnosed for years to decades.
Blood tests
There are three types of blood tests for evaluating patients with hepatitis: liver enzymes, antibodies to the hepatitis viruses, and viral proteins or genetic material (viral DNA or RNA).
Liver enzymes. Among the most sensitive and widely used blood tests for evaluating patients with hepatitis are the liver enzymes, called aminotransferases. They include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes normally are contained within liver cells. If the liver is injured (as in viral hepatitis), the liver cells spill the enzymes into the blood, raising the enzyme levels in the blood and signaling that the liver is damaged.
The normal range of values for AST is from 5 to 40 units per liter of serum (the liquid part of the blood). The normal range of values for ALT is from 7 to 56 units per liter of serum. Patients with acute viral hepatitis (for example, due to hepatitis A or hepatitis B) can develop very high AST and ALT levels (sometimes in the thousands of units per liter range). These high AST and ALT levels will become normal in several weeks or months as the patients recover completely from their acute hepatitis. In contrast, patients with chronic hepatitis B and hepatitis C infection typically have only mildly elevated AST and ALT levels, but these abnormalities can last years or decades. Since most patients with chronic hepatitis are asymptomatic (no jaundice or nausea), their mildly abnormal liver enzymes are often unexpectedly encountered on routine blood screening tests during yearly physicals or insurance physicals.
Elevated blood levels of AST and ALT only means that the liver is inflamed, and elevations can be caused by many agents other than hepatitis viruses, such as medications, alcohol, bacteria, fungus, etc. In order to prove that a hepatitis virus is responsible for the elevations, blood must be tested for antibodies to each of the hepatitis viruses as well as for their genetic material.
Viral antibodies. Antibodies are proteins produced by white blood cells that attack invaders such as bacteria and viruses. Antibodies against the hepatitis A, B, and C viruses usually can be detected in the blood within weeks of infection, and the antibodies remain detectable in the blood for decades thereafter. Blood tests for the antibodies can be helpful in diagnosing both acute and chronic viral hepatitis.
In acute viral hepatitis, antibodies not only help to eradicate the virus, but they also protect the patient from future infections by the same virus, that is the patient develops immunity. In chronic hepatitis, however, antibodies and the rest of the immune system are unable to eradicate the virus. The viruses continue to multiply and are released from the liver cells into the blood where their presence can be determined by measuring the viral proteins and genetic material. Therefore in chronic hepatitis, both antibodies to the viruses and viral proteins and genetic material can be detected in the blood.
Examples of tests for viral antibodies are:

• anti-HAV (hepatitis A antibody)
• antibody to hepatitis B core, an antibody directed against the inner core (nucleus) of the virus (core antigen)
• antibody to hepatitis B surface, an antibody directed against the outer surface envelope of the virus (surface antigen)
• antibody to hepatitis B e, an antibody directed against the genetic material of the virus (e antigen)
• hepatitis C antibody-antibody against the C virus

Viral proteins and genetic material. Examples of tests for viral proteins and genetic material are:

• hepatitis B surface antigen
• hepatitis B DNA
• hepatitis B e antigen
• hepatitis C RNA

Other tests. Obstruction of the bile ducts, from either gallstones or cancer, occasionally can mimic acute viral hepatitis. Ultrasound testing can be used to exclude the possibility of gallstones or cancer.

How is viral hepatitis treated?
Treatment of acute viral hepatitis and chronic viral hepatitis are different. Treatment of acute viral hepatitis involves relieving symptoms and maintaining adequate intake of fluids. Treatment of chronic viral hepatitis involves medications to eradicate the virus and taking measures to prevent further liver damage.
Acute hepatitis
In patients with acute viral hepatitis, the initial treatment consists of relieving the symptoms of nausea, vomiting, and abdominal pain. Careful attention should be given to medications which can have adverse effects in patients with abnormal liver function. Only those medications that are considered necessary should be administered since the impaired liver is not able to eliminate drugs normally, and drugs may accumulate in the blood and reach toxic levels. In addition, sedatives and "tranquilizers" are avoided because they may accentuate the effects of liver failure on the brain and cause lethargy and coma. The patient must abstain from drinking alcohol since alcohol is toxic to the liver. It occasionally is necessary to provide intravenous fluids to prevent dehydration caused by vomiting. Patients with severe nausea and/or vomiting may need to be hospitalized for treatment and intravenous fluids.
Chronic hepatitis
Treatment of chronic infection with hepatitis B and hepatitis C usually involves medication or combinations of medications to eradicate the virus. Doctors believe that in properly selected patients, successful eradication of the viruses can stop progressive damage to the liver and prevent the development of cirrhosis, liver failure, and liver cancer. Alcohol aggravates liver damage in chronic hepatitis, and can cause more rapid progression to cirrhosis. Therefore, patients with chronic hepatitis should stop drinking alcohol. Smoking cigarettes also can aggravate liver disease and should be stopped.
Medications for chronic hepatitis C infection include:

• injectable interferon
• oral ribavirin

Medications for chronic hepatitis B infection include:

• injectable interferon
• oral lamivudine (Epivir)
• oral adefovir (Hepsera)
• oral entecavir (Baraclude)

Decisions regarding treatment of chronic hepatitis can be complex, and should be directed by gastroenterologists or hepatologists (doctors specially trained in treating diseases of the liver) for several reasons including:

1. The diagnosis of chronic viral hepatitis may not be straightforward. Sometimes a liver biopsy may have to be performed for confirmation of liver damage. Doctors experienced in managing chronic liver diseases must weigh the risk of liver biopsy against the potential benefits of the biopsy.
2. Not all patients with chronic viral hepatitis are candidates for treatment. Some patients need no treatment (since some patients with chronic hepatitis B and C do not develop progressive liver damage or liver cancer).
3. Medications for chronic infection with hepatitis B and hepatitis C are not always effective. Prolonged treatment (6 months to years) often is necessary. Even with prolonged treatment, rates of successful treatment (defined as complete and lasting eradication of the virus) often are low (usually less than 80% and often around 50%).
4. Some of the medications such as interferon and ribavirin can have serious side effects, and doses may have to be reduced.
5. There are several different strains of hepatitis C viruses with differing susceptibilities to medications. For example, hepatitis C type 3 is more likely to respond to interferon injections and ribavirin than type 1. Certain hepatitis B strains are resistant to lamivudine but respond to adefovir or entecavir.

Please read the hepatitis B and hepatitis C articles for more details in diagnosis and treatment.
Fulminant hepatitis. Treatment of acute fulminant hepatitis should be done in centers that can perform liver transplantation since acute fulminant hepatitis has a high mortality without liver transplantation.

How is viral hepatitis prevented?
Prevention of hepatitis involves measures to avoid exposure to the viruses, using immunoglobulin in the event of exposure, and vaccines. Administration of immunoglobulin is called passive protection because antibodies from patients who have had viral hepatitis are given to the patient. Vaccination is called active protection because killed viruses or noninfective components of viruses are given to stimulate the body to produce its own antibodies.
Avoidance if exposure to viruses
Prevention of viral hepatitis, like any other illness, is preferable to reliance upon treatment. Taking precautions to prevent exposure to another individual's blood (exposure to dirty needles), semen (unprotected sex), and other bodily waste (stool) will help prevent the spread of these viruses.
Use of immunoglobulins
Immune serum globulin (ISG) is human serum that contains antibodies to hepatitis A. ISG can be administered to prevent infection in individuals who have been exposed to hepatitis A. ISG works immediately upon administration, and the duration of protection is several months. ISG usually is given to travelers to regions of the world where there are high rates of hepatitis A infection and to close or household contacts of patients with hepatitis A. ISG is safe with few side effects.
Hepatitis B immune globulin or HBIG (BayHep B), is human serum that contains antibodies to hepatitis B. HBIG is made from plasma (a blood product) that is known to contain a high concentration of antibodies to the hepatitis B surface antigen. If given within 10 days of exposure to the virus, HBIG almost always is successful in preventing infection. Even if given a bit later, however, HBIG may lessen the severity of HBV infection. The protection against hepatitis B lasts for about three weeks after the HBIG is given. HBIG also is given at birth to infants born to mothers known to have hepatitis B infection. In addition, HBIG is given to individuals exposed to HBV because of sexual contact or to healthcare workers accidentally stuck by a needle known to be contaminated with blood from an infected person.
Vaccination
Hepatitis A. Two hepatitis A vaccines are available in the US, Havrix and Vaqta. Both contain inactive (killed) hepatitis A virus. For adults, two doses of the vaccine are recommended. After the first dose, protective antibodies develop in 70% of vaccine recipients in 2 weeks and more than 95% of recipients in 4 weeks. After two doses of the hepatitis A vaccine, immunity against hepatitis A infection is believed to last for many years.
Individuals at increased risk for acquiring hepatitis A and individuals with chronic liver disease (e.g., cirrhosis or chronic hepatitis C) should be vaccinated. Although individuals with chronic liver disease are not at increased risk for acquiring hepatitis A, they can develop serious (sometimes fatal) liver failure if infected with hepatitis A and, thus, they should be vaccinated.
Individuals at increased risk of acquiring hepatitis A are:

• Travelers to countries where hepatitis A is common
• Men who have sex with men
• Illegal drug users (either injection or non-injection drug use)
• Researchers working with hepatitis A or primates that are susceptible to infection with hepatitis A
• Patients with clotting factor disorders who are receiving clotting factor concentrates that can transmit hepatitis A

Some local health authorities or private companies may require hepatitis A vaccination for food handlers.
Because protective antibodies take weeks to develop, travelers to countries where hepatitis A is common should be vaccinated at least 4 weeks before departure. The Centers for Disease Control (CDC) recommends immunoglobulin be given in addition to vaccination if departure is prior to 4 weeks. Immunoglobulin provides quicker protection than the vaccines, but the protection is short-lived.
Hepatitis B
For active vaccination, a harmless hepatitis B antigen is given to stimulate the body's immune system to produce protective antibodies against the surface antigen of hepatitis B. Vaccines that are currently available in the United States are made (synthesized) using recombinant DNA technology (joining DNA segments). These recombinant hepatitis B vaccines (Energix-B and Recombivax-HB) are constructed to contain only that part of the surface antigen that is very potent in stimulating the immune system to produce antibodies. The vaccine contains no viral component other than the surface antigen and is not infectious. Hepatitis B vaccines should be given in three doses with the second dose 1-2 months after the first dose, and the third dose 4-6 months after the first dose. For the best results, the vaccinations should be given in the deltoid (shoulder) muscles and not in the buttocks.
Hepatitis B vaccines are 95% effective. Five percent of vaccinated individuals will fail to develop the necessary antibodies for immunity after the three doses. Patients with weakened immunity (such as HIV infection), elderly patients, and patients undergoing kidney hemodialysis are more likely to fail to respond to the vaccines.
Hepatitis B vaccine is recommended for:

• All infants
• Adolescents under 18 years of age who did not receive hepatitis B vaccine as infants
• People occupationally exposed to blood or body fluids
• Residents and staff of institutions for the developmentally disabled
• Patients receiving kidney hemodialysis
• Hemophiliacs and other patients receiving clotting factor concentrates
• Household contacts and sexual partners of patients infected with hepatitis B chronically
• Travelers who will spend more than 6 months in regions with high rates of hepatitis B infection
• Injection drug users and their sexual partners
• Men who have sex with men, men or women with multiple sex partners, or recent infection with a sexually transmitted infection
• Inmates of long-term correctional facilities

All pregnant women should have a blood test for the antibody to hepatitis B surface antigen. Women who test positive for hepatitis B risk transmitting the virus to their infants during labor, and, therefore, infants born to mothers with hepatitis B infection should receive HBIG in addition to hepatitis B vaccine at birth. The reason for giving both immunoglobulin and vaccine is that even though hepatitis B vaccine can offer long lasting, active immunity, immunity takes weeks or months to develop. Until active immunity develops, the short-lived, passive antibodies from the HBIG protect the infant.
Unvaccinated individuals exposed to materials infected with hepatitis B (such as healthcare workers stuck by a contaminated needle) will need HBIG in addition to hepatitis B vaccine for the same reason as infants born to mothers with hepatitis B infection.
Hepatitis C
There is currently no vaccine for hepatitis C.

Viral Hepatitis At A Glance

• Many illnesses and conditions can cause inflammation of the liver (hepatitis).
• Viruses that primarily attack the liver are called hepatitis viruses. There are several types of hepatitis viruses including types A, B, C, D, E, F (not yet confirmed), and G. Types A, B, and C are the most common.
• Those at risk for viral hepatitis include workers in the health care profession, people with multiple sexual partners, intravenous drug abusers, and hemophiliacs. Blood transfusion is a rare cause of viral hepatitis.
• All hepatitis viruses can cause acute hepatitis.
• Viral hepatitis types B and C can cause chronic hepatitis.
• Symptoms of acute viral hepatitis include fatigue, flu-like symptoms, dark urine, light-colored stools, fever, and jaundice. Rarely, acute viral hepatitis causes fulminant hepatic failure.
• The symptoms of chronic viral hepatitis often are mild and nonspecific, and the diagnosis of chronic hepatitis often is delayed.
• Chronic viral hepatitis often requires treatment in order to prevent progressive liver damage, cirrhosis, liver failure, and liver cancer
• Hepatitis infections can be prevented by avoiding exposure to viruses, injectable immunoglobulins or vaccines.

Medical Author:

Dennis Lee, MD

Medical Editor:

Jay W. Marks, MD
Source:Medicinenet.com.