Hepatitis

What is hepatitis ?


It is a disease characterized by inflammation of the liver.




Viral hepatitis definition and overview

1. Hepatitis viruses replicate (multiply) in the liver cells. Newly-produced viruses are released into the blood stream where they can be spread to other organs or to other persons exposed to the infected blood 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 any type of hepatitis. Each viral type has both articles and books describing the details of infection with that specific virus. This article is designed to give the reader an overview of the predominant viruses that causes viral hepatitis and should help the reader choose the subject(s) for more in depth information.






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 ofmononucleosis and thecytomegalovirus can inflame the liver. Most viruses, however, do not attack primarily the liver; the liver is just one of several organs that the viruses affect. When doctors speak of viral hepatitis, they are using the definition that means hepatitis caused by a few specific viruses that primarily attack the liver and are responsible for about half of all human hepatitis. 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. Reference to the hepatitis viruses often occurs in an abbreviated form. (For example, HAV, HBV, HCV represent hepatitis viruses A, B, and C, respectively.)




What are the common types of viral hepatitis?


Although the most common types of viral hepatitis are HAV, HBV and HCV, some clinicians have considered the acute and chronic phases of hepatic infections as "types" of viral hepatitis. HAV was considered to be acute viral hepatitis because the HAV infections seldom caused permanent liver damage with chronic or fulminant hepatic (liver) failure. HBV and HCV produced chronic viral hepatitis. However, these terms are not used as frequently because all of the viruses that cause hepatitis may have acute phase symptoms (see symptoms below). Prevention techniques and vaccinationshave markedly reduced the current incidence of common viral hepatitis infections; however, there remains a population of about 800,000 to 1.4 million people in the U.S. with chronic HBV, and about 2.9 to 3.7 million with chronic HCV according to the U.S. Centers for Disease Control (CDC).

Hepatitis A (HAV)


HAV accounted for an estimated 17,000 infections in 2010 according to the newest CDC data. 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 inrestaurants and among children and workers in day care centers if hand washing and sanitary precautions are not observed.

Hepatitis B (HBV)


There were an estimated 38,000 new cases of HBV infection in 2010 in the United States according to the CDC. HBV hepatitis was at one time referred to as "serum hepatitis," because it was thought that the only way HBV could spread was through blood or serum (the liquid portion of blood) containing the virus. It is now known that HBV 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% to 10% of patients with HBV hepatitis 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 HBV 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 U.S. and 200 to 300 million people world-wide who suffer with chronic HBV infection.

Hepatitis C (HCV)

The CDC reported that there were about 17,0000 new cases of hepatitis Cin 2010. HCV 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 HAV nor HBV. 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 HCV. Transmission of the virus by sexual contact has been reported, but is considered rare. An estimated 50% to 70% of patients with acute HCV infection develop chronic infection. Patients with chronic HCV infection can continue to infect others. Patients with chronic HCV 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 HCV infection in the U.S.

Types D, E, and G Hepatitis


There also are viral hepatitis types D, E, 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 HBV to survive. HDV cannot survive on its own because it requires a protein that the HBV makes (the envelope protein, also called surface antigen) to enable it to infect liver cells. The ways in which HDV is spread are by shared needles among drug abusers, contaminated blood, and by sexual contact; essentially the same ways as HBV.


Hepatitis E virus (HEV) is similar to HAV in terms of disease, and mainly occurs in Asia where it is transmitted by contaminated water.


Hepatitis G virus (HGV) was recently discovered and resembles HCV; the virus and its effects are under investigation but some investigators do not recognize it as a cause of hepatitis.


Patients who already have chronic HBV infection can acquire HDV infection at the same time as they acquire the HBV infection or, alternatively, on top of a chronic HBV infection. Patients with chronic hepatitis due to HBV and HDV develop cirrhosis (severe liver scarring) rapidly. Moreover, the combination of HDV and HBV 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,
• sewage and water treatment workers,
• people with multiple sexual partners,
• intravenous drug users,
• HIV patients, and
• hemophiliacs who receive blood clotting factors.

What are the symptoms and signs of viral hepatitis?


Many patients infected with HAV, HBV, and HCV 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 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 virus has an incubation period of about 15 to 45 days; Hepatitis B virus from 45 to 160 days, and Hepatitis C virus from about 2 weeks to 6 months.




How is viral hepatitis diagnosed?


Diagnosis of viral hepatitis is based on symptoms and 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 HBV and HCV 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) while the normal range of values for ALT is from 7 to 56 units per liter of serum. (These normal levels may vary slightly in the literature.) Patients with acute viral hepatitis (for example, due to HAV or HBV) can develop very high AST and ALT levels, sometimes in the thousands of units per liter. 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 HBV and HCV 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 physical examinations 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.



What is the treatment for viral hepatitis?



Acute hepatitisTreatment 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.


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. Moreover, sedatives and "tranquilizers" are avoided because they may accentuate the effects of liver failure on the brain and causelethargy 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.


Acute HBV is not treated with antiviral drugs. Acute HCV - though rarely diagnosed - can be treated with several of the drugs used for treating chronic HCV. Treatment of HCV is recommended primarily for the 80% of patients who do not eradicate the virus early. Treatment results in clearing of the virus in the majority of patients.

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 (Rebetol, Copegus)
• oral telaprevir (Incivek) (Note that on 12/19/2012, FDA warned that a few patients can develop a fatal rash, especially when telaprevir is used in combination with other antivirals)
• oral boceprevir (Victrelis)

Medications for chronic hepatitis B infection include:

• injectable alpha 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.

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 all 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 infection. 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.

Hepatitis Vaccinations


Hepatitis A. Two hepatitis A vaccines are available in the US, hepatitis A vaccine(Havrix, 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 (for example, 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 infection with hepatitis A is common should be vaccinated at least 4 weeks before departure. The Centers for Disease Control (CDC) recommends that 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 U.S. are made (synthesized) using recombinant DNA technology (joining DNA segments). These recombinant hepatitis B vaccines, hepatitis B vaccine (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 therefore, cannot cause HBV infections. Hepatitis B vaccines should be given in three doses with the second dose 1 to 2 months after the first dose, and the third dose 4 to 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. However, researchers claim preliminary research results suggest that a vaccine can be made that will be effective against the multitude of HCV antigenic types that infect humans. They predict it may become available in about 3 to 5 years.

What is the prognosis of viral hepatitis?

The prognosis of viral hepatitis for most patients is good; however, this prognosis varies somewhat depending on the infecting virus. For example those patients that develop chronic hepatitis may have a worse prognosis because of cirrhosis, fulminant hepatitis (liver failure), and occasionally death . 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 HAV and most adults (greater than 95%) with acute HBV recover completely. Complete recovery from viral hepatitis means that:

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

Unfortunately, not all patients with viral hepatitis recover completely. Five percent of patients with acute HBV infection and about 60% of patients with acute HCV infection develop chronic hepatitis. Patients (about 0.5% to 1%) that develop fulminant hepatitis have about an 80% fatality rate. Chronic HCV infections are the leading cause for liver transplants.


Because the liver works to detoxify substances, this task is compromised during acute and chronic viral hepatitis infections. Consequently, avoiding items that may stress the compromised livers function (for example, alcohol, smoking, taking drugs that require liver processing) should be strongly considered by the patient to improve their prognosis. .