Viral Hepatitis

Medically Reviewed on 8/8/2022

What is viral hepatitis?

Hepatitis, or inflammation of the liver, most often is caused by hepatitis A, B, and C viruses.
Hepatitis, or inflammation of the liver, most often is caused by hepatitis A, B, and C viruses.

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 causing mononucleosis and the cytomegalovirus, 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 most 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, this alphabetical list will likely 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, and HCV represent hepatitis viruses A, B, and C, respectively.) The focus of this article is on these viruses that cause the majority of human viral hepatitis.

Hepatitis viruses replicate (multiply) primarily in the liver cells. This can cause the liver to be unable to perform its functions.

The following is a list of the major functions of the liver:

  • 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.
  • 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.
  • The liver stores many sugars, fats, and vitamins until they are needed elsewhere in the body.
  • The liver builds smaller chemicals into larger, more complicated chemicals that are needed elsewhere in the body. Examples of this type of function are the manufacture of fat, cholesterol, and protein bilirubin.

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 hepatitis viral type (A-F) 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 cause viral hepatitis, their symptoms, diagnosis, and treatments, and should help the reader choose the subject(s) for more in-depth information.

What are the common types of viral hepatitis?

Although the most common types of viral hepatitis are HAV, HBV, and HCV, some clinicians had previously 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 that led to hepatic (liver) failure. HBV and HCV produced chronic viral hepatitis. However, these terms are outdated and not currently used as frequently because all of the viruses that cause hepatitis may have acute phase symptoms (see symptoms below).

Prevention techniques and vaccinations have markedly reduced the current incidence of common viral hepatitis infections; however, there remains a population of about 1 to 2 million people in the U.S. with chronic HBV, and about 3.5 million with chronic HCV according to the CDC. Statistics are incomplete for determining how many new infections occur each year; the CDC documented infections but then goes on to estimate the actual numbers by further estimating the number of unreported infections (see the following sections and reference 1).

Hepatitis A (HAV)

In 2016, there were 2,007 new HAV cases reported to the CDC. 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 easily 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 infections spread to customers in restaurants and among children and workers in daycare centers if hand washing and sanitary precautions are not observed.

Hepatitis B (HBV)

There were 3,218 new cases of HBV infection estimated by the CDC in 2016 and more than 1,698 people died due to the consequences of chronic hepatitis B infection 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 5% 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 2.2 million people in the U.S. and 2 billion people worldwide who suffer from chronic HBV infections.

Hepatitis C (HCV)

The CDC reported that there were 2,967 reported new cases of hepatitis C in 2016. The CDC reports that the actual number of acute cases is estimated to be 13.9 times the number of reported cases in any year, thus, it is estimated that 41,200 acute hepatitis C cases were occurring in 2016. 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 75%-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 75% to 85% 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 of 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. How HDV is spread is by shared needles among drug abusers, contaminated blood, and sexual contact; essentially the same ways as HBV.

Individuals who already have chronic HBV infection can acquire HDV infection at the same time as they acquire the HBV infection, or at a later time. Those 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.

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, also termed GBV-C) was recently discovered and resembles HCV, but more closely, the flaviviruses. The virus and its effects are under investigation, and its role in causing disease in humans is unclear.

QUESTION

Liver disease refers to any abnormal process that affects the liver. See Answer

Who is at risk for viral hepatitis?

People who are most at risk for developing viral hepatitis include:

  • Workers in the healthcare professions
  • Asians and Pacific Islanders
  • Sewage and water treatment workers
  • People with multiple sexual partners
  • Intravenous drug users
  • HIV patients
  • People with hemophilia 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 10 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 a person does not have to be in a high-risk group to be infected with a hepatitis virus. In countries with poor sanitation, food, and water contamination with HAV increases the risk. Some daycare centers may become contaminated with HAV, so children at such centers are at a higher risk for HAV infections.

What are the symptoms of viral hepatitis?

The period 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.

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:

Less common symptoms include:

  • Dark urine
  • Light-colored stools
  • Fever
  • Jaundice (a yellow appearance to the skin and white portion of the eyes)

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 the 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 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 depending on the laboratory.) 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 mean that the liver is inflamed, and elevations can be caused by many agents other than hepatitis viruses, such as medications, alcohol, bacteria, fungi, etc. 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 help diagnose 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 material 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, the 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?

Treatment of acute viral hepatitis and chronic viral hepatitis are different. Treatment of acute viral hepatitis involves resting, relieving symptoms, and maintaining an 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 (supportive care). Careful attention should be given to medications or compounds, which can have adverse effects in patients with abnormal liver function (for example, acetaminophen [Tylenol and others], alcohol, etc.). 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 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.

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 the 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:

  • oral daclatasvir (Daklinza)
  • oral ledipasvir/sofosbuvir (Harvoni)
  • Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir and Ribavirin
  • Simeprevir + Sofosbuvir
  • Daclatasvir + Sofosbuvir
  • Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir

Medications for chronic hepatitis B infection include:

Because of constant ongoing research and development of new antiviral agents, the current list of medications for chronic hepatitis B and C infections is likely to change every year. Many of those drugs that are currently available are rarely used because of newer, safer, and more effective alternatives.

Decisions regarding the treatment of chronic hepatitis can be complex and should be directed by gastroenterologists, hepatologists (doctors specially trained in treating diseases of the liver), or infectious disease specialists 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 for up to 6 months is often necessary. 
  4. The success rate for a sustained viral response for chronic hep C is 90%.

In addition, recent research has shown that a combination of certain antiviral medications results in a cure (viral clearance) in many patients with chronic hepatitis C. Further studies and FDA approval are pending.

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 (about 80%) without liver transplantation.

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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 who develop chronic hepatitis have a worse prognosis because of the potential to develop cirrhosis, liver failure, liver cancer (hepatocellular carcinoma), 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. 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 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 to 10 percent of patients with acute HBV infection and about 75% to 80% of patients with acute HCV infection develop chronic hepatitis. Patients (about 0.5% to 1%) who develop fulminant hepatitis have about an 80% fatality rate. Chronic HCV infections are the leading cause of 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 liver function (for example, alcohol, smoking, and taking drugs that require liver processing) should be strongly considered by the patient to improve their prognosis.

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 non-infectious components of viruses are given to stimulate the body to produce its antibodies.

Avoidance of 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 secretions and waste (stool, vomit) will help prevent the spread of all of these viruses.

Use of immunoglobulins

Immune serum globulin (ISG) is a 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 a 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 within 2 weeks, and almost 100% of recipients within 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 they become 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 with 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 before 4 weeks. Immunoglobulin provides quicker protection than 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, the 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 90% effective in healthy adults and 95% in infants, children, and adolescents. 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), older 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 the 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
  • People with hemophilia 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 the hepatitis B virus surface antigen. Women who test positive for hepatitis B virus (positive hepatitis B surface antigen) 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 the hepatitis B vaccine at birth. The reason for giving both immunoglobulin and vaccine is that even though the 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 the hepatitis B vaccine for the same reason as infants born to mothers with hepatitis B infection.

Hepatitis C and D

There is currently no vaccine for hepatitis C. Development of such a vaccine is difficult due to the six different forms (genotypes) of hepatitis C. No vaccine for hepatitis D is available. However, the HBV vaccine can prevent an individual not infected with HBV from contracting hepatitis D because the hepatitis D virus requires live HBV to replicate in the body.

SLIDESHOW

Hepatitis C, Hep B, Hep A: Symptoms, Causes, Treatment See Slideshow
Medically Reviewed on 8/8/2022
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Medscape. Hepatitis C Medication.

Medscape. Viral Hepatitis.

UpToDate. GB virus C (hepatitis G) infection.

WHO. Hepatitis B: Are you at risk?

WHO. Hepatitis B.