Diseases

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 findingsDiagnosis 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 testsThere 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 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 means that the liver is inflamed, and elevations can be caused by many agents other than hepatitis viruses, such as medications, alcohol, bacteria, fungi, 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 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.

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 own antibodies.Avoidance of exposure to virusesPrevention 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 immunoglobulinsImmune 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.

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 or 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 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 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 following sections and reference 1).Hepatitis A (HAV)HAV accounts for an estimated 1,781 new infections per year according to the most recent 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 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 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 (HBV)There were an more than 19,000 new cases of HBV infection estimated by the CDC in 2013 and more than 1,800 people die each year 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 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 2.2 million people in the U.S. and 2 billion people world-wide who suffer with chronic HBV infections.Hepatitis C (HCV)The CDC reported that there were about 16,500 reported new cases per year (unreported is 13.4 times more than reported) of hepatitis C. 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 3.2 million people with chronic HCV infection in the U.S.Types D, E, and G HepatitisThere 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.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.

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. 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)

Rarely, individuals with acute infections with HAV and HBV 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), as well as 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 HBV will develop acute fulminant hepatitis. This is even less common with HCV alone, although it becomes more frequent when both HBV and HCV are present together.

Patients infected with HBV and HCV 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, and 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 U.S. Patients with chronic viral hepatitis can transmit the infection to others with blood or body fluids (for example, sharing needles, sexually, and infrequently by organ donation) as well as infrequently by transmission from mother to newborn.

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. 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.

Treatment of acute viral hepatitis and chronic viral hepatitis are different. Treatment of acute viral hepatitis involves resting, 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 hepatitisIn 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 clearing of the virus in the majority of patients.Chronic hepatitisTreatment 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 alpha interferons (Pegasys)
• oral ribavirin (Rebetol, Copegus)
• oral boceprevir (Victrelis)
• simeprevir (Olysio)
• oral sofosbuvir (Sovaldi)
• oral simeprevir (Olysio)
• oral daclatasvir (Daklinza)
• oral ledipasvir/sofosbuvir (Harvoni)
• oral ombitasvir/paritaprevir/ritonavir (Technivie)
• oral ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak)

Medications for chronic hepatitis B infection include:

• injectable alpha interferons
• oral lamivudine (Epivir)
• oral adefovir (Hepsera)
• oral entecavir (Baraclude)
• orak telbivudine (Tyzeka)
• oral tenofovir (Viread)

Because of constantly 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 which are currently available are rarely used because of newer, safer, and more effective alternatives.Decisions regarding 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 (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. Most 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.

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

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

• Workers in the health care 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 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 a person does not have to be in a high risk group in order to be infected with a hepatitis virus. In countries with poor sanitation, food and water contamination with HAV increases risk. Some day care centers may become contaminated with HAV, so children at such centers are at a higher risk for HAV infections.