Hepatitis can be caused by viruses and several other agents, including drugs and toxins. Approximately 95% of hepatitis cases are due to five major virus types: hepatitis A, B, C, D, and E (Table 8.4). Diagnosing the specific virus is difficult because the symptoms (e.g., chills, weight loss, fever, distaste for cigarettes and food, darker urine and lighter stool) presented by each viral type are similar. Additionally, some individuals may have no symptoms or have very mild symptoms that are ascribed to the “flu.” Serologic tests for hepatitis virus markers have made it easier to define the specific type.

Hepatitis A virus (HAV), which is acquired through enteric transmission, infects the gastrointestinal tract and is eliminated through the feces. Serologically, the presence of the IgM antibody to HAV (IgM anti-HAV) and the total antibody to HAV identifies the disease and determines previous exposure to or recovery from HAV.

Hepatitis B virus (HBV) demonstrates a central core containing the core antigen and a surrounding envelope containing the surface antigen: <0.01 pg/mL for viral load. Detection of hepatitis B core antigen (HBcAg), envelope antigen (HBeAg), and surface antigen (HBsAg) or their corresponding antibodies constitutes hepatitis B serologic or plasma assessment. Viral transmission occurs through exposure to contaminated blood or blood products through an open wound (e.g., needlesticks, lacerations). Hepatitis monitoring panel for serial testing includes four B markers: HBsAg, HBeAg, antibody to HBeAg (anti-HBe), and antibody to HBsAg (anti-HBs). Interpretation depends on clinical setting. Hepatitis B DNA ultrasensitive quantitative PCR is the most sensitive test available for hepatitis B viral load.

Hepatitis C virus (HCV), formerly known as non-A, non-B hepatitis, is also transmitted parenterally. HCV infection is characterized by presence of antibodies to HCV (anti-HCV) and levels of alanine aminotransferase (ALT) that fluctuate between normal and markedly elevated. Levels of anti-HCV remain positive for many years; therefore, a reactive test indicates infection with HCV or a carrier state but not infectivity or immunity. PCR or reverse transcriptase PCR (RT-PCR) (viral load), which detects HCV RNA, should be used to confirm infection when acute hepatitis C is suspected. A negative hepatitis C antibody (recombinant immunoblot assay [RIBA]) does not exclude the possibility of HCV infection because seroconversion may not occur for up to 6 months after exposure.

Hepatitis D virus (HDV) is encapsulated by the HBsAg. Without the HBsAg coating, HDV cannot survive. Because HDV can cause infection only in the presence of active HBV infection, it is usually found where a high incidence of HBV occurs. Transmission is parenteral. Serologic HDV determination is made by detection of the hepatitis D antigen (HDAg) early in the course of the infection and by detection of antibody to HDV in the later stages of the disease.

Hepatitis E virus (HEV) is transmitted enterically and is associated with poor hygienic practices and unsafe water supplies, especially in developing countries. It is quite rare in the United States. Specific serologic tests include detection of IgM and IgG antibodies to HEV. See Table 8.5 for a summary of the features of the different hepatitis agents.

The following terms are used:

• ALT (alanine aminotransferase): An enzyme normally produced by the liver; blood levels may increase in cases of liver damage

• Anti-HBc: Antibody to hepatitis B core antigen

• Anti-HBe: Antibody to hepatitis B envelope antigen

• Anti-HBs: Antibody to hepatitis B surface antigen

• Antibody: A Y-shaped protein molecule (immunoglobulin) in serum or body fluid that either neutralizes an antigen or tags it for attack by other cells or chemicals; acts by uniting with and firmly binding to an antigen. The prefix anti- followed by initials of a virus refers to specific antibody against the virus.

• Chronic hepatitis: A condition in which symptoms or signs of hepatitis persist for >6 months

• Cirrhosis: Irreversible scarring of the liver that may occur after acute or chronic hepatitis

• Delta agent: A unique RNA virus that causes acute or chronic hepatitis; requires HBV for replication and infects only patients who are HBsAg positive; is composed of a delta antigen core and an HBsAg coat; also known as HDV

• Endemic: Present in a community at all times but occurring in a small number of cases

• Enteric route: Spread of organisms through the oral–intestinal–fecal cycle

• Flavivirus: A family of small RNA viruses; HCV is similar to members of the Flavivirus family

• Fulminant hepatitis: The most severe form of hepatitis; may lead to acute liver failure and death

• HBcAg: Hepatitis B core antigen

• HBsAg: Hepatitis B surface antigen

• Hepatotropic: Having an affinity for or exerting a specific effect on the liver

• IgG: A form of immunoglobulin that occurs late in an infectious process

• IgM: A form of immunoglobulin that occurs early in an infectious process

• IgM anti-HAV: M class immunoglobulin antibody to HAV

• IgM anti-HBc: M class immunoglobulin antibody to HBcAg

• Immune globulin (IG): A sterile solution of water-soluble proteins that contains those antibodies normally present in adult human blood; used as a passive immunizing agent against various viruses such as HAV

• Negative-sense RNA virus: A virus in which the viral proteins are encoded by messenger RNA molecules that are complementary to the viral genome

• New viruses—GBV-A, GBV-B, and GBV-C: May be causative agents in non-A through E hepatitis

• Non-A, non-B hepatitis: Viral hepatitis caused by viruses other than A, B, or D (e.g., C, E)

• Parenteral: Entering the body subcutaneously, intramuscularly, or intravenously or other means whereby the organisms reach the bloodstream directly

• Positive-sense RNA virus: A virus in which the parenteral (or genomic) RNA serves as the messenger RNA for protein synthesis

• Recombinant antigen: An antigen that results from the recombination of genetic components, which then are artificially introduced into a cell, leading to synthesis of a new protein

• Viral load: The amount or concentration of virus in the circulation

These measurements are used for differential diagnosis of viral hepatitis, viral load. Serodiagnosis of previous exposure and recovery of viral hepatitis is complex because of the number of serum or plasma markers necessary to determine the stage of illness. Testing methods include ELISA, microparticle enzyme immunoassay (MEIA), PCR, and RT-PCR and tests for viral genome (viral load).

1. Negative (nonreactive) for hepatitis A, B, C, D, or E by ELISA, MEIA, PCR, RIBA, or RT-PCR.

2. Negative or undetected viral load (not used for primary infection, only to monitor). PCR requires a separate specimen collection.

3. Hepatitis B viral DNA negative or nonreactive viral load (less than 0.01 pg/mL) in an infected individual before treatment.

1. Collect a 7-mL blood serum sample in a red-topped tube or two lavender-topped ethylenediaminetetraacetic acid (EDTA) tubes, 5 mL each, for plasma. Observe standard precautions. Centrifuge promptly and aseptically. Label the specimen with the patient’s name, date, and test(s) ordered and place in a biohazard bag for transport to the laboratory. Send specimens frozen on dry ice. Check with your laboratory for protocols and whether plasma or serum is needed.

2. Some specimens need to be split into two plastic vials before freezing and sent frozen on dry ice. Check with your laboratory.

1. Individuals with hepatitis may have generalized symptoms resembling the flu and may dismiss their illness as such.

2. A specific type of hepatitis cannot be differentiated by clinical observations alone. Testing is the only sure method to define the category (see Tables 8.6 and 8.7).

3. Rapid diagnosis of acute hepatitis is essential for the patient so that treatment can be instituted and for those who have close patient contact so that protective measures can be taken to prevent disease spread.

4. Persons at higher risk for acquiring hepatitis A include patients and staff in healthcare and custodial institutions, people in day care centers, IV drug abusers, and those who travel to undeveloped countries or regions where food and water supplies may be contaminated.

5. Persons at higher risk for HBV include those with a history of drug abuse, those who have sexual contact with infected persons, those who have household contact with infected persons, and especially those with skin and mucosal surface lesions (e.g., impetigo, saliva from chronic HBV-infected persons on toothbrush racks and coffee cups in their homes); in addition, infants born to infected mothers (during delivery), patients who undergo hemodialysis, and healthcare employees are at higher risk for infection. Of all persons with HBV infection, 38%–40% contract HBV during early childhood.

6. Healthcare workers should be periodically tested for hepatitis exposure and should always observe standard precautions when caring for all patients.

7. Persons at risk for HCV include those who have received blood transfusions, engage in IV drug abuse, undergo hemodialysis, have had organ transplantation, or have sexual contact with an infected person; HCV can also be transmitted during delivery from mother to neonate. Most people have no symptoms at the time of diagnosis for hepatitis C. See Table 8.8 for hepatitis markers that appear after infection.

8. Both total (IgG + IgM) and IgM anti-HBc are positive in acute infection, whereas typically only total anti-HBc is present in chronic infection.

Pretest Patient Care

1. Assess patient’s social and clinical history and knowledge of test. Explain test purpose and procedure.

2. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.