AUTHOR INFORMATION

Section 1 of 11

Authored by Adrienne M Buggs, MD, FACEP, Consulting Staff, Department of Emergency Medicine, Dewitt Army Community Hospital, Fort Belvoir, Virginia

Coauthored by Joseph K Lim, MD, Director, Yale Viral Hepatitis Program, Assistant Professor of Medicine, Section of Digestive Diseases, Yale University School of Medicine

Adrienne M Buggs, MD, FACEP, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Edited by Robert M McNamara, MD, FAAEM, Professor of Emergency Medicine, Temple University; Chief, Department of Internal Medicine, Section of Emergency Medicine, Temple University Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eugene Hardin, MD, FACEP, FAAEM, Chair and Associate Professor, Department of Emergency Medicine, Charles R Drew University of Medicine and Science; Chair, Department of Emergency Medicine, Martin Luther King, Jr/Drew Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center

Author's Email:	Adrienne M Buggs, MD, FACEP
Editor's Email:	Robert M McNamara, MD, FAAEM

eMedicine Journal, July 12 2006, VOLUME 7, Number 7

INTRODUCTION

Section 2 of 11

Background: Hepatitis is a general term that refers to inflammation of the liver. This condition may result from various infectious and noninfectious etiologies.

Infectious etiologies include viral, bacterial, fungal, and parasitic organisms.

Medications, toxins, and autoimmune disorders may cause noninfectious hepatitis. This article focuses on acute infectious hepatitis with a brief discussion of drug-induced and autoimmune hepatitis at the end of the article.

Frequency:

• In the US: During the years 1984-1993, annual reported cases of acute hepatitis ranged from 43,012-64,075. In 1994, 44,227 cases of infectious hepatitis were reported to the Centers for Disease Control and Prevention (CDC). Hepatitis A accounted for 61% of those cases and hepatitis B for 28% of the reported cases. These numbers grossly underestimate the actual number of cases of infectious hepatitis in the United States because the diagnosis is often missed and because many cases are never reported. The CDC estimates a more accurate number to be 500,000-750,000 new cases per year.

• Internationally: Worldwide, 400-500 million people are estimated to be infected with hepatitis B virus (HBV); this virus leads to 1 million deaths annually. An estimated 170 million people worldwide are infected with hepatitis C virus (HCV).

Mortality/Morbidity:

• Acute hepatitis may result in serious illness or even fatality; it is the leading cause of fulminant acute hepatic failure in the United States. Liver disease induced by viral hepatitis accounts for 4000-5000 deaths per year.

• Chronic viral hepatitis infection causes even greater morbidity and mortality rates. Chronic liver disease associated with persistent hepatitis virus infection accounts for an estimated 16,000 deaths per year; 70% from HCV, 20% from HBV, and 10% from combined infection with HCV and HBV.

CLINICAL

Section 3 of 11

History: Clinical presentation of infectious hepatitis varies from person to person as well as with the etiology of infection. Some patients may present as entirely asymptomatic or only mildly symptomatic. Others may present with rapid onset of fulminant hepatic failure. The classic presentation of infectious hepatitis involves 4 phases.

• Phase 1 - Viral replication

• Patients are asymptomatic during this phase.

• Laboratory studies demonstrate serologic and enzyme markers of hepatitis.

• Phase 2 - Prodromal phase

• Patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias, malaise, fatigue, urticaria, and pruritus. Some even develop an aversion to cigarette smoke.

• When seen by a health care provider during this phase, patients are often diagnosed as having gastroenteritis or a viral syndrome.

• Phase 3 - Icteric phase

• Patients may note darkening of the urine, followed by pale-colored stools.

• In addition to the predominant gastrointestinal symptoms and malaise, patients become icteric and may develop right upper quadrant pain with hepatomegaly.

• Phase 4 - Convalescent phase

• Symptoms and icterus resolve.

• Liver enzymes return to normal.

Physical:

• Physical findings in patients with hepatitis vary with the type of hepatitis and time of presentation.

• Patients often present with low-grade fever.

• Patients experiencing significant vomiting and anorexia may show signs of dehydration such as tachycardia, dry mucous membranes, loss of skin turgor, and delayed capillary refill.

• Patients in the icteric phase may have icterus of the sclerae or mucous membranes or discoloration of the tympanic membranes.

• The skin may be jaundiced and may reveal macular, papular, or urticarial rashes.

• In viral hepatitis, the liver may be tender and diffusely enlarged with a firm, sharp, smooth edge.

• If the patient has a nodular liver or a mass is palpated, clinicians should be suspicious for an abscess or tumor.

Causes:

• Infectious hepatitis, viral
  • Five major hepatotropic viruses cause the majority of clinical cases of viral hepatitis. These are hepatitis A virus (HAV), HBV, HCV, hepatitis D virus (HDV), and hepatitis E virus (HEV).

  • HAV, HBV, and HCV cause more than 90% of cases of acute viral hepatitis in the United States.

  • Researchers suspect that other viral agents (not completely characterized or identified) may cause a small percentage of cases of acute hepatitis. In the literature, these agents are referred to as hepatitis F (HFV), hepatitis G (HGV), or other non-ABC viruses.

  • Hepatitis viruses A, B, C, and D are the only hepatitis viruses endemic to the United States.

• Hepatitis A

• Epidemiology: HAV is a picornavirus that is resistant to environmental factors (eg, temperature, certain chemicals). As the predominant etiologic agent of viral hepatitis in the United States, HAV is thought to account for 25-50% of new cases per year. The CDC estimates that in 1991 the actual number of new cases of HAV approached 136,000.

• Transmission
  • HAV exists in highest concentration in the feces of infected individuals; the greatest fecal viral load tends to occur near the end of the incubation period of HAV.

  • Most commonly, the virus spreads from person to person via the fecal-oral route. Contaminated water and food, including shellfish collected from sewage-contaminated water, have also resulted in epidemics of HAV.

  • Finally, the virus may also spread via infected serum.

  • Infection with HAV occurs throughout the world. However, risk of infection is greatest in developing countries, areas of low socioeconomic status, and areas without sufficient sanitation. Higher infection rates also exist in settings where fecal-oral spread is likely, such as daycare centers.

  • Other groups at high risk for HAV infection include international travelers, users of injected drugs, military personnel stationed abroad, and homosexual men. Maternal-neonatal transmission is not established.

  • Close contacts of infected individuals are also at risk. The secondary infection rate for HAV in household contacts of patients with acute HAV infection is around 20%. Thus, secondary infection plays a significant role in the maintenance of HAV outbreaks.

• Clinical course
  • The incubation period of HAV is 2-7 weeks, with an average of 28 days. Clinical symptoms then develop, often with a presentation similar to that of gastroenteritis or a viral respiratory infection.

  • Most common signs and symptoms include fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia, and rash.

  • HAV infection usually occurs as a mild self-limited disease and confers lifelong immunity to HAV. Chronic infection with HAV does not occur.

• Morbidity and death
  • Although HAV usually causes mild disease, the older the patient, the more severe the disease is likely to be. While icteric disease occurs in fewer than 10% of children younger than 6 years with HAV, it occurs in 40-50% of older children and in 70-80% of adults with HAV. Other complications can include acute liver failure, cholestatic hepatitis, and relapsing hepatitis.

  • The overall mortality rate for HAV is approximately 0.01%. Children younger than 5 years and adults older than 50 years have the highest case-fatality rates.

• Hepatitis B

• Epidemiology
  • A major cause of infectious hepatitis worldwide, HBV belongs to the class of hepadna viruses. HBV is responsible for approximately 28-43% of acute viral hepatitis cases reported in the United States. In actuality, HBV is thought to account for about half of the cases of acute hepatitis in the United States. An estimated 50,000 to 250,000 people in the United States become infected with HBV each year. Adults and adolescents account for the majority of cases.

  • Estimates suggest that 400 to 500 million people worldwide are HBV carriers. The virus leads to 1 million deaths annually as a result of viral hepatitis–induced liver disease.

  • The incidence of childhood HBV infection is not well established because more than 90% of HBV infections in this age group are asymptomatic.

• Transmission
  • The major reservoir of HBV in the United States consists of the 1.25 million people with chronic HBV infection. In this group, those with hepatitis B e antigen (HBeAg) in their serum tend to have higher viral titers and thus greater infectivity.

  • HBV transmits both parenterally and sexually, most often by mucous membrane exposure or percutaneous exposure to infectious body fluids. Saliva, serum, and semen all have been determined to be infectious.

  • Percutaneous exposures leading to the transmission of HBV include transfusion of blood or blood products, injection drug use with shared needles, hemodialysis, and needlesticks (or other wounds caused by sharp implements) in health care workers.

  • Another significant mode of transmission is perinatal transmission. The greatest risk of perinatal transmission occurs in infants of HBeAg-positive women. By age 6 months, these children have a 70-90% risk of infection and, of those, about 90% will go on to develop chronic infection with HBV.

  • For infants born to HBeAg-negative women, risk of infection approximates 10-40%, with a chronic infection rate of 40-70%. Even if transmission does not occur in the perinatal period, these children still have a significant risk of developing infection during early childhood.

  • High-risk groups for infection with HBV include intravenous drug users, persons born in endemic areas, and men who are homosexually active.

  • Other groups at risk include health care workers with exposure to infected blood or bodily fluids, recipients of multiple blood transfusions, patients undergoing hemodialysis, heterosexual persons with multiple partners or a history of sexually transmitted disease, institutionalized persons including prisoners, people who are developmentally disabled, and household contacts or sexual partners of HBV carriers.

• Clinical course
  • The incubation period for HBV varies from 30-180 days, with the average approximately 75 days. Patients then enter the prodromal or preicteric phase, developing gradual onset of anorexia, malaise, and fatigue. During this phase, as the liver becomes inflamed, liver enzymes start to elevate, and the patient may experience right upper quadrant pain. Fifteen percent of patients develop an illness resembling serum sickness. These patients may experience fever, arthritis, arthralgias, or an urticarial rash.

  • As the disease progresses to the icteric phase, the liver becomes tender, and jaundice develops. Patients may note that their urine darkens and that their stools lighten in color. Other symptoms in this stage include nausea, vomiting, and pruritus.

  • From this point on, patients may have quite a variable course. Some experience fairly rapid improvements in their symptoms, while others go on to a prolonged disease course with slow resolution. Still others may have symptoms that periodically improve, only to worsen later (relapsing hepatitis).

  • Finally, an unfortunate subset of patients suffers rapid progression of their disease to the point of fulminant hepatic failure. This may occur over days to weeks.

• Complications
  • One of the major complications of HBV infection is the development of chronic infection. Patients with chronic HBV infection are at risk of later developing chronic active hepatitis, cirrhosis of the liver, and eventual hepatocellular cancer.

  • Patients infected at an early age have the greatest risk of developing chronic HBV infection. While 90% of those infected at birth develop chronic HBV, only 5-10% of older children or adults go on to develop chronic infection. The risk of chronic infection is also higher in patients who are immunocompromised.

  • Patients with chronic HBV infection have a significantly increased risk of developing hepatocellular cancer. In fact, hepatocellular cancer is the leading cause of cancer-related deaths in areas where HBV is endemic. The cancer is believed to result from repeated bouts of chronic inflammation and cellular regeneration. Hepatocellular cancer develops an average of 25-30 years after initial infection.

  • Another major complication of HBV infection is development of fulminant hepatic failure. In approximately 0.5-1% of HBV-infected patients, the disease progresses to fulminant hepatic failure, with coagulopathy, encephalopathy, and cerebral edema. The case-fatality rate for these patients approaches 80%.

• Hepatitis C

• Epidemiology
  • Hepatitis C is a single-stranded ribonucleic acid (RNA) virus that is the most frequent cause of parenteral non-A, non-B hepatitis worldwide. Estimates suggest that 170 million people are chronically infected with HCV. In the United States, approximately 4 million people are infected with HCV; of those, nearly 3 million have chronic infection.

  • HCV causes approximately 17-20% of acute hepatitis cases in the United States, and the CDC estimates that 150,000 new cases of HCV occur annually. Highest rates of disease prevalence are found in patients with hemophilia and in injection drug users. Before the newer universal plasma screening measures, HCV accounted for 90% of posttransfusion hepatitis cases.

  • HCV is the most common cause of chronic viral hepatitis in the United States. About 80% of people infected progress to chronic HCV infection.

• Transmission
  • HCV can be transmitted parenterally, perinatally, and sexually. HCV is transmitted most reliably through transfusion of infected blood or blood products, transplantation of organs from infected donors, and sharing contaminated needles among intravenous drug users.

  • Needlestick injuries among health care workers place them at significant risk of infection. Incidence of HCV infection in health care workers with history of needlestick exposure to infected blood approaches 10%. Even more concerning is the 0.4-1% chance of developing irreversible liver injury from a needlestick infection in this setting.

• Clinical course
  • Incubation period for HCV runs 15-150 days, with symptoms developing anywhere from 5-12 weeks after exposure.

  • During acute infection with HCV, symptoms may appear similar to those of HBV infection. In up to 80% of cases, however, patients are asymptomatic and do not develop icterus.

• Complications
  • Acute infection with HCV may cause fulminant hepatic failure and is associated with aplastic anemia.

  • Approximately 50-85% of patients with HCV become chronically infected with HCV; of those, 29-76% later develop chronic active hepatitis or cirrhosis. In fact, HCV is a leading cause of chronic hepatitis and cirrhosis worldwide.

  • In the United States and Europe, chronic HCV infection is the leading indication for liver transplant. Moreover, chronic HCV infection causes 10,000 deaths per year in the United States.

  • Chronic HCV infection is also strongly linked to the development of hepatocellular cancer, which usually develops after 30 years in patients who are chronically infected and have cirrhosis.

• Hepatitis D

• Epidemiology
  • HDV, an incomplete virus, requires the presence of HBV to replicate; therefore, HDV infection develops only in patients who are positive for the hepatitis B surface antigen (HBsAg).

  • Patients may acquire HDV as a co-infection (at the same time that they contract HBV), or the HDV may superinfect patients who are chronic HBV carriers.

  • Although HDV is not a reportable disease, the CDC estimates that it results in 7500 infections each year. Approximately 4% of cases of acute HBV are thought to involve co-infection with HDV.

• Transmission: Modes of transmission for HDV are similar to those for HBV, although perinatal transmission rarely occurs and has not been documented in the United States.

• Clinical course
  • The incubation period of HDV is approximately 35 days. Patients co-infected with HBV and HDV tend to have a more severe disease course than those infected with HBV alone. As many as one third of those with co-infection go on to develop fulminant hepatitis.

  • Chronic HBV carriers superinfected with HDV usually also develop chronic HDV infection. Chronic co-infection often leads to rapidly progressive subacute or chronic hepatitis, resulting in a more rapid progression to cirrhosis.

  • Over the long term, as many as 70-80% of these patients have evidence of chronic liver disease with cirrhosis, compared to only 15-30% of patients with chronic HBV alone.

• Hepatitis E

• Epidemiology
  • Hepatitis E virus is the primary cause of enterically transmitted non-A, non-B hepatitis; most outbreaks occur in developing countries.

  • Until 1997, HEV transmission was undocumented in the United States. All previously documented HEV cases occurred in travelers from countries where HEV is endemic. In 1997, a case report was published of a US patient with no history of travel who developed hepatitis caused by HEV.

• Transmission
  • HEV is transmitted primarily by the fecal-oral route, with fecally contaminated water providing the most common means of transmission.

  • Transmission by person-to-person contact is undocumented.

• Clinical course
  • The incubation period is 2-9 weeks with an average of 45 days.

  • HEV usually causes an acute self-limited disease similar to HAV. Fulminant disease does occur in about 10% of cases. In women who are pregnant, HEV infection has a case fatality rate of 15-20%. No reports of chronic infection with HEV exist.

• Other types of viral hepatitis
  • Other proposed agents of viral hepatitis (now referred to as non-ABCDE viral hepatitis) are currently under investigation, since researchers suspect that other forms of parenterally transmitted hepatitis may exist.

  • Hepatitis F is proposed as another enterically transmitted hepatitis virus. A small number of cases have been documented in France.

  • Hepatitis G virus, characterized in 1996, is associated with acute and chronic liver disease, but studies have not clearly implicated HGV as an etiologic agent of hepatitis.

  • Other known viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex, varicella-zoster) may also cause inflammation of the liver.

• Infectious hepatitis, nonviral
  • Hepatic abscesses may cause infectious hepatitis. These occur more often in patients with chronic illness. The two general categories of abscess are amebic (most commonly caused by Entamoeba histolytica in developing countries) and pyogenic (tending to affect those at the extremes of age).

  • In neonates, sepsis and catheterization of the umbilical vein may result in abscesses caused by gram-positive aerobic cocci.

  • In adults, biliary disease can result in pyogenic abscess formation with the mortality rate of pyogenic abscesses at almost 40%. Gram-negative rods are the typical causative organisms in adults.

  • In elderly persons, malignancy is the most common underlying disease.

DIFFERENTIALS

Section 4 of 11

Abdominal Trauma, Blunt
Aneurysm, Abdominal
Cholangitis
Cholecystitis and Biliary Colic
Cholelithiasis
Gastritis and Peptic Ulcer Disease
Gastroenteritis
Obstruction, Small Bowel
Pancreatitis
Pediatrics, Gastroenteritis
Pediatrics, Intussusception

Other Problems to be Considered:

Liver abscess
Drug-induced hepatitis
Autoimmune hepatitis
Hepatocellular cancer
Pancreatic cancer

WORKUP

Section 5 of 11

Lab Studies:

• A simple screening test for the nonicteric patient with suspected viral hepatitis involves checking the urine for presence of bilirubin. As an alternative, a liver enzyme panel (generally a costly test) could be obtained.

• Bedside fingerstick glucose testing is important in evaluating for hypoglycemia in patients with an altered or questionable mental status.

• Serum bilirubin (total and fractionated): Total bilirubin may be elevated in infectious hepatitis. Bilirubin levels higher than 30 mg/dL indicate more severe disease.

• Alkaline phosphatase usually is in the reference range but may elevate to no higher than twice the normal level. If alkaline phosphatase is elevated significantly, consider abscess or biliary obstruction.

• Prothrombin time (PT), if prolonged, is a grave finding indicating impaired synthetic function of the liver.

• Draw BUN and serum creatinine to look for evidence of renal impairment. Decreased renal function suggests fulminant hepatic disease.

• Measure serum ammonia in patients with altered mental status or other evidence of hepatic encephalopathy.

• Hepatitis A antibody (immunoglobulin M [IgM] anti-HAV): Detecting the presence of IgM anti-HAV in serum is the standard for diagnosing acute infection with HAV.

• Hepatitis B core antibody (IgM anti-HBc): Determining the presence of IgM anti-HBc in serum is required to make the diagnosis of acute HBV infection.

• Hepatitis B surface antigen may be present in acute infection or in patients who are chronic carriers. Its presence in patients with symptoms of acute hepatitis strongly suggests acute HBV infection but does not rule out chronic HBV with acute superinfection by another hepatitis virus. The presence of HBsAg in the serum for 6 months or longer is indicative of chronic infection.

• Hepatitis C infection can be confirmed with serologic assays to detect antibodies to HCV (anti-HCV) or by molecular tests for the presence of viral particles. The third-generation assays for anti-HCV are sensitive and specific and can detect such antibodies within 4-10 weeks of infection. The qualitative PCR assay for presence of viral particles is the most specific test of HCV infection and may be helpful in diagnosing acute HCV infection before antibodies have developed.

• Assays to detect IgM antibody to HDV do not need to be routinely performed in all patients with suspected hepatitis.

Imaging Studies:

• No specific imaging studies are required to make the diagnosis of hepatitis.

• Obtain the appropriate diagnostic imaging studies (eg, ultrasound, computed tomography) if the differential diagnosis favors gallbladder disease, biliary obstruction, or liver abscess.

Other Tests:

• Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic hepatitis B or chronic hepatitis C.

TREATMENT

Section 6 of 11

Emergency Department Care:

• Viral hepatitis: No specific emergency department treatment is indicated other than supportive care including intravenous rehydration.

• A liver abscess requires intravenous antibiotic therapy directed toward the most likely pathogens and consultation for possible surgical or percutaneous drainage.

Consultations:

• Gastroenterologist or hepatologist

• General surgeon

MEDICATION

Section 7 of 11

Certain patients may benefit from pharmacologic therapy. For chronic HBV and chronic HCV infections in particular, the goals of therapy are to reduce liver inflammation and fibrosis and to prevent progression to cirrhosis and the complications of cirrhosis.

Because the treatment regimens for hepatitis are being actively researched, medication recommendations, indications, and dosages are all subject to change. Make any decision to administer medications in consultation with a gastroenterologist or hepatologist.

In addition to the medications listed below, the nucleoside analogues lamivudine and adefovir have shown promising results in the treatment of patients with chronic HBV. Other antiviral agents that are being studied for treatment of chronic HBV include entecavir and tenofovir. In addition to being active against HBV, lamivudine, adefovir and tenofovir are also active against human immunodeficiency virus (HIV), making them useful in the treatment of patients who are co-infected with HBV and HIV.

For patients with chronic HCV infection, one current treatment option is combination therapy with pegylated interferon (PEG-IFN) and the antiviral ribavirin. This regimen may be recommended for a certain subset of patients with moderate or severe inflammation and/or fibrosis. The combination of the 2 drugs provides a more sustained clearance of HCV RNA from the serum of infected individuals when compared to monotherapy. Other therapeutic options are being explored for treatment of chronic HCV with the goals of increasing efficacy and decreasing toxicity. These include protease inhibitors, ribozymes, and viral vaccines.

Drug Category: Interferons -- These are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, and intralesionally.

Drug Name	Interferon alpha-2b (Intron A) -- Protein product manufactured by recombinant DNA technology that uses genetically engineered Escherichia coli bacterium. Mechanisms by which it exerts antiviral activity are not clearly understood; however, modulation of host-immune response may play an important role. Induces remission in 25-50% of patients with chronic HBV and 40% of patients with chronic HCV and decreases abnormal aminotransferase concentrations in chronic HBV/HCV. Also may play a role in delaying or preventing development of hepatocellular cancer, independent of its antiviral effect, in patients with cirrhosis.
Adult Dose	5 million IU/d or 10 million IU 3 times/wk IM/SC for 16 wk; reduce dose by 50% if severe adverse reactions occur
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; anaphylactic sensitivity to mouse IgG, egg protein, or neomycin
Interactions	Interleukin-2 increases potential risk of renal failure; theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Depression and suicidal ideation may be adverse effects; infrequently, severe or fatal GI hemorrhage reported in association with therapy; prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment

Drug Category: Antivirals -- These agents inhibit viral replication.

Drug Name	Amantadine (Symmetrel) -- Antiviral agent that prevents penetration of virus into host by inhibiting uncoating of virus; may be useful in patients with HCV who do not respond to interferon.
Adult Dose	100 mg PO bid for 6 mo
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic or CNS stimulant activity increase toxicity; hydrochlorothiazide plus triamterene may increase plasma concentrations
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and those receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not discontinue this medication abruptly

Drug Name	Famciclovir (Famvir) -- Prodrug that, when biotransformed into active metabolite penciclovir, may inhibit viral DNA synthesis/replication.
Adult Dose	500 mg PO tid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Probenecid or cimetidine may increase toxicity; increases bioavailability of digoxin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal failure or coadministration of nephrotoxic drugs

Drug Name	Entecavir (Baraclude) -- Guanosine nucleoside analogue with activity against HBV polymerase. Competes with natural substrate deoxyguanosine triphosphate to inhibit HBV polymerase activity (ie, reverse transcriptase). Less effective for lamivudine-refractory HBV infection. Indicated for treatment of chronic hepatitis B infection. Available as tab and oral solution (0.05 mg/mL; 0.5 mg = 10 mL).
Adult Dose	Treatment for nucleoside naive: 0.5 mg PO qd 2 h ac or 2 h pc CrCl 30-49 mL/min: 0.25 mg PO qd CrCl 10-29 mL/min: 0.15 mg PO qd CrCl <10 mL/min: 0.05 mg PO qd Receiving lamivudine or lamivudine resistance: 1 mg PO qd 2 h ac or 2 h pc CrCl 30-49 mL/min: 0.5 mg PO qd CrCl 10-29 mL/min: 0.3 mg PO qd CrCl <10 mL/min: 0.1 mg PO qd
Pediatric Dose	<16 years: Not established >16 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Not a substrate, inhibitor, or inducer of cytochrome P450; coadministration with drugs that reduce renal function (eg, aminoglycosides, cidofovir, cyclosporine) or that compete for active tubular secretion (eg, probenecid, salicylates) may increase serum concentration of either entecavir or coadministered drug
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Reduce dose with renal impairment; if on hemodialysis, administer afterwards; common adverse effects include headache, tiredness, dizziness, and nausea; may elevate liver enzyme levels; may cause lactic acidosis; severe acute exacerbations of hepatitis B may occur in patients who discontinue antihepatitis B therapy

Drug Category: Corticosteroids -- These agents may be used in cholestatic HAV. A brief course may shorten the illness; however, it may be most effective in a milder disease.

Drug Name	Prednisone (Deltasone, Sterapred, Orasone) -- Inactive and must be metabolized to active metabolite prednisolone; conversion may be impaired in patients with liver disease.
Adult Dose	5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric Dose	4-5 mg/m2/d PO; alternatively, administer 1-2 mg/kg PO qd; taper over 2 wk as symptoms resolve
Contraindications	Documented hypersensitivity; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Interactions	Estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Admit patients with hepatitis if they are showing any signs or symptoms suggestive of severe complications.

• Admit and evaluate for hepatic encephalopathy any patients with altered mental status, agitation, behavior or personality changes, or changes in sleep-wake cycle.

• Other admission criteria that are suggestive of severe disease include a PT prolonged greater than 3 seconds, bilirubin greater than 30 mg/dL, and hypoglycemia.

• Admit any patients with intractable vomiting, significant electrolyte or fluid disturbances, or significant comorbid illness; those who are immunocompromised; and those who are older than 50 years.

Further Outpatient Care:

• Most patients with viral hepatitis can be monitored as outpatients.

• Ensure that patients are able to maintain adequate hydration, and arrange close follow-up care with their primary care physicians.

• Instruct patients to refrain from using any potential hepatotoxins, such as ethanol or acetaminophen.

• Advise patients to avoid prolonged or vigorous physical exertion until their symptoms improve.

• Patients who are found subsequently to have HBV or HCV should be referred to a gastroenterologist or hepatologist for further evaluation and treatment.

Deterrence/Prevention:

• Hepatitis A

• Improved sanitation, strict personal hygiene, and hand washing all may help to prevent transmission of HAV. The virus is inactivated by household bleach or by heating to 85°C for 1 minute.

• Travelers to endemic areas should not drink untreated water or ingest raw seafood or shellfish. Fruits and vegetables should not be eaten unless they are cooked or can be peeled.

• Certain inactivated viral vaccines have proven highly effective in preventing infection with HAV when given before exposure. These vaccines are not recommended for children younger than 2 years. In this age group, passively acquired maternal anti-HAV antibodies may decrease the immunogenicity of the vaccine.

• Active immunization is recommended for health care workers, daycare personnel, and travelers to endemic areas. HAV vaccine also is recommended for sewage and wastewater workers and veterinarians working with imported nonhuman primates.

• Passive postexposure immunization with immune globulin (dose 0.02 mL/kg) can protect persons exposed to HAV against clinical illness. Effectiveness is highest if given within 48 hours of exposure, but it may be helpful when given as far as 2 weeks into the incubation period. These patients also should receive active immunization with the HAV vaccine.

• Immune globulin also is recommended before exposure for children younger than 2 years who are at risk of exposure to HAV.

• Hepatitis B

• Active immunization with the 3-dose recombinant DNA HBV vaccine may prevent infection.

• Use of this vaccine has proven very successful in preventing infection among those at risk for HBV infection because of occupational exposure. Unfortunately, approximately 5-32% of those vaccinated do not develop an adequate antibody response to the HBV vaccine. Because of the nonresponse rate, many recommend that health care workers undergo postvaccination testing to confirm response within 1-2 months of receiving the vaccine. The duration of immunity conferred by the vaccine is not clearly known. Some authors recommend that a booster be given at 5-10 years.

• This vaccine is recommended for all children as part of the usual immunization schedule as well as to infants born to mothers who are potentially infectious.

• Nonimmunized persons who are close contacts of patients with acute HBV infection or who suffer percutaneous exposure to HBV, and infants born to potentially infectious mothers, should receive passive immunization with the HBV immune globulin in addition to active immunization.

• Combined active and passive immunization in these settings is 80-95% effective in preventing transmission of HBV.

• Hepatitis C

• No vaccine against HCV is available, and immune globulin is not proven to prevent transmission. In fact, immune globulin administration has been associated with HCV.

• At the present time, the major means of preventing transmission is to prevent infected blood, organs, and semen from entering the donor pools.

• Hepatitis D

• Since HDV can infect patients only when HBV is present, transmission of this disease can be decreased by effectively immunizing patients against HBV.

• Unfortunately, at this time, no means is known of preventing HDV superinfection in patients with chronic HBV.

• Hepatitis E

• No vaccine exists for prevention of HEV.

• Administration of immune globulin does not prevent development of clinical disease.

Complications:

• Acute/subacute hepatic necrosis

• Chronic active hepatitis

• Chronic hepatitis

• Cirrhosis

• Hepatic failure

• Hepatocellular carcinoma (HBV, HCV)

Prognosis:

• Varies with causative virus

• Hepatitis A virus

• HAV hepatitis usually is mild and self-limited.

• Infection confers lifelong immunity against HAV.

• Three rare complications include relapsing hepatitis, cholestatic hepatitis, and fulminant hepatic failure.

• Mortality rate for HAV hepatitis is 0.01%.

• Hepatitis B virus

• Risk of chronic infection in infected older children and adults approaches 5-10%.

• Patients with chronic HBV infection are at risk for cirrhosis and hepatocellular cancer.

• Fulminant hepatic failure develops in 0.5-1% of patients infected with HBV; their case-fatality rate is 80%.

• Hepatitis C virus

• Chronic infection develops in 50-60% of patients with HCV.

• Chronically infected patients are at risk for chronic active hepatitis, cirrhosis, and hepatocellular cancer.

• Chronic HCV infection is the leading indication for liver transplant in the United States.

• Chronic HCV infection is responsible for 10,000 deaths each year in the United States.

• Hepatitis D virus

• Patients with chronic HBV who are co-infected with HDV also tend to develop chronic HDV infection.

• Chronic co-infection with HBV and HDV often leads to rapidly progressive subacute or chronic hepatitis with as many as 70-80% of these patients eventually developing cirrhosis.

• Hepatitis E virus

• Disease usually is mild and self-limited.

• Case-fatality rate reaches 15-20% in pregnant women.

• HEV does not result in chronic disease.

Patient Education:

• Refer patients with infectious hepatitis to their primary care providers for further counseling specific to their disease, as the specific etiologic virus is unlikely to be known at time of discharge from the ED.

• Counsel patients regarding the importance of follow-up care to monitor for evidence of disease progression or development of complications.

• Advise patients in general to exercise meticulous personal hygiene including strict hand washing.

• Instruct patients not to share any articles with potential for contamination with blood, semen, or saliva, including needles, toothbrushes, or razors.

• Inform food handlers suspected of having HAV not to return to work until their primary care physician can confirm that they are no longer shedding virus.

• Instruct patients to refrain from using any hepatotoxins, including ethanol and acetaminophen.

• For excellent patient education resources, visit eMedicine's Hepatitis Center; Liver, Gallbladder, and Pancreas Center; and Public Health Center. Also, see eMedicine's patient education articles Hepatitis A; Hepatitis B; Hepatitis C; Cirrhosis; Immunization Schedule, Children; and Immunization Schedule, Adults.

MISCELLANEOUS

Section 9 of 11

Special Concerns:

• Pregnancy

• In general, none of the hepatitis viruses are known to be teratogenic.

• Except in the case of HEV, the disease courses of the various hepatitis viruses are no different in pregnancy.

• Treatment usually consists of supportive care. Patients with significant vomiting or dehydration may require admission for hydration as well as monitoring for fetal well-being and preterm uterine irritability.

• Nonimmunized patients who are pregnant and exposed to HAV or HBV should receive active and passive immunization with the appropriate immune globulin and viral vaccine. Immune globulin, HBV immune globulin, HAV vaccine, and HBV vaccine all currently are approved for use during pregnancy.

• Hepatitis A: HAV has an incidence of less than 1 per 1000 in pregnancy. HAV is not transmitted to the fetus in utero but may be transmitted to the neonate during delivery or during the postpartum period (fecal-oral route). Infants born to women infected with HAV during the third trimester should receive postexposure prophylaxis with immunoglobulin.

• Hepatitis B: Acute infection with HBV occurs at a rate of 1-2 per 1000 pregnancies. In addition, 0.5-1.5% of pregnant women are chronic carriers of HBV. No evidence exists of transplacental infection; perinatal infection of the neonate usually occurs during delivery. Infants born to mothers who are chronic carriers of HBV or who acquire acute HBV infection during the third trimester should receive active and passive immunization. When these neonates receive HBV vaccine and immune globulin within 12 hours of delivery, the rate of vertical transmission decreases so that fewer than 5% of exposed neonates become chronic carriers.

• Hepatitis C: The most common risk factor for HCV infection in pregnancy is history of substance abuse. Vertical transmission does occur, but the exact frequency of this occurrence is unknown.

• Hepatitis D: Perinatal transmission rarely occurs.

• Hepatitis E: The disease course of HEV may be more severe during pregnancy, with a high case-fatality rate, especially when the disease is contracted during the second or third trimester. Perinatal transmission occurs but with undetermined frequency. When vertical transmission of HEV does occur, it is associated with significant perinatal morbidity and death.

• Alternatively, acute hepatitis occurring during pregnancy may also be caused by certain disease states of pregnancy. These conditions include HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), acute fatty liver of pregnancy, ruptured liver hematoma, and intrahepatic cholestasis of pregnancy.

• Drug-induced Hepatitis

• A large number of prescription medicines, drugs, and chemical agents are known to cause hepatotoxicity. Some agents cause hepatic damage directly, while others induce an autoimmune response against the liver. Damage can occur acutely or from chronic exposure. Moreover, drug-induced hepatitis follows viral hepatitis as a leading cause of fulminant hepatic failure in the United States.

• Prescription medications that have been associated with drug-induced hepatitis include acetaminophen, amiodarone, amoxicillin-clavulanate, minocycline, nitrofurantoin, telithromycin, trimethoprim-sulfa, and trovafloxacin. Hepatitis induced by medications accounts for up to 5% of hospitalizations for hepatitis in the United States.

• A variety of herbal preparations and toxic plants have been implicated in causing hepatitis. Some products that have been associated with significant hepatotoxicity include Comfrey, Germander, Jin Bu Huan, Kava, Ma Huang, Pennyroyal, Senna, and Valerian.

• Several drugs of abuse are known to cause hepatic injury, including cocaine, methylenedioxymethamphetamine (ecstasy), toluene, trichloroethylene, phencyclidine, and ethanol. Patients hospitalized with hepatitis induced by ethanol have a reported mortality rate of 20-65%.

• Occupational exposure to a variety of industrial agents may produce liver injury.

• Acute hepatitis can result from a single large exposure to one of the hepatotoxic agents. These substances may be ingested, inhaled as toxic fumes, or absorbed through the skin. In general, once significant exposure has occurred, a 3-phase clinical syndrome of acute hepatic injury occurs.
  • During phase 1, patients develop gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain. They also may exhibit delirium, seizures, or coma representing associated central nervous system toxicity.

  • Between 24-48 hours after exposure, patients enter phase 2; they often experience resolution of their symptoms.

  • Phase 3 occurs 48-72 hours after exposure with the development of fulminant hepatic failure, often accompanied by renal failure. Some of these patients may deteriorate to the point that they face death or require emergent liver transplantation.

• Autoimmune hepatitis

• Autoimmune hepatitis is a progressive inflammatory disease of the liver that occurs more commonly in young women and girls. The etiology is not known, but indications are that a certain environmental trigger incites an autoimmune response directed against the liver. These triggers might be viruses, chemicals, or other unknown agents.

• The resulting chronic hepatitis eventually leads to fibrosis and cirrhosis. Autoimmune hepatitis also is associated with progression to primary hepatocellular carcinoma but not with the same frequency as viral hepatitis.

• As with other forms of hepatitis, the clinical presentation of autoimmune hepatitis may vary.

• Patients may be asymptomatic, or they may present with insidious onset of constitutional symptoms and jaundice. Occasionally, patients may develop acute onset of symptoms, significant jaundice, and elevated transaminases mimicking severe viral hepatitis.

• Patients with autoimmune hepatitis have circulating autoantibodies in their serum and often have elevated serum globulins, gamma globulins in particular.

• Other autoimmune diseases that may affect these patients include Graves disease, idiopathic thrombocytopenic purpura, pulmonary fibrosis, vitiligo, ulcerative colitis, glomerulonephritis, insulin-dependent diabetes mellitus, and myasthenia gravis.

TEST QUESTIONS

Section 10 of 11

CME Question 1: A 20-year-old man who works in a daycare center presents with 1 week of vomiting and fatigue. He denies diarrhea but notes vague abdominal discomfort and states that his stools have turned pale in color. His wife complains that he has not been quite himself over the past few days. He seems a little agitated and now sleeps all day. Once an avid cigarette smoker, he now refuses to let anyone in the house smoke. Appropriate management of this patient includes which of the following?

A: Assure the family that the patient has gastroenteritis and discharge home.
B: Order an immediate abdominal CT scan.
C: Send labs for liver function tests, viral hepatitis panel, and ammonia level. Consider admission for early hepatic encephalopathy.
D: Send labs for liver function tests and viral hepatitis panel. If tolerating oral fluids, discharge home.
E: Send stool for Clostridium difficile toxin test.

The correct answer is C: This patient’s employment certainly puts him at risk for exposure to hepatitis. His history of vomiting, fatigue, pale-colored stools, and aversion to cigarette smoke should make the physician strongly consider hepatitis in the differential diagnosis. Furthermore, subtle behavior changes, such as altered sleep-wake cycle and agitation, may be indicative of early hepatic encephalopathy. Bedside glucose testing also is indicated.

CME Question 2: A 20-year-old man who works in a daycare center presents with 1 week of vomiting and fatigue. He denies diarrhea but notes vague abdominal discomfort and states that his stools have turned pale in color. His wife complains that he has not quite been himself over the past few days. He seems a little agitated and now sleeps all day. Once an avid cigarette smoker, he now refuses to let anyone in the house smoke. The patient's wife, who is 2 months pregnant, inquires about risks to other family members. What should the physician tell her?

A: Instruct the wife to get immediate perinatal counseling, as the hepatitis viruses are known teratogens.
B: Assure family members that they are not at risk of contracting anything. This type of hepatitis can only be spread via blood transfusions and injection drug use.
C: Advise the wife that she should not attempt postexposure prophylaxis, as the hepatitis vaccines are not safe to give during pregnancy.
D: Tell the family members that although they are at risk for hepatitis, no vaccines effective against this type of hepatitis are available.
E: Advise close family contacts and the wife to receive postexposure prophylaxis if the patient is diagnosed with either hepatitis A virus or hepatitis B virus.

The correct answer is E: Passive and active immunization against HAV and HBV are effective in preventing the spread of disease and in preventing the onset of clinical symptoms. This patient’s close contacts, including his wife, should be referred for appropriate immunizations as soon as the etiologic agent of his hepatitis is identified.

Pearl Question 1 (T/F): No effective vaccines are available against any of the hepatitis viruses.

The correct answer is False: Vaccines are available that effectively prevent the spread of infection with hepatitis A and hepatitis B viruses.

Pearl Question 2 (T/F): Viral hepatitis and drug-induced hepatitis are the 2 leading causes of fulminant hepatic failure in the United States.

The correct answer is True: Liver disease induced by viral hepatitis accounts for 4000-5000 deaths per year.

Pearl Question 3 (T/F): Infection with hepatitis A virus can cause chronic hepatitis and later lead to chronic liver disease and cirrhosis.

The correct answer is False: Hepatitis A virus does not cause any chronic infectious state. Infection with hepatitis B, C, and D viruses can lead to chronic hepatitis as well as chronic liver disease and cirrhosis.

Pearl Question 4 (T/F): Infection with hepatitis E virus during pregnancy can result in increased rates of maternal and perinatal mortality.

The correct answer is True: The disease course of HEV during pregnancy may be more severe than in nonpregnant individuals, with a high case-fatality rate, especially when the disease is contracted during the second or third trimester. Perinatal transmission occurs but with undetermined frequency. When vertical transmission of HEV does occur, it is associated with significant perinatal morbidity and mortality.

BIBLIOGRAPHY

Section 11 of 11

• Alter MJ, Mast EE: The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am 1994 Sep; 23(3): 437-55[Medline].
• Alter MJ, Gallagher M, Morris TT, et al: Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection. Sentinel Counties Viral Hepatitis Study Team. N Engl J Med 1997 Mar 13; 336(11): 741-6[Medline].
• Baffis V, Shrier I, Sherker AH, Szilagyi A: Use of interferon for prevention of hepatocellular carcinoma in cirrhotic patients with hepatitis B or hepatitis C virus infection. Ann Intern Med 1999 Nov 2; 131(9): 696-701[Medline].
• Balfour HH Jr: Antiviral drugs. N Engl J Med 1999 Apr 22; 340(16): 1255-68[Medline].
• Barash C, Conn MI, DiMarino AJ, et al: Serologic hepatitis B immunity in vaccinated health care workers. Arch Intern Med 1999 Jul 12; 159(13): 1481-3[Medline].
• Bondesson JD, Saperston AR: Hepatitis. Emerg Med Clin North Am 1996 Nov; 14(4): 695-718[Medline].
• Boni C, Bertoletti A, Penna A, et al: Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998 Sep 1; 102(5): 968-75[Medline].
• Buti M, Esteban R: Entecavir, FTC, L-FMAU, LdT and others. J Hepatol 2003; 39 Suppl 1: S139-42[Medline].
• Clay KD, Hanson JS, Pope SD: Brief Communication: Severe Hepatotoxicity of Telithromycin: Thre Case Reports and Literature Review. Annals of Internal Medicine 2006; 144(6): 415-420.
• de Groen PC: Hepatitis E in the United States: a case of "hog fever"?. Mayo Clin Proc 1997 Dec; 72(12): 1197-8[Medline].
• Dinsmoor MJ: Hepatitis in the obstetric patient. Infect Dis Clin North Am 1997 Mar; 11(1): 77-91[Medline].
• Dusheiko G, Barnes E, Webster G, Whalley S: The science, economics, and effectiveness of combination therapy for hepatitis C. Gut 2000 Aug; 47(2): 159-61[Medline].
• Dykhuizen RS, Brunt PW, Atkinson P, et al: Ecstasy induced hepatitis mimicking viral hepatitis. Gut 1995 Jun; 36(6): 939-41[Medline].
• Fishman LN, Jonas MM, Lavine JE: Update on viral hepatitis in children. Pediatr Clin North Am 1996 Feb; 43(1): 57-74[Medline].
• Furbee RB, Barlotta KS, Allen MK: Hepatotoxicity Associated with Herbal Products. Clinics in Laboratory Medicine 2006; 26: 227-241.
• Galan MV, Potts JA, Silverman AL: The Burden of Acute Nonfulminant Drug-Induced Hepatitis in a United States Tertiary Referral Center. Journal of Clinical Gastroenterology 2005; 39(1): 64-67.
• Gross JB: Clinician's guide to hepatitis C. Mayo Clin Proc 1998 Apr; 73(4): 355-60; quiz 361[Medline].
• Guntupalli SR, Steingrub J: Hepatic disease and pregnancy: An overview of diagnosis and management. Critical Care Medicine 2005; 33(10) Supplement: S332-S339.
• Hirschman SZ: Current therapeutic approaches to viral hepatitis. Clin Infect Dis 1995 Apr; 20(4): 741-3; quiz 746[Medline].
• Hoofnagle JH, di Bisceglie AM: The treatment of chronic viral hepatitis. N Engl J Med 1997 Jan 30; 336(5): 347-56[Medline].
• Hugle T, Cerny A: Current therapy and new molecular approaches to antiviral treatment and prevention of hepatitis C. Rev Med Virol 2003 Nov-Dec; 13(6): 361-71[Medline].
• Kane MA: Hepatitis viruses and the neonate. Clin Perinatol 1997 Mar; 24(1): 181-91[Medline].
• Kanel GC, Cassidy W, Shuster L, Reynolds TB: Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models. Hepatology 1990 Apr; 11(4): 646-51[Medline].
• Koff RS: Hepatitis A. Lancet 1998 May 30; 351(9116): 1643-9[Medline].
• Krawitt EL: Autoimmune hepatitis: classification, heterogeneity, and treatment. Am J Med 1994 Jan 17; 96(1A): 23S-26S[Medline].
• Krawitt EL: Autoimmune hepatitis. N Engl J Med 1996 Apr 4; 334(14): 897-903[Medline].
• Kwo PY, Schlauder GG, Carpenter HA, et al: Acute hepatitis E by a new isolate acquired in the United States. Mayo Clin Proc 1997 Dec; 72(12): 1133-6[Medline].
• Lai CL, Ratziu V, Yuen MF, Poynard T: Viral hepatitis B. Lancet 2003 Dec 20; 362(9401): 2089-94[Medline].
• Lee WM: Hepatitis B virus infection. N Engl J Med 1997 Dec 11; 337(24): 1733-45[Medline].
• Lemon SM, Thomas DL: Vaccines to prevent viral hepatitis. N Engl J Med 1997 Jan 16; 336(3): 196-204[Medline].
• Levy MJ, Herrera JL, DiPalma JA: Immune globulin and vaccine therapy to prevent hepatitis A infection. Am J Med 1998 Nov; 105(5): 416-23[Medline].
• Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH: Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000 Feb 15; 132(4): 296-305[Medline].
• Lutwick LI: Postexposure prophylaxis. Infect Dis Clin North Am 1996 Dec; 10(4): 899-915[Medline].
• Mieli-Vergani G, Vergani D: Autoimmune hepatitis. Arch Dis Child 1996 Jan; 74(1): 2-5[Medline].
• Poordad FF, Tran T, Martin P: Developments in hepatitis C therapy during 2000-2002. Expert Opin Emerg Drugs 2003 May; 8(1): 9-25[Medline].
• Poynard T, Yuen MF, Ratziu V, Lai CL: Viral hepatitis C. Lancet 2003 Dec 20; 362(9401): 2095-100[Medline].
• Public Health: Hepatitis A. CMAJ 1997 Feb 15; 156(4): 545-6[Medline].
• Purcell RH: The discovery of the hepatitis viruses. Gastroenterology 1993 Apr; 104(4): 955-63[Medline].
• Sagliocca L, Amoroso P, Stroffolini T, et al: Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. Lancet 1999 Apr 3; 353(9159): 1136-9[Medline].
• Sjogren MH: Serologic diagnosis of viral hepatitis. Gastroenterol Clin North Am 1994 Sep; 23(3): 457-77[Medline].
• Tepper MI, Gully PR: Viral hepatitis: know your D, E, F and Gs. CMAJ 1997 Jun 15; 156(12): 1735-8[Medline].
• The Centers for Disease Control and Prevention: From the Centers for Disease Control and Prevention. Update: recommendations to prevent hepatitis B virus transmission--United States. JAMA 1999 Mar 3; 281(9): 790[Medline].
• Thomas DL, Astemborski J, Rai RM, et al: The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000 Jul 26; 284(4): 450-6[Medline].
• Zimmerman HJ, Lewis JH: Chemical- and toxin-induced hepatotoxicity. Gastroenterol Clin North Am 1995 Dec; 24(4): 1027-45[Medline].

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