(See also Causes of Hepatitis Causes of Hepatitis Hepatitis is an inflammation of the liver characterized by diffuse or patchy necrosis. Hepatitis may be acute or chronic (usually defined as lasting > 6 months). Most cases of acute viral hepatitis... read more and Neonatal Hepatitis B Virus Infection Neonatal Hepatitis B Virus (HBV) Infection Neonatal hepatitis B virus infection is usually acquired during delivery. It is usually asymptomatic but can cause chronic subclinical disease in later childhood or adulthood. Symptomatic infection... read more .)
Acute viral hepatitis is a common, worldwide disease that has different causes; each type shares clinical, biochemical, and morphologic features. The term acute viral hepatitis often refers to infection of the liver by one of the hepatitis viruses. Other viruses (eg, Epstein-Barr virus Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more , yellow fever virus Yellow Fever Yellow fever is a mosquito-borne flavivirus infection endemic in tropical South America and sub-Saharan Africa. Symptoms may include sudden onset of fever, relative bradycardia, headache, and... read more , cytomegalovirus Cytomegalovirus (CMV) Infection Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe... read more ) can also cause acute viral hepatitis but less commonly.
Etiology of Acute Viral Hepatitis
At least 5 specific viruses appear to be responsible (see table Characteristics of Hepatitis Viruses Characteristics of Hepatitis Viruses Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more ) for acute viral hepatitis:
Other unidentified viruses probably also cause acute viral hepatitis.
Symptoms and Signs of Acute Viral Hepatitis
Some manifestations of acute hepatitis are virus-specific (see discussions of individual hepatitis viruses), but in general, acute infection tends to develop in predictable phases:
Incubation period: The virus multiplies and spreads without causing symptoms (see table Characteristics of Hepatitis Viruses Characteristics of Hepatitis Viruses Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more ).
Prodromal (pre-icteric) phase: Nonspecific symptoms occur; they include profound anorexia, malaise, nausea and vomiting, a newly developed distaste for cigarettes (in smokers), and often fever or right upper quadrant abdominal pain. Urticaria and arthralgias occasionally occur, especially in HBV infection.
Icteric phase: After 3 to 10 days, the urine darkens, followed by jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more . Systemic symptoms often regress, and patients feel better despite worsening jaundice. The liver is usually enlarged and tender, but the edge of the liver remains soft and smooth. Mild splenomegaly occurs in 15 to 20% of patients. Jaundice usually peaks within 1 to 2 weeks.
Recovery phase: During this 2- to 4-week period, jaundice fades.
Appetite usually returns after the first week of symptoms. Acute viral hepatitis usually resolves spontaneously 4 to 8 weeks after symptom onset.
Anicteric hepatitis (hepatitis without jaundice) occurs more often than icteric hepatitis in patients with HCV infection and in children with HAV infection. It typically manifests as a minor flu-like illness.
Recrudescent hepatitis occurs in a few patients and is characterized by recurrent manifestations during the recovery phase.
Manifestations of cholestasis may develop during the icteric phase (called cholestatic hepatitis) but usually resolve. When they persist, they cause prolonged jaundice, elevated alkaline phosphatase, and pruritus, despite general regression of inflammation.
Diagnosis of Acute Viral Hepatitis
Liver tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevated out of proportion to alkaline phosphatase, usually with hyperbilirubinemia)
Viral serologic testing
Prothrombin/international normalized ratio (PT/INR) measurement
Initial diagnosis of acute hepatitis
Acute hepatitis must first be differentiated from other disorders that cause similar symptoms. In the prodromal phase, hepatitis mimics various nonspecific viral illnesses and is difficult to diagnose. Anicteric patients suspected of having hepatitis based on risk factors are tested initially with liver tests, including aminotransferases, bilirubin, and alkaline phosphatase. Acute hepatitis often manifests in the icteric phase and so should be differentiated from other disorders causing jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more (see figure Simplified diagnostic approach to possible acute viral hepatitis Simplified diagnostic approach to possible acute viral hepatitis Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more ).
Acute hepatitis can usually be differentiated from other causes of jaundice by
Its marked elevations of AST and ALT: Typically ≥ 400 IU/L (6.68 microkat/L)
ALT is typically higher than AST, but absolute levels correlate poorly with clinical severity. Values increase early in the prodromal phase, peak before jaundice is maximal, and fall slowly during the recovery phase. Urinary bilirubin usually precedes jaundice. Hyperbilirubinemia in acute hepatitis varies in severity, and fractionation has no clinical value. Alkaline phosphatase is usually only moderately elevated; marked elevation suggests extrahepatic cholestasis and prompts imaging tests (eg, ultrasonography).
Liver biopsy is usually not needed unless the diagnosis is uncertain.
If laboratory results suggest acute hepatitis, particularly if ALT and AST are > 1000 IU/L (16.7 microkat/L), PT/INR is measured to assess liver function.
Manifestations of portosystemic encephalopathy Portosystemic Encephalopathy Portosystemic encephalopathy is a neuropsychiatric syndrome that can develop in patients with liver disease. It most often results from high gut protein or acute metabolic stress (eg, gastrointestinal... read more , bleeding diathesis, or prolongation of INR suggest acute liver failure Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses. Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive... read more , indicating fulminant hepatitis Fulminant Hepatitis Fulminant hepatitis is a rare syndrome of rapid (usually within days or weeks), massive necrosis of liver parenchyma and a decrease in liver size (acute yellow atrophy); it usually occurs after... read more .
If acute hepatitis is suspected, efforts are next directed toward identifying its cause. A history of exposure may provide the only clue of drug-induced or toxic hepatitis. The history should also elicit risk factors for viral hepatitis.
Prodromal sore throat and diffuse adenopathy suggest infectious mononucleosis rather than viral hepatitis.
Simplified diagnostic approach to possible acute viral hepatitis
In patients with findings suggesting acute viral hepatitis, the following studies are done to screen for hepatitis viruses A, B, and C:
IgM antibody to HAV (IgM anti-HAV)
Hepatitis B surface antigen (HBsAg)
IgM antibody to hepatitis B core (IgM anti-HBc)
Antibody to HCV (anti-HCV)
Hepatitis C RNA (HCV-RNA) polymerase chain reaction (PCR)
If any are positive, further serologic testing may be necessary to differentiate acute from past or chronic infection (see tables Hepatitis A Serology Hepatitis A Serology Hepatitis A is caused by an enterically transmitted RNA virus that, in older children and adults, causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Young... read more , Hepatitis B Serology Hepatitis B Serology* Hepatitis B is caused by a DNA virus that is often parenterally transmitted. It causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and... read more , and Hepatitis C Serology Hepatitis C Serology Hepatitis C is caused by an RNA virus that is often parenterally transmitted. It sometimes causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice but may be asymptomatic... read more ).
If serologically confirmed HBV infection is severe, anti-HDV is measured.
If the patient has recently traveled to an endemic area or is immunosuppressed, IgM antibody to HEV (IgM anti-HEV) should be measured if the test is available.
Biopsy is usually unnecessary but, if done, usually reveals similar histopathology regardless of the specific virus:
Patchy cell dropout
Acidophilic hepatocellular necrosis
Mononuclear inflammatory infiltrate
Histologic evidence of regeneration
Preservation of the reticulin framework
HBV infection can occasionally be diagnosed based on the presence of ground-glass hepatocytes (caused by HBsAg-packed cytoplasm) and using special immunologic stains for the viral components. However, these findings are unusual in acute HBV infection and are much more common in chronic HBV infection.
Liver biopsy may help predict prognosis in acute hepatitis but is rarely done solely for this purpose. Complete histologic recovery occurs unless extensive necrosis bridges entire acini (bridging necrosis). Most patients with bridging necrosis recover fully. However, some cases progress to chronic hepatitis Overview of Chronic Hepatitis Chronic hepatitis is hepatitis that lasts > 6 months. Common causes include hepatitis B and C viruses, nonalcoholic steatohepatitis (NASH), alcohol-related liver disease, and autoimmune liver... read more .
Treatment of Acute Viral Hepatitis
No treatments attenuate acute viral hepatitis. Alcohol should be avoided because it can increase liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no scientific basis.
For cholestatic hepatitis, cholestyramine 8 g orally once or twice a day can relieve itching.
Viral hepatitis should be reported to the local or state health department.
Prevention of Acute Viral Hepatitis
Because treatments have limited efficacy, prevention of viral hepatitis is very important.
Good personal hygiene helps prevent transmission, particularly fecal-oral transmission, as occurs with HAV and HEV.
Blood and other body fluids (eg, saliva, semen) of patients with acute HBV and HCV infection and stool of patients with HAV infection are considered infectious. Barrier protection is recommended, but isolation of patients does little to prevent spread of HAV and is of no value in HBV or HCV infection.
Posttransfusion infection is minimized by avoiding unnecessary transfusions and by screening all donors for hepatitis B and C. Screening has decreased the incidence of posttransfusion hepatitis B and hepatitis C, which are now extremely rare in the US.
Immunoprophylaxis can involve active immunization using vaccines and passive immunization.
Vaccines for and are available in the US.
Routine vaccination for hepatitis A and B is recommended in the US for all children and for adults at high risk (see Adult Immunization Schedule).
A vaccine for hepatitis E is not available in the US but is available in China.
Standard immune globulin prevents or decreases the severity of HAV infection and should be given to nonimmune family members and close contacts of patients. Hepatitis B immune globulin (HBIG) probably does not prevent infection but prevents or attenuates clinical illness.
No product exists for immunoprophylaxis of HCV or HDV. However, prevention of HBV infection prevents HDV infection. The propensity of HCV for changing its genome hampers vaccine development.
Transmission is the fecal-oral route for hepatitis A and parenterally or via blood for hepatitis B and C.
Hepatitis B and C, unlike hepatitis A, predispose to chronic hepatitis and liver cancer.
Patients with acute viral hepatitis may be anicteric or even asymptomatic.
Do viral serologic testing (IgM anti-HAV, HBsAg, anti-HCV) if clinical findings are consistent with acute viral hepatitis and AST and ALT are elevated out of proportion to alkaline phosphatase.
Treat patients supportively.
Routine vaccination for hepatitis A and B is recommended in the US for all children and for adults at high risk.