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Hepatitis, a general term referring to inflammation of the liver, may result from various causes, both infectious (ie, viral, bacterial, fungal, and parasitic organisms) and noninfectious (eg, alcohol, drugs, autoimmune diseases, and metabolic diseases); this article will focus on acute viral hepatitis.
Acute hepatic injury is confirmed by a raised serum alanine transaminase activity. The activity may be 100 times normal and no other biochemical test has been shown to be a better indicator
Acute viral hepatitis Hepatitis can be caused by the hepatitis viruses A, B, C, D, or E. The D and E forms are rare.
A large proportion of infections with hepatitis viruses of all types are asymptomatic or result in anicteric illnesses that may not be diagnosed as hepatitis. Hepatitis A virus causes a typically minor illness in childhood, with more than 80% of cases being asymptomatic. In adult life infection is more likely to produce clinical symptoms, although only a third of patients with acute hepatitis A infections are jaundiced. Infections with hepatitis B and C viruses are also usually asymptomatic except in intravenous drug users, in whom 30% of hepatitis B infections are associated with jaundice. Before jaundice, patients often have non-specific systemic symptoms together with discomfort in the right upper quadrant of the abdomen. Some may present with maculopapular rash and joint pains typically affecting the wrist, knees, elbows, and ankles. It is due to formation of immune complexes, and patients often test positive for rheumatoid factor. It is almost always self limiting, and usually settles rapidly after the onset of jaundice.
Physical examination of patients before the development of jaundice usually shows no abnormality, although hepatomegaly (10% of patients), splenomegaly (5%), and lymphadenopathy (5%) may be present. Patients with an acute illness should not have signs of chronic liver disease. The presence of these signs suggests that the illness is either the direct result of chronic liver disease or that the patient has an acute event superimposed on a background of chronic liver disease—for example, hepatitis D virus super infection in a carrier of hepatitis B virus.
Acute liver failure (fulminant hepatitis); Death from acute viral hepatitis is usually due to the development of fulminant hepatitis. This is usually defined as development of hepatic encephalopathy within eight weeks of symptoms or within two weeks of onset of jaundice. The risk of developing fulminant liver failure is generally low, but there are groups with higher risks. Pregnant women with acute hepatitis E infection have a risk of fulminant liver failure of around 15% with a mortality of 5%. Fulminant hepatitis B is seen in adult infection and is relatively rare. The primary clinical features of acute liver failure are encephalopathy and jaundice. Jaundice almost always precedes encephalopathy in acute liver failure. Prolonged coagulation is the biochemical hallmark of liver failure and is due to lack of synthesis of liver derived factors.
The following are typical patterns by which hepatitis viruses are transmitted, with + symbols indicating the frequency of transmission (ie, more + symbols indicate increased frequency).
Fecal-oral transmission frequency is as follows:
Parenteral transmission frequency is as follows:
Sexual transmission frequency is as follows:
Perinatal transmission frequency is as follows:
Sporadic (unknown) transmission frequency is as follows:
Diagnosis of acute hepatitis Hepatitis A. Hepatitis A infection can be reliably diagnosed by the presence of antihepatitis A IgM. This test has high sensitivity and specificity. Occasional false positive results occur in patients with liver disease due to other causes if high titres of immunoglobulin are present, but the clinical context usually makes this obvious.
Hepatitis B infection is usually characterized by the presence of hepatitis B surface antigen. Other markers are used to determine if the virus is active and replicating, when it can cause serious liver damage. Because of the immune response attempting to eradicate hepatitis B virus, viral replication may already have ceased by the time a patient presents with acute hepatitis B, and the patient may be positive for hepatitis B surface antigen and negative for e antigen. It is difficult in this situation to be certain that the patient had acute hepatitis B and that the serology does not imply past infection unrelated to the current episode. To enable a clear diagnosis, most reference centres now report the titre of IgM antibody to hepatitis B core antigen (IgM anticore). As core antigen never appears in serum, its presence implies an immune response against hepatitis B virus within liver cells and is a sensitive and specific marker of acute hepatitis B infection.
Hepatitis C. Screening tests for hepatitis C virus infection use enzyme linked immunosorbent assays (ELISA) with recombinant viral antigens on patients’ serum. Acute hepatitis C cannot be reliably diagnosed by antibody tests as these often do not give positive results for up to three months. Hepatitis C virus was the cause of more than 90% of all post-transfusion hepatitis in Europe and the United States, but this has fallen since the introduction of routine serological screening of blood donors. Acute hepatitis C infection is therefore now seen commonly only in intravenous drug users. Antibodies to hepatitis C appear relatively late in the course of the infection, and if clinical suspicion is high, the patient’s serum should be tested for hepatitis C virus RNA to establish the diagnosis.
Non-A-E viral hepatitis Epstein Barr virus causes rises in liver enzyme activities in almost all cases of acute infection, but it is uncommon for the liver injury to be sufficiently severe to cause jaundice. When jaundice does occur in patients with Epstein Barr virus infection, it can be prolonged with a large cholestatic element. Diagnosis is usually relatively easy because the typical symptoms of Epstein Barr infection are almost always present and serological testing usually gives positive results. Cytomegalovirus can also cause acute hepatitis. This is unusual, rarely severe, and runs a chronic course only in immunosuppressed patients. The cause of about 7% of all episodes of acute presumed viral hepatitis remains unidentified. It seems certain that other viral agents will be identified that cause acute liver injury.
Management of acute viral hepatitis Hepatitis A. Most patients with hepatitis A infection have a self limiting illness that will settle totally within a few weeks. Management is conservative, with tests being aimed at identifying the small group of patients at risk of developing fulminant liver failure.
Hepatitis B. Acute hepatitis B is also usually self limiting, and most patients who contract the virus will clear it completely. All cases must be notified and sexual and close household contacts screened and vaccinated. Patients should be monitored to ensure fulminant liver failure does not develop and have serological testing three months after infection to check that the virus is cleared from the blood. About 5-10% of patients will remain positive for hepatitis B surface antigen at three months, and a smaller proportion will have ongoing viral replication (e antigen positive). All such patients require expert follow up.
Hepatitis C. Early identification and referral of cases of acute hepatitis C infection is important because strong evidence exists that early treatment with interferon alpha reduces the risk of chronic infection. The rate of chronicity in untreated patients is about 80%; treatment with interferon reduces this to below 50%.