Hepatitis E natural history
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Most patients with the acute form of hepatitis E are asymptomatic. Acute hepatitis E progresses according to the following stages: incubation, which usually lasts a mean of 40 days; prodrome or preicteric phase; and symptomatic or icteric phase. The prodromal phase starts with unspecific symptoms, such as fever, weakness, malaise, anorexia, nausea and vomiting, and abdominal pain. The icteric phase usually begins with jaundice, follows the offset of the prodromal symptoms, and may include cholestatic symptoms, such as acholic stools and dark-colored urine. Pregnant women may experience more severe forms of the disease, possibly progressing into hepatic failure. Chronic hepatitis E is commonly found in immunocompromised patients, such as those infected with HIV, undergoing chemotherapy, or with a history of organ transplant. Complications of hepatitis E may include: cirrhosis and liver failure. Extra-hepatic complications may also be noted: peripheral neuropathy; encephalitis; acute transverse myelitis; and Guillain-Barré syndrome. The prognosis of hepatitis E is good in asymptomatic cases, however, immunocompromised patients and pregnant women have higher mortality rates.
Hepatitis E is often asymptomatic, particularly in children. Patients in highly endemic areas often present anicteric hepatitis, without developing symptoms. In these cases, the disease is only identifiable by HEV viremia, with elevated liver enzymes and normal bilirubin levels. Although the severity of the disease is poorly understood, it has been associated with an higher viral load. Hepatitis E may be classified in acute and chronic disease.
Acute Hepatitis E
In endemic areas, hepatitis E commonly presents as anicteric hepatitis, or as acute icteric hepatitis. The clinical course of acute hepatitis E progresses according to the following phases:
|Stage of Infection||Symptoms|
|Prodromal or Preicteric Phase||
|Symptomatic or Icteric Phase||
Pregnant women may experience more severe cases of hepatitis, possibly progressing into hepatic failure. The more complicated course of the disease is thought to be due to the characteristic immunity and hormonal changes that occur during pregnancy. Additionally, fatal outcomes of hepatitis E in pregnant women were associated with the decrease of progesterone receptors.
Viral superinfection may occur in patients with chronic liver disease (symptomatic or asymptomatic) of any etiology. These patients may present with severe "acute on chronic" liver disease. Superinfection and liver decompensation are associated with poor outcomes.
In areas with lower disease prevalence, hepatitis E may present as:
- Icteric hepatitis
- Anicteric hepatitis, with unspecific symptoms
- Asymptomatic disease, with transaminase elevation
The typical hepatitis E patient in these areas is an old male, with either alcohol consumption, or other underlying liver disease. Possibly due to the older age and existence of concomitant disorders, the mortality rate is higher in these regions.
Chronic Hepatitis E
Chronic infection is defined by detection of HEV RNA in blood, or in stool, for more than 6 months. The predominant genotype causing chronic infection is HEV3, as HEV 1 and HEV 2 have not been reported in chronic disease. Although it might occur in immunocompetent adults, chronic disease is commonly found in immunocompromised patients, such as:
- Persons with organ transplants
- Persons undergoing chemotherapy
- Persons infected with HIV, with low CD4 counts
Common complications of hepatitis E include:
- "Acute-on-chronic disease"
- Chronic hepatitis
- Liver cirrhosis, which may be diagnosed and monitored by ultrasound and abdominal CT
- Liver failure:
- Peripheral neuropathy
- Acute transverse myelitis
- Acute meningoencephalitis
- Bell's palsy
- Guillain-Barré syndrome
- Neuralgic amyotrophy
- Acute pancreatitis
- Aplastic anemia
- Decrease of GFR (Chronic hepatitis E)
- Membranoproliferative Glomerulonephritis
- Membranous glomerulonephritis
Newborns of Infected Mothers
- Icteric hepatitis
- Anicteric hepatitis
Hepatitis E is self-limited in most immunocompetent patients. For these cases the prognosis is good. Immunocompromised patients, and those with end-stage liver disease are at higher risk of developing chronic hepatitis and other complications. This last group of patients has poor prognosis.
- In developing countries, mortality rate during epidemics is 0.2 - 4.0%. In these countries, mortality rate in pregnant women ranges from 10 - 25%, and is often due to fulminant hepatic failure, hemorrhage or eclampsia.
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