Complications
Although the definition of acute liver failure varies globally, the most commonly used definition in the US and Europe is: an illness duration of <26 weeks in a patient with no evidence of prior liver disease or cirrhosis with any degree of mental status alteration (encephalopathy) and coagulopathy (international normalised ratio [INR] ≥1.5).[50]
A rare sequela of acute HEV infection and more of a concern in patients with existing chronic liver disease (when symptoms occur in a patient with pre-existing liver disease, the term 'acute-on-chronic liver failure' is used).[2][11] However, acute HEV infection in pregnancy in endemic areas can lead to acute liver failure in upwards of 20% of women.[10]
Patients who progress to acute or acute-on-chronic liver failure may present with symptoms including:[51][52][53]
Abdominal pain
Nausea
Vomiting
Malaise
Confusion, changes in personality, or somnolence (due to hepatic encephalopathy).
Patients with acute liver failure may have similar signs to those presenting with acute hepatitis infection, but may have features of hepatic encephalopathy evident on examination. Hepatic encephalopathy encompasses a spectrum of neurological and psychiatric changes; initial signs and symptoms may be subtle and may include:[55]
Asterixis
Hypertonia
Hyperreflexia
Clonus
Rigidity.
Patients with acute liver failure may also have hepatomegaly, as well as right upper quadrant tenderness. Less commonly patients may present with features of coagulopathy.
Consider treatment with ribavirin for patients with severe acute HEV infection, patients who are at increased risk of progression to hepatic decompensation, and those with acute-on-chronic liver failure.[2] Case reports of ribavirin in acute HEV infection (or acute HEV infection occurring in underlying liver disease) suggest that liver enzymes may rapidly normalise, with HEV RNA levels becoming undetectable within days of initiation of treatment.[62]
Early recognition and diagnosis of acute liver failure is key in establishing a plan for optimal management. Refer patients who develop signs that may be suggestive of acute liver failure to a transplant centre for monitoring and consideration of a liver transplant.[63]
Chronic HEV infection, which develops almost exclusively in immunosuppressed patients, can progress to cirrhosis if treatment is unsuccessful.[38][72] A solid organ transplant recipient infected with HEV has between 50% and 70% risk of developing chronic HEV infection, which can progress to cirrhosis within several years.[38][49]
Patients with chronic HEV infection who have developed cirrhosis of the liver may have stigmata of chronic liver disease including:
Palmar erythema
Spider naevi (in the distribution of the superior vena cava)
Scleral icterus
Ascites
Splenomegaly
Peripheral pitting oedema of the ankles/legs
Loss of secondary sexual characteristics, such as loss of secondary sexual hair and testicular atrophy in men.
Cirrhosis may lead to portal hypertension, liver failure, and hepatocellular carcinoma.
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