Investigation of liver dysfunction: who should we test for hepatitis E?
OBJECTIVE
Hepatitis E virus (HEV) is endemic in developed countries, but unrecognized infection is common. Many national guidelines now recommend HEV testing in patients with acute hepatitis irrespective of travel history. The biochemical definition of 'hepatitis' that best predicts HEV infection has not been established. This study aimed to determine parameters of liver biochemistry that should prompt testing for acute HEV.


METHODS
This was a retrospective study of serial liver function tests (LFTs) in cases of acute HEV (n=74) and three comparator groups: common bile duct stones (CBD, n=87), drug-induced liver injury (DILI, n=69) and patients testing negative for HEV (n=530). To identify the most discriminating parameters, LFTs from HEV cases, CBD and DILI were compared. Optimal LFT cutoffs for HEV testing were determined from HEV true positives and HEV true negatives using receiver operating characteristic curve analysis.


RESULTS
Compared with CBD and DILI, HEV cases had a significantly higher maximum alanine aminotransferase (ALT) (P<0.001) and ALT/alkaline phosphatase (ALKP) ratio (P<0.001). For HEV cases/patients testing negative for HEV, area under receiver operating characteristic curve was 0.805 for ALT (P<0.001) and 0.749 for the ALT/ALKP ratio (P<0.001). Using an ALT of at least 300 IU/l to prompt HEV testing has a sensitivity of 98.6% and a specificity of 30.3% compared with an ALT/ALKP ratio higher than or equal to 2 (sensitivity 100%, specificity 9.4%).


CONCLUSIONS
Patients with ALT higher than or equal to 300 IU/l should be tested for HEV. This is simple, detects nearly all cases and requires fewer samples to be tested than an ALT/ALKP ratio higher than or equal to 2. Where clinically indicated, patients with an ALT less than 300 IU/l should also be tested, particularly if HEV-associated neurological injury is suspected.
Royal Cornwall Hospital Trust and European Centre for Environment and Human Health, University of Exeter, Truro, UK.
Sebastian J
SJ
Wallace
Glynn W
GW
Webb
Richie G
RG
Madden
Hugh C
HC
Dalton
Joanne
J
Palmer
Richard T
RT
Dalton
Adam
A
Pollard
Rhys
R
Martin
Vasilis
V
Panayi
Gwyn
G
Bennett
Richard P
RP
Bendall
Harry R
HR
Dalton
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000469:Alkaline Phosphatase / Q000097:blood*; D019540:Area Under Curve; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D042883:Choledocholithiasis / Q000097:blood*; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000097:blood* / Q000175:diagnosis; D016752:Hepatitis E virus / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D012372:ROC Curve; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012367:RNA, Viral; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase