Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.
OBJECTIVE
Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection.


METHODS
Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B.


RESULTS
Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation.


CONCLUSIONS
Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV-related CLD.
Kumar
Manoj
M
Department of Gastroenterology, G.B. Pant Hospital, University of Delhi, Delhi, India.
Sharma
Barjesh C
BC
Sarin
Shiv K
SK
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006512:Hepatitis B Core Antigens / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D016751:Hepatitis E / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D016752:Hepatitis E virus / Q000302:isolation & purification*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D015415:Biomarkers; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007075:Immunoglobulin M