Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: A role for ribavirin?
Authors: J.M. Péron, H. Dalton, J. Izopet, N. Kamar
Journal: Journal of Hepatology (2011)

Hepatitis E: Water, water everywhere – Now a Global DiseaseJournal of HepatologyVol. 54Issue 1PreviewHepatitis E virus (HEV) is an enterically transmitted virus of 27–34 nm diameter whose genome consists of a poly-adenylated single stranded RNA of 7.2 kb length with 3′ and 5′ non-coding end and three partially overlapping open reading frames (ORFs) [1]. While ORF1 codes for non-structural proteins necessary for its replication, ORF2 and ORF3 code for the viral capsid protein [1]. The genome of HEV has been cloned, sequenced, its structural regions have been expressed in vitro, and both serological diagnosis and detection of HEV-RNA in sera, stool, and bile have been established by RT-PCR [1,2]. Full-Text PDF Open AccessReply to the Letter to the Editor 'Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: A role for ribavirin?'Journal of HepatologyVol. 54Issue 6PreviewThis is a reply to the Letter to the Editor by Peron et al. Full-Text PDF Open Access We read with interest the recent editorial in the Journal of Hepatology entitled "Hepatitis E: Water, water everywhere – Now a Global Disease" [[1]Acharya S.K. Panda S.K. Hepatitis E: water, water everywhere–now a global disease.J Hepatol. 2011; 54: 9-11Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar]. The authors state that in industrialized nations, acute liver failure and acute-on-chronic liver failure due to autochthonous acute hepatitis E genotype 3 (HEV3) infection have not yet been documented. This statement is inaccurate. A series of seven patients with fulminant liver failure from acute autochthonous HEV3 infection have been reported from south-west France [[2]Péron J.M. Bureau C. Poirson H. Mansuy J.M. Alric L. Selves J. et al.Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathy.J Viral Hepat. 2007; 14: 298-303Crossref PubMed Scopus (217) Google Scholar]. Six of these patients had chronic liver disease and five were active drinkers. Five of these patients died. In addition, acute HEV3 infection was reported as a cause of decompensation in three patients with chronic liver disease in the UK [[3]Dalton H.R. Hazeldine S. Banks M. Ijaz S. Bendall R. Locally acquired hepatitis E in chronic liver disease.Lancet. 2007; 369: 1260Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]. Two of these patients died from sub-acute liver failure. In the past three years (January 2008–December 2010) 35 more cases of acute hepatitis E in immunocompetent patients were diagnosed in the Toulouse University Hospital. Of these, nine patients (26%) had underlying chronic liver disease, of which seven were alcoholic. There were seven males and the median age was 47 years (36–79). All cases were autochthonous. Four patients (44%) had ascites and two had encephalopathy. Median serum bilirubin was 127 μmol/L (29.6–704.4). The strains were sequenced in four patients. They were all genotype 3; subtype 3f in three patients, subtype 3c in one. Three patients died (33%). The two most recent patients were treated with ribavirin monotherapy. A 79 year old patient with chronic liver disease was admitted for acute hepatitis and acute kidney failure requiring renal replacement therapy. HEV RNA was found to be positive both in the serum and the stools and all other causes of hepatitis were ruled out, including acute alcoholic hepatitis. Because of the severe presentation, the advanced age of the patient, and since we had shown earlier this year that ribavirin is effective and well tolerated in the treatment of chronic hepatitis E in kidney-transplant patients [[4]Kamar N. Rostaing L. Abravanel F. Garrouste C. Lhomme S. Esposito L. et al.Ribavirin therapy inhibits viral replication in patients with chronic hepatitis E virus infection.Gastroenterology. 2010; 139: 1612-1618Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar], he was given ribavirin monotherapy in order to rapidly contain viral replication. Ribavirin was started off at a dose of 200 mg every other day because of the acute kidney failure. The treatment was scheduled for a 3 month period. Serum HEV RNA concentration decreased from 6.36 log copies/ml at the initiation of the therapy to 4.6 log copies/ml at day 10, 2.9 log copies/ml at day 17, and was negative at one month. The patient completely recovered and dialysis was stopped at month two. The second patient was treated for 10 days at a dose of 1000 mg per day in two divided doses. Viral load was 4.07 log-copies/ml before treatment, 3.08 after 3 days, 2.54 after 6 days and undetectable one month later. Hemoglobin levels dropped from 12.6 g/dl before treatment to 11.6 g/dl after 6 days of treatment. There were no other ribavirin induced side effects. There was no viral relapse in these two patients. These data show that the prognosis of acute autochthonous hepatitis E can be poor in industrialized nations, particularly in patients with chronic liver disease (acute on chronic liver failure), and is similar to that reported for HEV genotype 1 infection in patients with chronic liver disease in the Indian sub-continent [[5]Kumar A.S. Kumar S.P. Singh R. Kumar M.S. Madan K. Kumar J.J. et al.Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death.J Hepatol. 2007; 46: 387-394Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar]. An Anglo-French multicentre study is ongoing to assess its frequency and its induced-mortality in a larger number of patients. Short term ribavirin treatment may be useful in these patients. However, this hypothesis needs to be further investigated. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.