Reply to the Letter to the Editor ‘Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: A role for ribavirin?’
Authors: Subrat Kumar Acharya
Journal: Journal of Hepatology (2011)

Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: A role for ribavirin?Journal of HepatologyVol. 54Issue 6PreviewWe read with interest the recent editorial in the Journal of Hepatology entitled “Hepatitis E: Water, water everywhere – Now a Global Disease” [1]. 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]. Full-Text PDF Open Access This is a reply to the Letter to the Editor by Peron et al. We deeply appreciate the information provided by Peron et al. [[1]Peron JM, Dalton H, Izopet J, Kumar N. Acute autochthonous hepatitis E in Western patients with underlying chronic liver disease: a role for ribavirine? J Hepatol 2011Google Scholar] about two short reports emanating from 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] and 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] indicating that Genotype 3 HEV have been implicated in the cause of Acute on Chronic Liver Failure (ACLF) in 9 out of 10 patients, most of whom (n = 7) had underlying alcoholic cirrhosis. Indeed, it confirmed our suggestion that, such events might be occurring in industrialized nations and HEV may be associated with causing ACLF even in non-endemic developed nation [[4]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]. In these geographical areas, autochthonous Genotype 3 HEV infections in human are implicated as a zoonotic disease and pigs have been identified as the reservoir of Genotype 3 HEV. Interestingly, a national survey of acute hepatitis E in France, which included 19 centres reported that 47 among 53 autochthonous HEV (majority Genotype 3) infection documented during the study period might have been due to contaminated water in many of them [[5]Renou C. Moreau X. Pariente A. Cadranel J.F. Maringe E. Morin T. Causse X. Payen J.L. et al.A national survey of acute hepatitis E in France.Aliment Pharmacol Ther. 2008; 27: 1086-1093Crossref PubMed Scopus (91) Google Scholar]. Further, Peron et al in their letter to editor [[1]Peron JM, Dalton H, Izopet J, Kumar N. Acute autochthonous hepatitis E in Western patients with underlying chronic liver disease: a role for ribavirine? J Hepatol 2011Google Scholar] stated that 26% (9 out of 35) of acute hepatitis E documented at their centre had underlying chronic liver disease, most of whom were alcoholic (7 out of 9) [unpublished observation]. This observation may indicate that, patients with underlying chronic liver disease may be more prone to contract acute HEV infection which we have documented and reported [[6]Acharya S.K. Sharma P.K. Singh R. Mohanty S.K. Madan K. Jha J.K. 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 (214) Google Scholar]. As mentioned earlier, the source of HEV infection may be from water and not necessarily due to only zoonotic transmission, as documented in France [[5]Renou C. Moreau X. Pariente A. Cadranel J.F. Maringe E. Morin T. Causse X. Payen J.L. et al.A national survey of acute hepatitis E in France.Aliment Pharmacol Ther. 2008; 27: 1086-1093Crossref PubMed Scopus (91) Google Scholar]. Therefore, Genotype 3 may also be transmitted through contaminated water and may cause severe liver disease, particularly in those with underlying alcoholic liver disease; it thus needs to be confirmed by prospective evaluation whether contaminated water is the source of such infection causing ACLF. However, after diagnostic assays for HEV became available, prospective studies including large number of patients with acute liver failure (ALF) from developed nation [7Lee W.M. Squires Jr, R.H. Nyberg S.L. Doo E. Hoofnagle J.H. Acute liver failure: summary of a workshop.Hepatology. 2008; 47: 1401-1415Crossref PubMed Scopus (536) Google Scholar, 8Ostapowicz G. Fontana R.J. Schiødt F.V. Larson A. Davern T.J. Han S.H. et al.Acute liver failure study group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.Ann Intern Med. 2002; 137: 947-954Crossref PubMed Scopus (1669) Google Scholar] did not report HEV as an etiological agent. Furthermore, reviews on HEV in high income countries [[9]Pavio N. Mansuy J.M. Hepatitis E in high-income countries.Curr Opin Infect Dis. 2010; 23: 521-527Crossref PubMed Scopus (33) Google Scholar] and case series of acute HEV infection from France [[10]Mansuy J.M. Abravanel F. Miedouge M. Mengelle C. Merviel C. Dubois M. Kamar N. et al.Acute hepatitis E in south-west France over a 5-year period.J Clin Virol. 2009; 44: 74-77Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar] and UK [[11]Dalton H.R. Thurairajah P.H. Fellows H.J. Hussaini H.S. Mitchell J. Bendall R. et al.Autochthonous hepatitis E in southwest England.J Viral Hepat. 2007; 14: 304-309Crossref PubMed Scopus (132) Google Scholar] also did not identify it as an etiological agent of ALF and ACLF. For this reason, we stated that HEV Genotype 3 and 4 (documented as the cause of autochthonous HEV infection) probably cause more benign disease than the Genotype 1 and 2 HEV infections [[4]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 information provided by Peron et al. [[1]Peron JM, Dalton H, Izopet J, Kumar N. Acute autochthonous hepatitis E in Western patients with underlying chronic liver disease: a role for ribavirine? J Hepatol 2011Google Scholar] may therefore indicate that HEV genotype 3 is associated with the causation of liver failure (i.e. ACLF) in individuals with pre-existing liver disease (particularly alcoholic liver disease) and ALF. Although such infection may be infrequent, prospective studies in ALF, particularly in France and UK, are needed to establish HEV genotype 3 as an etiological agent of ALF in these geographical areas. We also agree with the authors of the letter to editor that the initial promise of Ribavirin as an antiviral agent against HEV infection needs prospective evaluation in a well designed study with a large number of patients with active viremia. The author declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.