Reply to: “Encephalopathy or hepatic encephalopathy?”
Authors: François Durand, Pere Ginès, Faouzi Saliba, Javier Fernández
Journal: Journal of Hepatology (2012)

Encephalopathy or hepatic encephalopathy?Journal of HepatologyVol. 57Issue 4PreviewWe read with interest the paper by Ginès and co-authors on the management of critically-ill cirrhotic patients [1]. However, we have some concerns on the section on management of hepatic encephalopathy. The authors seem to base their recommendations on a 'statistical' rather than a pathophysiological definition of the syndrome, grouping under the heading 'severe hepatic encephalopathy' a set of different neuropsychiatric symptoms arising in critically-ill cirrhotic patients, to include mental abnormalities relating to sepsis, electrolyte imbalance, and even the side- or desired-effects of drugs such as opioids and benzodiazepines. Full-Text PDF Open Access In response to Montagnese et al. [[1]Montagnese S. Merkel C. Amodio P. Encephalopathy or hepatic encephalopathy?.J Hepatol. 2012; 57: 928-929Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar], we fully agree that hepatic encephalopathy is a multifactorial syndrome which may result from impaired liver function, portosystemic shunts as well as from non-hepatic factors including sepsis, electrolyte imbalance, and sedative agents. None of the manifestations of hepatic encephalopathy are specific to any of the mechanisms involved. Although we do not clearly understand what a "statistical definition" means in this context, we also agree that, as it is multifactorial and non-specific, "hepatic encephalopathy" might be better termed as "encephalopathy" in critically-ill cirrhotic patients who frequently have several precipitating factors. Elevated blood ammonia levels are the hallmark of encephalopathy in cirrhosis. However, the correlation between blood ammonia and severity of encephalopathy is weak [[2]Kramer L. Tribl B. Gendo A. Zauner C. Schneider B. Ferenci P. et al.Partial pressure of ammonia versus ammonia in hepatic encephalopathy.Hepatology. 2000; 31: 30-34Crossref PubMed Scopus (142) Google Scholar]. In addition, due to a marked impairment in liver function, any critically-ill cirrhotic patient is expected to have elevated blood ammonia levels, whatever the severity of encephalopathy. Practically, the findings of elevated blood ammonia levels in this population may not exclude the contribution of non-hepatic factors in the occurrence of neuropsychiatric changes. This is the reason why, in line with others [[3]Bajaj J.S. Review article: the modern management of hepatic encephalopathy.Aliment Pharmacol Ther. 2010; 31: 537-547Crossref PubMed Scopus (170) Google Scholar], we have suggested that the systematic determination of blood ammonia levels is unlikely to be useful in the management of critically-ill cirrhotic patients [[4]Gines P. Fernandez J. Durand F. Saliba F. Management of critically-ill cirrhotic patients.J Hepatol. 2012; 56: S13-S24Abstract Full Text PDF PubMed Scopus (99) Google Scholar]. As pointed out by Montagnese et al. [[1]Montagnese S. Merkel C. Amodio P. Encephalopathy or hepatic encephalopathy?.J Hepatol. 2012; 57: 928-929Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar], whether or not non-hepatic factors are involved in the occurrence of encephalopathy, in patients with acute liver failure, is a crucial issue. Indeed, while the prognostic value of "spontaneous" encephalopathy (i.e. encephalopathy only related to impaired liver function) is unequivocally poor in acute liver diseases, it would be highly questionable to consider transplantation if encephalopathy is only related to non-hepatic factors. However, the issue of patients with acute liver failure is clearly different from that of critically-ill cirrhotic patients. In addition, any patient with acute liver failure is expected to have high blood ammonia levels, whatever non-hepatic factors are involved in the mechanisms of encephalopathy [[5]Rolando N. Wade J. Davalos M. Wendon J. Philpott-Howard J. Williams R. The systemic inflammatory response syndrome in acute liver failure.Hepatology. 2000; 32: 734-739Crossref PubMed Scopus (607) Google Scholar]. No threshold value of blood ammonia would allow a clear differentiation between "hepatic encephalopathy" and "non-hepatic encephalopathy". Careful analysis of the potential contributing factors is still essential in the management of patients with acute liver failure as well as critically-ill cirrhotic patients. Finally, Montagnese et al. raise concerns about the variables to be included in the West-Haven criteria [[1]Montagnese S. Merkel C. Amodio P. Encephalopathy or hepatic encephalopathy?.J Hepatol. 2012; 57: 928-929Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar]. Indeed, the criteria presented in Table 3 [[4]Gines P. Fernandez J. Durand F. Saliba F. Management of critically-ill cirrhotic patients.J Hepatol. 2012; 56: S13-S24Abstract Full Text PDF PubMed Scopus (99) Google Scholar] do not correspond to the "original" West Haven criteria [[6]Conn H.O. Leevy C.M. Vlahcevic Z.R. Rodgers J.B. Maddrey W.C. Seeff L. et al.Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.Gastroenterology. 1977; 72: 573-583Abstract Full Text PDF PubMed Scopus (627) Google Scholar]. Unfortunately, numerous studies have employed variations of these criteria [[7]Blei A.T. Cordoba J. Hepatic encephalopathy.Am J Gastroenterol. 2001; 96: 1968-1976Crossref PubMed Google Scholar]. In this review, we have selected one of these criteria including level of consciousness, intellectual behavior, neurological findings, and electroencephalographic (EEG) abnormalities [[8]Bismuth M. Funakoshi N. Cadranel J.F. Blanc P. Hepatic encephalopathy: from pathophysiology to therapeutic management.Eur J Gastroenterol Hepatol. 2011; 23: 8-22Crossref PubMed Scopus (76) Google Scholar] in an attempt to be exhaustive. Montagnese et al. are right in that there may not be a parallel between consciousness, behavior, other neurological findings, and EEG changes, which represents a limitation of these criteria. An index score comparable to the Child–Pugh score, combining the independent scores of these variables could be more accurate [[6]Conn H.O. Leevy C.M. Vlahcevic Z.R. Rodgers J.B. Maddrey W.C. Seeff L. et al.Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.Gastroenterology. 1977; 72: 573-583Abstract Full Text PDF PubMed Scopus (627) Google Scholar]. However, no consensus exists yet on an optimal scoring system. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.