1 examined liver biopsy samples from 72 of 204 patients (i.e., 35% of the total cohort). However, the use of different liver biopsy techniques, such as transjugular liver biopsy, native liver biopsy, and postmortem biopsy, may have induced variations in the histological patterns. Centrilobular necrosis (CN), which corresponds to massive hepatic necrosis type 1 in this study, is an important but infrequent histopathological pattern of autoimmune hepatitis; centrilobular necrosis with

sparing of the portal tracts was present in 3.5% of the cases reported by Hofer et al.2 This particular pattern is of crucial DZNeP nmr importance because it may be indicative of an early stage of the disease. For the series described by Stravitz et al., it would be interesting to have a description of the phenotype and, more PARP inhibitor specifically, the prognosis of the patients with isolated centrilobular necrosis. The fact that the centrilobular zone is damaged during an early stage by the immune process is intriguing and suggests that specific autoantigens in this area could be presented to the immune system early during the course of liver

disease. Clearly, the identification of these potential targets during an initial phase of the disease would be of considerable interest. In addition, it is unfortunate that the identification of a pattern typical of severe autoimmune hepatitis (AIH) is based only on this experience; in several reports, researchers have attempted to describe this entity, and experiences besides those of the US Acute Liver Failure Study Group should be cited.3-6 In particular, the characteristics of the patients may differ between the studies. In our cohort,

8 of 16 patients (50%) suffered from grade 3/4 encephalopathy,3 whereas 26 of 72 patients (39%) in Stravitz et al.’s study did. The most important and problematic issue in the management of severe autoimmune liver disease is corticosteroid therapy. Of course, if a response to corticosteroid therapy is an important argument in favor Sitaxentan of an autoimmune process, it is important that any decision to administer this therapy be balanced against the high potential risk of sepsis; infections occurred in 5 of 12 patients (42%) during steroid therapy in our study.3 If treatment failure seems to be predicted by changes in the Model for End-Stage Liver Disease–Sodium score and the UK Model for End-Stage Liver Disease score on day 7,7 specific scores on entry must be defined for making decisions about the administration of steroid therapy. Jean-Charles Duclos-Vallée M.D., Ph.D.* † ‡, Philippe Ichai M.D.* † ‡, Didier Samuel M.D., Ph.D.* † ‡, * Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique–Hôpitaux de Paris, Villejuif, France, † Unités Mixtes de Recherche en Santé 785, Université Paris-Sud, Villejuif, France, ‡ Unité 785, Institut National de la Santé et de la Recherche Médicale, Villejuif, France.