Reply:
Authors: Pierre Bedossa, Rami Moucari, Emna Chelbi, Tarik Asselah, Valerie Paradis, Michel Vidaud, Dominique Cazals-Hatem, Nathalie Boyer, Dominique Valla, Patrick Marcellin
Journal: Hepatology (2008)

We thank Dr. Chavez-Tapia and colleagues for their interesting comments. It gives us the opportunity to clarify the terminology of steatohepatitis. Since the original description by Ludwig et al., the term nonalcoholic steatohepatitis (NASH) has been associated in the minds of most pathologists and hepatologists to metabolic-associated and/or obesity-associated liver disease, by contrast to the previously well-known form of steatohepatitis occurring in alcoholic patients, previously called "acute alcoholic hepatitis" or alcoholic steatohepatitis (ASH). With more than 25 years of experience, the time has come to change the current terminology. Steatohepatitis is a pathologic entity whose diagnosis relies on liver biopsy. Its definition is based on the association of key elementary features (steatosis, clarification and ballooning of liver cells, lobular inflammation with eventual Mallory's hyaline, polymorphonuclear, and other accessory features) which have been well-described in several important papers.2, 3 This constellation of features realizes a single pathologic entity, that is, steatohepatitis that can arise in many different etiological contexts. Although there is still discussion on how to quote and associate the elementary lesions, steatohepatitis is the morphologic counterpart of a standardized pathobiologic reaction of the liver parenchyma to various types of aggressions: alcohol, viruses, metabolic syndrome and/or obesity, drug use, rapid weight loss, inherited metabolic disease. Strictly speaking, the acronym NASH includes all these situations except alcohol, although, for many pathologists or hepatologists, NASH brings to mind steatohepatitis associated with a metabolic syndrome. It should therefore be appropriate to discard the acronym NASH and change the current terminology. Rather than referring to it as a "non" disease, this lesion should be referred to according to its etiology, such as VASH (viral-associated steatohepatitis), DASH (drug-associated steatohepatitis), AASH (alcohol-associated steatohepatitis), or MASH (metabolic-associated steatohepatitis), or simply steatohepatitis of unknown origin. Although steatosis is a common histological feature in chronic hepatitis C (CHC), NASH has not yet been clearly characterized in this context. In our study, among 278 consecutive patients with CHC, we observed CHC alone (57%), CHC plus steatosis (34%), or CHC plus NASH (9%).4 Patients with CHC plus NASH had significantly more steatosis and higher fibrosis stage than did those with CHC plus steatosis. As emphasized by Chavez-Tapia and colleagues, the diagnosis and appropriate treatment of the etiology of steatohepatitis are of importance in patients with CHC. In CHC, steatosis-like steatohepatitis could either be induced by the virus, especially in patients with genotype 3, and/or represents a feature of the metabolic syndrome and insulin resistance.5 In our study, patients with excessive alcohol consumption were excluded so that either a metabolic or a viral cytopathic effect should be the origin of steatohepatitis in these patients. The challenge for the clinician in care of patients with CHC and steatosis is to be able to differentiate between those with pure steatosis alone and a benign course from those with progressive disease, a consideration that reinforces the need for liver biopsy in these patients. In a patient with CHC, the physician has to look for and correct all the features of the metabolic syndrome. In particular, because insulin resistance seems to be associated with fibrosis progression, weight loss and increased exercise should be recommended. Regarding patients with genotype 4, 6 of the 57 patients had steatohepatitis (11%). An important proportion of these patients were originally from Egypt. Although the number is too low to draw definitive conclusions, patients with CHC related to genotype 4 with steatosis or steatohepatitis have higher metabolic disturbances (HOMA-IR, triglyceride, and insulinemia) than those with CHC alone. This suggests that patients with steatohepatitis and genotype 4 are more likely to have MASH than VASH. Pierre Bedossa*, Rami Moucari*, Emna Chelbi*, Tarik Asselah*, Valerie Paradis*, Michel Vidaud*, Dominique Cazals-Hatem*, Nathalie Boyer*, Dominique Valla*, Patrick Marcellin*, * Service d'Anatomie Pathologique, Service d'Hépatologie, Service de Biochimie, Hôpital Beaujon–Assistance Publique-Hôpitaux de Paris, Clichy, France.