Nonalcoholic fatty liver: a spectrum, not an entity

Nonalcoholic fatty liver represents a spectrum of morphologic changes, all of which have in common the presence of fatty change (steatosis) with or without other features, such as lobular inflammation, necrosis, fibrosis, and even cirrhosis—all in the (apparent) absence of significant alcohol consumption. It is still a matter of debate whether fatty change alone will progress to fibrosis and possibly cirrhosis or whether other changes, such as episodes of active inflammation, are necessary for such a progression. The difficulties for the anatomic pathologist ranges from terminology (steatosis versus steatohepatitis versus steatoncrosis versus nonalcoholic steatohepatitis (NASH)) to the prediction of likely outcome based on morphologic features on liver biopsies. The study by Matteoni et al. investigated the clinical characteristics and outcomes of patients with fatty change as the single common feature in their biopsy with or without other changes. This was done in a retrospective manner (1979–1987) in 772 biopsy specimens, 132 of which had complete follow-up (up to 18 years). The biopsy findings were divided into four groups: Type I: fatty liver alone Type II: fatty liver plus lobular inflammation (steatohepatitis) Type III: fatty liver plus ballooning degeneration (“steatonecrosis”- why ballooning degeneration is referred to as “necrosis” is somewhat puzzling?) Type IV: fatty liver plus ballooning degeneration plus Mallory bodies or fibrosis (steatoncrosis plus either Mallory hyaline or fibrosis). The authors found that Type I fatty liver did not differ from the three other groups with respect to gender, race, age, and presence or absence of obesity and diabetes. The overall mortality, presence of histologic stainable iron and incidence of Hepatitis C (as determined by revers transcription—polymerase chain reaction, RT-PCR) did also not differ between these groups. However, cirrhosis developed in only 4% of Type I fatty liver while 21% and 26% of Type III and Type IV, respectively, developed cirrhosis. Liver-related death was seen in 13% of Type IV, compared to only 2% in Type I fatty change. Once again, Type II did not result in any liver-related death. The authors conclude that fatty change alone (Type I) is a relatively benign disease while fatty change associated with ballooning degeneration and Mallory bodies of fibrosis follows a more aggressive course.