The “Almost Normal” Liver Biopsy: A Differential for a Problematic Area of Liver Pathology
Laura D Wood, Michael S Torbenson. Johns Hopkins University, Baltimore, MD
Background: A persistently challenging area of liver pathology is when biopsies are performed for chronic elevations in liver enzymes or for unexplained ascites, yet the liver biopsy appears almost normal. In these cases, generating a differential is very difficult, much to the disappointment of the clinical team and patients. There is to date essentially no information on the differential or natural history for the “almost normal” liver biopsy.
Design: All liver biopsies signed out by a single liver pathologist over a 5-year period were searched for cases in which a biopsy was performed for elevated liver enzymes or unexplained ascites, but the biopsy was essentially normal and no specific histological diagnosis could be made. All cases had no significant inflammation, fatty change, biliary tract disease, vascular disease, nodular regenerative hyperplasia, iron overload, metabolic disorders, or fibrosis. None had viral hepatitis or evidence for a drug effect. We also excluded all liver transplant biopsies, all mass-directed biopsies, and all biopsies for specific indication such as pre-transplant biopsies or evaluation of methotrextate toxicity.
Results: Over this 5-year time period, 94/2528 (4%) liver biopsies met the inclusion criteria of minimal nonspecific histological changes; 26 cases were then excluded for lack of follow-up, leaving 68 study cases. The most common clinical indications for biopsy were chronic enzyme elevations (74%) and unexplained ascites, splenomegaly, or gastroesophageal varices (18%). For the 68 study cases, subsequent clinicopathological follow-up identified a cause in 66% of cases. The top three causes were systemic autoimmune disorders such as lupus or rheumatoid arthritis (16% of cases); vascular abnormalities including thromboses or unusual vascular shunts (13%); and the metabolic syndrome (10%), even though no fat was present on biopsy. In the remaining cases, 9% eventually went on to develop a typical autoimmune hepatitis or primary biliary cirrhosis, 5% were associated with gastric inflammation such as Crohn's disease, 5% were associated with low grade liver ischemia, and 9% had a variety of miscellaneous conditions. In 23 cases (34%), no cause was identified, and liver enzymes eventually self-normalized in 1/3 of cases but persisted in the remaining 2/3.
Conclusions: This study provides a differential for the “almost normal" liver biopsy. Knowing this differential will allow pathologists to help direct subsequent clinical and laboratory work up in efforts to identify an etiology. An etiology can be identified in the majority (66%) of cases.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 143, Tuesday Afternoon