Prospective Evaluation of Unexplained Chronic Liver Transaminase Abnormalities in Asymptomatic and Symptomatic Patients

TLDR

Current guidelines recommend liver biopsy for patients with chronically elevated liver function tests of unknown etiology, yet the necessity and benefits of this practice remain unclear. This study aimed to determine the prevalence of marker‑negative chronic LFT, identify associated diseases, and evaluate whether biopsy changes patient management. In a prospective observational study of 1,124 adults, 81 marker‑negative patients who consented to biopsy were evaluated, with biopsy eligibility based on absence of known serum markers, alcohol/drug use, and chronic liver disease signs. Biopsies of the 81 marker‑negative patients revealed steatosis in 41, steatohepatitis in 26, fibrosis in 4, cirrhosis in 2, and normal histology in 8, with steatosis present in all abnormal samples and no significant associations with obesity, hyperlipidemia, diabetes, gender, or symptoms, indicating fatty metamorphosis as the most common diagnosis.

Abstract

It is currently recommend to perform a liver biopsy for patients with chronically elevated liver function tests (LFT) of unknown etiology (marker negative). The necessity and benefits of these recommendations are unknown. The aims of this study were to determine the prevalence of marker-negative LFT in patients referred for evaluation of chronically elevated LFT; to determine the prevalence of diseases that may be associated with marker-negative abnormal LFT; and to assess whether a liver biopsy alters the management of such patients.We conducted a prospective observational study of 1124 adults referred for evaluation of chronically elevated LFT. Patients who consented to a liver biopsy were eligible. Marker-negative abnormal LFT was defined as the absence of accepted serum markers for infectious, metabolic, autoimmune, or hereditary liver disease, the absence of a history of alcohol or hepatotoxic drug use, and the absence of signs of chronic liver disease.Eighty-one of 1124 eligible patients were marker-negative. Liver biopsies in the 81 marker-negative patients revealed: normal histology (eight), steatosis (41), steatohepatitis (26), fibrosis (four), and cirrhosis (two). All 73 abnormal liver biopsies had some degree of steatosis. There were no significant associations between histological findings and the presence of obesity (p = 0.13), hyperlipidemia (p = 0.4), or diabetes (p = 0.9). There were no significant associations when classifying patients by gender or by symptoms.In the setting of marker-negative elevated LFT, the most likely histological diagnosis is fatty metamorphosis of the liver with occasional associated fibrosis.