Abstract

Purpose: Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic liver disease. The presence of steatosis on liver biopsy and features of metabolic syndrome (MS) have been associated with more advanced fibrosis in other chronic liver diseases. The primary goal of this study is to determine if steatosis on liver biopsy is associated with more advanced fibrosis in patients with PBC. Methods: The medical records of all patients with PBC seen at the Hepatology Clinic of the University of Miami from January 1985 until January 2008 were reviewed. Subjects were included if they had a positive antimitochondrial antibody (AMA) and if they had undergone at least one liver biopsy during the disease course. Other chronic liver diseases were excluded. A single liver pathologist, blinded to all clinical information, reviewed the liver biopsies and evaluated sections for the grade of steatosis, inflammation and ballooning, and fibrosis stage. Chi square and t-test were used for statistical comparisons where appropriate. Results: Forty nine patients met inclusion criteria. Of these, 21 (43%) had grade 1 (<33% steatosis), 19 (39%) had grade 2 (33-66% steatosis) and 9 (18%) had grade 3 (>66% steatosis). Advanced fibrosis (stage 3 or 4) was present in 5/21 (24%) patients with grade 1 steatosis, 11/19 (57%) patients with grade 2, and 9/9 (100%) patients with grade 3 (p-value <0.0001). The degree of inflammation and the presence of ballooning did not correlate with advanced fibrosis. Overweight (BMI≥25) patients had a significantly higher proportion of advanced fibrosis compared to those with normal BMI (71% vs. 32%, p=0.007). Overweight status was also associated with higher degree of steatosis (p=0.02). The presence of other features of MS (diabetes mellitus, elevated triglycerides, low HDL and hypertension), individually, was not associated with advanced fibrosis or steatosis grade in these patients. There was a trend towards more advanced fibrosis in patients with more features of MS, but this was not statistically significant: 6/20 (30%) patients with no features,10/18 (55%) patients with 1 feature, 3/3 (100%) patients with 2 features, 5/7 (71%) patients with 3 features and 1/1 (100%) patients with 4 features of MS had advanced fibrosis (p=0.07). Conclusion: Histological finding of steatosis in patients with PBC is associated with more advanced fibrosis. The only feature of MS associated with advanced fibrosis and the degree of steatosis was a BMI ≥25, which could become a useful non-invasive tool to predict advanced fibrosis in PBC if validated in a larger scale study.

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