Sa1681 Mitochondria-Targeting Antioxidant Attenuates Cholestasis-Induced Liver Fibrosis in Mice

Abstract

BACKGROUND: Hepatic fibrosis is seen in patients with chronic liver injury. It occurs when damaged regions of the liver undergo unregulated production and degradation of the extracellular matrix. Hepatic fibrosis pathology is frequently reported in 5 stages (0,1,2,3,4): stage 0 representing no fibrosis and stage 4 representing advanced bridging fibrosis with cirrhosis. The gold standard for establishing the stage of fibrosis has been a liver biopsy. It is a preconceived notion that transaminase markers remain normal across the stages of fibrosis, however there has been limited published data to support this claim. We set out to prove: (a) serum markers remain normal amongst stages of hepatic fibrosis and (b) lack of correlation between lab values and progressive stages of fibrosis. METHODS: A retrospective observational study was conducted evaluating liver biopsies from 2010 to 2014. Serum markers (AST, ALT, INR, BUN) were extracted within 90 days before and after liver biopsy. Acute decompensated liver failure patients were also excluded. Mean and 95% confidence intervals (95%CI) were used to describe the distributions of serum markers in different fibrosis stages. A logistic regression model was used to estimate the relative risk of elevated serum markers (over normal value) in the fibrosis stages 1-4 compared to in the stage 0. P-values and 95 percent confidence intervals were calculated using the logistic regression model. All analyses were done in SAS 9.4 (SAS Institute Inc., Cary, NC, USA). P<0.05 was considered as statistically significant. RESULTS: A total of 771 liver biopsies were screened, after exclusion criteria were applied, roughly 600 samples were analyzed. AST 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis including stage 4. ALT 95% confidence interval of fibrosis stage 0, 1, and 4 overlapped. BUN 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis including stage 4. INR 95% confidence interval for fibrosis stage 0 overlapped with all stages of fibrosis, except stage 4. Conclusion: Lab values (AST, ALT) are poor predictors of chronic liver disease. Specifically, these lab values may remain statistically the same throughout the spectrum of chronic liver disease ranging from (stage 0) to cirrhosis (stage 4). One statistically significant value was represented by INR in stage 4 fibrosis, consistent with diminished synthetic function amongst these patients. With the rapidly rising incidence of chronic liver disease largely in part due to NAFLD, it is imperative for clinicians to keep in mind: normal serum markers don't convey a disease free liver.