Value of ALT Levels for NASH and Advanced Fibrosis in NAFLD
Value of ALT Levels for NASH and Advanced Fibrosis in NAFLD
Background: Non-alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non-alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD.
Aim: To determine ALT value that will accurately predict NASH and advanced fibrosis using area under the receiver operating characteristics curve (AUROC) analysis.
Methods: Demographic, clinical and laboratory data of an ethnically diverse cohort of biopsy proven NAFLD patients were retrospectively analysed under univariate and multivariate analyses. Liver biopsies were scored using NASH clinical research network (NASH CRN) system. AUROC were performed for NAFLD Activity Score ≥5 (NASH) and fibrosis score ≥2 (advanced fibrosis).
Results: Two hundred and twenty-two patients were analysed. Fifty six (23%) had normal ALT. There was no difference in the rate of advanced fibrosis between normal and elevated ALT (26.8% vs. 18.1%, P = 0.19). However, significantly lower percentage of normal ALT group had NASH compared with elevated ALT group (10.7% vs. 28.9%, P < 0.01). Overall, 37.5% of normal ALT group had NASH or advanced fibrosis, whereas 53% of elevated ALT had no NASH or advanced fibrosis. Higher ALT values correlated with higher specificity, but lower sensitivity for both NASH and advanced fibrosis. AUROC for ALT level correlating NASH and advanced fibrosis were 0.62 and 0.46 respectively.
Conclusion: There is no optimal ALT level to predict NASH and advanced fibrosis. Metabolic risk factors should be evaluated to select patients for a liver biopsy to confirm NASH and advanced fibrosis.
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of clinical and histological manifestation, ranging from mild steatosis, NASH, progressive fibrosis, cirrhosis and ultimately to hepatocellular carcinoma. Non-alcoholic steatohepatitis (NAFLD) is considered to be the hepatic manifestation of metabolic syndrome (MS), which has been shown to be a strong predictor for hepatic steatosis and advanced liver disease. In general, elevated serum alanine aminotransferase (ALT) levels are further evaluated with a liver biopsy to determine whether patients with NAFLD have progressed to NASH and advanced fibrosis. Prior studies have suggested that elevated ALT levels correlate with NASH and advanced fibrosis. However, patients with normal ALT may also have NASH and advanced fibrosis as well. The lack of a systematic association between ALT level and advanced form of NAFLD has important clinical relevance, as it raises the issue of whether NAFLD patients with normal ALT should undergo a liver biopsy to confirm NASH or advanced fibrosis. Therefore, predictive values of ALT levels are needed to determine a level that could assess for advanced liver injury, including NASH and advanced fibrosis, while potentially avoiding the need for a liver biopsy.
Although studies have included NAFLD patients with normal and elevated ALT levels, investigations into the best cut-off value of ALT to predict NASH and advanced fibrosis using AUROC are lacking. In addition, previous studies comparing clinical characteristics of NAFLD in patients with normal and elevated ALT levels were limited because of a lack of multi-ethnic patient population, small sample size or for not utilizing the updated NASH clinical research network (CRN) grading system for histological evaluation. The aim of our study was to identify a critical threshold of ALT by performing AUROC analysis that would predict NASH or advanced fibrosis in an ethnically diverse patient population. In addition, we compared demographic, biochemical, metabolic and histological variables between patients with normal and elevated ALT levels using the updated NASH CRN grading system.
Abstract and Introduction
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non-alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD.
Aim: To determine ALT value that will accurately predict NASH and advanced fibrosis using area under the receiver operating characteristics curve (AUROC) analysis.
Methods: Demographic, clinical and laboratory data of an ethnically diverse cohort of biopsy proven NAFLD patients were retrospectively analysed under univariate and multivariate analyses. Liver biopsies were scored using NASH clinical research network (NASH CRN) system. AUROC were performed for NAFLD Activity Score ≥5 (NASH) and fibrosis score ≥2 (advanced fibrosis).
Results: Two hundred and twenty-two patients were analysed. Fifty six (23%) had normal ALT. There was no difference in the rate of advanced fibrosis between normal and elevated ALT (26.8% vs. 18.1%, P = 0.19). However, significantly lower percentage of normal ALT group had NASH compared with elevated ALT group (10.7% vs. 28.9%, P < 0.01). Overall, 37.5% of normal ALT group had NASH or advanced fibrosis, whereas 53% of elevated ALT had no NASH or advanced fibrosis. Higher ALT values correlated with higher specificity, but lower sensitivity for both NASH and advanced fibrosis. AUROC for ALT level correlating NASH and advanced fibrosis were 0.62 and 0.46 respectively.
Conclusion: There is no optimal ALT level to predict NASH and advanced fibrosis. Metabolic risk factors should be evaluated to select patients for a liver biopsy to confirm NASH and advanced fibrosis.
Introduction
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of clinical and histological manifestation, ranging from mild steatosis, NASH, progressive fibrosis, cirrhosis and ultimately to hepatocellular carcinoma. Non-alcoholic steatohepatitis (NAFLD) is considered to be the hepatic manifestation of metabolic syndrome (MS), which has been shown to be a strong predictor for hepatic steatosis and advanced liver disease. In general, elevated serum alanine aminotransferase (ALT) levels are further evaluated with a liver biopsy to determine whether patients with NAFLD have progressed to NASH and advanced fibrosis. Prior studies have suggested that elevated ALT levels correlate with NASH and advanced fibrosis. However, patients with normal ALT may also have NASH and advanced fibrosis as well. The lack of a systematic association between ALT level and advanced form of NAFLD has important clinical relevance, as it raises the issue of whether NAFLD patients with normal ALT should undergo a liver biopsy to confirm NASH or advanced fibrosis. Therefore, predictive values of ALT levels are needed to determine a level that could assess for advanced liver injury, including NASH and advanced fibrosis, while potentially avoiding the need for a liver biopsy.
Although studies have included NAFLD patients with normal and elevated ALT levels, investigations into the best cut-off value of ALT to predict NASH and advanced fibrosis using AUROC are lacking. In addition, previous studies comparing clinical characteristics of NAFLD in patients with normal and elevated ALT levels were limited because of a lack of multi-ethnic patient population, small sample size or for not utilizing the updated NASH clinical research network (CRN) grading system for histological evaluation. The aim of our study was to identify a critical threshold of ALT by performing AUROC analysis that would predict NASH or advanced fibrosis in an ethnically diverse patient population. In addition, we compared demographic, biochemical, metabolic and histological variables between patients with normal and elevated ALT levels using the updated NASH CRN grading system.
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