Correlation Between Liver Histology and Novel MRI in NAFLD
Correlation Between Liver Histology and Novel MRI in NAFLD
Background Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T2* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD).
Aim To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis.
Methods A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system.
Results The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0–3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning.
Conclusions MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the western world, affecting 20–40% of the adult population. Non-alcoholic steatohepatitis (NASH) represents a subset of patients with NAFLD characterised by ballooning degeneration, lobular inflammation with or without peri-sinusoidal fibrosis on liver biopsy. Patients with NASH are at increased risk of progression to cirrhosis. Approximately 3% of individuals in developed countries may have NASH; although this is an underestimation, as many patients with NAFLD do not have liver biopsy. It is estimated that approximately 10% of patients with NASH may progress to cirrhosis. and 10–20% of those may die from complications of liver failure or require liver transplant.
The diagnosis of NAFLD and NASH is reliant on performing a liver biopsy to assess degree of steatosis, necroinflammation and stage of fibrosis, but this is an invasive procedure, and is limited by sampling error and variability. In addition, studies monitoring patient response to clinical intervention often require multiple liver biopsies to evaluate disease progression. Recent studies have shown magnetic resonance imaging (MRI) to be a promising non-invasive tool to assess hepatic steatosis. MRI fat fraction calculated by the Dixon in- and out of phase (IOP) method correlates well with hepatic steatosis in patients with liver disease of any aetiology, and is more accurate than ultrasound and other imaging modalities such as computed tomography (CT). Although MRS has also been shown to be an accurate technique in quantifying hepatic steatosis, it remains largely a research tool. Pacifico et al. demonstrated in paediatric patients with NAFLD that MRI fat fraction calculated via a modified Dixon IOP method is both a sensitive and specific method for quantifying hepatic steatosis when compared with controls. Recent development of MRI-determined proton density fat fraction (PDFF) technique improves upon previous Dixon IOP method limitations by correcting for T1 bias, effect of T2* decay, the multi-frequency signal-interference effects of protons in fat to provide a quantitative, standardised and objective MRI measurement of hepatic fat based upon inherent tissue properties. This method has been shown to be both accurate, using MR spectroscopy as a reference standard and reproducible.
Although there is increasing support for MRI-determined PDFF use to predict hepatic steatosis, this modality has not been studied specifically in adult patients with NAFLD. Furthermore, although the inverse relationship between hepatic fibrosis and steatosis has been examined in patients with hepatitis C, it is not clearly understood how increasing fibrosis stage and more advanced liver disease influences grade of steatosis and MRI-determined fat fraction in patients with NAFLD.
This study investigates the relationship between MRI-determined PDFF and histology-determined steatosis grade in middle-aged adults with NAFLD. It then explores the relationship between fibrosis stage and degree of hepatic steatosis as measured by both MRI-determined PDFF and histology-determined steatosis grade. We aimed to test following hypotheses: (i) MRI-determined PDFF is highly correlated with histology-determined hepatic steatosis obtained from percutaneous liver biopsy specimen and (ii) increased liver fibrosis is associated with lower levels of hepatic steatosis.
Abstract and Introduction
Abstract
Background Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T2* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD).
Aim To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis.
Methods A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system.
Results The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0–3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning.
Conclusions MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease.
Introduction
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the western world, affecting 20–40% of the adult population. Non-alcoholic steatohepatitis (NASH) represents a subset of patients with NAFLD characterised by ballooning degeneration, lobular inflammation with or without peri-sinusoidal fibrosis on liver biopsy. Patients with NASH are at increased risk of progression to cirrhosis. Approximately 3% of individuals in developed countries may have NASH; although this is an underestimation, as many patients with NAFLD do not have liver biopsy. It is estimated that approximately 10% of patients with NASH may progress to cirrhosis. and 10–20% of those may die from complications of liver failure or require liver transplant.
The diagnosis of NAFLD and NASH is reliant on performing a liver biopsy to assess degree of steatosis, necroinflammation and stage of fibrosis, but this is an invasive procedure, and is limited by sampling error and variability. In addition, studies monitoring patient response to clinical intervention often require multiple liver biopsies to evaluate disease progression. Recent studies have shown magnetic resonance imaging (MRI) to be a promising non-invasive tool to assess hepatic steatosis. MRI fat fraction calculated by the Dixon in- and out of phase (IOP) method correlates well with hepatic steatosis in patients with liver disease of any aetiology, and is more accurate than ultrasound and other imaging modalities such as computed tomography (CT). Although MRS has also been shown to be an accurate technique in quantifying hepatic steatosis, it remains largely a research tool. Pacifico et al. demonstrated in paediatric patients with NAFLD that MRI fat fraction calculated via a modified Dixon IOP method is both a sensitive and specific method for quantifying hepatic steatosis when compared with controls. Recent development of MRI-determined proton density fat fraction (PDFF) technique improves upon previous Dixon IOP method limitations by correcting for T1 bias, effect of T2* decay, the multi-frequency signal-interference effects of protons in fat to provide a quantitative, standardised and objective MRI measurement of hepatic fat based upon inherent tissue properties. This method has been shown to be both accurate, using MR spectroscopy as a reference standard and reproducible.
Although there is increasing support for MRI-determined PDFF use to predict hepatic steatosis, this modality has not been studied specifically in adult patients with NAFLD. Furthermore, although the inverse relationship between hepatic fibrosis and steatosis has been examined in patients with hepatitis C, it is not clearly understood how increasing fibrosis stage and more advanced liver disease influences grade of steatosis and MRI-determined fat fraction in patients with NAFLD.
This study investigates the relationship between MRI-determined PDFF and histology-determined steatosis grade in middle-aged adults with NAFLD. It then explores the relationship between fibrosis stage and degree of hepatic steatosis as measured by both MRI-determined PDFF and histology-determined steatosis grade. We aimed to test following hypotheses: (i) MRI-determined PDFF is highly correlated with histology-determined hepatic steatosis obtained from percutaneous liver biopsy specimen and (ii) increased liver fibrosis is associated with lower levels of hepatic steatosis.
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