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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

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: r2 = 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

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

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.[1] 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.[2, 3] 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.[4, 5] and 10–20% of those may die from complications of liver failure or require liver transplant.[6]

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[7] 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).[8-10] Although MRS has also been shown to be an accurate technique in quantifying hepatic steatosis,[11, 12] 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.[13] 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.[14, 15] This method has been shown to be both accurate, using MR spectroscopy as a reference standard and reproducible.[16]

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,[17] 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.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Study design and patient population

This is a cross sectional analysis of a prospective cohort study consisting of 51 consecutive patients who underwent novel MRI imaging with biopsy-proven NAFLD, and did not have any evidence of other causes of liver disease. All patients had a diagnosis of NAFLD based on both histology and MRI-PDFF imaging with steatosis >5%. The mean (±s.d.) interval between the MRI and liver biopsy was 2.1 (±1.6) months. They attended a research visit and underwent standardised history, physical exam, anthropometric exam, biochemical testing and an MRI examination at the UCSD. All patients provided written informed consent and the study was approved by the UCSD institutional review board.

Inclusion and exclusion criteria

Patients were included if they had serum alanine (ALT) or aspartate (AST) aminotransferase activity above the upper limits of normal: 19 U/L or more for women and 30 U/L or more for men and had evidence of NAFLD on liver biopsy. Exclusion criteria included alcohol intake of more than 30 g/day in the previous 10 years or greater than 10 g/day in the previous 1 year. Subjects were also excluded if they had decompensated liver disease with Child-Pugh score greater than 7 points, had active substance abuse or significant systemic illnesses, were taking drugs known to cause hepatic steatosis or had other forms of liver disease shown by a positive serum hepatitis B surface antigen, hepatitis C viral RNA, autoimmune serologies, low ceruloplasmin, alpha-1-antitrypsin deficiency or evidence of hemochromatosis by 3+ or 4+ stainable iron on biopsy or homozygosity on genetic analysis. Biochemical, liver biopsy and MRI data were used to investigate the aims of this study.

Clinical evaluation

Patients were evaluated in the research clinic with routine history and physical exam, height, weight measurements performed by a trained investigator. Body mass index (BMI) was calculated by dividing body weight (in kilograms) by the square of the height (in metres). Alcohol consumption was documented in clinical visits and then confirmed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, a validated tool used to screen for heavy drinking and/or active alcohol abuse or dependence.[18] A detailed history of medications was also obtained and none of the patients included in this study were taking medications that are known or suspected to induce steatosis or steatohepatitis. Subjects underwent biochemical profiling, which consisted of Alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), total bilirubin, direct bilirubin, albumin, haemoglobin A1c (HbA1c), fasting glucose and insulin, homeostatic model assessment of insulin resistance (HOMA) as defined by the product of glucose and insulin divided by 405, protime/INR, lipid panel, free fatty acids (FFA), C-reactive protein (CRP) and platelet count.

Histology assessment

All patients underwent liver biopsy, which was scored using the NASH-CRN[19] histological scoring system by a single liver pathologist (MP) who was blinded to the clinical as well as the MRI data. Liver biopsies were assessed for degree of steatosis (0–3), lobular inflammation (0–3), hepatocellular ballooning (0–2) and fibrosis (0–4). The first three components were added together to determine the NAFLD activity score (NAS) that ranges from 0 to 8. Per the NASH-CRN histological scoring system, stage 4 fibrosis is characteristic of cirrhosis.

MRI protocol

To measure hepatic PDFF, a state-of-the-art MR imaging technique was performed. The technique utilises a gradient echo sequence with low flip angle (FA) to minimise T1 bias, and it acquires multiple echoes at echo times at which fat and water signals are nominally in phase or out of phase (OP) relative to each other. Data obtained at each of the echo times are passed to a nonlinear least-squares fitting algorithm that estimates and corrects T2* effects, models the fat signal as a superposition of multiple frequency components, and estimates fat and water proton densities from which the fat content is calculated. Using custom analysis software developed at the UCSD Liver Imaging Group, the mathematical model is applied pixel by pixel on the source images to generate parametric PDFF maps that depict the quantity and distribution of fat throughout the entire liver. Imaging PDFF was recorded in regions of interest (ROI) approximately 300–400 mm2 in area placed on the PDFF parametric maps, avoiding vessels, bile ducts, lesions and artefacts. Three ROIs were placed in each of the nine liver segments (27 separate ROIs) on the MR exams. The 27 per-liver PDFF measurements were averaged.

The MR examinations were performed by experienced research MR technologists with expertise in the utilised procedures and analysed, under the supervision of the radiology investigator (CS), by a single trained image analyst who was blinded to clinical and histological data.

Statistical analysis

Patients were stratified by steatosis grade on liver biopsy and mean (±S.E.M.) values for demographic variables, biochemical parameters, histology data and MRI-PDFF were calculated. Two-tailed, t-tests were performed on these variables in the group with steatosis grades 1 and 3 to look for statistically significant differences. Categorical variables were analysed with chi-squared test to examine differences between grades 1 and 3 steatosis. Linear regression was used to analyse correlation between MRI PDFF and steatosis grade as well as fibrosis stage and PDFF. Statistical analyses were performed using Excel (Microsoft Corporation, Redmond, WA, USA) and spss software packages (IBM, Armonk, NY, USA). A two-tailed P-value ≤0.05 was considered statistically significant.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Demographic data and biochemical profile by steatosis grade

Between 1/2010 and 2/2011, 51 patients with biopsy-confirmed NAFLD were enrolled. The demographic and biochemical data of patients included in this study are shown in Table 1 stratified by the histology-determined steatosis grade. The average (S.E.M) age, body weight and body mass index of subjects were 48.1 (1.7) years, 88.6 (2.8) kg and BMI 31.4 (0.7) kg/m2 respectively. There were no significant differences among the three groups in age, gender and BMI. However, compared to patients with histology-determined grade 3 steatosis, patients with grade 1 steatosis were more likely to have diabetes (54% vs. 29%, P = 0.03). There were no statistically significant differences between grade 1 and grade 3 steatosis groups with respect to serum ALT, AST, fasting glucose or insulin, triglycerides, total cholesterol, LDL, HDL, FFA, CRP, HbA1c, alkaline phosphatase, total or direct bilirubin, platelets, creatinine or HOMA.

Table 1. Demographic and biochemical characteristics of patients with NAFLD by steatosis grade
 Steatosis Grade-1 (N = 13)Steatosis Grade-2 (N = 24)Steatosis Grade-3 (N = 13)P-value
  1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRP, c-reactive protein; FFA, free fatty acids; HDL, high-density lipoprotein; Hgb A1c, haemoglobin A1c; HOMA, homeostatic model assessment; LDL, low-density lipoprotein; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; PDFF, proton density fat fraction.

  2. Data are expressed as mean with standard error in parentheses unless otherwise noted.

  3. Glucose and insulin levels were measured while fasting.

  4. t-test assuming equal variance between steatosis grade 1 and grade 3 was performed on all continuous/ordinal variables and chi-squared analysis was performed on all categorical variables.

  5. NASH-CRN histological scoring system was used for histological grading and staging of liver biopsy.

Demographics
Gender (% male)53.8%54.2%50.0%0.89
Age48.8 (3.4)46.8 (2.9)49.9 (1.8)0.76
Weight89.0 (5.2)88.0 (4.5)89.3 (5.1)0.97
Height1.65 (0.03)1.69 (0.02)1.63 (0.04)0.71
BMI32.5 (1.5)30.4 (1.0)32.0 (1.3)0.81
Diabetes (%)53.8%29.2%28.6%0.03
Biochemical profile
AST61.5 (8.9)48.3 (9.5)53.6 (8.6)0.77
ALT82.3 (16.1)79.9 (13.9)87.8 (10.2)0.52
Glucose109.2 (6.0)102.8 (4.3)116.5 (11.4)0.58
Insulin39.5 (15.3)26.3 (5.2)17.6 (3.0)0.16
Trigylcerides148.5 (14.5)206.4 (32.9)172.5 (13.6)0.24
Total cholesterol197.7 (11.7)195.2 (8.4)214.6 (10.1)0.28
LDL119.2 (10.1)114.5 (6.8)127.9 (9.9)0.54
HDL48.8 (3.4)44.7 (3.7)52.3 (5.2)0.6
FFA0.45 (0.03)0.48 (0.04)0.56 (0.04)0.09
CRP0.72 (0.30)0.65 (0.14)1.13 (0.6)0.57
Hgb A1C6.18 (0.23)6.08 (0.15)6.43 (0.32)0.54
Alk Phos81.2 (5.8)77.8 (5.4)78.4 (4.7)0.71
Total bilirubin0.68 (0.17)0.58 (0.06)0.51 (0.04)0.31
Direct bilirubin0.13 (0.02)0.13 (0.01)0.11 (0.01)0.21
Platelets246.6 (23.1)266.9 (13.5)242.6 (18.0)0.89
Creatinine0.74 (0.05)0.80 (0.03)0.80 (0.06)0.45
HOMA11.82 (4.80)7.14 (1.74)5.64 (1.44)0.21
MRI
MRI-PDFF (%)8.90 (1.03)16.3 (1.13)25.02 (1.61)<0.00001

Histology parameters by steatosis grade

Liver biopsies were examined using the NASH-CRN histological scoring system and then categorised by histology-determined steatosis grade (Table 2). Mean lobular inflammation was not significantly different in patients with grade 1 vs. grade 3 steatosis. Compared to patients with grade 3 steatosis, patients with grade 1 steatosis were more likely to have higher ballooning scores (1.38 vs. 0.86, P = 0.047), and fibrosis stage (2.31 vs. 0.93, P = 0.02) both of which are associated with advanced NASH, but a lower NAS (4.08 vs. 5.36, P = 0.007) which includes the steatosis score a component. Since steatosis can drive NAS score, we assessed NAS minus the steatosis score, and found that the three groups did not differ.

Table 2. Liver histology and magnetic resonance imaging data by steatosis grade
 Steatosis Grade-1 (N = 13)Steatosis Grade-2 (N = 24)Steatosis Grade-3 (N = 13)P-value
  1. MRI, magnetic resonance imaging; NAS, NAFLD activity score; PDFF, proton density fat fraction.

  2. Data are expressed as mean with standard error in parentheses unless otherwise noted.

  3. t-test assuming equal variance between steatosis grade 1 and grade 3 was performed on all continuous/ordinal variables.

Lobular Inflammation1.69 (0.21)1.58 (0.13)1.5 (0.2)0.51
Hepatocellular Ballooning1.38 (0.18)0.96 (0.14)0.86 (0.18)0.047
Fibrosis2.31 (0.47)0.79 (0.22)0.93 (0.30)0.0197
NAS4.08 (0.26)_4.54 (0.23)5.36 (0.34)0.007
NAS without steatosis3.08 (0.26)2.54 (0.22)2.36 (0.34)0.11
MRI
MRI-PDFF (%)8.90 (1.03)16.3 (1.13)25.02 (1.61)<0.00001

Histology-determined steatosis grade and MRI-determined PDFF

We confirmed a robust association between histology-determined steatosis grade and MRI-determined PDFF (Figure 1) and showed that there was a parallel and dose-dependent increase in MRI-determined PDFF as histology-determined steatosis grade increased from grade 1–3. The average MRI-determined PDFF at steatosis grade 1, 2 and 3 increased from 8.9% to 16.3% to 25.0%, respectively, and was clinically as well as statistically significant (P ≤ 0.0001). By linear regression, histology-determined steatosis grade significantly correlated with MRI-determined PDFF (r2 = 0.54, P < 0.0001).

image

Figure 1. Magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF) (%, y-axis as MRI-PDFF) is plotted by histology-determined steatosis grade (x-axis) using the NASH-CRN histological scoring system. The blue diamonds show each individual patients' (N = 51) PDFF at their respective steatosis grade. The red diamonds represent the average PDFF seen at the specified steatosis grade. The average value of MRI-determined PDFF increases with increasing steatosis grade: at steatosis grade 1, average fat fraction is 8.9%, at grade-2 it is 16.3%, and at grade-3 it is 25.0%, and comparisons between all groups are statistically significant, P-value ≤ 0.0001. MRI PDFF increased with increasing steatosis grade: r2 = 0.56 P < 0.0001.

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Association between stage of fibrosis, and histology-determined steatosis grade and MRI-determined PDFF

Average MRI-determined PDFF and histology-determined steatosis grade remained relatively stable at fibrosis stage 0–3, but dropped significantly at stage 4 (Figure 2). Patients with cirrhosis, defined as stage 4 fibrosis on liver biopsy, had lower average MRI-determined PDFF than patients with lesser degree of fibrosis, stages 0–3 (7.6% vs. 17.8% P < 0.005) and lower average histology-determined steatosis grade (1.4 vs. 2.2, P = 0.03). MRI-determined PDFF inversely correlated with hepatic fibrosis (r2 = −0.13 P = 0.008).

image

Figure 2. Fibrosis stage (0–4) determined by liver biopsy is seen on the x-axis while average histology-determined steatosis grade (blue) and average MRI-determined proton density fat fraction (red) are seen on the y-axis with scale on the left and right, respectively. Standard error bars are shown. Average MRI-PDFF and histology-determined steatosis grade remain relatively stable at fibrosis stage 0–3, but drop significantly at stage-4 (cirrhosis). Those patients with advanced (stage-4) fibrosis on liver biopsy had lower average MRI-PDFF than patients with lesser (stages 0–3) fibrosis (7.6% vs. 17.8%, P < 0.005) and lower average histology-determined steatosis grade (1.4 vs. 2.2, P = 0.03).

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Biochemical parameters of advanced liver disease

We conducted sensitivity analysis to further assess if there is a true association between lower MRI-determined PDFF & histology-determined steatosis grade, and stage 4 fibrosis (Table 3). We hypothesised that patients with grade 4 fibrosis have more advanced liver disease that is associated with lower MRI-determined PDFF and histological steatosis. We examined clinical parameters of advanced liver disease such as AST to ALT ratio, increased GGT and INR. When stratified by histology-determined steatosis grade, subjects with grade 1 steatosis had higher AST: ALT ratio (0.87 vs. 0.60, P = 0.012), GGT (140.2 vs. 66.6 units/L, P = 0.007), and INR (1.06 vs. 0.993, P = 0.009) compared to subjects with grade 3 steatosis.

Table 3. Biochemical parameters of advanced liver disease
 Steatosis Grade-1 (N = 13)Steatosis Grade-2 (N = 24)Steatosis Grade-3 (N = 13)P-value
  1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase; INR, international normalised ratio.

  2. Data are expressed as mean with standard error in parentheses.

AST:ALT0.87 (0.10)0.64 (0.04)0.60 (0.04)0.012
GGT140.2 (25.0)51.6 (7.8)66.6 (7.3)0.007
Albumin4.45 (0.08)4.65 (0.05)4.64 (0.06)0.09
INR1.06 (0.024)0.996 (0.011)0.993 (0.007)0.009

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Main findings

In this cohort of adult patients with NAFLD, MRI-determined PDFF is closely associated with histology-determined steatosis grade. The average PDFF at grades 1, 2 and 3 steatosis were 8.9%, 16.3% and 25.0% respectively, (P < 0.0001). Previous studies have shown that MRI fat fraction calculated by the Dixon/IOP method correlates well with hepatic steatosis in adult patients with liver disease consisting of various aetiologies and in paediatric patients with NAFLD.[8-10] In addition, MRS has also been shown to be an accurate technique in quantifying hepatic steatosis,[11, 12] but remains largely a research tool. This study uses an improved, well-validated PDFF technique in a middle-aged, adult cohort of patients with biopsy-proven NAFLD. Two general approaches for MRI-determined PDFF estimation have been developed- one technique uses complex data,[14, 15] and the other technique uses magnitude data.[20-23] Based on phantom studies and comparisons with MR spectroscopy, both approaches appear to be superior to conventional approaches and similar to one another. Our study selected the magnitude technique because our team had expertise in its use and UCSD liver imaging group is developing tools to apply this technique in the clinical setting. Using this magnitude approach, we found that that MRI-PDFF quantification significantly correlates with grade of steatosis by liver biopsy. This lends support to the potential use of MRI-determined PDFF as a non-invasive and quantitative means to quantify hepatic steatosis in patients with NAFLD.

Furthermore, the inverse relationship between advanced fibrosis and degree of hepatic steatosis as seen in our subset analysis of patients with stage 4 fibrosis and grade 1 steatosis was previously not well understood in adult patients with NAFLD. This study suggests that stage 4 fibrosis is associated with decreased hepatic steatosis by both a lower MRI-determined PDFF and histology-determined steatosis grade than patients with stage 0-3 fibrosis (7.6% vs. 17.8%, P < 0.005; and 1.4 vs. 2.2, P = 0.03 respectively). Compared to patients with histology-determined grade 3 steatosis, when patient's with grade 1 steatosis were examined further, their biochemical profile on average suggested more severe liver disease as reflected by higher GGT, AST to ALT ratio, INR, as well as hepatocellular ballooning on liver histology.

As more and more clinicians utilise non-invasive assessment of NAFLD using imaging techniques it is critical to understand the caveats associated with assessment of imaging-determined hepatic steatosis in NAFLD. This study illustrates that a lower hepatic fat content on imaging should not be confused as mild NAFLD but other parameters should be considered and a liver biopsy may be entertained if there is a suspicion of advanced NASH or fibrosis despite lower hepatic fat content on imaging. We would like to propose that less hepatic steatosis (measured either by MRI-PDFF or liver biopsy) is perhaps bi-modally distributed with respect to disease severity: with a group of mild NAFLD having less fibrosis (no fibrosis) and a group of severe NAFLD or even NASH-related cirrhosis where hepatic steatosis is replaced by collagen (more advanced fibrosis). Thus, imaging-determined hepatic steatosis may not be a reliable measure of the severity of NAFLD, and one should remain cautious about interpreting low levels of hepatic steatosis as early or mild NAFLD. The exact mechanisms underlying this association remain to be elucidated and are beyond the scope of the present study.

Strengths and limitations of the study

The major strengths of the study include the use of well-characterised adult patients with liver biopsy-confirmed NAFLD, and novel (and detailed) MRI imaging techniques, prospectively collected biochemical and MRI data, and inclusion of both genders. The study utilised a well-validated, MRI-determined PDFF technique which improves on previous technique of Dixon/IOP methods by correcting for T1 bias and bias, T2* decay, eddy currents and the spectral complexity of fat. Furthermore, the biopsy and MRI data were obtained within an average time between biopsy and MRI of 2.1 months. The radiologist and the pathologists were blinded to clinical as well as pathology and MRI data, respectively. Statistical analyses were performed after all data collections and quality control procedures were completed. Despite these strengths, the study is limited by the small number patients and lacks the power to detect differences in stage by stage changes in liver fat content. Secondly, there was no control or non-NAFLD arm, although this would not have supported the primary aim to study MRI-PDFF specifically in NAFLD patients. Lastly, we only used one of the two available MRI-PDFF techniques, and this selection of technique was due to availability of local expertise in the magnitude technique at UCSD.[14, 15] We recently showed that this MRI-PDFF technique has an excellent correlation with MRS (r2 = 0.98).[24] Therefore, we believe that our results are valid for NAFLD patients examined in this study.

Conclusions

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

The MRI-determined PDFF is well correlated with histology-determined steatosis grade in patients with NAFLD. Furthermore, cirrhosis is associated with lower levels of hepatic steatosis both by histology and MRI-determined PDFF. Future studies will be needed to explore the natural history of NAFLD, the interplay between hepatic steatosis and fibrosis, and to decide whether or not novel MRI techniques can be used as a non-invasive means to study disease progression in NAFLD by fat mapping and changes in fat distribution over time.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References

Declaration of personal interests: None. Declaration of funding interests: The study sponsor(s) had no role in the study design, collection, analysis, interpretation of the data, and/or drafting of the manuscript. This work is supported in part by the American Gastroenterological Association (AGA) Foundation - Sucampo - ASP Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award. Funding was provided by Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors and the American Gastroenterological Association and 1K23DK090303 to RL.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Acknowledgements
  9. References