Stephen Glancy

Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study

OBJECTIVE Type 2 diabetes is an established risk factor for development of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and clinical correlates of these conditions in a large cohort of people with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 939 participants, aged 61–76 years, from the Edinburgh Type 2 Diabetes Study (ET2DS)—a large, randomly selected population of people with type 2 diabetes—underwent liver ultrasonography. Ultrasound gradings of steatosis were compared with magnetic resonance spectroscopy in a subgroup. NAFLD was defined as hepatic steatosis in the absence of a secondary cause (screened by questionnaire assessing alcohol and hepatotoxic medication use, plasma hepatitis serology, autoantibodies and ferritin, and record linkage to determine prior diagnoses of liver disease). Binary logistic regression was used to analyze independent associations of characteristics with NAFLD. RESULTS Hepatic steatosis was present in 56.9% of participants. After excluding those with a secondary cause for steatosis, the prevalence of NAFLD in the study population was 42.6%. Independent predictors of NAFLD were BMI, lesser duration of diabetes, HbA1c, triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis. CONCLUSIONS Prevalences of hepatic steatosis and NAFLD were high in this unselected population of older people with type 2 diabetes, but lower than in studies in which ultrasound gradings were not compared with a gold standard. Associations with features of the metabolic syndrome could be used to target screening for this condition.

The use of ultrasound to diagnose hepatic steatosis in type 2 diabetes: intra- and interobserver variability and comparison with magnetic resonance spectroscopy.

AIM To compare ultrasound gradings of steatosis with fat fraction (FF) on magnetic resonance spectroscopy (MRS; the non-invasive reference standard for quantification of hepatic steatosis), and evaluate inter- and intraobserver variability in the ultrasound gradings. MATERIALS AND METHODS Triple grading of hepatic ultrasound examination was performed by three independent graders on 131 people with type 2 diabetes. The stored images of 60 of these individuals were assessed twice by each grader on separate occasions. Fifty-eight patients were pre-selected on the basis of ultrasound grading (normal, indeterminate/mild steatosis, or severe steatosis) to undergo (1)H-MRS. The sensitivity and specificity of the ultrasound gradings were determined with reference to MRS data, using two cut-offs of FF to define steatosis, ≥9% and ≥6.1%. RESULTS Median (intraquartile range) MRS FF (%) in the participants graded on ultrasound as normal, indeterminate/mild steatosis, and severe steatosis were 4.2 (1.2-5.7), 4.1 (3.1-8.5) and 19.4 (12.9-27.5), respectively. Using a liver FF of ≥6.1% on MRS to denote hepatic steatosis, the unadjusted sensitivity and specificity of ultrasound gradings (severe versus other grades of steatosis) were 71 and 100%, respectively. Interobserver agreement within one grade was observed in 79% of cases. Exact intraobserver agreement ranged from 62 to 87%. CONCLUSION Hepatic ultrasound provided a good measure of the presence of significant hepatic steatosis with good intra- and interobserver agreement. The grading of a mildly steatotic liver was less secure and, in particular, there was considerable overlap in hepatic FF with those who had a normal liver on ultrasound.

Magnetic Resonance Follow-through Imaging for Evaluation of Disease Activity in Ileal Crohn's Disease: An Observational, Retrospective Cohort Study

Background: Magnetic resonance follow‐through (MRFT) is a new cross‐sectional imaging modality with the potential to accurately stage ileal Crohns disease (CD), while avoiding ionizing radiation and the discomfort associated with enteroclysis. We aimed to assess the reliability of this technique in assessing the extent and activity of ileal CD, and to assess its influence on subsequent management. Methods: Out of a total of 342 patients undergoing MRFT between 2004 and 2008, 221 were performed in 191 patients with confirmed CD. Case notes were reviewed in detail with documentation of all investigations pre‐ and post‐MRFT. Agreement between inflammatory markers, histopathology, and MRFT findings was determined. Results: Overall, 116/221 (52.5%) of MRFTs showed active ileal CD, and 76/221 (34.4%) quiescent CD, while 29/221 (13.1%) were suboptimal. Overall, 66 strictures and 18 fistulae were identified. There was substantial agreement between active ileal CD on MRFT and histopathology (n = 59; &kgr; = 0.66; P = 0.0006; sensitivity 85.1%, specificity 85.7%) and fecal calprotectin (n = 14; &kgr; = 0.72; P = 0.047), while C‐reactive protein (CRP) showed moderate agreement (n = 107; &kgr; = 0.402; P = 0.00028). Management was influenced by MRFT reports following active (52/84, 62% treated medically) or quiescent (48/62, 77.4% managed conservatively) disease. Fibrotic strictures were predominantly treated surgically (7/14, 50%). In all, 13/32 (40.6%) patients with inflammatory ileal strictures required surgery, mostly due to steroid‐resistant disease. Overall, 75 MR findings were documented in 221 MRFTs, including 1 renal cancer. Conclusions: MRFT provides accurate information on ileal CD activity, with close agreement to inflammatory markers and histopathology. It represents a substantial advance in the staging of CD, while avoiding painful enteroclysis and radiation exposure in young patients. (Inflamm Bowel Dis 2010)

Non‐invasive hepatic biomarkers (ELF and CK18) in people with type 2 diabetes: the Edinburgh type 2 diabetes study

Type 2 diabetes is an established risk factor for the presence and progression of fatty liver. Little is known about the distributions and correlates of hepatic non‐invasive biomarkers in community‐based populations with diabetes, unselected for liver disease. We aimed to identify the distribution of, and metabolic risk factors associated with serum cytokeratin‐18 (CK18) and the Enhanced Liver Fibrosis score (ELF), in a large, representative cohort of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study, ET2DS).

Clinically significant chronic liver disease in people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools.

Sa1212 Faecal Calprotectin and Ileal Crohn's Disease: Correlation With a Small Bowel MRI Score for Disease Activity

Introduction Small bowel MRI (SBMRI) is the current standard for assessing ileal inflammation in Crohn’s disease. Faecal calprotectin (FC) is closely correlated with colonic inflammation, but is thought to be of less utility in ileal disease. Interpretation of existing data linking FC with SBMRI findings have been confounded by the presence of colonic inflammation. We therefore aimed to ascertain how FC best reflects MRI findings exclusively in the small bowel. Methods 150 SBMRI studies with matched FC results (±30 days) were identified from the Edinburgh FC Register (2008–12; n = 18,138). Scans were entered into an anonymous ‘teaching’ list on PACS and each re-read independently by 2 expert GI radiologists blind to all clinical and lab data. Technical, quality and disease parameters were recorded onto standard proformas. Scans rated by one or other radiologist as being of poor quality were excluded (n = 31/150). 7/13 disease parameters were excluded due to poor interobserver variability (Cohen’s kappa Results 150 SBMRI scans were re-evaluated from 123 patients with purely ileal Crohn’s (Montreal L1, n = 109; L3 + previous panproctocolectomy, n = 14; 65% female; median age at MRI 45 years (IQR 32–56); median follow-up 34 months (IQR 25–44). The median (IQR) FC was 80 μg/g (20–142) where SBMRI demonstrated no active ileal disease (simple MRI score = 0, n = 38), 198 μg/g (120–444) for mild to moderate (1–6, n = 30) and 398 μ/g (168–771) for severe disease (>6, n = 24) (p Conclusion FC correlates closely with SBMRI findings in ileal Crohn’s disease and outperforms other laboratory tests. In future, following validation, we will derive clinical useful MRI and FC cut-offs that predicate on important patient outcomes. Disclosure of Interest None Declared.