[Show abstract][Hide abstract] ABSTRACT: 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.AimsTo 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.DesignProspective cohort studyMethods939 participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of NASH, hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources.ResultsEight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000person-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.
Preview · Article · Oct 2015 · QJM: monthly journal of the Association of Physicians
[Show abstract][Hide abstract] ABSTRACT: We examined the association of prevalent and incident cardiovascular disease (CVD) with chronic liver disease in a cohort of community-based people with type 2 diabetes, in order to clarify the relationship between these two important conditions.
1,066 participants with type 2 diabetes aged 60-75 years underwent assessment of a range of liver injury markers (non-specific injury, steatosis, steatohepatitis, fibrosis, portal hypertension). Individuals were followed up for incident cardiovascular events.
At baseline there were 370/1,033 patients with prevalent CVD, including 317/1,033 with coronary artery disease (CAD). After a mean follow-up of 4.4 years there were 44/663 incident CVD events, including 27/663 CAD events. There were 30/82 CVD-related deaths. Risk of dying from or developing CVD was no higher in participants with steatosis than in those without (HR 0.90; 95% CI 0.40, 2.00; p > 0.05). The only notable relationship was with γ-glutamyltransferase (GGT) (incident CVD: adjusted HR for doubling GGT 1.24 [95% CI 0.97, 1.59] p = 0.086; incident CAD: adjusted HR 1.33 [95% CI 1.00, 1.78] p = 0.053), suggesting that in our study population, chronic liver disease may have little effect on the development of, or mortality from, CVD.
An independent association between GGT and CVD warrants further exploration as a potentially useful addition to current cardiovascular risk prediction models in diabetes. However, overall findings failed to suggest that there is a clinical or pathophysiological association between chronic liver disease and CVD in elderly people with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Background & Aims
It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research.
In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60–74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured.
Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9–16%).
We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups.
No preview · Article · Feb 2014 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: 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).
939 ET2DS participants, aged 60-74 years underwent physical examination including ultrasound for assessment of liver fat. Representative subgroups were assessed for markers of chronic liver disease (CK18 and ELF).
CK18 values ranged from 29-993 U/L (median 102, IQR 76-137 U/L) and ELF scores ranged from 6.9-11.6 (mean 8.9, SD 0.8). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres).
We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much of the variation in biomarkers remained unexplained. Prospective studies are required to determine the extent to which CK18 and/or ELF predict the development of symptomatic liver disease and to identify additional risk factors which may influence the development of advanced liver disease in people with type 2 diabetes. This article is protected by copyright. All rights reserved.
No preview · Article · Nov 2013 · Liver international: official journal of the International Association for the Study of the Liver
[Show abstract][Hide abstract] ABSTRACT: Traditional methods of investigating suspected colorectal carcinoma (CRC) such as barium enema, colonoscopy and computerized tomography (CT) pneumocolon are often poorly tolerated by frail or elderly patients. Comparatively, minimal-preparation CT (MPCT) is a non-invasive investigation that does not require bowel preparation. The aim of this study was to review MPCTs carried out at the Western General Hospital, Edinburgh, and compare findings with current published data. Retrospective analysis of 85 patients (age range 55-99 years) who underwent MPCTs at the Western General Hospital between May 2005 and June 2008 was undertaken. Results were followed up using clinical notes, pathological and surgical databases. Subsequent outcomes were analysed (average follow-up 22 months). The prevalence of CRC within the study cohort was 0.14. Sensitivity of MPCT was 1 (95% confidence interval [CI], 0.69-1) with a specificity of 0.93 (95% CI, 0.84-0.97). Thirty percent of patients were found to have extracolonic findings requiring further investigation or intervention. Of the patients, 4.7% had an extracolonic malignancy diagnosed on MPCT. MPCT is a sensitive and specific method of investigating CRC in the elderly, infirm or immobile. Our results were found to be comparable with that of current published data, validating the service provided at the Western General Hospital.
No preview · Article · Aug 2012 · Scottish medical journal
[Show abstract][Hide abstract] ABSTRACT: To evaluate the variance in current UK clinical practice and clinical outcomes for direct percutaneous radiologically inserted gastrostomy (RIG).
A prospective UK multicentre survey of RIG performed between October 2008 and August 2010 was performed through the British Society of Gastrointestinal and Abdominal Radiology (BSGAR).
Data from 684 patients were provided by 45 radiologists working at 17 UK centres. Two hundred and sixty-three cases (40%) were performed with loop-retained catheters, and 346 (53%) with balloon-retained devices. Sixty percent of all patients experienced pain in the first 24 h, but settled in the majority thereafter. Early complications, defined as occurring in the first 24 h, included minor bleeding (1%), wound infection (3%), peritonism (2%), and tube misplacement (1%). Late complications, defined as occurring between day 2 and day 30 post-procedure, included mild pain (30%), persisting peritonism (2%), and 30 day mortality of 1% (5/665). Pre-procedural antibiotics or anti-methicillin-resistant Staphylococcus aureus (MRSA) prophylaxis did not affect the rate of wound infection, peritonitis, post-procedural pain, or mortality. Ninety-three percent of cases were performed using gastropexy. Gastropexy decreased post-procedural pain (p < 0.001), but gastropexy-related complications occurred in 5% of patients. However, post-procedure pain increased with the number of gastropexy sutures used (p < 0.001). The use of gastropexy did not affect the overall complication rate or mortality. Post-procedure pain increased significantly as tube size increased (p < 0.001). The use of balloon-retention feeding tubes was associated with more pain than the deployment of loop-retention devices (p < 0.001).
RIG is a relatively safe procedure with a mortality of 1%, with or without gastropexy. Pain is the commonest complication. The use of gastropexy, fixation dressing or skin sutures, smaller tube sizes, and loop-retention catheters significantly reduced the incidence of pain. There was a gastropexy-related complication rate in 5% of patients. Neither pre-procedural antibiotics nor anti-MRSA prophylaxis affected the rate of wound infection.
No preview · Article · Jun 2012 · Clinical Radiology
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes is a risk factor for progression of non-alcoholic fatty liver disease (NAFLD) to fibrosis and cirrhosis. We examined the prevalence of advanced liver disease in people with type 2 diabetes and analysed the effectiveness of liver function tests (LFTs) as a screening tool.
Participants (n = 939, aged 61-76 years) from the Edinburgh Type 2 Diabetes Study, a randomly selected population of people with type 2 diabetes, underwent abdominal ultrasonography. Hyaluronic acid (HA) and platelet count/spleen diameter ratio (PSR) were used as non-invasive markers of hepatic fibrosis and portal hypertension. Subjects were screened for secondary causes of liver disease that excluded them from a diagnosis of NAFLD. The efficacy of LFTs [alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT)] in screening for liver disease was determined.
Cirrhosis was identified by ultrasound in four participants (0.4%). Ten (1.1%) had evidence of portal hypertension (PSR < 909), and two (0.2%) had hepatocellular carcinoma. Fifty-three participants (5.7%) had evidence of hepatic fibrosis (HA > 100 ng/ml in the absence of joint disease); a further 169 had HA > 50 ng/ml. In participants with NAFLD-related fibrosis (HA > 100 ng/ml), 12.5% had an elevated ALT level and 17.5% had an elevated GGT level.
The prevalence of hepatic fibrosis and cirrhosis were lower than expected. The use of LFTs to screen for liver disease missed most cases of fibrosis predicted by raised HA levels.
No preview · Article · Dec 2011 · QJM: monthly journal of the Association of Physicians
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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, HbA(1c), triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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%.
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%.
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.
No preview · Article · Feb 2011 · Clinical Radiology
[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance follow-through (MRFT) is a new cross-sectional imaging modality with the potential to accurately stage ileal Crohn's 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.
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.
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; kappa = 0.66; P = 0.0006; sensitivity 85.1%, specificity 85.7%) and fecal calprotectin (n = 14; kappa = 0.72; P = 0.047), while C-reactive protein (CRP) showed moderate agreement (n = 107; kappa = 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.
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.
Full-text · Article · Nov 2009 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: Colonic obstruction may be relieved by the insertion of a self-expanding metallic stent (SEMS), either for permanent palliative relief or as a bridge to surgery. Lesions proximal to the descending colon can be more difficult to intubate and stent . SEMS placement in the more proximal colon lesions has been reported in only a few cases [2,4]. The aim of this study was to review the outcome of SEMS for obstruction at the splenic flexure and above.
A study of all colonic stents inserted in one specialist unit was undertaken. Patients' demographics, site and aetiology of the underlying obstruction, success or other outcome of the procedures were collected. Thirty-day morbidity and mortality were documented.
Seven patients had proximal lesions: four in the transverse colon and three at the splenic flexure. Six patients had colorectal carcinoma and one had extrinsic compression from a gastric carcinoma. Six of the SEMS were inserted for permanent palliation, and one as a bridge to surgery. Stent placement was technically successful in six of the seven patients. In the seventh patient, there was a failure of expansion of the stent, after successful intubation of the lesion, which was in the distal transverse colon. One patient suffered from minor self-limiting abdominal pain in the first 24 h after the procedure. There was no other SEMS related morbidity or mortality. All of the successfully stented patients were discharged from the surgical ward within 3 days after the procedure. Median survival time was 4.3 months (range 3-12 months). Three patients are still alive.
The SEMS is a useful tool in managing acute bowel obstruction. Placement of colonic stents proximal to the descending colon is safe, feasible and effective.
No preview · Article · Mar 2008 · Colorectal Disease