ABSTRACT
BACKGROUND AND AIMS: Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS. METHODS: Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan® ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants. RESULTS: Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2 ). A total of 80% (24/30) were diabetic; 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles. CONCLUSIONS: NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS.
Subject(s)
Adipose Tissue/pathology , Alstrom Syndrome/complications , Liver Cirrhosis/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology , Adult , Cohort Studies , Female , Fibrosis , Gene Expression , Humans , Insulin Resistance , Liver/pathology , Liver Cirrhosis/pathology , Male , Non-alcoholic Fatty Liver Disease/pathology , Obesity/complications , United Kingdom , Young AdultABSTRACT
OBJECTIVES: To prospectively use a non-invasive algorithm to identify asymptomatic, advanced non-alcoholic fatty liver disease (NAFLD) in a secondary care diabetes clinic and to determine the short-term effect of a multi-disciplinary team (MDT) approach in a liver clinic. RESEARCH DESIGN AND METHODS: NAFLD Fibrosis Score (NFS) was calculated in 64 asymptomatic patients with type 2 diabetes. Advanced fibrosis was identified using transient elastography and confirmed with liver biopsy. In a subsequent retrospective study, 95 patients newly referred to the NAFLD MDT clinic were investigated and the impact of the MDT approach assessed. RESULTS: 25/64 (39.0%) of patients with diabetes had a low NFS (<-1.455). 39/64 (61.0%) patients had a high or indeterminate NFS and were referred for review in the NAFLD MDT clinic, of which 23/39 attended for assessment. 19/23 (82.6%) were diagnosed with NAFLD, of which 6/19 (31.6%) patients had a positive transient elastography (≥8 kPa). Liver biopsy confirmed advanced fibrosis in 5/6 cases, with moderate fibrosis in 1 case. In the retrospective study, 65/95 (68.4%) new referrals to the NAFLD MDT clinic had a diagnosis of NAFLD. Over a median 98 days (IQR 70-182) follow-up, there was a significant improvement in weight (-0.8 kg; P = 0.024), total cholesterol (-0.2 mmol/L; P = 0.044), ALT (alanine transmaminase, -12.5 IU/L; P < 0.001) and GGT (gammu-glutamyl transferase, -13.0 IU/L; P < 0.0001). 7/28 (25%) of patients with diabetes achieved >5% weight loss. CONCLUSIONS: A significant proportion of asymptomatic patients attending type 2 diabetes clinics have undiagnosed advanced NAFLD fibrosis. An MDT approach to NAFLD results in short-term improvements in metabolic and liver parameters.
