Research Article Details

Article ID: A25192
PMID: 22103042
Source: Acta Gastroenterol Belg
Title: Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease.
Abstract: AIMS: Non-alcoholic fatty liver disease (NAFLD) is strongly associated to obesity and type 2 diabetes, but may occur in the absence of these factors. Based on a large series of liver biopsies, we have evaluated the clinical, biochemical, metabolic and pathological characteristics of a new entity, which we refer to as "lean-NAFLD". METHODS: Among 1,777 patients, who underwent liver biopsy for chronic liver disease, Lean-NAFLD, defined as patients with NAFLD without obesity (BMI < 30 kg/m2) and without diabetes was found in 50 of them (2.8%), being the most frequent cause (38%) of cryptogenic liver disease. Thirty-one patients from the Lean-NAFLD group were compared to 48 Obese-NAFLD patients diagnosed during the same period and 8 healthy control patients. Insulin resistance was determined using the homeostasis model assessment method. RESULTS: In the Lean-NAFLD group as compared to the obese-NAFLD group, patients were younger : median 40 vs. 49 years, p = 0.047, with male predominance: 71 vs. 46%, p = 0.037. Fasting glucose and HbA1c were lower, as was insulin sensitivity: 1.7 vs. 3.0, p = 0.049. Blood pressure was significantly lower (p = 0.001) while triglycerides and HDL-cholesterol were similar. Although there was less inflammation (p = 0.038) and fibrosis (p = 0.029), non-alcoholic steatohepatitis and fibrosis were present in 61% and 55% of the Lean-NAFLD group, respectively. Compared to healthy controls, Lean-NAFLD were less insulin sensitive, with a insulin sensitivity index of 59 vs. 110 (p = 0.015), and more hypertriglyceridemic (p = 0.003). CONCLUSIONS: Lean-NAFLD is a new unrecognized clinicopathological entity, a frequent cause of cryptogenic liver disease.
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Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I14 9970 Obesity An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details