Research Article Details

Article ID: A37506
PMID: 15526543
Source: Rom J Intern Med
Title: The risk factors of fibrosis in nonalcoholic steatohepatitis.
Abstract: UNLABELLED: Nonalcoholic steatohepatitis (NASH) can be a severe progressive liver disease leading to the development of cirrhosis. The aim of this study was to assess the risk factors of fibrosis in NASH. METHODS: The clinical, biochemical and histological features of 80 patients with NASH admitted at University Hospital from 1998 to 2000, were analyzed. The patients had no alcoholic, viral, autoimmune, drug induced or genetic liver disease. The fibrosis and necroinflammatory activity was associated with clinico-biochemical parameters and with oxidative stress. The clinical and biochemical parameters consist of: age, sex, body mass index (BMI), serum glucose, tryglycerides, alanine aminotransferase (ALT) and serum iron study (transferring saturation and ferritin). Liver iron overload was assessed by Pearls'staining and graded in four classes. The oxidative stress was evaluated by the levels of serum malon-dyaldehide (MDA) and serum total gluthatione (GSI4). RESULTS: Septal fibrosis was present in 30 patients (27%) including cirrhosis in 4 patients (5%). Age > 45 years, B.M.I. >30 Kg/m2, serum tryglycerides >180 mg/dl, hyperglycemia > 220 mg/dl, serum ALT > 3N, increased hepatic iron and transferrin saturation percentage were independently associated with sepal fibrosis. Linear regression analysis showed that increased hepatic iron had the greatest association with the increase of lipid peroxidation (MDA > 250 nanomol/dl) and the decrease of serum gluthatione (< 40 micromol/dl). CONCLUSIONS: The clinical and biochemical parameters which consist of age, BMI, serum ALT, glucose and tryglycerides, Perls' grade and the serum index of oxidative stress (MDA and GSH) are independent risk factors for fibrosis in NASH raising therapeutic implications for the management of these patients.
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Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
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
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

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

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D199 L-alanine Chemical drug DB00160 KYNU -- Failed in clinical trials Details
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D593 GSI Miscellany -- Notch inhibitor Anti-fibrosis Under investigation Details
D083 CLA Chemical drug DB01211 KCNH2; SLCO1B1; SLCO1B3 -- Under clinical trials Details
D158 Glutathione Chemical drug DB00143 MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor -- Under clinical trials Details