Research Article Details

Article ID: A27908
PMID: 17048997
Source: Rev Esp Enferm Dig
Title: Hepatitis C and insulin resistance: steatosis, fibrosis and non-response.
Abstract: Insulin resistance is more often seen in hepatitis C than in other liver diseases, including non-alcoholic steatohepatitis. The Homeostasis Model for Assessment [HOMA= fasting insulin (mUI/ml) * fasting glucose (mmol/L) / 22.5] has proved useful in the measurement of insulin sensitivity in euglycemic patients. Cross-sectional and case-cohort studies support a role for hepatitis C as a factor implied in the development of type-2 diabetes in high-risk patients (male patients, older than 40 years, and overweight). In transgenic mice models the HCV core protein has been found to induce insulin resistance via TNF production. Insulin resistance has been associated with steatosis development and fibrosis progression in a genotype-dependent manner. In genotype-1 patients, the mechanisms by which insulin resistance promotes fibrosis progression include: a) steatosis; b) hyperleptinemia; c) increased TNF production; and d) impaired expression of PPARg receptors. Indeed, insulin resistance has been found as a common denominator to the majority of features associated with difficult-to-treat patients. Patients with cirrhosis, obesity, coinfected with HIV, and Afro-American, all of them showed insulin resistance. Insulin resistance strongly influences sustained response rates, at least in genotype-1 patients. Insulin resistance decreases during and after treatment in patients that achieved virus C clearance. Moreover, the incidence of type-2 diabetes seems to be lower in responders than in non-responders. In summary, hepatitis C promotes insulin resistance and insulin resistance induces steatosis, fibrosis, and interferon resistance. The treatment of insulin resistance by decreasing hyperinsulinemia could improve sustained response rates in patients with chronic hepatitis C treated with peginterferon plus ribavirin.
DOI: 10.4321/s1130-01082006000800006

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
T08 Tumor necrosis factor TNF inhibitor Cytokine P01375 TNFA_HUMAN Details
T10 Caspase-1 CASP1 inhibitor Enzyme P29466 CASP1_HUMAN Details
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details
T05 Peroxisome proliferator-activated receptor gamma PPARG agonist Nuclear hormone receptor P37231 PPARG_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
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D094 Cysteamine Chemical drug DB00847 GSS stimulant Renal drug Under clinical trials Details
D095 Cysteamine bitartrate Chemical drug DB00847 -- -- Under clinical trials Details