bms-790052 and Insulin-Resistance

The achievement of virological response in the treatment of hepatitis C virus (HCV) can improve the extrahepatic manifestations. The present study aimed to investigate the effect of HCV eradication after sofosbuvir/daclatasvir (SOF/DCV) therapy on hematological and inflammatory biomarkers in type 2 diabetic patients infected with HCV genotype 4. Between October 2017 and August 2018, among 145 patients with HCV genotype 4, 30 patients were enrolled in the study based on the fact that they have type 2 diabetes. Enrolled HCV-diabetic patients were treated for 12 weeks with SOF/DCV regimen. Patients were screened by laboratory investigations before treatment (baseline values) and after HCV treatment (post-treatment values). Additionally, 30 healthy individuals were enrolled as a control group. Among the patient's cohort, the sustained virological response was achieved by 100% of the treated patients after 12 weeks of SOF/DCV therapy. Moreover, the levels of insulin resistance (HOMA-IR), nitric oxide, interleukin-1β, red cell distribution width, platelet distribution width, mean platelet volume were improved significantly (P < 0.001) in treated patients after successful viral clearance compared to baseline values. In addition, virological clearance exhibited positive correlations with interleukin-1β, nitric oxide, leukocytes count, red cell distribution width, and mean platelet volume. In conclusion, the data suggest the potential amelioration effect of HCV eradication after treatment with SOF/DCV regimen on the inflammatory status among HCV-diabetic patients which is reflected by the noticeable improvement of altered hematological indices and inflammatory biomarkers.

Topics: Adult; Antiviral Agents; Biomarkers; Carbamates; Diabetes Mellitus, Type 2; Female; Genotype; Glycated Hemoglobin; Hepacivirus; Hepatitis C; Humans; Imidazoles; Inflammation; Insulin Resistance; Interleukin-1beta; Male; Middle Aged; Pyrrolidines; Sofosbuvir; Sustained Virologic Response; Treatment Outcome; Valine

Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta-cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype-1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta-cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta-cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR.

Topics: 2-Naphthylamine; Aged; Anilides; Antiviral Agents; Carbamates; Cyclopropanes; Drug Therapy, Combination; Female; Genotype; Glucose; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Insulin Resistance; Insulin-Secreting Cells; Isoquinolines; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Prospective Studies; Pyrrolidines; Ritonavir; Sofosbuvir; Sulfonamides; Uracil; Valine