Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection.

OBJECTIVE: To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN: Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS: Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 ß-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS: Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.

Tumor necrosis factor-alpha production from mononuclear cells in nephrotic syndrome.

Tumor necrosis factor-alpha (TNF-alpha) levels in supernatant fluid from cultured peripheral blood mononuclear cells (PBMC) were measured by ELISA in 54 children with active non-inherited forms of primary nephrotic syndrome (PNS), 10 nephrotics in remission, and 10 healthy controls. Children with active PNS included 21 patients with steroid-sensitive (SS) minimal change nephrotic syndrome (MCNS), 5 patients with steroid-resistant (SR) MCNS, 11 with SR focal segmental glomerulosclerosis (FSGS), 6 patients with SS diffuse mesangial proliferation (DMP), 5 patients with SR DMP, and 6 patients with mesangiocapillary glomerulonephritis (MCGN). Patients with active PNS had elevated TNF-alpha production compared with controls. Remission was associated with normalization of TNF-alpha production. There was a positive correlation between TNF-alpha production and the degree of proteinuria ( r=0.34, P=0.013), mesangial hypercellularity ( r=0.42, P=0.028), and glomerulosclerosis ( r=0.46, P=0.001). By using ROC curve, TNF-alpha production greater or equal to a cut-off point of 50 pg/ml could be used to predict resistance to steroid therapy (predictability 93.2%). By discriminate analysis, TNF-alpha production could be used to discriminate between patients with SR MCNS, SR FSGS, and SR DMP (predictability 100%). In conclusion, TNF-alpha from cultured PBMC might be involved in the pathogenesis of proteinuria as well as the pathological changes that occur in non-inherited forms of PNS. TNF-alpha levels in PBMC culture could be used to predict the pathological type of PNS and the response of these patients to steroid therapy.