Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.2%)(P < 0.001). The G allele of LDL receptor exon8 c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8 c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders(P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for nonresponse. There was a significant association between LDL receptors exon8 c.1171G>A and HAI(P < 0.011). There was a significant association between LDL receptors exon8 c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype(28.7 ± 4.7 kg/m2) followed by the GA genotype(28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype(26.6 ± 4.3 kg/m2)(P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis(P < 0.001).CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptiansinfected with chronic HCV.

Comparison on Efficacy and Safety of Three Inpatient Insulin Regimens for Management of Non-Critical Patients with Type 2 Diabetes

Background: Hyperglycemia in hospitalized patients is associated with poor clinical outcomes. Scheduled Subcutaneous Insulin therapy has been recommended for better glycemic control. Aims: To compare efficacy and safety of traditional sliding scale insulin (SSI) versus modified 70/30 insulin versus basal plus supplemental scale (SS) insulin regimens for glycemic control of inpatients with diabetes. Methods: In a prospective trial, 62 patients with diabetes were randomized to receive either hospital SSI (N = 22), or twice daily 70/30 insulin plus supplemental lunchtime insulin for BG ≥ 150 mg/dL (N = 21) or once every night glargine plus prandial glulisine for BG ≥ 150 mg/dL (N = 19). 70/30 insulin and glargine were started respectively at 0.4 and 0.2 U/kg/day for BG ≤ 200 mg/dL or 0.5 and 0.3 U/kg/day for BG above 200 mg/dL. Results: Starting at BG level of 204 ± 68, 200 ± 50 and 241 ± 94 mg/dL in SSI, 70/30 insulin and glargine/glulisine groups respectively, (F(2,35.47) = 1.467, p = 0.244, Welch test), mean daily BG after first day of hospitalization was statistically significant (F(2,35.58) = 7.043, p = 0.003, Welch test) lower in 70/30 insulin group (171 ± 38 mg/dL) compared to (218 ± 71 mg/dL) in SSI group (p = 0.026) and (225 ± 65 mg/dL) in glargine/glulisine group (p = 0.01). Conclusions: With poorly educated nursing staff, basal plus SS insulin failed to provide adequate glycemic control. However, tailored 70/30 insulin regimen resulted in statistically significant glycemic control compared to traditional SSI.