ABSTRACT
This study aimed to evaluate the prevalence, pattern and predisposing factors for hepatic adverse effects with statins in a regional hospital in Sultanate of Oman. A retrospective review of the patient files in Department of Medicine during the year 2011 was done to evaluate any hepatic dysfunction possibly related to statins among the patients. For each case of suspected statin induced hepatic effect, additional details on temporal relationship, pattern of presentation, management, final outcome and any contributing factors were obtained. Difference in the occurrence of hepatic effects based on the patient demographics and drug characteristics was additionally evaluated. A total of 927 patients meeting the inclusion criteria were included for the study. Mean age of the evaluated patients was 63.1 + 11.37 and median duration of use of statin in months was 22 [IQR, 43.25]. In 40 [4%] of the 927 patients, there was presence of a hepatic effect considered to be statin related and only in 12 [1%] patients a significant transaminase rise [>3 times] was observed. Median duration of use of statin among those patients who developed suspected statin induced hepatic effects and those who did not was 45 [IQR,52] and 21 [IQR, 43] months, respectively and the difference observed was statistically significant. A significant difference in the prevalence of hepatic effects was observed only based on the duration of statin use. There was an infrequent occurrence of significant hepatic effects associated with statins in the study population. Our results support the latest recommendations including from United States Federal Drug Administration [US PDA] that statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of transaminases does not appear to detect or prevent serious liver injury in association with statins use
ABSTRACT
SLE is a systemic autoimmune disease with polyclonal B cell hyperactivity, spontaneous lymphocyte proliferation, and the production of pathogenic antibodies to self-antigens. Interleukin-6 is a pleiotropic cytokine with diverse functions including B-cell growth and differentiation. IL-6 levels have been shown to be affected by single nucleotide change from G to C at position -174 in the promoter region of the IL-6 gene.To find out whether single nucleotide polymorphisms in the promoter region of the IL-6 gene [-174 G/C] constitute a genetic susceptibility for SLE and its association with various disease clinical and immunological features. Forty-two female SLE patients and 40 healthy controls were genotyped for IL-6 gene promoter region [-174 G/C] polymorphism using PCR. SLE patients satisfied the 1982 revised criteria of the American Rheumatism Association for the classification of SLE, with a mean age of 32.4 +/- 5.5 years and mean disease duration of 5.7 +/- 1.5 years. The healthy controls were matched for age and sex, with a mean age of 31.7 +/- 4.9 years. All subjects were recruited from the Rheumatology and Rehabilitation and Internal Medicine Departments, Kasr El Aini Hospitals. SLE clinical and laboratory features were recorded including constitutional, hematological, joint, renal, and neuropsychiatric manifestations, oral ulcers, serositis, malar rash, and photosensitivity and CBC, liver, kidney functions and serum C3 and C4 levels. Positivity for ANAs, Anti-dsDNA and Anti-Sm antibodies were determined. Genotypic and allelic distributions showed no significant differences between SLE patients and controls. The frequency of G allele was higher than C allele in both patients [83.3% vs. 16.7%] and controls [85% vs. 15%]. SLE patients with GG genotype showed significantly higher frequencies and increased risk of; constitutional manifestations at disease onset [P = 0.02], OR [95% CI] = 6.55 [1.22-35.12], photosensitivity [P = 0.03], OR [95% CI] = 4.67 [1.11-19.54], hematological disorders [P = 0.02], OR [95% CI] = 5.5 [1.29-23.39] and positivity of ANAs and Anti-dsDNA [P = 0.046, 0.03: OR [95% CI] = 7 [1.1-45.44], 6.43 [1.23-33.65], respectively]. Furthermore, those patients had significantly lower mean WBCs counts when compared to SLE patients with [GC and CC] genotypes [4.54 +/- 1.31 vs. 5.98 +/- 1.04/dl, P = 0.002]. Twenty-five patients had lupus nephritis [LN] proved by renal biopsy but none of them had CC genotype. LN patients with GG genotype had nearly similar mean 24-h proteinuria to those with GC genotype [2.93 +/- 1.07 vs. 2.68 +/- 1.06 g/24 h and P = 0.39]. No significant difference was found in IL-6 genotype and allele distributions when patients with diffuse proliferative glomerulonephritis [class IV], which has the worst prognostic outcome, were compared to patients with non-class IV glomerulonephritis [classes II and III] [P = 0.12, 0.15, respectively]. IL-6 promoter region [-174 G/C] polymorphism does not confer susceptibility to SLE but it is related to the presence of distinct clinical and immunological features. Furthermore, the increased frequency of the high-response G allele suggests that a genetically determined high IL-6 response may have a pathogenic role