Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.     

Corneal elevation indices and pachymetry values of Saudi myopes using scheimpflug imaging

Objectives:To report the corneal elevation and thickness values for Saudi myopes and to evaluate the differences between these parameters in subgroups of this target population.Methods:Pentacam corneal topographic maps of the right eyes of patients visiting Al-Hokama Eye Clinic, Riyadh, Saudi Arabia, a tertiary eye center between January 2009 and December 2015 were retrospectively analyzed in this cross-sectional study. The patients were grouped into 3 categories based on their spherical readings: mild (-0.25 to -2.75D), moderate (-3.00 to -5.75D), and severe (≥-6.00D). Furthermore, patients with cylindrical readings of ≥-1.00 diopter were categorized as having myopic astigmatism, whereas those with less than -1.00 cylindrical diopter were categorized as having simple myopia.Results:Our sample was comprised of 1,276 patients; 838 (65.7%) had simple myopia and 438 (34.3%) had myopic astigmatism. The values for the whole myopic group were as follows: anterior corneal elevation (AE) at the apex= 2.60±1.48 (standard deviation), thinnest AE= 2.56±1.68, posterior elevation (PE) at the apex= 3.67±3.58, thinnest PE= 4.92±3.81, central pachymetry= 550.09±34.29, apical pachymetry=550.73±34.64, and thinnest pachymetry= 546.30±34.61. All of the measurements, except the apical PE and thinnest PE, were statistically significant across the simple and myopic astigmatism groups (p<0.05). Comparing the mild to moderate myopia groups revealed a significant difference in the apical AE (p=0.037). Moreover, the comparison between the mild and severe myopia groups revealed that the apical PE and the thinnest PE, as well as the central, apical, and thinnest pachymetry values were statistically significantly different (p<0.05).Conclusion:The corneal elevation indices and thicknesses specific to the Saudi myopes were found to be comparable to the international databases in terms of the elevation and thickness in some of the parameters.     

Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia

Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.     

Comparative efficacy of exenatide versus insulin glargine on glycemic control in type 2 diabetes mellitus patients inadequately treated with metformin monotherapy

PurposeComparative efficacy of exenatide versus insulin glargine primarily on glucemic control, and secondarily on body mass index (BMI), lipid profile and blood pressure, in type 2 diabetes mellitus (T2DM) patients suboptimally treated with metformin monotherapy.Material/MethodsForty-seven inadequately treated T2DM patients on metformin assigned to exenatide (n=18) or insulin glargine (n=29) for 26 weeks. Glycosylated hemoglobin (HbA1c), serum lipids, BMI, systolic and diastolic blood pressure, and adverse events, including episodes of hypoglycemia and gastrointestinal symptoms, were recorded.ResultsEither treatment had a similar favorable mean reduction in HbA1c. However, more patients in exenatide group achieved HbA1c ≤ 7% at the 26th week compared with insulin glargine group (p=0.036). Insulin glargine group had significantly more episodes of hypoglycemia compared with exenatide group (p=0.039). Gastrointestinal adverse events were non-significantly higher in the exenatide group. A significantly greater BMI reduction was observed in exenatide group, whereas BMI was not altered in insulin glargine group. Total and LDL cholesterol (p=0.012), and triglycerides (p=0.016) significantly decreased, whereas HDL cholesterol increased (p=0.021) in the exenatide group, whereas only total cholesterol decreased in insulin glargine group. Changes in systolic and diastolic blood pressure were insignificant in both groups.ConclusionsExenatide provided similar reduction in HbA1c, but fewer episodes of hypoglycemia, compared with insulin glargine. Exenatide had also a favorable effect on weight loss, although more gastrointestinal adverse events. Exenatide may provide a justified alternative in second line treatment of T2DM, but more trials are required to elucidate its long-term safety and cost-effectiveness.     

Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用

目的 观察Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用,在分子水平上寻找软骨损伤及修复的分子学生物标志,为探讨关节软骨损伤疾病的防治措施提供理论依据.方法 Wistar大鼠80只,按体质量随机分为4组:阴性对照组、阳性对照组、高剂量干预组、低剂量干预组,每组20只.阴性对照组食用常规成品颗粒饲料,其他3组食用含100 ng/kg T-2毒素染毒饲料;阴性对照组和阳性对照组饮自来水;低、高剂量干预组饮用含Ⅱ型胶原0.5、5.0 g/L的自来水.在3、5个月时处死大鼠,光镜下观察大鼠透明软骨的组织病理学改变,用酶联免疫吸附试验(ELISA法)检测大鼠血清Ⅱ型胶原羧基末端肽(CTX-Ⅱ)、软骨寡聚基质蛋白(COMP)及尿中吡啶啉(DPD)含量.结果 光镜下阳性对照组大鼠关节软骨细胞排列紊乱,软骨细胞变形、变性,可见大面积的软骨细胞坏死,而高、低剂量干预组表现为软骨表面原纤维形成,表层软骨细胞肿胀变圆,扁平的软骨细胞减少,软骨细胞簇集等骨关节炎早期病理改变.在3、5个月时,阴性对照组、阳性对照组、高剂量干预组、低剂量干预组大鼠血清CTX-Ⅱ含量分别为(18.77±4.61)、(25.07±9.17),(24.43±5.23)、(39.17±10.49),(21.11±5.02),(33.20±9.74),(19.87±4.53)、(29.73±9.32)μg/L;血清COMP含量分别为(5.43±2.75)、(6.38±2.23),(21.37±4.72)、(24.52±4.26),(17.27±4.77)、(20.32±4.74),(20.13±5.07)、(19.44±4.92)μg/L.其中,3个月时,与阴性对照组比较,阳性对照组血清CTX-Ⅱ含量明显升高(P＜0.05),而低、高剂量干预组未见明显改变(P均＞ 0.05);5个月时,与阴性对照组比较,其他3组血清CTX-Ⅱ含量明显升高(P均＜ 0.05),而高、低剂量干预组明显低于阳性对照组(P均＜0.05).3个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高剂量干预组血清COMP含量明显降低(P＜0.05);5个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高、低剂量干预组血清COMP含量明显降低(P均＜0.05).3、5个月时,上述4组大鼠尿液DPD含量分别为( 3.47±2.20)、(4.14±1.06),(4.09±2.48)、(4.33±3.43),(3.86±2.31)、(5.72±3.89),(3.58±2.77)、(4.23±2.90)μg/L,组间比较,差异无统计学意义(F值分别为2.608、2.436,P均＞0.05).结论 Ⅱ型胶原能拮抗T-2毒素的软骨损伤作用,延缓关节软骨的破坏进程,降低大鼠血清中CTX-Ⅱ及COMP水平.