COVID-19 and liver injury: An ongoing challenge

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.     

Tumour necrosis factor gene polymorphisms and migraine in Greek children

Introduction

Migraine is considered to be a multifactorial, complex disease. Various genetic and environmental factors contribute to the manifestation of this disease. The aim of this study was to determine whether polymorphisms in the tumour necrosis factor (TNF) region are associated with the risk of migraine. We examined the association between 6 single nucleotide polymorphisms in the coding regions of TNF-α and TNF-β genes and migraine.

Material and methods

The study included two groups of children (group A and group B). Group A consisted of 103 unrelated children with typical migraine without aura 5–14 years of age. Group B (control group) consisted of 178 unrelated healthy children. The diagnosis of migraine was, in all patients, made according to the International Classification of Headache Disorders (ICHD II).

Results

According to our results positive family history was present in 62.2% of patients of group A. No significant differences were found in the frequencies of genotypes or alleles between patients and controls. The non-parametric analyses of variance showed no significant differences in the age at onset between genotype groups of the TNF-α and TNF-β gene polymorphisms. Comparison of genotype frequencies between boys and girls in affected patients and control individuals were not significantly different (p = 0.089, p =0.073 respectively). The distribution of TNF polymorphisms was not associated with the presence of family history of migraine in patients.

Conclusions

Our data indicate that TNF-α and TNF-β gene polymorphisms are not a significant risk factor for migraine without aura in Greek children.     

Enzyme-linked immunosorbent assay gliadin assessment in processed food products available for persons with celiac disease: a feasibility study for developing a gluten-free food database

Inappropriate food labeling and unwillingness of food companies to officially register their own gluten-free products in the Greek National Food Intolerance Database (NFID) result in a limited range of processed food products available for persons with celiac disease (CDP). The objective of the study was to evaluate the feasibility of developing a gluten-free food product database based on the assessment of the gluten content in processed foods available for CDP. Gluten was assessed in 41 processed food products available for CDP. Group A consisted of 26 products for CDP included in the NFID, and group B contained 15 food products for CDP not registered in the NFID but listed in the safe lists of the local Celiac Association (CA). High-sensitivity ω-gliadin enzyme-linked immunosorbent assay (ELISA) was used for analysis. Gluten was lower than 20 ppm in 37 of 41 analyzed products (90.2%): in 24 of 26 (92.3%) products in group A and in 13 of 15 (86.7%) products in group B (P = .61). No significant difference was found between the 2 groups regarding gluten content. No product in either group contained gluten in excess of 100 ppm. Most of the analyzed products included in the Greek NFID or listed in the lists of the local CA, even those not officially labeled "gluten free," can be safely consumed by CDP. The use of commercially available ω-gliadin ELISA is able to identify those products that contain inappropriate levels of gluten, making feasible it to develop an integrated gluten-free processed food database.     

Associations between multiple indicators of objectively-measured and self-reported sedentary behaviour and cardiometabolic risk in older adults

Objective

To examine the associations between sedentary behaviour (SB) measured objectively and by self-report and cardiometabolic risk factors.

Method

Cross-sectional analyses of adults ≥ 60 years who participated in the 2008 Health Survey for England. Main exposures were self-reported leisure-time SB consisting of TV/DVD viewing, non-TV leisure-time sitting, and accelerometry-measured SB. Outcomes included body mass index (BMI), waist circumference, cholesterol ratio (total/HDL), Hb1Ac and prevalent diabetes.

Results

2765 participants (1256 men) had valid self-reported SB and outcomes/confounding variables data, of whom 649 (292 men) had accelerometer data. Total self-reported leisure-time SB showed multivariable-adjusted (including for moderate-to-vigorous physical activity) associations with BMI (beta for mean difference in BMI per 30 min/day extra SB: 0.088 kg/m², 95% CI 0.047 to 0.130); waist circumference (0.234, 0.129 to 0.339 cm); cholesterol ratio (0.018, 0.005 to 0.032) and diabetes (odds ratio per 30 min/day extra SB: 1.059, 1.030 to 1.089). Similar associations were observed for TV time while non-TV self-reported SB showed associations only with diabetes (1.057, 1.017 to 1.099). Accelerometry SB was associated with waist circumference only (0.633, 0.173 to 1.093).

Conclusion

In older adults SB is associated with cardiometabolic risk factors, but the associations are more consistent when is measured by self-report that includes TV viewing.     

Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (non-nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial

PURPOSE: Tumor volume (TV) is one of the main reported factors determining the outcome of treatment in head-and-neck carcinomas. In this study, the prognostic impact of TV was explored in the context of a randomized trial with the patients assigned to receive standard radiotherapy (RT) alone or RT plus platinum compounds (RT alone, RT plus cisplatin, or RT plus carboplatin). METHODS AND MATERIALS: The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied. Taking into account the magnification factor of the scan and CT slice thickness, a computer with specifically designed software calculated the TV in cubic centimeters. RESULTS: The median overall survival for the whole group of patients was 21.6 months (95% confidence interval, 13.0-30.2) and the 3-year survival rate was 40%. The addition of platinum compounds to RT (Groups 2 and 3) significantly improved the survival rate (RT alone vs. RT plus cisplatin, hazard ratio 0.36, p = 0.002; RT alone vs. RT plus carboplatin, hazard ratio 0.53, p = 0.029). In univariate analysis, the most significant parameters for survival were treatment group, total gross tumor volume (TGTV), complete response, nodal GTV, primary GTV, and performance status. In multivariate analysis, treatment group, TGTV, gender, and primary site were independent prognostic factors for survival. A prognostic threshold of 22.8 cm(3) was detected for TGTV. Patients with a TGTV of <22.8 cm(3) were more likely to achieve a complete response and had a median survival of 45.3 months, and those with a TGTV >22.8 cm(3) had a median survival of 12.3 months (log-rank test, p = 0.0102). CONCLUSION: The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3) derived. Our data indicated that locally advanced head-and-neck carcinomas should not be treated by standard (once-daily) RT alone. Tumor size and disease subsite should be taken into account in future randomized trials to increase their statistical power.     

Thyroid substitution therapy induces high-density lipoprotein-associated platelet-activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect.

BACKGROUND: Subclinical hypothyroidism (SH) has been associated with an increased risk of ischemic heart disease, which has been partly attributed to lipid abnormalities. Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with lipoproteins (both low-density lipoproteins [LDL], and high-density lipoproteins [HDL]). Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. OBJECTIVE: To evaluate qualitative changes in lipoprotein metabolism with respect to PAF-AH and PON1 activities in patients with SH before and after the restoration of euthyroidism. DESIGN AND METHODS: We determined the PAF-AH activity in plasma and on HDL and PON1 activities as well as the lipid profile patients with SH at baseline and after 6 months of levothyroxine substitution therapy. Thirty normolipidemic healthy individuals comprised the control group. RESULTS: Compared to controls, patients with SH showed higher levels of total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B. Triglycerides were significantly reduced after levothyroxine treatment. Patients with SH exhibited higher plasma baseline PAF-AH activity (63.0 +/- 16.5 versus 44.3 +/- 9.5 nmol/mL per minute p < 0.0001) and lower baseline HDL associated PAF-AH (2.9 +/- 1.1 versus 3.6 +/- 0.9 nmol/mL per minute p = 0.02) compared to the control group. PON1 activities were similar in both groups. Levothyroxine treatment had no effect on plasma PAF-AH activity or PON1 activities but resulted in a significant elevation of HDL-associated PAF-AH activity (from 2.9 +/- 1.1 to 3.5 +/- 1.0 nmol/mL per minute, p = 0.003). CONCLUSIONS: Patients with SH exhibit increased plasma PAF-AH activity and low HDL-associated PAF-AH activity. Levothyroxine induces a significant increase in HDL-PAF-AH activity. This action may represent a potential antiatherogenic effect of thyroid replacement therapy.     

Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease

In the present study, the changes in circulating IGF-1 and its binding protein IGFBP-3 were determined in adult patients with active inflammatory bowel disease (IBD) in order to assess the effect of this inflammatory condition on the IGF system. IGF-1 and IGFBP-3, as well as interleukin-6 (IL-6) were measured in serum obtained from 22 consecutive newly diagnosed patients (mean age 41.3 years) with active IBD, including 10 patients with Crohn's disease (CD), and 12 with ulcerative colitis (UC). For comparison the same parameters were determined in 30 healthy volunteers matched for age, sex and Body Mass Index (BMI). Serum IGF-1 and IGFBP-3 levels were similar in the two subgroups of patients and the values from all patients were combined for comparison with those from the control group. The mean (+/- SD) serum IGF-1 concentration (178 +/- 91 ng/ml) in the patients with IBD was lower compared with that in the controls (227 +/- 79 ng/ml, P<0.035). Similarly, the mean IGFBP-3 concentration in the patients was lower than in the controls (1.6 +/- 0.6 ng/ml vs 3.2 +/- 0.7 ng/ml respectively, P<0.001), Serum IL-6 levels were higher in the patients compared with the controls (5.5 +/- 4.2 vs 0.65 +/- 0.11 pg/ml, P<0.0001). The reduced IGF-1 and IGFBP-3 levels in patients with active IBD suggest that this systemic inflammatory condition is associated with a degree of acquired GH resistance, possibly induced by inflammatory cytokines.     

Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB

Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A(2) that is primarily associated with low density lipoprotein (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL), although it has recently been indicated that there is no PAF-AH protein in HDL. Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits PAF-AH-like activity. The effect of atorvastatin (20 mg per day for 4 months) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (n=55) or type IIB (n=21) was studied. In both patient groups, atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group. However, because of the reduction in LDL cholesterol levels, the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration. The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin.