Correlation Between Aspartate Aminotransferase to Platelet Ratio Index Score and the Degree of Esophageal Varices with Liver Cirrhosis

Background: Esophageal varices is the most common complication in liver cirrhosis. Bleeding varices is a serious complication causing increased mortality rate. In anticipation of those complications, the role of screening test is essential. Endoscopy is the standard method for assessing esophageal varices, but it carries certain risks for patients if it is contraindicated. Moreover, it is an invasive, expensive and uncomfortable procedure. Accordingly, a non-invasive method, aspartat aminotransferase to platelet ratio index (APRI) score, has been developed for evaluating esophageal varices. Method: An analytic cross-sectional observational study was conducted in patients with liver cirrhosis who underwent endoscopy between March 2011 and August 2012. Data were obtained from medical records of hospitalized patients in Mohammad Hoesin General Hospital. The degree of esophageal varices was assessed based on endoscopic findings and APRI score. Spearman test was performed to analyze the correlation between APRI score and the degree of esophageal varices.Results: There were 55 patients, 30 (54.5%) male and 25 (45.5%) female patients, with a range of age between 15-70 years and a mean value of age of 47.09 ± 12.8. APRI score < 0.5 was found in 21.81% subjects, APRI score of 0.5-1.5 was obtained in 41.81% subjects and APRI score > 1.5 was noted in 36.36% subjects with a mean value of 2.32 ± 3.92. There was a correlation between APRI score and degree of esophageal varices with p = 0.011 Conclusion: APRI score can indirectly predict esophageal varices in patients with liver cirrhosis

Table_2_Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease.xlsx

Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.</p

Image_1_Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease.jpeg

Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.</p

Table_1_Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease.xlsx

Aging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma-associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging- and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissues from 38 SSc-ILD and 18 healthy controls and found that markers (GDF15, COMP, and CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found that epithelial and fibroblast senescence signatures had a 3.6- and 3.7-fold enrichment, respectively, in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, and NAPI12) were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in the lung tissue and found that, independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.</p

SAA levels are correlated with pulmonary function.

<p>Correlation between serum levels of SAA and pulmonary function tests (A, B); pulmonary artery pressure (C); serum BNP levels (D). The horizontal line represents the SAA cut-off (19.5μg/ml) and vertical line cut-off for pulmonary arterial hypertension (right heart catheterization mPAO≥25 mmHg). Spearman correlation coefficient (r), p value, and number of patients (n) are shown.</p

Comparison of clinical and laboratory features of the SSc patients with normal and elevated SAA

<p>FVC, forced vital capacity (percent predicted); DLCO, diffusing capacity for carbon monoxide (percent predicted); BNP, brain natriuretic peptide; MRSS, modified Rodnan skin score; RVSP, right ventricular systolic pressure; PASP, pulmonary artery systolic pressure estimated by Echo/Doppler measurement; PA, pulmonary artery pressure determined by right heart catheterization; BMI, body mass index; M/F, male/female. Median and intraquartile range (IQR) are shown due to non-normality of data distribution. Mann-Whitney U tests were used to compare groups with elevated and normal SAA levels for each parameter.</p><p>Comparison of clinical and laboratory features of the SSc patients with normal and elevated SAA</p

Correlations between serum levels of SAA, CRP, and ESR.

<p>r—Spearman correlation coefficients; p—significance</p><p>Correlations between serum levels of SAA, CRP, and ESR.</p

Levels of circulating SAA are elevated in SSc.

<p>SAA levels were determined in SSc patients with early (<36 months) and late (>36 months) stage disease and healthy controls. The horizontal line signifies the cut-off value (19.5 μg/ml). Bold horizontal lines represent the medians.</p

Correlation of circulating SAA with respiratory symptoms.

<p>SGRQ, St. George’s respiratory questionnaire; FACIT, Functional assessment of chronic illness therapy; MRC-DS, Medical Research Council dyspnea score. PRO, Patient-reported outcome. PRO measures were collected within 6 months of serum collection.</p><p>Correlation of circulating SAA with respiratory symptoms.</p

SAA levels correlate weakly with CRP and ESR.

<p>Vertical lines indicate cut-off values for CRP (0.8 mg/dl) and ESR (20 mm/h), horizontal line shows cut-off for SAA (19.5 μg/ml). Spearman correlation coefficient (r), p value and number of patients (n) are shown.</p