Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis

Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis Ling Mei, Ying Ma, Lili Zhao, QingLing Chen, Li Zhou, Hang Yang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1796375/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background and aim : portal hypertension is a common complication of chronic liver diseases that is responsible for most clinical consequences of liver cirrhosis. In patients with portal hypertension, esophagogastric variceal bleeding is a leading cause of death. The majority of research focuses on high-risk esophageal and gastric varices and bleeding, with only a few on early varices. However, it is found that early intervention of gastroesophageal varices can better improve the prognosis and reduce mortality, there is still no relevant research. Ultrasonic endoscopy is a combination of endoscopy and ultrasonic imaging. It can detect varices around the esophagus and gastric based on a gastroscope, and detect esophageal collateral veins and perforating veins earlier, which is helpful for the early diagnosis of varices. Therefore, this study aimed to explore the correlation between serum fibrosis markers and early gastroesophageal varices in patients with compensated cirrhosis. Methods: This study included 477 patients with compensated cirrhosis. The selected patients were categorized into two groups. The early gastroesophageal varices group was gastroesophageal varices found by endoscopic ultrasonography, but not by gastroscopy, whereas the no gastroesophageal varices group was endoscopic ultrasonography and gastroscope without varices. Multiple logistic regression analysis was used to explore the association of serum fibrosis markers with early gastroesophageal varices. Results: Among the 477 compensated liver cirrhosis patients 198 patients without gastroesophageal varices and 279 patients with early gastroesophageal varices. There was a positive correlation between serum fibrosis markers and early gastroesophageal varices. In univariate logistic regression analysis, patients with early gastroesophageal varices had lower platelet count (P = 0.034), higher aspartate aminotransferase ( P = 0.046), total bilirubin ( P = 0.041), hyaluronic acid ( P < 0.001), laminin ( P < 0.001), type III procollagen ( P = 0.005), type IV collagen ( P = 0.002) and liver stiffness measurement ( P = 0.001). Multivariate analysis showed that laminin（OR 1.011;95% CI 1.004-1.017, P =0.001） was an independent risk factor for predicting early gastroesophageal varices in patients with compensated cirrhosis. Conclusion: Higher laminin was independently associated with early gastroesophageal varices among patients with compensated cirrhosis. early gastroesophageal varices endoscopic ultrasonography hyaluronic acid laminin type III procollagen and type IV collagen Introduction Portal hypertension, defined as increased pressure in the portal venous system, is a major complication of liver cirrhosis[ 1 ]. Vasodilation of the splanchnic capillary beds and arterioles increases portal blood flow, which combined with an increase in intrahepatic vascular resistance, increases portal pressure[ 2 ]. Its complications, which include ascites, gastroesophageal varices, hepatic encephalopathy, and hepatorenal syndrome, cause significant morbidity and mortality[ 3 ]. Collaterals develop at the sites of communication between the portal and systemic circulation when the portal pressure increase above a threshold. The most significant collaterals are gastroesophageal varices[ 4 , 5 ]. Anatomic studies have revealed that early gastroesophageal varices (GEVs) are dilated deep intrinsic veins in the submucosa of the distal esophagus and proximal stomach in patients with portal hypertension[ 6 , 7 ]. Patients with varices have a one-third probability of developing a variceal bleed two years after diagnosis, with a 20–40% mortality rate per episode[ 8 ]. Gastroesophageal variceal bleeding is a leading cause of death in patients with cirrhosis[ 9 ]. Therefore, early detection of early gastroesophageal varices is significant in reducing mortality, reducing medical costs, and improving patient survival and prognosis. However, most of the current studies focus on high-risk esophageal and gastric varices and bleeding-related research. It is necessary for cirrhotic patients to undergo routine gastroscopy, but the scope of gastroscopy is limited to the intramucosal and submucosal blood vessels, and the hemodynamic changes in cirrhotic patients with portal hypertension cannot be understood. Endoscopic ultrasound (EUS) is a non-invasive method that can provide anatomic high-resolution images and hemodynamic features of collateral vessels surrounding the distal esophagus and upper stomach in patients with portal hypertension[ 10 ]. Therefore, when judging the changes in the collateral circulation of portal hypertension, we can not only observe the esophageal and gastric varices that can be seen under conventional gastroscopy but also detect the vascular images inside and outside the esophageal wall that can not be seen under ordinary endoscopy. EUS is capable of objectively imaging gastroesophageal varices (GEVs) and is more sensitive than conventional endoscopy in detecting GEVs[ 6 , 11 , 12 ]. In Gin-Ho Lo’s study, EUS detected Gastric varices (GV) in 28 patients (35%) while routine endoscopy found only 6 patients (7%) in whom GV was found by conventional endoscopy[ 13 ]. Changjun men et al reported that a patient with hepatitis B cirrhosis whose varices were not detected by plain endoscopy and whose esophageal and gastric varices were detected by EUS developed esophageal and gastric variceal bleeding 6 months after the examination.[ 14 ]. EUS is widely accepted as useful for assessing esophagogastric varices that provide good delineation of the cross-sectional anatomy of the distal esophagus and proximal stomach, can detect gastroesophageal varices along with periesophageal collateral veins, paraesophageal collateral veins, and perforating vein, so EUS can detect gastroesophageal varices earlier than gastroscopy[ 15 , 16 ]. Previous studies also have shown that EUS has more advantages in detecting esophageal and gastric varices caused by portal hypertension and early liver fibrosis[ 6 , 17 ]. According to Y. T. Lee‘s research, the advantage of EUS is that it can provide information about venous abnormalities at the gastroesophageal junction due to elevated portal vein pressure in early cirrhosis[ 6 ].In recent years, EUS technology has developed rapidly, and EUS has become more and more important in the diagnosis and treatment of portal hypertension-related varices. However, this examination is expensive, time-consuming, difficult to operate and has high technical requirements, and the patient can also feel pain during the test. it is difficult to repeat the examination and long-term follow-up, and it cannot be widely popularized in clinical practice. In the Baveno VII portal hypertension consensus, it is suggested that the possibility of high-risk varices can be confirmed by liver stiffness and platelet test to avoid unnecessary endoscopy[ 18 ]. However, for early portal hypertension, no alternative non-invasive markers have been found. Therefore, it is of great significance to find a non-invasive marker to evaluate esophageal and gastric varices in patients with compensatory cirrhosis. Serum liver fibrosis markers include hyaluronic acid(HA), laminin(LN), type III procollagen, and type IV collagen. These four markers of liver fibrosis have been proved to be highly correlated with liver fibrosis in patients with chronic liver disease[ 19 , 20 ]. It has been proved that liver fibrosis markers have a high predictive value for the diagnosis and prognosis of patients with chronic liver disease of different etiologies[ 21 – 23 ]. However, there are still few studies on the relationship between serum liver fibrosis markers and the severity and complications of esophageal and gastric varices. Therefore, we conducted a retrospective cross-sectional study to evaluate the correlation between indicators of liver fibrosis and early gastroesophageal varices in patients with compensatory cirrhosis. Materials And Methods Study population In this retrospective study, a total of 477 patients with compensated cirrhosis enrolled between November 2015 to December 2019. Eligible patients aged 18 years or older who were diagnosed with compensated cirrhosis according to imaging by ultrasonography, Computed tomography (CT), or Magnetic Resonance Imaging(MRI) of irregular and nodular liver together with impaired liver synthetic function are sufficient for the diagnosis of cirrhosis[ 24 ]. All patients completed esophagogastroduodenoscopy(EGD), EUS, Fibroscan, imaging, and laboratory examinations within 6 months before and after hospitalization. The exclusion criteria were as follows: 1. primary prevention with non-selective β-blockers or endoscopic ligation; 2. thrombosis of cavernous transformation of the portal vein system; 3. history of malignancy (including hepatocellular carcinoma); 4. incomplete clinical data. This study protocol was approved by the Ethics Committee of Tianjin Second People’s Hospital and conforms to the principles of the 1975 Declaration of Helsinki. An informed consent was obtained from all patients. All methods were performed in accordance with relevant guidelines and regulations. General characteristics and Laboratory Investigations Demographic data (age and sex) and laboratory results (routine blood tests, biochemistry tests, and immunology tests) were collected and analyzed. Blood samples were collected 1 week before EUS and EGD. albumin (ALB), aspartate aminotransferase (AST), Serum alanine aminotransferase (ALT), and total bilirubin (TBIL) were detected by a Hitachi 7180 Automatic Biochemical Analyser (Hitachi, Ltd, Tokyo, Japan). platelet (PLT) was measured using a Sysmex XN-2000 hematology analyzer (Sysmex Corporation, Kobe, Japan) according to the manufacturer’s recommendation. prothrombin time (PT) was performed by the clotting method on the automatic coagulometer "STAGO Compact" ("Diagnostica Stago", France). The serum markers of liver fibrosis were measured with AutoLumo A2000 Plus. The upper reference value of laminin ln was 130ng/ml, the upper reference value of type III procollagen was 15ng/ml, the upper reference value of hyaluronic acid was 120ng/ml, and the upper reference value of type IV collagen was 95ng/ml. The coefficient of variation CV (%) was not exceeding 15%. Assessment of varices The EGD was performed by two experienced operators using the equipment (Olympus CV-260SL, Japan). The variance was described according to the expert guideline[ 24 ]. EUS was conducted by skilled professional doctors using the equipment (Olympus GF-UE260, Japan). According to the results of gastroscopy and endoscopic ultrasonography, the patients were divided into two groups: no gastroesophageal varices (negative for EUS and EGD) and early gastroesophageal varices (positive for EUS and negative for EGD). Transient elastography liver stiffness (LS) was measured by transient elastography (Echosens, Fibroscan 520, Paris, France) by two experienced practitioners with professional training. The right lobe of the liver was accessed with maximal abduction of the right arm during the operation. It was considered valid that ten measurements were obtained with a success rate of 60% total measurements, with an interquartile range of less than 30%. Spleen size The patients fasted overnight and routinely underwent abdominal ultrasound examinations to measure the spleen size. Spleen diameters were reported and recorded. Ultrasound was performed by professional operators not known the clinical information about patients. Statistical analysis SPSS statistical 26 (IBM, New York, USA) was used for statistical analysis. P < 0.05 was considered statistically significant. Kolmogorov-Smirnov test is used to analyze whether continuous variables obey normal distribution. The nonnormal distribution variables are expressed as median (quartile 25, quartile 75). Data for categorical variables are presented as the number (n) and proportion (%). The correlation between variables and early gastroesophageal varices was evaluated by Spearman correlation coefficient (r), Mann-Whitney U test, chi-square test, and binary logistic regression analysis. The "enter" method was used for Univariate logistic regression, and the statistically significant variables were included in the Univariate Logistic regression analysis. Results General characteristics of the patients A total of 477 compensated cirrhosis patients with the median age of 50 years were included in this study. Child-Pugh class A were 442(92.7%), and Child-Pugh class B were 35(7.3%). According to different etiological classifications, there were 362 patients with hepatitis B (75.9%), 60 patients with hepatitis C (12.6%), and 55 patients with other liver diseases (11.5%). The further demographic data and laboratory blood markers of all patients are shown in Table 1 . Table 1 General characteristics of the patients with compensated liver cirrhosis Variables n = 477 Age(years) 50(40, 57) Male, n(%) 263(55.1) Aetiology of cirrhosis, n(%) HBV 362(75.9) HCV 60(12.6) others 55(11.5) Child category, n(%) A 442(92.7) B 35(7.3) ALT(U/L) 52(26, 135) AST(U/L) 45(27, 99) TBIL(umol/L) 15.9(12.45, 22.2) ALB(g/L) 43.2(39.5, 46.4) PLT(x10 9 /L) 146(109.25, 179) PT(s) 13.4(12.8, 14.3) Hyaluronic acid(ng/ml) 125(92, 254) Laminin(ng/ml) 94(76, 113) type III pro-collagen(ng/ml) 9.5(6.9, 14) Collagen type IV(ng/ml) 69(61, 130) LS(kPa) 12.9(8.45, 21.2) Splenic diameter(mm) 113(99, 123) Data are expressed as median (quartile 25, quartile 75) or number (proportion) ALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness General characteristics of patients by gastroesophageal varices The included patients were divided into the non-GEVs group by EUS(-) EGD(-)and the early GEVs group by EUS(+) EGD(-). Among the 477 patients,279(58.5%) had early GEVs, and 198(41.5%) did not. No significant difference in age, sex, and etiology proportion were observed between the two groups, P = 0.617, P = 0.437, and P = 0.428 respectively. The total bilirubin, liver stiffness(LS), and serum liver fibrosis markers (hyaluronic acid, laminin, type III procollagen, and type IV collagen) in the early GEVs group were significantly higher than those in the non-GEVs group ( P < 0.05), while PLT was significantly lower than those in the non-GEVs group ( P 0.05),as shown in Table 2 . Table 2 General characteristics of subjects by early gastroesophageal varices Variables EUS-EGD-(n = 198) EUS + EGD-(n = 279) P Age(years) 50(39.75, 56.5) 51(40, 57) 0.617 Male, n(%) 105(53) 158(60) 0.436 Aetiology of cirrhosis (HBV/HCV/other) 145/26/27 217/34/28 0.428 Child category (A/B) 189/9 253/26 0.049 ALT(U/L) 46(24, 116) 57(28, 164) 0.143 AST(U/L) 42.5(24, 86) 45(28, 120) 0.084 TBIL(umol/L) 15.2(11.6, 20.725) 16.1(13, 23.8) 0.021 ALB(g/L) 43.8(39.5, 46.425) 42.7(39.3, 46.4) 0.143 PLT(X109/L) 152(120.5, 180.5) 137(105, 176) 0.006 PT(s) 13.4(12.7, 14.0) 13.5(12.8, 14.4) 0.029 Hyaluronic acid(ng/ml) 106.5(87, 192.25) 141(93, 322) 0.002 Laminin(ng/ml) 91(68.75, 98.0) 97(89, 130) <0.001 type III pro-collagen(ng/ml) 6.5(9.0, 12.0) 9.7(7.2, 16) 0.006 Collagen type IV(ng/ml) 55(68, 114.75) 72(62, 137) 0.005 LS(kPa) 11.55(7.675, 17.35) 14.2(8.8, 23.2) 0.001 Splenic diameter(mm) 110.5(99.25, 120.75) 114(99, 125) 0.226 Data are expressed as median (quartile 25, quartile 75) or number (proportion) ALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness Correlations between serum liver fibrosis markers and the clinical characteristics of patients. The correlations between serum liver fibrosis markers variables and clinical characteristics are summarized in Table 3 . As expected, Serum liver fibrosis markers were positively correlated with ALT, AST, TBIL, PT, LS, and child-pugh (C-P) classification ( P < 0.05), and negatively correlated with ALB and PLT ( P < 0.05). The length and diameter of the spleen were positively correlated with hyaluronic acid, type III procollagen, and type IV collagen ( P < 0.05). Hyaluronic acid, laminin, type III procollagen, and type IV collagen were positively correlated with early gastroesophageal varices ( P < 0.05). Table 3 Correlations between serum fibrosis markers and clinical characteristics of patients Variables statistics Hyaluronic acid(ng/ml) Laminin(ng/ml) Type III pro-collagen(ng/ml) Collagen type IV(ng/ml) r P r P r P r P Age(years) 0.168 <0.001 0.006 0.895 -0.131 0.004 -0.116 0.011 Child class (A/B) 0.273 <0.001 0.216 <0.001 0.301 <0.001 0.291 <0.001 ALT(U/L) 0.210 <0.001 0.254 <0.001 0.439 <0.001 0.420 <0.001 AST(U/L) 0.331 <0.001 0.352 <0.001 0.518 <0.001 0.529 <0.001 TBIL (µmol/L) 0.266 <0.001 0.290 <0.001 0.289 <0.001 0.256 <0.001 ALB(g/L) -0.401 <0.001 -0.302 <0.001 -0.431 <0.001 -0.494 <0.001 PLT(X109/L) -0.314 <0.001 -0.249 <0.001 -0.150 <0.001 -0.267 <0.001 PT(s) 0.212 <0.001 0.217 <0.001 0.300 <0.001 0.339 <0.001 LS(kPa) 0.484 <0.001 0.430 <0.001 0.469 <0.001 0.568 <0.001 Splenic diameter(mm) 0.149 0.001 0.088 0.059 0.159 0.001 0.204 <0.001 EGD(-)EUS(-/+) 0.142 0.002 0.253 <0.001 0.130 0.004 0.127 0.006 ALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness EGD (-)esophagogastroduodenoscopy negative, EUS༈-/+༉ endoscopic ultrasound negative or positive Analysis of risk factors associated with early GEVs Binary logistic regression analysis was used to explore the risk factors associated with early GEVs in patients with compensated cirrhosis (Table 4 ). In univariate analysis, patients with early portal hypertension had lower PLT ( P = 0.034), higher AST (P = 0.046), TBIL ( P = 0.041), HA ( P < 0.001), LN ( P < 0.001), procollagen III ( P = 0.005), collagen IV ( P = 0.002) and LSM ( P = 0.001). However, after the multivariate logistic regression analysis, it was found that LN was an independent risk factor for predicting early GEVs in patients with compensated cirrhosis, with an odds ratio (OR) (95% confidence interval CI) of 1.011 (1.004, 1.017), P = 0.001. Table 4 Univariate and multivariate analysis of factors associated with gastroesophageal varices Variables Univariate analysis Multivariate analysis OR(95%CI) P OR(95%CI) Age(years) 1.004(0.989, 1.020) 0.612 Male, n(%) 0.865(0.600, 1.247) 0.436 Aetiology of cirrhosis (HBV/HCV/other) 0.839(0.643, 1.095) 0.197 Child category (A/B) 2.158(0.988, 4.713) 0.054 ALT(U/L) 1.001(1.000, 1.001) 0.246 AST(U/L) 1.001(1.000, 1.002) 0.046 0.999(0.998,1.001) 0.529 TBIL(umol/L) 1.008(1.000, 1.016) 0.041 1.004(0.995,1.012) 0.387 ALB(g/L) 0.981(0.949, 1.015) 0.247 PLT(X10 9 /L) 0.996(0.993, 1.000) 0.034 0.999(0.996,1.003) 0.676 PT(s) 1.056(0.971, 1.149) 0.205 Hyaluronic acid(ng/ml) 1.001(1.001, 1.002) <0.001 1.000(0.999,1.001) 0.562 Laminin(ng/ml) 1.015(1.009, 1.020) <0.001 1.011(1.004, 1.018) 0.001 type III pro-collagen(ng/ml) 1.040(1.012, 1.069) 0.005 0.999(0.995,1.002) 0.494 Collagen type IV(ng/ml) 1.004(1.001, 1.006) 0.002 1.003(0.968,1.040) 0.862 LS(Kpa) 1.032(1.113, 1.051) 0.001 1.013(0.988,1.038) 0.308 Splenic diameter(mm) 1.003(0.993, 1.013) 0.569 ALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness Discussion Previous research has mostly focused on identifying non-invasive serological indications of high-risk esophagogastric varices to reduce unnecessary endoscopy in patients. Many studies have now shown that non-invasive indicators including platelet count, albumin, spleen size, and liver stiffness are related to the severity of high-risk esophagogastric varices and cirrhosis[ 25 – 28 ]. Non-invasive indications of early esophagogastric varices are the subject of comparatively few investigations. Therefore, the purpose of this study is to develop non-invasive indicators of esophagogastric varices, decrease unnecessary gastroscopy and endoscopic ultrasonography, improve prognosis, and reduce mortality and medical expenditures. We performed a correlation analysis between serum liver fibrosis markers and clinical indicators in this study. First, we discovered that serum liver fibrosis markers are related to other indicators of gastroesophageal varices, platelets, and liver Liver stiffness, suggesting that serum liver fibrosis markers could be used as a substitute for other indicators in the prediction of gastroesophageal varices. Second, we found a correlation between serum liver fibrosis markers and early gastroesophageal varices, demonstrating that an increase in serum liver fibrosis markers could indicate the presence of gastroesophageal varices. We also discovered a correlation between serum markers of liver fibrosis and C-P class, suggesting that serum markers of liver fibrosis are related to the severity of cirrhosis. [ 29 ]. In the study, we found that hyaluronic acid, laminin, type III procollagen, and type IV collagen were positively correlated with gastroesophageal varices in univariate analysis and that the increase of laminin concentration was independently correlated with gastroesophageal varices in compensated liver cirrhosis in multivariate analysis after adjusting for confounding factors. Laminin is a simple and non-invasive marker used in clinical detection. Therefore, laminin can be used as a routine reference index for monitoring gastroesophageal varies in patients with compensated liver cirrhosis. Chronic liver injury can result in fibrosis, which is characterized by the accumulation of extracellular matrix(ECM) in the liver. Hepatic stellate cells are activated by chronic liver cell injury. The fibrotic myofibroblast phenotype is acquired by these cells, resulting in collagen synthesis and per sinus contraction, leading to liver fibrosis and portal hypertension. Laminin is one of the major glycoproteins in the basement membrane. Hepatic stellate cells (HSCs) generate it and deposit it in the liver's basement membrane. It is involved in biological tasks such as cell adhesion, matrix component interaction with collagen and glycosaminoglycans, cytoskeleton maintenance, and liver fibrosis.[ 21 , 30 , 31 ]. The proportion of type I collagen, type III collagen, and laminin increases in the diseased state, while the mixture of laminin, type IV collagen, and proteoglycan is increased in ECM in normal liver.[ 19 , 30 , 32 ]. According to several research, serum liver fibrosis indicators are related to the severity of liver fibrosis caused by various etiologies and are significant predictors of disease prognosis. [ 33 , 34 ]. Serum laminin concentration has also been related to gastroesophageal varices in cirrhosis in other research. This study also found that laminin concentration is related to early gastroesophageal varices in cirrhosis. Long Fei Wu's study found that in a one-year prospective analysis, laminin and type IV collagen are possible predictors of rebleeding after esophagogastric varices surgery and that is related to esophageal and gastric varices. [ 35 ]. This study has some limitations. This is a retrospective cross-sectional study. Not all patients have received EUS examination and detection of serum markers of liver fibrosis, which increases the possibility of bias. Therefore, a prospective large-scale study is needed to further clarify the causal relationship between laminin and early portal hypertension. In addition, although there are standard procedures, there may be variability among different observers. In conclusion, we found that indicators of liver fibrosis were associated with early gastroesophageal varices, especially laminin was independently associated with early gastroesophageal varices in patients with compensatory cirrhosis. Therefore, laminin can be used to predict the existence of early gastroesophageal varices, but it still needs to be verified by large sample prospective studies. Abbreviations EUS Endoscopic ultrasound GEVs gastroesophageal varices GV Gastric varices EGD esophagogastroduodenoscopy HA hyaluronic acid, LN:laminin, CT:Computed tomography, MRI:Magnetic Resonance Imaging, ECM:extracellular matrix HSCs Hepatic stellate cells ALT alanine aminotransferase AST aspartate aminotransferase TBIL total bilirubin ALB albumin PLT platelet PT prothrombin time LS liver stiffness OR odds ratio CI confidence interval, C-P:child-pugh. Declarations Ethics approval and consent to participate This study protocol was approved by the Ethics Committee of Tianjin Second People’s Hospital and conforms to the principles of the 1975 Declaration of Helsinki. An informed consent was obtained from all patients. All methods were performed in accordance with relevant guidelines and regulations. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. Competing interests All authors declare no competing interest. Funding This work was funded by Natural Science Foundation of Tianjin City (20JCYBJC01150); Tianjin Health Science and Technology Project (No. TJWJ2021QN063, No. TJWJ2021ZD010 and No. TJWJ2021MS034). Authors’ contributions Study concept and design (Ling Mei，Jia Li) drafting manuscript (Ling Mei，Ying Ma) statistical analysis (Qingling Chen，Ling Mei) data collection (Lili Zhao，Li Zhou，Hang Yang，Jie Liu) the revision of the manuscript for important intellectual content (Ying Ma ，Jia Li) All authors read and approved the final manuscript. Acknowledgements We thank the medical staff at Tianjin Second People’s Hospital for their essential support and assistance with data collection. 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Maurice JB, Brodkin E, Arnold F, Navaratnam A, Paine H, Khawar S, Dhar A, Patch D, O'Beirne J, Mookerjee R et al : Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices . J Hepatol 2016, 65 (5):899–905. Lubel JS, Angus PW: Modern management of portal hypertension . Intern Med J 2005, 35 (1):45–49. Zheng KI, Liu C, Li J, Zhao L, Zheng MH, Wang F, Qi X: Validation of Baveno VI and expanded Baveno VI criteria to identify high-risk varices in patients with MAFLD-related compensated cirrhosis . J Hepatol 2020, 73 (6):1571–1573. Zhao L, Wang T, Guo C, Zhou L, Han P, Wang C, Ma Y, Wang J, Gao M, Li J: Modified and alternative Baveno VI criteria based on age for ruling out high-risk varices in patients with compensated cirrhosis . Hepatol Int 2022. Qi X, Liu X, Zhang Y, Hou Y, Ren L, Wu C, Chen J, Xia C, Zhao J, Wang D et al : Serum Liver Fibrosis Markers in the Prognosis of Liver Cirrhosis: A Prospective Observational Study . Med Sci Monit 2016, 22 :2720–2730. El-Mezayen HA, Habib S, Marzok HF, Saad MH: Diagnostic performance of collagen IV and laminin for the prediction of fibrosis and cirrhosis in chronic hepatitis C patients: a multicenter study . Eur J Gastroenterol Hepatol 2015, 27 (4):378–385. Younesi S, Parsian H: Diagnostic accuracy of glycoproteins in the assessment of liver fibrosis: A comparison between laminin, fibronectin, and hyaluronic acid . The Turkish Journal of Gastroenterology 2019, 30 (6):524–531. Jarcuska P, Janicko M, Veseliny E, Jarcuska P, Skladany L: Circulating markers of liver fibrosis progression . Clin Chim Acta 2010, 411 (15–16):1009–1017. Halfon P, Bourliere M, Penaranda G, Deydier R, Renou C, Botta-Fridlund D, Tran A, Portal I, Allemand I, Rosenthal-Allieri A et al : Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus . Comp Hepatol 2005, 4 :6. Niemelä O, Risteli J, Blake JE, Risteli L, Compton KV, Orrego H: Markers of fibrogenesis and basement membrane formation in alcoholic liver disease . Gastroenterology 1990, 98 (6):1612–1619. Wu LF, Xiang XX, Bai DS, Jin SJ, Zhang C, Zhou BH, Qian JJ, Jiang GQ: Novel noninvasive liver fibrotic markers to predict postoperative re-bleeding after laparoscopic splenectomy and azygoportal disconnection: a 1-year prospective study . Surg Endosc 2021, 35 (11):6158–6165. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 21 Sep, 2022 Reviews received at journal 23 Aug, 2022 Reviewers agreed at journal 22 Aug, 2022 Reviewers invited by journal 28 Jun, 2022 Editor assigned by journal 28 Jun, 2022 Editor invited by journal 28 Jun, 2022 Submission checks completed at journal 28 Jun, 2022 First submitted to journal 26 Jun, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1796375","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":117030342,"identity":"2dfe1d00-1b57-4509-8c94-246dc117d52e","order_by":0,"name":"Ling Mei","email":"","orcid":"","institution":"Department of Hepatology, Second People’s Clinical College of Tianjin Medical University, Tianjin","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Mei","suffix":""},{"id":117030344,"identity":"09f9c07a-eb41-4e3a-848f-66f09614f4db","order_by":1,"name":"Ying Ma","email":"","orcid":"","institution":"Department of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin 30019","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Ma","suffix":""},{"id":117030345,"identity":"47c74333-e3df-4642-8edb-662a5ee309de","order_by":2,"name":"Lili Zhao","email":"","orcid":"","institution":"Department of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin 30019","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Zhao","suffix":""},{"id":117030346,"identity":"4b7c578f-841a-4a86-ab51-1938c75921b0","order_by":3,"name":"QingLing Chen","email":"","orcid":"","institution":"Department of Hepatology, Second People’s Clinical College of Tianjin Medical University, Tianjin","correspondingAuthor":false,"prefix":"","firstName":"QingLing","middleName":"","lastName":"Chen","suffix":""},{"id":117030347,"identity":"3ac53795-2351-4681-931b-f32079ebeef4","order_by":4,"name":"Li Zhou","email":"","orcid":"","institution":"Department of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin 30019","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Zhou","suffix":""},{"id":117030348,"identity":"0dfd3b5d-f6ca-4f55-8f15-1d65f4f52cb4","order_by":5,"name":"Hang Yang","email":"","orcid":"","institution":"Department of Hepatology, Second People’s Clinical College of Tianjin Medical University, Tianjin","correspondingAuthor":false,"prefix":"","firstName":"Hang","middleName":"","lastName":"Yang","suffix":""},{"id":117030349,"identity":"7da4749e-7e7e-442d-9f15-40556ded21cb","order_by":6,"name":"Jie Liu","email":"","orcid":"","institution":"Department of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin 30019","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Liu","suffix":""},{"id":117030350,"identity":"2dd42be3-dcb9-4c73-b6ca-de213c491d6a","order_by":7,"name":"Jia Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYBACNvbmgw8+VNjY2R9mbHyQUFFDWAsfz7Fkwxln0pIZjjcfNnhw5hhhLXISOWrSvC2HGBvOHEuTfNjCTITDeM4wSPA2HGBmnJFjVpHYwMbA396dQMAvvQcMJHfc4WOWyDG7kbhDhkHizNkNBGw5l5BgeOYZMxtYyxk2BgOJXAJaJHIMDiS2HWbsAWopSGxjJkqLYcNBoJYZPMfSGIjTAgxkYGilJRuwNx+WSDhzjIegX+Tbm4///gOMSgNmxsaPPypq5Pjbe/FrwQA8pCkfBaNgFIyCUYAVAABgo08P9SSeGQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Hepatology, Tianjin Second People’s Hospital, No. 7, Sudi South Road, Nankai District, Tianjin 30019","correspondingAuthor":true,"prefix":"","firstName":"Jia","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2022-06-26 10:14:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1796375/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1796375/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23540638,"identity":"dbb3aff2-10df-4509-8049-d5a2bdef0641","added_by":"auto","created_at":"2022-07-06 16:49:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1089052,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1796375/v1/f98ee817-7946-4f85-a0ac-3d11f40e0e5d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePortal hypertension, defined as increased pressure in the portal venous system, is a major complication of liver cirrhosis[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Vasodilation of the splanchnic capillary beds and arterioles increases portal blood flow, which combined with an increase in intrahepatic vascular resistance, increases portal pressure[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Its complications, which include ascites, gastroesophageal varices, hepatic encephalopathy, and hepatorenal syndrome, cause significant morbidity and mortality[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Collaterals develop at the sites of communication between the portal and systemic circulation when the portal pressure increase above a threshold. The most significant collaterals are gastroesophageal varices[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Anatomic studies have revealed that early gastroesophageal varices (GEVs) are dilated deep intrinsic veins in the submucosa of the distal esophagus and proximal stomach in patients with portal hypertension[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Patients with varices have a one-third probability of developing a variceal bleed two years after diagnosis, with a 20\u0026ndash;40% mortality rate per episode[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Gastroesophageal variceal bleeding is a leading cause of death in patients with cirrhosis[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, early detection of early gastroesophageal varices is significant in reducing mortality, reducing medical costs, and improving patient survival and prognosis. However, most of the current studies focus on high-risk esophageal and gastric varices and bleeding-related research.\u003c/p\u003e \u003cp\u003eIt is necessary for cirrhotic patients to undergo routine gastroscopy, but the scope of gastroscopy is limited to the intramucosal and submucosal blood vessels, and the hemodynamic changes in cirrhotic patients with portal hypertension cannot be understood. Endoscopic ultrasound (EUS) is a non-invasive method that can provide anatomic high-resolution images and hemodynamic features of collateral vessels surrounding the distal esophagus and upper stomach in patients with portal hypertension[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, when judging the changes in the collateral circulation of portal hypertension, we can not only observe the esophageal and gastric varices that can be seen under conventional gastroscopy but also detect the vascular images inside and outside the esophageal wall that can not be seen under ordinary endoscopy. EUS is capable of objectively imaging gastroesophageal varices (GEVs) and is more sensitive than conventional endoscopy in detecting GEVs[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In Gin-Ho Lo\u0026rsquo;s study, EUS detected Gastric varices (GV) in 28 patients (35%) while routine endoscopy found only 6 patients (7%) in whom GV was found by conventional endoscopy[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Changjun men et al reported that a patient with hepatitis B cirrhosis whose varices were not detected by plain endoscopy and whose esophageal and gastric varices were detected by EUS developed esophageal and gastric variceal bleeding 6 months after the examination.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. EUS is widely accepted as useful for assessing esophagogastric varices that provide good delineation of the cross-sectional anatomy of the distal esophagus and proximal stomach, can detect gastroesophageal varices along with periesophageal collateral veins, paraesophageal collateral veins, and perforating vein, so EUS can detect gastroesophageal varices earlier than gastroscopy[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Previous studies also have shown that EUS has more advantages in detecting esophageal and gastric varices caused by portal hypertension and early liver fibrosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. According to Y. T. Lee\u0026lsquo;s research, the advantage of EUS is that it can provide information about venous abnormalities at the gastroesophageal junction due to elevated portal vein pressure in early cirrhosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].In recent years, EUS technology has developed rapidly, and EUS has become more and more important in the diagnosis and treatment of portal hypertension-related varices. However, this examination is expensive, time-consuming, difficult to operate and has high technical requirements, and the patient can also feel pain during the test. it is difficult to repeat the examination and long-term follow-up, and it cannot be widely popularized in clinical practice. In the Baveno VII portal hypertension consensus, it is suggested that the possibility of high-risk varices can be confirmed by liver stiffness and platelet test to avoid unnecessary endoscopy[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, for early portal hypertension, no alternative non-invasive markers have been found. Therefore, it is of great significance to find a non-invasive marker to evaluate esophageal and gastric varices in patients with compensatory cirrhosis.\u003c/p\u003e \u003cp\u003eSerum liver fibrosis markers include hyaluronic acid(HA), laminin(LN), type III procollagen, and type IV collagen. These four markers of liver fibrosis have been proved to be highly correlated with liver fibrosis in patients with chronic liver disease[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. It has been proved that liver fibrosis markers have a high predictive value for the diagnosis and prognosis of patients with chronic liver disease of different etiologies[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, there are still few studies on the relationship between serum liver fibrosis markers and the severity and complications of esophageal and gastric varices. Therefore, we conducted a retrospective cross-sectional study to evaluate the correlation between indicators of liver fibrosis and early gastroesophageal varices in patients with compensatory cirrhosis.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eIn this retrospective study, a total of 477 patients with compensated cirrhosis enrolled between November 2015 to December 2019. Eligible patients aged 18 years or older who were diagnosed with compensated cirrhosis according to imaging by ultrasonography, Computed tomography (CT), or Magnetic Resonance Imaging(MRI) of irregular and nodular liver together with impaired liver synthetic function are sufficient for the diagnosis of cirrhosis[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. All patients completed esophagogastroduodenoscopy(EGD), EUS, Fibroscan, imaging, and laboratory examinations within 6 months before and after hospitalization. The exclusion criteria were as follows: 1. primary prevention with non-selective β-blockers or endoscopic ligation; 2. thrombosis of cavernous transformation of the portal vein system; 3. history of malignancy (including hepatocellular carcinoma); 4. incomplete clinical data.\u003c/p\u003e \u003cp\u003e This study protocol was approved by the Ethics Committee of Tianjin Second People\u0026rsquo;s Hospital and conforms to the principles of the 1975 Declaration of Helsinki. An informed consent was obtained from all patients. All methods were performed in accordance with relevant guidelines and regulations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics and Laboratory Investigations\u003c/h2\u003e \u003cp\u003eDemographic data (age and sex) and laboratory results (routine blood tests, biochemistry tests, and immunology tests) were collected and analyzed. Blood samples were collected 1 week before EUS and EGD. albumin (ALB), aspartate aminotransferase (AST), Serum alanine aminotransferase (ALT), and total bilirubin (TBIL) were detected by a Hitachi 7180 Automatic Biochemical Analyser (Hitachi, Ltd, Tokyo, Japan). platelet (PLT) was measured using a Sysmex XN-2000 hematology analyzer (Sysmex Corporation, Kobe, Japan) according to the manufacturer\u0026rsquo;s recommendation. prothrombin time (PT) was performed by the clotting method on the automatic coagulometer \"STAGO Compact\" (\"Diagnostica Stago\", France).\u003c/p\u003e \u003cp\u003eThe serum markers of liver fibrosis were measured with AutoLumo A2000 Plus. The upper reference value of laminin ln was 130ng/ml, the upper reference value of type III procollagen was 15ng/ml, the upper reference value of hyaluronic acid was 120ng/ml, and the upper reference value of type IV collagen was 95ng/ml. The coefficient of variation CV (%) was not exceeding 15%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of varices\u003c/h2\u003e \u003cp\u003eThe EGD was performed by two experienced operators using the equipment (Olympus CV-260SL, Japan). The variance was described according to the expert guideline[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. EUS was conducted by skilled professional doctors using the equipment (Olympus GF-UE260, Japan). According to the results of gastroscopy and endoscopic ultrasonography, the patients were divided into two groups: no gastroesophageal varices (negative for EUS and EGD) and early gastroesophageal varices (positive for EUS and negative for EGD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTransient elastography\u003c/h2\u003e \u003cp\u003eliver stiffness (LS) was measured by transient elastography (Echosens, Fibroscan 520, Paris, France) by two experienced practitioners with professional training. The right lobe of the liver was accessed with maximal abduction of the right arm during the operation. It was considered valid that ten measurements were obtained with a success rate of 60% total measurements, with an interquartile range of less than 30%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSpleen size\u003c/h2\u003e \u003cp\u003eThe patients fasted overnight and routinely underwent abdominal ultrasound examinations to measure the spleen size. Spleen diameters were reported and recorded. Ultrasound was performed by professional operators not known the clinical information about patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS statistical 26 (IBM, New York, USA) was used for statistical analysis. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Kolmogorov-Smirnov test is used to analyze whether continuous variables obey normal distribution. The nonnormal distribution variables are expressed as median (quartile 25, quartile 75). Data for categorical variables are presented as the number (n) and proportion (%). The correlation between variables and early gastroesophageal varices was evaluated by Spearman correlation coefficient (r), Mann-Whitney U test, chi-square test, and binary logistic regression analysis. The \"enter\" method was used for Univariate logistic regression, and the statistically significant variables were included in the Univariate Logistic regression analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003eGeneral characteristics of the patients\u003c/h2\u003e\n\u003cp\u003eA total of 477 compensated cirrhosis patients with the median age of 50 years were included in this study. Child-Pugh class A were 442(92.7%), and Child-Pugh class B were 35(7.3%). According to different etiological classifications, there were 362 patients with hepatitis B (75.9%), 60 patients with hepatitis C (12.6%), and 55 patients with other liver diseases (11.5%). The further demographic data and laboratory blood markers of all patients are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eGeneral characteristics of the patients with compensated liver cirrhosis\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u0026thinsp;=\u0026thinsp;477\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50(40, 57)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale, n(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e263(55.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAetiology of cirrhosis, n(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHBV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e362(75.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHCV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60(12.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eothers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55(11.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChild category, n(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e442(92.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35(7.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52(26, 135)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45(27, 99)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTBIL(umol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.9(12.45, 22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALB(g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.2(39.5, 46.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePLT(x10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e146(109.25, 179)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT(s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.4(12.8, 14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHyaluronic acid(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e125(92, 254)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLaminin(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94(76, 113)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003etype III pro-collagen(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.5(6.9, 14)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCollagen type IV(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e69(61, 130)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLS(kPa)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.9(8.45, 21.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSplenic diameter(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e113(99, 123)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\"\u003eData are expressed as median (quartile 25, quartile 75) or number (proportion)\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\"\u003eALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eGeneral characteristics of patients by gastroesophageal varices\u003c/h2\u003e\n\u003cp\u003eThe included patients were divided into the non-GEVs group by EUS(-) EGD(-)and the early GEVs group by EUS(+) EGD(-). Among the 477 patients,279(58.5%) had early GEVs, and 198(41.5%) did not. No significant difference in age, sex, and etiology proportion were observed between the two groups, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.617, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.437, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.428 respectively. The total bilirubin, liver stiffness(LS), and serum liver fibrosis markers (hyaluronic acid, laminin, type III procollagen, and type IV collagen) in the early GEVs group were significantly higher than those in the non-GEVs group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while PLT was significantly lower than those in the non-GEVs group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There was no significant difference in other indexes between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05),as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eGeneral characteristics of subjects by early gastroesophageal varices\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEUS-EGD-(n\u0026thinsp;=\u0026thinsp;198)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEUS\u0026thinsp;+\u0026thinsp;EGD-(n\u0026thinsp;=\u0026thinsp;279)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50(39.75, 56.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51(40, 57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.617\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale, n(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e105(53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e158(60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.436\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAetiology of cirrhosis (HBV/HCV/other)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e145/26/27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e217/34/28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.428\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChild category (A/B)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e189/9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e253/26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.049\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46(24, 116)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57(28, 164)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.5(24, 86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45(28, 120)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.084\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTBIL(umol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.2(11.6, 20.725)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.1(13, 23.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALB(g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.8(39.5, 46.425)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.7(39.3, 46.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePLT(X109/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e152(120.5, 180.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e137(105, 176)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT(s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.4(12.7, 14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.5(12.8, 14.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.029\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHyaluronic acid(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e106.5(87, 192.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e141(93, 322)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLaminin(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91(68.75, 98.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e97(89, 130)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003etype III pro-collagen(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.5(9.0, 12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.7(7.2, 16)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCollagen type IV(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55(68, 114.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72(62, 137)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLS(kPa)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.55(7.675, 17.35)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.2(8.8, 23.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSplenic diameter(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110.5(99.25, 120.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e114(99, 125)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.226\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eData are expressed as median (quartile 25, quartile 75) or number (proportion)\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelations between serum liver fibrosis markers and the clinical characteristics of patients.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe correlations between serum liver fibrosis markers variables and clinical characteristics are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. As expected, Serum liver fibrosis markers were positively correlated with ALT, AST, TBIL, PT, LS, and child-pugh (C-P) classification (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and negatively correlated with ALB and PLT (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The length and diameter of the spleen were positively correlated with hyaluronic acid, type III procollagen, and type IV collagen (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Hyaluronic acid, laminin, type III procollagen, and type IV collagen were positively correlated with early gastroesophageal varices (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelations between serum fibrosis markers and clinical characteristics of patients\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables statistics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHyaluronic acid(ng/ml)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLaminin(ng/ml)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eType III pro-collagen(ng/ml)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCollagen type IV(ng/ml)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.168\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.895\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.131\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.116\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.011\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChild class (A/B)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.273\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.216\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.301\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.291\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.210\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.254\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.439\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.420\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.331\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.352\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.518\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.529\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTBIL (\u0026micro;mol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.266\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.290\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.289\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.256\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALB(g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.401\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.302\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.431\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.494\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePLT(X109/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.314\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.249\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.150\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.267\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT(s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.212\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.217\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.300\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.339\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLS(kPa)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.484\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.430\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.469\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.568\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSplenic diameter(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.149\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.059\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.159\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.204\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEGD(-)EUS(-/+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.142\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.253\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.130\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.127\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eEGD (-)esophagogastroduodenoscopy negative, EUS༈-/+༉ endoscopic ultrasound negative or positive\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eAnalysis of risk factors associated with early GEVs\u003c/h2\u003e\n\u003cp\u003eBinary logistic regression analysis was used to explore the risk factors associated with early GEVs in patients with compensated cirrhosis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). In univariate analysis, patients with early portal hypertension had lower PLT (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034), higher AST (P\u0026thinsp;=\u0026thinsp;0.046), TBIL (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041), HA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LN (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), procollagen III (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), collagen IV (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) and LSM (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). However, after the multivariate logistic regression analysis, it was found that LN was an independent risk factor for predicting early GEVs in patients with compensated cirrhosis, with an odds ratio (OR) (95% confidence interval CI) of 1.011 (1.004, 1.017), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eUnivariate and multivariate analysis of factors associated with gastroesophageal varices\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eUnivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMultivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOR(95%CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOR(95%CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.004(0.989, 1.020)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.612\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale, n(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.865(0.600, 1.247)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.436\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAetiology of cirrhosis (HBV/HCV/other)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.839(0.643, 1.095)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.197\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChild category (A/B)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.158(0.988, 4.713)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.054\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.001(1.000, 1.001)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.246\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST(U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.001(1.000, 1.002)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.999(0.998,1.001)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.529\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTBIL(umol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.008(1.000, 1.016)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.041\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.004(0.995,1.012)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.387\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALB(g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.981(0.949, 1.015)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.247\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePLT(X10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.996(0.993, 1.000)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.034\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.999(0.996,1.003)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.676\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT(s)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.056(0.971, 1.149)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.205\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHyaluronic acid(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.001(1.001, 1.002)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000(0.999,1.001)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.562\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLaminin(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.015(1.009, 1.020)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.011(1.004, 1.018)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003etype III pro-collagen(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.040(1.012, 1.069)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.999(0.995,1.002)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.494\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCollagen type IV(ng/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.004(1.001, 1.006)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.003(0.968,1.040)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.862\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLS(Kpa)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.032(1.113, 1.051)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.013(0.988,1.038)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.308\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSplenic diameter(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.003(0.993, 1.013)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.569\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eALT alanine aminotransferase, AST aspartate aminotransferase, TBIL total bilirubin, ALB albumin, PLT platelet, PT prothrombin time, LS liver stiffness\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrevious research has mostly focused on identifying non-invasive serological indications of high-risk esophagogastric varices to reduce unnecessary endoscopy in patients. Many studies have now shown that non-invasive indicators including platelet count, albumin, spleen size, and liver stiffness are related to the severity of high-risk esophagogastric varices and cirrhosis[\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Non-invasive indications of early esophagogastric varices are the subject of comparatively few investigations. Therefore, the purpose of this study is to develop non-invasive indicators of esophagogastric varices, decrease unnecessary gastroscopy and endoscopic ultrasonography, improve prognosis, and reduce mortality and medical expenditures.\u003c/p\u003e \u003cp\u003eWe performed a correlation analysis between serum liver fibrosis markers and clinical indicators in this study. First, we discovered that serum liver fibrosis markers are related to other indicators of gastroesophageal varices, platelets, and liver Liver stiffness, suggesting that serum liver fibrosis markers could be used as a substitute for other indicators in the prediction of gastroesophageal varices. Second, we found a correlation between serum liver fibrosis markers and early gastroesophageal varices, demonstrating that an increase in serum liver fibrosis markers could indicate the presence of gastroesophageal varices. We also discovered a correlation between serum markers of liver fibrosis and C-P class, suggesting that serum markers of liver fibrosis are related to the severity of cirrhosis. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the study, we found that hyaluronic acid, laminin, type III procollagen, and type IV collagen were positively correlated with gastroesophageal varices in univariate analysis and that the increase of laminin concentration was independently correlated with gastroesophageal varices in compensated liver cirrhosis in multivariate analysis after adjusting for confounding factors. Laminin is a simple and non-invasive marker used in clinical detection. Therefore, laminin can be used as a routine reference index for monitoring gastroesophageal varies in patients with compensated liver cirrhosis.\u003c/p\u003e \u003cp\u003eChronic liver injury can result in fibrosis, which is characterized by the accumulation of extracellular matrix(ECM) in the liver. Hepatic stellate cells are activated by chronic liver cell injury. The fibrotic myofibroblast phenotype is acquired by these cells, resulting in collagen synthesis and per sinus contraction, leading to liver fibrosis and portal hypertension. Laminin is one of the major glycoproteins in the basement membrane. Hepatic stellate cells (HSCs) generate it and deposit it in the liver's basement membrane. It is involved in biological tasks such as cell adhesion, matrix component interaction with collagen and glycosaminoglycans, cytoskeleton maintenance, and liver fibrosis.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The proportion of type I collagen, type III collagen, and laminin increases in the diseased state, while the mixture of laminin, type IV collagen, and proteoglycan is increased in ECM in normal liver.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. According to several research, serum liver fibrosis indicators are related to the severity of liver fibrosis caused by various etiologies and are significant predictors of disease prognosis. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Serum laminin concentration has also been related to gastroesophageal varices in cirrhosis in other research. This study also found that laminin concentration is related to early gastroesophageal varices in cirrhosis. Long Fei Wu's study found that in a one-year prospective analysis, laminin and type IV collagen are possible predictors of rebleeding after esophagogastric varices surgery and that is related to esophageal and gastric varices. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has some limitations. This is a retrospective cross-sectional study. Not all patients have received EUS examination and detection of serum markers of liver fibrosis, which increases the possibility of bias. Therefore, a prospective large-scale study is needed to further clarify the causal relationship between laminin and early portal hypertension. In addition, although there are standard procedures, there may be variability among different observers.\u003c/p\u003e \u003cp\u003eIn conclusion, we found that indicators of liver fibrosis were associated with early gastroesophageal varices, especially laminin was independently associated with early gastroesophageal varices in patients with compensatory cirrhosis. Therefore, laminin can be used to predict the existence of early gastroesophageal varices, but it still needs to be verified by large sample prospective studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEUS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndoscopic ultrasound\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGEVs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egastroesophageal varices\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGastric varices\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEGD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eesophagogastroduodenoscopy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehyaluronic acid, LN:laminin, CT:Computed tomography, MRI:Magnetic Resonance Imaging, ECM:extracellular matrix\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHSCs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHepatic stellate cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealanine aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003easpartate aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTBIL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etotal bilirubin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealbumin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eplatelet\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprothrombin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eliver stiffness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval, C-P:child-pugh.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study protocol was approved by the Ethics Committee of Tianjin Second People\u0026rsquo;s Hospital and conforms to the principles of the 1975 Declaration of Helsinki. An informed consent was obtained from all patients. All methods were performed in accordance with relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by Natural Science Foundation of Tianjin City (20JCYBJC01150); Tianjin Health Science and Technology Project (No. TJWJ2021QN063, No. TJWJ2021ZD010 and No. TJWJ2021MS034).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design (Ling Mei，Jia Li)\u003c/p\u003e\n\u003cp\u003edrafting manuscript (Ling Mei，Ying Ma)\u003c/p\u003e\n\u003cp\u003estatistical analysis (Qingling Chen，Ling Mei)\u003c/p\u003e\n\u003cp\u003edata collection (Lili Zhao，Li Zhou，Hang Yang，Jie Liu)\u003c/p\u003e\n\u003cp\u003ethe revision of the manuscript for important intellectual content (Ying Ma\u0026nbsp;，Jia Li)\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the medical staff at Tianjin Second People\u0026rsquo;s Hospital for their essential support and assistance with data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u0026nbsp;\u003c/sup\u003eDepartment of Hepatology, Second People\u0026rsquo;s\u0026nbsp;Clinical College of Tianjin Medical University, Tianjin, China\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e Department of Hepatology, Tianjin Second People\u0026apos;s Hospital, Tianjin, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMauro E, Gadano A: \u003cb\u003eWhat's new in portal hypertension?\u003c/b\u003e Liver Int 2020, \u003cb\u003e40 Suppl 1\u003c/b\u003e:122\u0026ndash;127.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGin\u0026egrave;s P, Krag A, Abraldes JG, Sol\u0026agrave; E, Fabrellas N, Kamath PS: \u003cb\u003eLiver cirrhosis\u003c/b\u003e. 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Clin Chim Acta 2010, \u003cb\u003e411\u003c/b\u003e(15\u0026ndash;16):1009\u0026ndash;1017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalfon P, Bourliere M, Penaranda G, Deydier R, Renou C, Botta-Fridlund D, Tran A, Portal I, Allemand I, Rosenthal-Allieri A \u003cem\u003eet al\u003c/em\u003e: \u003cb\u003eAccuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus\u003c/b\u003e. Comp Hepatol 2005, \u003cb\u003e4\u003c/b\u003e:6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNiemel\u0026auml; O, Risteli J, Blake JE, Risteli L, Compton KV, Orrego H: \u003cb\u003eMarkers of fibrogenesis and basement membrane formation in alcoholic liver disease\u003c/b\u003e. Gastroenterology 1990, \u003cb\u003e98\u003c/b\u003e(6):1612\u0026ndash;1619.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu LF, Xiang XX, Bai DS, Jin SJ, Zhang C, Zhou BH, Qian JJ, Jiang GQ: \u003cb\u003eNovel noninvasive liver fibrotic markers to predict postoperative re-bleeding after laparoscopic splenectomy and azygoportal disconnection: a 1-year prospective study\u003c/b\u003e. Surg Endosc 2021, \u003cb\u003e35\u003c/b\u003e(11):6158\u0026ndash;6165.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"early gastroesophageal varices, endoscopic ultrasonography, hyaluronic acid, laminin, type III procollagen, and type IV collagen","lastPublishedDoi":"10.21203/rs.3.rs-1796375/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1796375/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and aim\u003c/strong\u003e: portal hypertension is a common complication of chronic liver diseases that is responsible for most clinical consequences of liver cirrhosis. In patients with portal hypertension, esophagogastric variceal bleeding is a leading cause of death. The majority of research focuses on high-risk esophageal and gastric varices and bleeding, with only a few on early varices. However, it is found that early intervention of gastroesophageal varices can better improve the prognosis and reduce mortality, there is still no relevant research. Ultrasonic endoscopy is a combination of endoscopy and ultrasonic imaging. It can detect varices around the esophagus and gastric based on a gastroscope, and detect esophageal collateral veins and perforating veins earlier, which is helpful for the early diagnosis of varices. Therefore, this study aimed to explore the correlation between serum fibrosis markers and early gastroesophageal varices in patients with compensated cirrhosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This study included 477 patients with compensated cirrhosis. The selected patients were categorized into two groups. The early gastroesophageal varices group was gastroesophageal varices found by endoscopic ultrasonography, but not by gastroscopy, whereas the no gastroesophageal varices group was endoscopic ultrasonography and gastroscope without varices. Multiple logistic regression analysis was used to explore the association of serum fibrosis markers with early gastroesophageal varices.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Among the 477 compensated liver cirrhosis patients 198 patients without gastroesophageal varices and 279 patients with early gastroesophageal varices. There was a positive correlation between serum fibrosis markers and early gastroesophageal varices. In univariate logistic regression analysis, patients with early gastroesophageal varices had lower platelet count (P = 0.034), higher aspartate aminotransferase (\u003cem\u003eP\u003c/em\u003e = 0.046), total bilirubin (\u003cem\u003eP\u003c/em\u003e = 0.041), hyaluronic acid (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), laminin (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), type III procollagen (\u003cem\u003eP\u003c/em\u003e = 0.005), type IV collagen (\u003cem\u003eP\u003c/em\u003e = 0.002) and liver stiffness measurement (\u003cem\u003eP\u003c/em\u003e = 0.001). Multivariate analysis showed that laminin（OR 1.011;95% CI 1.004-1.017, \u003cem\u003eP\u003c/em\u003e=0.001） was an independent risk factor for predicting early gastroesophageal varices in patients with compensated cirrhosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eHigher laminin was independently associated with early gastroesophageal varices among patients with compensated cirrhosis.\u003c/p\u003e","manuscriptTitle":"Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-06 16:49:44","doi":"10.21203/rs.3.rs-1796375/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-09-21T07:13:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-08-23T18:39:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"86b14161-cfc8-4059-a70a-bb929a7ab5cf","date":"2022-08-22T15:16:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-06-28T15:52:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-06-28T15:49:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-06-28T13:36:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-06-28T13:30:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2022-06-26T10:03:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1ecb7887-1d4e-422e-837b-22462e5cd881","owner":[],"postedDate":"July 6th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-10-19T06:29:24+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-06 16:49:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1796375","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1796375","identity":"rs-1796375","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}