The Combination of Shear Wave Elastography and Platelet Counts Can Effectively Predict High-Risk Varices in Patients with Hepatitis B-Related Cirrhosis.

BACKGROUND: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. AIMS: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. METHODS: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. RESULTS: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). CONCLUSIONS: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.

Novel albumin, bilirubin and platelet criteria for the exclusion of high-risk varices in compensated advanced chronic liver disease: A validation study.

BACKGROUND AND AIMS: Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40 g/l, Bilirubin <22 µmol/l and Platelet >114,000/µl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients. METHODS: Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort. RESULTS: Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60-0.76) and 0.66 (0.60-0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were -0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, p < 0.001), without missing more HRVs. CONCLUSION: We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE.

The value of platelet parameters and related scoring system in predicting esophageal varices and collateral veins in patients with liver cirrhosis.

OBJECTIVE: To explore the value of platelet parameters and related scoring system in predicting esophageal varices and collateral veins in patients with liver cirrhosis. METHOD: A total of 94 patients with liver cirrhosis diagnosed in our hospital from March 2017 to July 2018 were divided into without esophageal varices group (NEV) and esophageal varices group (EV) into mild, moderate, and severe subgroups according to the results of general gastroscopy. The differences of biological indexes among different degrees of esophageal varices and collateral veins were analyzed, and the related factors of esophageal varices and collateral veins were analyzed. RESULTS: PLT count and PCT decreased gradually with the increase of esophageal varices in EV group. There were significant differences in PLT count and PCT, which were negatively correlated with the degree of collateral vein in esophageal collateral vein group. The maximum cross-sectional diameter and mean diameter of esophageal collateral veins in EV group were wider than those in NEV group. Further study showed that the maximum cross-sectional total diameter and mean diameter of esophageal collateral veins in severe esophageal varices group were wider than those in NEV group and mild esophageal varices group. Sequential Logistic regression analysis showed that PCT could effectively predict the existence of esophageal varices. Platelet parameters had no significant diagnostic value in predicting peri-ECV and Para-ECV. For platelet-related FI, APRI, FIB-4, King, Lok, GUCI, and FibroQ scoring systems, multivariate Logistic regression showed that FI, FIB-4, Lok and FibroQ scoring systems could effectively predict the presence of EV and Para-ECV (P<0.05), and its Lok Index is better than other rating systems, with AUROC values of 0.773 and 0.747, respectively. There is no significant predictive value for above scoring systems of peri-ECV. CONCLUSIONS: PCT and LOK index can effectively predict the existence of esophageal varices and para-esophageal veins in patients with liver cirrhosis, and can be used as an effective filling method for common gastroscopy and endoscopic ultrasonography to detect EV and ECV in liver cirrhosis.

Porto-Sinusoidal Vascular Disease as the Cause of Portal Hypertension in Felty's Syndrome: A Case Report and Literature Review.

Felty's syndrome (FS) is a disorder wherein patients with rheumatoid arthritis develop splenomegaly, neutropenia, and in some cases, portal hypertension without underlying cirrhosis. Esophageal variceal bleeding is a complication of FS in patients with portal hypertension. In contrast to splenectomy, few reports exist on the management of variceal bleeding with endoscopic therapy. Moreover, the long-term outcome has not been reported. We present a patient with esophageal variceal bleeding due to portal hypertension secondary to Felty's syndrome. The patient was followed up for two years postendoscopy intervention. Literature review was performed and the histological features of portal hypertension in FS are discussed. The patient presented with a typical triad of rheumatoid arthritis (RA), splenomegaly, and neutropenia and was diagnosed as Felty's syndrome in 2012. She was admitted to our hospital in September 2017 for esophageal variceal bleeding. At the time of admission, her liver function test was normal. Abdominal CT showed no signs of cirrhosis and portal vein obstruction. Liver biopsy further excluded diagnosis of cirrhosis and supported the diagnosis of porto-sinusoidal vascular disease (PSVD), which was previously named as noncirrhotic idiopathic portal hypertension (NCIPH). An upper abdominal endoscopy revealed gastric and esophageal varices. A series of endoscopies was performed to ligate the esophageal varices. The patient was followed up for two years and did not show rebleeding. In conclusion, comorbid PSVD might be a cause of portal hypertension in FS patients. The present case had excellent outcome in two years, which supported the use of endoscopic therapy for the management of variceal bleeding in FS patients. Further large prospective study is needed to confirm the findings.

[Performance of the FIB-4 index in esophageal varices screening in patients with the diagnosis of liver cirrhosis]. / Desempeñ o del índice FIB-4 en el despistaje de vá rices esofá gicas en pacientes con el diagnóstico de cirrosis hepá tica.

INTRODUCTION: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. MATERIALS AND METHODS: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. RESULTS: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). CONCLUSIONS: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients.

Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease.

BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.

Desempeño del índice FIB-4 en el despistaje de várices esofágicas en pacientes con el diagnóstico de cirrosis hepática / Performance of the FIB-4 index in esophageal varices screening in patients with the diagnosis of liver cirrhosis

RESUMEN Introducción: El diagnóstico de várices esofágicas en pacientes cirróticos se realiza mediante la endoscopía digestiva alta. Se han estudiado predictores no invasivos para el diagnóstico de estas. Objetivo: El objetivo de este estudio es evaluar el desempeño del índice FIB-4 en el despistaje de várices esofágicas en pacientes con diagnóstico de cirrosis hepática. Materiales y métodos: Se realizó un estudio transversal analítico en cuatro hospitales nacionales utilizando historias clínicas de pacientes cirróticos. Se realizó el análisis univariado y bivariado, cálculo de sensibilidad, especificidad, valor predictivo positivo y negativo, razón de verosimilitud positiva y negativa del índice FIB-4 para el despistaje de várices esofágicas, tamaño de estas y profilaxis. Se construyeron curvas ROC para cada grupo de análisis. Resultados: Se incluyó 289 pacientes con diagnóstico de cirrosis hepática, la mayor parte fueron de sexo masculino (54,33%). 77,85% presentaron várices esofágicas. La distribución del tamaño de várices fue de 19,03%, 35,99% y 22,84% para várices grandes, medianas y pequeñas, respectivamente. En el análisis del índice FIB-4 con la presencia de várices se encontró una sensibilidad de 81,3% y una especificidad de 37,5% (AUC: 0,57). Para el tamaño de várices se encontró una sensibilidad 81,8% y una especificidad de 23,9% (AUC: 0,50). En el análisis de FIB-4 para grupos de profilaxis se encontró una sensibilidad de 81,8% y una especificidad de 28,5% (AUC: 0,54). Conclusiones: El índice FIB-4 no tiene un buen desempeño en el despistaje de la presencia várices esofágicas y su tamaño en pacientes con diagnóstico de cirrosis hepática.

ABSTRACT Introduction: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. Materials and methods: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. Results: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). Conclusions: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients.

Influence of esophageal variceal bleeding on iron status in chronic hepatitis C patients.

BACKGROUND: Disorders of serum iron balance are frequently observed in chronic hepatitis C (CHC) patients. Iron overload as well as iron deficiency anemia are common clinical findings in these patients. Variceal bleeding is also a common complication. To date, no study has discussed the influence of esophageal bleeding on iron status in anemic CHC bleeders. OBJECTIVE: Was to study reticulocyte hemoglobin content (CHr) and serum hepcidin levels in anemic CHC and to evaluate the influence of variceal bleeding on patients' iron status. METHODS: Serum hepcidin levels and CHr were assessed in 65 early phase CHC patients (20 nonanemic, 23 anemic nonbleeders, and 22 anemic bleeders), and 20 healthy controls; and were compared with the conventional indices of iron deficiency including mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, serum iron, total iron binding capacity, transferrin saturation and ferritin. RESULTS: Hepcidin levels were comparable in patients groups, but were significantly lower in patients than in controls (P = 0.01). Child-Pugh class B patients showed significantly lower hepcidin levels than class A patients. CHr levels were comparable in all groups as well as all iron deficiency indices. Patients with ferritin values or less 100 ng/ml and CHr or less 29 pg/cell or Tfsat or less 16% are more likely to have iron deficiency [odds ratio (OR = 3.93, 95% confidence interval (CI) = 2.54-6.08; OR = 10.50, 95% CI = 1.94-56.55, respectively). CONCLUSION: Esophageal bleeding has an almost no influence on iron status in CHC patients. Serum hepcidin content is influenced by CHC disease rather than by anemia associated with or without esophageal bleeding and it could be used as a marker of early hepatic insufficiency. Assessing CHr content could add a potential utility in the detection of iron deficiency in CHC patients.

[Study on correlation between serum 25-hydroxyvitamin D3 level and esophageal variceal bleeding in cirrhotic patients].

Objective: To explore the correlation between serum 25-hydroxyvitamin D3 (25[OH]D(3)) levels and esophageal variceal bleeding (EVB) in cirrhotic patients. Methods: Eighty-three cases with liver cirrhosis hospitalized from November 2016 to January 2017 were collected. The patients were divided into bleeding group (51 cases) and non-bleeding group (32 cases) depending on the presence or absence of bleeding under gastroscopy. Serological tests were performed on both groups, including hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP),γ-glutamyltransferase (GGT), interleukin-6 (IL-6), and 25-hydroxyvitamin D3 (25[OH]D(3)). Both groups were analyzed by univariate analysis. The differences between both groups were compared by t-test, after normality test. The other variables were compared by Mann-Whitney U test. The correlation between the relevant variables and EVB were analyzed by Spearman's rank correlation and a multivariate analysis. Cases with primary biliary cirrhosis were relatively low in number (four cases in bleeding group, accounting for 8%, 10 cases in non-bleeding group, accounting for 31%). The effects of ALP and GGT on serum 25(OH)D(3) level were analyzed by stratified analysis. Moreover, ALP and GGT levels were divided into two and three groups: < 140 U/L and >140 U/L and < 30 U/L, > 30 U/L, and ~≤60 U/L. Results: Bleeding group had low levels of hemoglobin (t= -2.827,P= 0.005), alkaline phosphatase (t= -3.097,P= 0.002), gamma-glutamyltransferase (t= -2.292,P= 0.022), and 25(OH)D(3) (t= -3.134,P= 0.002) than non-bleeding group. Both groups (P> 0.05) had similar levels of albumin, interleukin-6, AAR, and FIB-4. Logistic regression analysis showed that 25(OH)D(3), alkaline phosphatase and hemoglobin were independent risk factors for EVB. Spearman's correlation coefficient analysis showed that 25(OH)D(3)was significantly positively and negatively correlated with interleukin-6 (r= 0.306,P= 0.005) and albumin (r= -0.327,P= 0.003). Stratified analysis showed that serum 25(OH)D(3) level was lower in ALP≤140U/L group and the bleeding group, and the difference was statistically significant than non-bleeding group (P= 0.007), while the serum level of 25(OH)D(3)was decreased in both groups for alkaline phosphatase > 140 U/L group, and the difference was not statistically significant (P= 0.051). Furthermore, in the GGT > 60 U/L group, the serum level of 25(OH)D(3)was significantly lower in the bleeding group, and the difference was statistically significant in non-bleeding group (P= 0.003), while the difference between the two groups was not statistically significant (P> 0.05) in GGT≤30 U/ L, > 30 U/L, and ~≤60 U/L group. Conclusion: Serum 25(OH)D(3)level was significantly lower in EVB cirrhotic patients, and it was an independent risk factor for EVB. Serum 25(OH)D(3) low levels was more apparent with ALP normalization or GGT level > 60 U/L.

Prediction of Aspartate Aminotransferase to Platelet Ratio Index with Size of Esophageal Varices in Liver Cirrhosis.

BACKGROUND: Liver cirrhosis is one of the major causes of morbidity and mortality. The threatening complication of Liver cirrhosis is variceal bleeding. Early diagnosis and initiation of therapy can reduce mortality associated with variceal bleeding. This study is designed to predict the esophageal varices by non-invasive method using aspartate aminotransferase to platelet count ratio index (APRI). METHODS: A total of 100 patients were studied between March 2016 and February 2017 with the diagnosis of Liver cirrhosis admitted at Bir Hospital fulfilling the inclusion and exclusion criteria. Ethical approval was obtained from Institutional review board of National Academy of Medical Sciences. RESULTS: Out of one hundred patients, 80 were males and 20 females. On endoscopy, small varices were present in 28 (28%) patients and large varices in 51(51%) patients. APRI with a cutoff value of 0.908 has sensitivity of 87.3% and specificity of 71.4%, positive predictive value of 92% and negative predictive value of 60% (p=0.001) for the detection of varices. CONCLUSIONS: Aspartate aminotransferase to platelet count ratio index can be a useful tool to indirectly predict esophageal varices in a patient with Liver Cirrhosis.

Machine Learning-based Development and Validation of a Scoring System for Screening High-Risk Esophageal Varices.

BACKGROUND & AIMS: Many patients with cirrhosis who undergo esophagogastroduodenoscopy (EGD) screening for esophageal varices (EVs) are found to have no or only small EVs. Endoscopic screening for EVs is therefore a potentially deferrable procedure that increases patient risk and healthcare cost. We developed and validated a scoring system, based on readily-available data, to reliably identify patients with EVs that need treatment. METHODS: We collected data from 238 patients with cirrhosis undergoing screening EGD from January 2016 through December 2017 at 3 separate hospitals in Los Angeles (training cohort). We abstracted data on patient sex, age, race/ethnicity, platelet counts, and levels of hemoglobin, serum sodium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, international normalized ratio, albumin, urea nitrogen, and creatinine. We also included etiology of cirrhosis, presence of ascites, and presence of hepatic encephalopathy. We used a random forest algorithm to identify factors significantly associated with the presence of EVs and varices needing treatment (VNT) and calculated area under the receiver operating characteristic curve (AUROC). We called the resulting formula the EVendo score. We tested the accuracy of EVendo in a prospective study of 109 patients undergoing screening EGDs at the same medical centers from January 2018 through December 2018 (validation cohort). RESULTS: We developed an algorithm that identified patients with EVs and VNT based on international normalized ratio, level of aspartate aminotransferase, platelet counts, urea nitrogen, hemoglobin, and presence of ascites. The EVendo score identified patients with EVs in the training set with an AUROC of 0.84, patients with EVs in the validation set with and AUROC of 0.82, and EVs in patients with cirrhosis Child-Turcotte-Pugh class A (n = 235) with an AUROC of 0.81. The score identified patients with VNT in the training set with an AUROC of 0.74, VNT in the validation set with and AUROC of 0.75, and VNT in patients with cirrhosis Child-Turcotte-Pugh class A with and AUROC of 0.75. An EVendo score below 3.90 would have spared 30.5% patients from EGDs, missing only 2.8% of VNT. The same cutoff would have spared 40.0% of patients with Child-Turcotte-Pugh class A cirrhosis from EGDs, missing only 1.1% of VNT. CONCLUSIONS: We algorithmically developed a formula, called the EVendo score, that can be used to predict EVs and VNT based on readily available data in patients with cirrhosis. This score could help patients at low risk for VNT avoid unnecessary EGDs.

Real-life experience of lusutrombopag for cirrhotic patients with low platelet counts being prepared for invasive procedures.

BACKGROUND AND AIMS: The present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts. METHODS: We studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed. RESULTS: In 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts <50,000/µL and needed platelet transfusions were 66% (n = 27/41) for radiofrequency ablation, 43% (n = 21/49) for transarterial chemoembolization, and 55% (n = 21/38) for endoscopic injection sclerotherapy / endoscopic variceal ligation, respectively. In 25 cirrhotic patients treated by lusutrombopag prior to the invasive procedures, platelet counts significantly increased compared with baseline (82,000 ± 26,000 vs. 41,000 ± 11,000/µL) (p < 0.01). Out of 25 patients, only 4 patients (16%) needed platelet transfusion before the invasive procedures. The proportion of patients with low platelet count and who needed platelet transfusions was significantly low in patients treated with lusutrombopag compared to those not treated with lusutrombopag (16% (4/25) vs. 54% (69/128), p = 0.001). Platelet counts after lusutrombopag treatment and prior to invasive procedures were lower in patients with a baseline platelet count ≤30,000/µL (n = 8) compared with those with a baseline platelet count >30,000/µL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/µL, p = 0.002). Patients with a baseline platelet count ≤30,000/µL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index <40 cm2 (n = 5) (0% vs. 100%, p = 0.02). Hemorrhagic complication was not observed. Recurrence of portal thrombosis was observed and thrombolysis therapy was required in one patient who had prior history of thrombosis. CONCLUSIONS: Lusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions.

Predicting gastroesophageal varices through spleen magnetic resonance elastography in pediatric liver fibrosis.

BACKGROUND: A recent retrospective study confirmed that hepatic stiffness and splenic stiffness measured with magnetic resonance elastography (MRE) are strongly associated with the presence of esophageal varices. In addition, strong correlations have been reported between splenic stiffness values measured with MRE and hepatic venous pressure gradients in animal models. However, most studies have been conducted on adult populations, and previous pediatric MRE studies have only demonstrated the feasibility of MRE in pediatric populations, while the actual clinical application of spleen MRE has been limited. AIM: To assess the utility of splenic stiffness measurements by MRE to predict gastroesophageal varices in children. METHODS: We retrospectively reviewed abdominal MRE images taken on a 3T system in pediatric patients. Patients who had undergone Kasai operations for biliary atresia were selected for the Kasai group, and patients with normal livers and spleens were selected for the control group. Two-dimensional spin-echo echo-planar MRE acquisition centered on the liver, with a pneumatic driver at 60 Hz and a low amplitude, was performed to obtain hepatic and splenic stiffness values. Laboratory results for aspartate aminotransferase to platelet ratio index (APRI) were evaluated within six months of MRE, and the normalized spleen size ratio was determined with the upper normal size limit. All Kasai group patients underwent gastroesophageal endoscopy during routine follow-up. The Mann-Whitney U test, Kendall's tau b correlation and diagnostic performance analysis using the area under the curve (AUC) were performed for statistical analysis. RESULTS: The median spleen MRE value was 5.5 kPa in the control group (n = 9, age 9-18 years, range 4.7-6.4 kPa) and 8.6 kPa in the Kasai group (n = 22, age 4-18 years, range 5.0-17.8 kPa). In the Kasai group, the APRI, spleen size ratio and spleen MRE values were higher in patients with portal hypertension (n = 11) than in patients without (n = 11) (all P < 0.001) and in patients with gastroesophageal varices (n = 6) than in patients without (n = 16) (all P < 0.05), even though their liver MRE values were not different. The APRI (τ = 0.477, P = 0.007), spleen size ratio (τ = 0.401, P = 0.024) and spleen MRE values (τ = 0.426, P = 0.016) also correlated with varices grades. The AUC in predicting gastroesophageal varices was 0.844 at a cut-off of 0.65 (100% sensitivity and 75% specificity) for the APRI, and 0.844 at a cut-off of 9.9 kPa (83.3% sensitivity and 81.3% specificity) for spleen MRE values. CONCLUSION: At a cut-off of 9.9 kPa, spleen MRE values predicted gastroesophageal varices as well as the APRI and spleen size ratio in biliary atresia patients after the Kasai operation. However, liver MRE values were not useful for this purpose.

Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

BACKGROUND: Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. AIM: To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. METHODS: Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. RESULTS: vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P < 0.001] and C-reactive protein [CRP; ρ = 0.249; P < 0.001]), and procoagulant imbalance (factor VIII/protein C ratio; ρ = 0.507; P < 0.001). Importantly, the associations between vWF and these parameters were independent of HVPG. Moreover, vWF (per 10%) independently predicted variceal bleeding (hazard ratio [HR]: 1.08 [95% confidence interval (95% CI): 1.01-1.16]; P = 0.023), requirement of paracentesis (HR: 1.05 [95% CI: 1.01-1.1]; P = 0.023) and bacterial infections (HR: 1.04 [95% CI: 1-1.09]; P = 0.04) including spontaneous bacterial peritonitis (HR: 1.09 [95% CI: 0.999-1.18]; P = 0.053) on a trend-wise level. After backward elimination, vWF (HR: 1.05 [95% CI: 1.02-1.08]; P = 0.003) and CRP (per 10 mg/L; HR: 1.53 [95% CI: 1.14-2.05]; P = 0.005) remained in the final model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. CONCLUSION: Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis.

Combination of albumin-bilirubin grade and platelets to predict a compensated patient with hepatocellular carcinoma who does not require endoscopic screening for esophageal varices.

BACKGROUNDS AND AIMS: There is no consensus on screening for high-risk esophageal varices (HRV) in patients with hepatocellular carcinoma (HCC). Here, we aimed to investigate the prevalence and risk factors of HRV in patients with HCC and to assess the combination of albumin-bilirubin grade and platelet count (ALBI-PLT score) for predicting compensated patients who do not need unnecessary endoscopic screening for HRV. METHODS: The ALBI-PLT score was calculated by adding the ALBI grade and points for platelet count (1 point if platelet count >150,000/mm3 and 2 points if ≤150,000/mm3). The predictive value of the ALBI-PLT score for HRV was analyzed in 887 compensated patients enrolled from October 2007 to April 2014 (study cohort). This was validated in 215 compensated patients from May 2014 to December 2015 (validation cohort). RESULTS: In the study cohort, the rates of HRV were 2.9% and 21.1% in compensated HCC patients with an ALBI-PLT score of 2 and >2, respectively. The negative predictive values of the ALBI-PLT score for predicting HRV were 97.1% and 98.1% in the study and validation cohorts, respectively. For compensated patients who did not receive endoscopic screening at the time of HCC diagnosis, the 5-year cumulative variceal hemorrhage rate was lower in patients with an ALBI-PLT score of 2 than in those with an ALBI-PLT score >2 (1.7% vs 9.1%, P = .007). CONCLUSION: In patients with HCC with compensated liver function, an ALBI-PLT score of 2 predicted a very low risk of HRV and variceal hemorrhage; therefore, endoscopic screening for esophageal varices is not recommended for these patients.

Noninvasive Methods of Predicting Large Esophageal Varices in Children With Intrahepatic Portal Hypertension.

OBJECTIVE: Esophageal variceal bleeding is a severe complication of portal hypertension. The standard diagnostic screening test and therapeutic procedure for esophageal varices (EV) is endoscopy, which is invasive in pediatric patients. This study aimed to evaluate the role of noninvasive parameters as predictors of large varices in children with intrahepatic portal hypertension. METHODS: Participants included in this cross-sectional study underwent a screening endoscopy. Variceal size, red marks, and portal gastropathy were assessed and rated. Patients were classified into two groups: Group 1 (G1) with small or no varices and Group 2 (G2) with large varices. The population consisted of 98 children with no history of gastrointestinal (GI) bleeding, with a mean age of 8.9 ±â€Š4.7 years. The main outcome evaluated was the presence of large varices. RESULTS: The first endoscopy session revealed the presence of large varices in 32 children. The best noninvasive predictors for large varices were platelets (Area under the ROC Curve [AUROC] 0.67; 95% CI 0.57-0.78), the Clinical Prediction Rule (CPR; AUROC 0.65; 95% CI 0.54-0.76), and risk score (AUROC 0.66; 95% CI 0.56-0.76). The logistic regression model showed that children with a CPR value under 114 were 8.59 times more likely to have large varices. Risk scores higher than -1.2 also increased the likelihood of large varices (OR 6.09; P = 0.014), as did a platelet count/spleen size z score lower than 25 (OR 3.99; P = 0.043). The combination of these three tests showed a high negative predictive value. CONCLUSIONS: The CPR, the risk score, and the platelet count/spleen size z score could be helpful in identifying cirrhotic children who may be eligible for endoscopy.

Gas6 as a predictor of esophageal varices in patients affected by hepatitis C virus related-chronic liver disease.

AIM: Plasma Gas6 was tested as an alternative to Baveno VI criteria (liver stiffness <20 kPa and platelet count >150 × 109/l) in an endoscopy-sparing strategy. METHODS:  A total of 160 patients with chronic hepatitis C and advanced fibrosis/cirrhosis underwent, on the same occasion, liver elastography, upper endoscopy, a platelet count and serum Gas6 measurement. RESULTS:  A total of 74/160 (46%) patients had esophageal varices, that were small (diameter <5 mm) in 57/160 (34%) and large in 17/160 (11%) cases. A total of 34/160 (21%) patients satisfied Baveno VI criteria, according to which screening for esophageal varices could have been omitted; 1/34 had large varices (sensitivity 94%). A plasma Gas6 value <45 ng/ml, detected in 34/160 (21%) patients, was also 94% sensitive. CONCLUSION: Plasma Gas6 might represent a feasible alternative to Baveno VI criteria when transient elastography is unavailable/unsuccessful.

Large oesophageal varice screening by a sequential algorithm using a cirrhosis blood test and optionally capsule endoscopy.

BACKGROUND & AIMS: Large oesophageal varice (LEV) screening is recommended in cirrhosis. We performed a prospective study to improve non-invasive LEV screening. DESIGN: 287 patients with cirrhosis had upper gastrointestinal endoscopy (LEV reference), oesophageal capsule endoscopy (ECE), liver elastography and blood marker analyses. CirrhoMeter (cirrhosis blood test), the most accurate non-invasive LEV test, was segmented for cirrhosis (reference comparator) or LEV. VariScreen, a sequential and partially minimally invasive diagnostic algorithm, was developed by multivariate analysis. It uses CirrhoMeter first, then ECE if CirrhoMeter cannot rule LEV out or in, and finally endoscopy if CirrhoMeter+ECE combination remains uninformative. RESULTS: Diagnostic effectiveness rates for LEV were: cirrhosis-segmented CirrhoMeter: 14.6%, LEV-segmented CirrhoMeter: 34.6%, ECE: 60.6% and VariScreen: 66.4% (P ≤ .001 for overall or pair comparison). The respective missed LEV rates were: 2.8%, 5.6%, 8.3% and 5.6% (P = .789). Spared endoscopy rates were, respectively: 15.6%, 36.0%, 70.6% and 69%, (P < .001 for overall or paired comparison except ECE vs VariScreen: P = .743). VariScreen spared 38% of ECE and reduced missed LEV by 87% compared to classical ECE performed in all patients. Excepting cirrhosis-segmented CirrhoMeter, these spared endoscopy rates were significantly higher than that of the Baveno VI recommendation (using platelets and Fibroscan): 18.4% (P < .001). Ascites and Child-Pugh class independently predicted endoscopy sparing by VariScreen: from 86.0% in compensated Child Pugh class A to 24.1% in Child-Pugh class C with ascites. CONCLUSION: VariScreen algorithm significantly reduced the missed LEV rate with ECE by 87%, ECE use by 38% and endoscopy requirement by 69%, and even 86% in compensated cirrhosis.

EVALUATION OF THE BEHAVIOR OF LEVELS OF HMGB1 AND IL6 AS PREDICTORS OF INFECTION, ACUTE KIDNEY INJURY AND MORTALITY IN CIRRHOTIC PATIENTS WITH VARICEAL BLEEDING.

BACKGROUND: Gastroesophageal varices and associated bleeding are a major cause of morbidity and mortality in cirrhotic patients. OBJECTIVE: To evaluate the potential role of the biomarkers HMGB1 (High Mobility Group Box 1) and IL-6 (Interleukin-6) as predictors of infection, acute kidney injury and mortality in these patients. METHODS: It is a prospective, observational study that included 32 cirrhotic patients with variceal bleeding. RESULTS: The subjects'mean age was 52±5 years and 20 (62.5%) were male. The average MELD was 17.53±5 and the average MELD-Na was 20.63±6.06. Thirty patients (93.3%) patients were Child-Pugh class B or C. Infection was present in 9 subjects (28.1%), acute kidney injury was present in 6 (18.1%) and 4 (12.5%) patients died. The median serum levels of HMGB1 were 1487 pg/mL (0.1 to 8593.1) and the median serum level of IL-6 was 62.1 pg/mL (0.1 to 1102.4). The serum levels of HMGB1 and IL-6 were significantly higher in patients who developed infection, acute kidney injury and death (P<0.05). The Spearman's correlations for HMGB1 and IL-6 were 0.794 and 0.374 for infection, 0.53 and 0.374 for acute kidney injury and 0.467 and 0.404 for death, respectively. CONCLUSION: Serum levels of HMGB1 and IL-6 were higher in patients with the three studied outcomes. HMGB1 serum levels showed a high correlation with infection and a moderate correlation with acute kidney injury and death, while IL-6 showed a moderate correlation with infection and death and a low correlation with acute kidney injury.

Chronic liver disease is universal in children with biliary atresia living with native liver.

AIM: To examine the medical status of children with biliary atresia (BA) surviving with native livers. METHODS: In this cross-sectional review, data collected included complications of chronic liver disease (CLD) (cholangitis in the preceding 12 mo, portal hypertension, variceal bleeding, fractures, hepatopulmonary syndrome, portopulmonary hypertension) and laboratory indices (white cell and platelet counts, total bilirubin, albumin, international normalized ratio, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase). Ideal medical outcome was defined as absence of clinical evidence of CLD or abnormal laboratory indices. RESULTS: Fifty-two children [females = 32, 62%; median age 7.4 years, n = 35 (67%) older than 5 years] with BA (median age at surgery 60 d, range of 30 to 148 d) survived with native liver. Common complications of CLD noted were portal hypertension (40%, n = 21; 2 younger than 5 years), cholangitis (36%) and bleeding varices (25%, n = 13; 1 younger than 5 years). Fifteen (29%) had no clinical complications of CLD and three (6%) had normal laboratory indices. Ideal medical outcome was only seen in 1 patient (2%). CONCLUSION: Clinical or laboratory evidence of CLD are present in 98% of children with BA living with native livers after hepatoportoenterostomy. Portal hypertension and variceal bleeding may be seen in children younger than 5 years of age, underscoring the importance of medical surveillance for complications of BA starting at a young age.