Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

Upregulation of ATG9b by propranolol promotes autophagic cell death of hepatic stellate cells to improve liver fibrosis.

Proranolol has long been recommended to prevent variceal bleeding in patients with cirrhosis. However, the mechanisms of propranolol in liver fibrosis have not yet been thoroughly elucidated. Autophagic cell death (ACD) of activated hepatic stellate cells (HSCs) is important in the alleviation of liver fibrosis. Our study aims to assess the mechanisms of propranolol regulating HSC ACD and liver fibrosis. ACD of HSCs was investigated using lentivirus transfection. The molecular mechanism was determined using a PCR profiler array. The role of autophagy-related protein 9b (ATG9b) in HSC ACD was detected using co-immunoprecipitation and co-localization of immunofluorescence. Changes in the signalling pathway were detected by the Phospho Explorer antibody microarray. Propranolol induces ACD and apoptosis in HSCs. ATG9b upregulation was detected in propranolol-treated HSCs. ATG9b upregulation promoted ACD of HSCs and alleviated liver fibrosis in vivo. ATG9b enhanced the P62 recruitment to ATG5-ATG12-LC3 compartments and increased the co-localization of P62 with ubiquitinated proteins. The PI3K/AKT/mTOR pathway is responsible for ATG9b-induced ACD in activated HSCs, whereas the p38/JNK pathway is involved in apoptosis. This study provides evidence for ATG9b as a new target gene and propranolol as an agent to alleviate liver fibrosis by regulating ACD of activated HSCs.

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma.

During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

BACKGROUND: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. METHODS: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. RESULTS: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. CONCLUSION: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. CLINICAL TRIAL NUMBER: UMIN trial no. 000044857.

Effectiveness of Rex shunt for improving the abnormal portal hemodynamics and portal venous pathology in EHPVO animal model.

PURPOSE: To investigate the feasibility of the re-patent EHPVO (r-EHPVO) as an animal model of Rex shunt and the effectiveness of Rex shunt in improving abnormal portal hemodynamics and portal venous pathology of EHPVO. METHODS: A total of 18 New Zealand white rabbits were randomly divided into three groups: normal control (NC) group, extrahepatic portal venous obstruction (EHPVO) group, and r-EHPVO group. The main portal vein was dissected only in the NC group. The main portal vein was narrowed by a cannula in the EHPVO group. The cannula narrowing the main portal vein was removed to restore the portal blood flow into the liver on day 14 in the r-EHPVO group. The portal pressure, splenic size, blood flow velocity, and diameter of the portal vein were measured on days 14 and 28. The shear stress (SS) and circumferential stress (CS) of the portal vein were calculated. The proximal end of the main portal vein was collected on day 28 for further pathological analysis, and the thickness and area of the intima and media were measured by Image J software. The portal pressure, splenic size, SS, CS, intima and media thickness, the ratio of intimal to medial area (I/M), and the ratio of intimal area to the sum of intimal and medial area (I/I + M) were compared among the three groups. The correlation between SS and intimal thickness and between CS and medial thickness were analyzed. RESULTS: On day 28, the portal pressure of the EHPVO group was significantly higher than that of the NC and r-EHPVO groups, but no significant difference was detected in the portal pressure between r-EHPVO and NC groups. The length and thickness of the spleen in the EHPVO and r-EHPVO groups were significantly higher than those in the NC group (P < 0.01) but were significantly lower in the r-EHPVO group than those in the EHPVO group (P < 0.05). The SS was significantly lower in the EHPVO group than in NC and r-EHPVO groups (P < 0.05) but was significantly higher in the NC group than in the r-EHPVO group (P = 0.003). The CS was significantly higher in the EHPVO and r-EHPVO groups than that in the NC group (P < 0.05) but was significantly lower in the r-EHPVO group than that in the EHPVO group (P < 0.001). The intimal thickness, I/M, and I/I + M of the EHPVO group were significantly higher than those of the NC and r-EHPVO groups (P < 0.05), but no significant difference was observed between the NC and r-EHPVO groups (P > 0.05). The SS is negatively related to intimal thickness (r = - 0.799, P < 0.001). CONCLUSION: The r-EHPVO model is feasible as an animal model of the Rex shunt. The Rex shunt could be beneficial to improving the abnormal portal hemodynamic and portal venous intimal hyperplasia by restoring the portal blood flow into the liver.

Combined model with acoustic radiation force impulse to rule out high-risk varices in HBV-related cirrhosis with viral suppression.

AIMS: To prospectively evaluate the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) via acoustic radiation force impulse (ARFI) imaging combined with platelet counts (PLT) in ruling out HRV in HBV-related cirrhotic patients with viral suppression. METHODS: Patients with cirrhosis enrolled between June 2020-March 2022 were divided into a derivation cohort and validation cohort. LSM and SSM ARFI-based, and esophagogastroduodenoscopy (EGD) were performed at enrollment. RESULTS: In the derivation cohort, overall, 236 HBV-related cirrhotic patients with maintained viral suppression were enrolled, and the prevalence of HRV was 19.5% (46/236). With the aim of identifying HRV, the most accurate LSM and SSM cut-offs were chosen of 1.46 m/s and 2.28 m/s, respectively. The combined model (LSM<1.46 m/s and PLT>150 × 109/L strategy combined with SSM ≤ 2.28 m/s) can spare 38.6% of EGDs and 4.3% of HRV cases were misclassified. In the validation cohort, we analysed 323 HBV-related cirrhotic patients with maintained viral suppression and validated the combined model can spare 33.4% (108/323) of EGD, and the HRV missed rate was 3.4%. CONCLUSIONS: A non-invasive prediction model combining LSM<1.46 m/s and PLT>150 × 109/L strategy with SSM ≤ 2.28 m/s exhibited excellent performance in ruling out HRV and avoided a significantly large number (38.6% vs 33.4%) of unnecessary EGDs in HBV-related cirrhotic patients with viral suppression.

Nodular Regenerative Hyperplasia Is Not a Rare Condition After Liver Transplantation: Incidence, Predictive Factors, and Impact on Survival.

BACKGROUND: The objectives of this study were to evaluate incidence and to identify the risk factors of occurrence and the predictive factors of symptomatic forms of nodular regenerative hyperplasia (NRH) after liver transplantation (LT). METHODS: To identify risk factors of NRH following LT, we included 1648 patients transplanted from 2004 to 2018 and compared the patients developing NRH after LT to those who did not. To identify predictive factors of symptomatic NRH, we selected 115 biopsies displaying NRH and compared symptomatic to asymptomatic forms. Symptomatic NRH was defined as the presence of ascites, esophageal varices, hepatic encephalopathy, portal thrombosis, retransplantation, or death related to NRH. RESULTS: The incidence of NRH following LT was 5.1%. In multivariate analysis, the independent factor of developing NRH after LT was the donor's age (odds ratio [OR] = 1.02; confidence interval, 1.01-1.03; P = 0.02). Symptomatic forms occurred in 29 (25.2%) patients: 19 (16.5%) patients presented with ascites, 13 (11.3%) with esophageal varices, 4 (3.5%) with hepatic encephalopathy, and 8 (7%) with portal thrombosis. The median period before the onset of symptoms was 8.4 (1.5-11.3) y after LT. The spleen size at diagnosis/before LT ratio (OR = 12.5; 114.17-1.37; P = 0.0252) and thrombectomy during transplantation (OR = 11.17; 1.48-84.11; P = 0.0192) were associated with symptomatic NRH in multivariate analysis. CONCLUSIONS: NRH following LT is frequent (5.1%) and leads to symptomatic portal hypertension in 25.2% of patients. Using older grafts increases the risk of developing NRH after LT. Clinicians should screen for signs of portal hypertension, particularly in measuring spleen size.

Long-term follow-up and liver outcomes in children with cystic fibrosis and nodular liver on ultrasound in a multi-center study.

BACKGROUND: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD. METHODS: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event. RESULTS: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×103/microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6-11.8) vs NL (5.3, 4.2-7, p < 0.0001). Over 6.3 years follow-up (1.3-10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events. CONCLUSIONS: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease.

Age, Sex, and Body Mass Index Should Be Considered When Assessing Spleen Length in Patients with Compensated Advanced Chronic Liver Disease.

Background/Aims: We investigated the factors related to spleen length and the diagnostic accuracy of a model using spleen length corrected by related factors, for the prediction of varices needing treatment (VNT). Methods: Various prediction models for VNT including spleen length were analyzed in the cohort of compensated advanced chronic liver disease (cACLD), defined as liver stiffness (LS) ≥10 kPa in a recent study. The associated factors for spleen length were identified in healthy subjects to improve the prediction of VNT. Results: Among 1,218 cACLD patients, VNT was noted in 249 patients (20.4%). On multivariate analysis, longer spleen length, lower platelet count, and higher LS value were independent predictors for VNT (all p<0.001). In multivariate analysis of 1,041 healthy subjects, age (ß=-0.027), sex (ß=0.762), and body mass index (ß=0.097) were found to be significant factors for spleen length (all p<0.001). Using the ß values, the estimated spleen length was calculated. To improve the prediction of VNT, the ratio of measured and estimated spleen length was calculated. Based on binary regression analysis results, the LS value-spleen ratio to platelet score (LSRPS) was calculated as follows: 0.027×LS value (kPa)+2.690×measured/estimated spleen ratio-0.011×platelet count (cells×109/L)-4.215. The area under the receiver operating characteristic of the LSRPS for VNT was 0.820, which was significantly higher than 0.797 of LS value-spleen diameter to platelet ratio score (LSPS) (p=0.006). Conclusions: Spleen length is influenced by age, sex, and body mass index in the Asian population. The LSRPS using the measured/estimated spleen ratio had higher diagnostic accuracy than LSPS in predicting VNT in patients with cACLD.

Combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging to predict esophagogastric variceal bleeding in hepatitis B-related cirrhotic patients: A prospective cohort study.

To evaluate whether combinations of liver lobe and spleen volumes obtained on magnetic resonance imaging (MRI) could predict esophagogastric variceal bleeding (EVB) in hepatitis B-related cirrhotic patients. Ninety-six consecutive patients with hepatitis B-related cirrhosis underwent upper abdominal contrast-enhanced MRI within 1 week after initial hospitalization, and grouped based on outcomes of EVB during the 2 years' follow-up after being discharged. Total liver volume (TLV), spleen volume (SV) and 4 liver lobe volumes including right lobe volume (RV), left medial lobe volume (LMV), left lateral lobe volume (LLV), and caudate lobe volume (CV) were measured on MRI. Percentages of individual liver lobe volumes in TLV (including RV/TLV, LMV/TLV, LLV/TLV, and CV/TLV), ratios of SV to individual liver lobe volumes (including SV/RV, SV/LMV, SV/LLV, and SV/CV), and SV/TLV were statistically analyzed to predict EVB. Patients with EVB had lower RV than without EVB (P value = .001), whereas no differences in LMV, LLV, CV, and TLV were found (P values >.05 for all). Among percentages of individual liver lobe volumes in TLV, RV/TLV was lower whereas LMV/TLV and LLV/TLV were greater in patients with EVB than without EVB (P values <.05 for all). SV, ratios of SV to individual liver lobe volumes, and SV/TLV in patients with EVB were larger than without EVB (P values <.05 for all). Among parameters with difference between patients with and without EVB, SV/RV could best predict EVB with an area under receiver operating characteristic curve of 0.84. SV/RV could best predict EVB in hepatitis B-related cirrhotic patients.

Evaluation of Laboratory and Sonographic Parameters for Detection of Portal Hypertension in Patients with Common Variable Immunodeficiency.

Timely detection of portal hypertension as a manifestation in a subgroup of patients with common variable immunodeficiency (CVID) represents a challenge since it is usually not associated with liver cirrhosis. To identify relevant markers for portal hypertension, we evaluated clinical history, laboratory parameters, and abdominal ultrasound including liver elastography and biomarkers of extracellular matrix formation. Twenty seven (6%) of 479 CVID patients presented with clinically significant portal hypertension as defined by either the presence of esophageal varices or ascites. This manifestation occurred late during the course of the disease (11.8 years after first diagnosis of CVID) and was typically part of a multiorgan disease and associated with a high mortality (11/27 patients died during follow up). The strongest association with portal hypertension was found for splenomegaly with a longitudinal diameter of > 16 cm. Similarly, most patients presented with a liver stiffness measurement (LSM) of above 6.5 kPa, and a LSM above 20 kPa was always indicative of manifest portal hypertension. Additionally, many laboratory parameters including Pro-C4 were significantly altered in patients with portal hypertension without clearly increasing the discriminatory power to detect non-cirrhotic portal hypertension in CVID. Our data suggest that a spleen size above 16 cm and an elevated liver stiffness above 6.5 kPa should prompt further evaluation of portal hypertension and its sequelae, but earlier and better liquid biomarkers of this serious secondary complication in CVID are needed.

The Efficacy and Safety of Anticoagulants in the Treatment of Cirrhotic Portal Vein Thrombosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhotic PVT, and compare differences in efficacy and safety among different anticoagulants. METHODS: We comprehensively searched Pubmed, Cochrane Library, EMBASE, and ClinicalTrials.gov from inception to April 2022 for studies using anticoagulants for cirrhotic PVT. Meta-analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 3 RCTs and 14 cohort studies involving 1270 patients were included. Anticoagulant therapy can increase the recanalization rate compared with non-anticoagulation therapy (OR 4.44, 95% CI 3.11-6.32, I2 = 2.5%) and can decrease the extension rate of cirrhotic PVT (OR 0.33, 95% CI 0.18-0.62, I2 = 41.0%), without increasing the incidence of total bleeding (OR 1.21, 95% CI 0.75-1.97, I2 = 9.8%), major bleeding (OR 0.98, 95% CI 0.49-1.95, I2 = 19.7%), and variceal bleeding (OR 0.35, 95% CI 0.12-1.01, I2 = 39.9%). Subgroup analysis showed that VKA, LMWH, and DOACs could increase the recanalization rate of PVT and were not associated with the risk of bleeding. Studies that compared direct oral anticoagulants (DOACs) with warfarin directly showed that the recanalization rate of PVT in the DOACs group might be higher than that in the warfarin group (OR 30.99, 95% CI 7.39-129.87, I2 = 0.0%), and there was no difference in the rate of total bleeding (OR 0.30, 95% CI 0.01-8.65, I2 = 79.6%). CONCLUSIONS: Anticoagulants are safe and effective in patients with cirrhotic PVT. The rate of PVT recanalization associated with DOACs may be higher than warfarin.

Spleen stiffness-spleen size-to-platelet ratio risk score as noninvasive predictors of esophageal varices in patients with hepatitis B virus-related cirrhosis.

ABSTRACT: This study was conducted to evaluate the predictive value of spleen stiffness-spleen size-to-platelet ratio risk score (SSPS) as a noninvasive predictor of esophageal varices (EVs) and to compare it with others.In this retrospective study, from April 2017 to October 2018, a total of 65 patients with hepatitis B virus-related cirrhosis who underwent the liver and spleen stiffness (LS, and SS) measurements by 2 dimensional-shear wave elastography and endoscopic evaluation for EVs were enrolled. Liver stiffness-spleen size-to-platelet ratio risk score (LSPS) and SSPS were calculated. The prognostic values were assessed by the area under the receiver operating characteristic curve (AUC).Twenty-six patients had no EV on endoscopy. Among 39 patients who had EVs, 12 patients had high risk EVs. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting EVs were 0.72, 0.77, 0.80, and 0.85, respectively. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting high-risk EVs were 0.55, 0.78, 0.67, and 0.80, respectively. SSPS had the highest specificity, at 96.15%, for predicting EVs.SSPS may be beneficial to exclude from having EVs and it is expected that the frequency of performing endoscopies for screening EVs can be reduced.

Comparison of sequential CT arterioportography-arteriosplenography with standard cross-sectional imaging and endoscopy in children with portal hypertension.

In this study the diagnostic capability and additional value of sequential CT arterioportography-arteriosplenography (CT AP-AS) in comparison to standard cross-sectional imaging and upper gastrointestinal endoscopy (UGE) in pediatric portal hypertension (PH) was analyzed. Patients with clinical signs of PH who underwent CT AP-AS in combination with additional contrast-enhanced magnetic resonance imaging (CE-MR) and/or contrast-enhanced computed tomography (CE-CT) were included. Two radiologists reviewed independently imaging regarding the capability to prove patency of (1) extrahepatic and intrahepatic main stem portal vein (PV), (2) intrahepatic PV system and (3) splenomesenteric venous axis. Imaging was reviewed for detection of abdominal varices and results were compared to UGE. Main venous supply of varices (PV and/or splenic vein system) and splenorenal shunting were evaluated. 47 imaging studies (20 CT AP-AS, 16 CE-MR, 11 CE-CT) and 12 UGE records of 20 patients were analyzed. CT AP-AS detected significantly more splenorenal shunts (p = 0.008) and allowed more confident characterization of the extra-/intrahepatic PV-system and splenomesenteric veins in comparison to CE-MR (p < 0.001). Extra- and intrahepatic PV-system were significantly more confidently assessed in CT AP-AS than in CE-CT (p = 0.008 and < 0.001 respectively). CT AP-AS was the only modality that detected supply of varices and additional gastric/duodenal varices. In this retrospective study CT AP-AS was superior to standard cross-sectional imaging concerning confident assessment of the venous portosplenomesenteric axis in pediatric patients. CT AP-AS detected additional varices, splenorenal shunting and supply of varices.

Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection.

AIMS: To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS: In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS: The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS: SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

Skeletal Muscle Pathological Fat Infiltration (Myosteatosis) Is Associated with Higher Mortality in Patients with Cirrhosis.

Myosteatosis (pathological fat accumulation in muscle) is defined by lower mean skeletal muscle radiodensity in CT. We aimed to determine the optimal cut-offs for myosteatosis in a cohort of 855 patients with cirrhosis. CT images were used to determine the skeletal muscle radiodensity expressed as Hounsfield Unit (HU). Patients with muscle radiodensity values below the lowest tertile were considered to have myosteatosis. Competing-risk analysis was performed to determine associations between muscle radiodensity and pre-transplant mortality. Muscle radiodensity less than 33 and 28 HU in males and females, respectively, were used as cut-offs to identify myosteatosis. In the univariate analysis, cirrhosis etiology, MELD score, refractory ascites, variceal bleeding, hepatic encephalopathy, sarcopenia and myosteatosis were predictors of mortality. Myosteatosis association with mortality remained significant after adjusting for confounding factors (sHR 1.47, 95% CI 1.17−1.84, p = 0.001). Patients with concurrent presence of myosteatosis and sarcopenia constituted 17% of the patient population. The cumulative incidence of mortality was the highest in patients with concomitant sarcopenia and myosteatosis (sHR 2.22, 95% CI 1.64−3.00, p < 0.001). In conclusion, myosteatosis is common in patients with cirrhosis and is associated with increased mortality. The concomitant presence of myosteatosis and sarcopenia is associated with worse outcomes.

Prediction of high-risk esophageal varices in patients with chronic liver disease with point and 2D shear wave elastography: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic performance of liver stiffness (LS) and spleen stiffness (SS) measured by point shear wave elastography (pSWE) and 2D shear wave elastography (2D-SWE) in the detection of high-risk esophageal varices (HREV) and to compare their diagnostic accuracy. METHODS: Through systematic search of PubMed, Embase, and Web of Science databases, we included 17 articles reporting the diagnostic performance of LS or SS measured by pSWE or 2D-SWE for HREV. We used a bivariate random-effects model to estimate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under summary receiver operator characteristic curve (AUSROC), and diagnostic odds ratio (DOR). RESULTS: For LS, there was no significant difference between the pooled sensitivity, 0.89 (95% confidence interval CI, 0.81-0.94) vs. 0.8 (95% CI, 0.72-0.86) (p = 0.13), and specificity, 0.81 (95% CI, 0.73-0.87) vs. 0.73 (95% CI, 0.65-0.79) (p = 0.07) of pSWE and 2D-SWE. The AUSROC and DOR of pSWE were higher than those of 2D-SWE: 0.92 (95% CI, 0.89-0.94) vs. 0.84 (95% CI, 0.80-0.87), p = 0.03, 33 (95% CI, 25-61) vs. 11 (95% CI, 5-22), (p < 0.01). For SS, there was no significant difference between the pooled sensitivity 0.91 (95% CI, 0.78-0.96) vs. 0.89 (95% CI, 0.80-0.94) (p = 0.43); specificity, 0.79 (95% CI, 0.72-0.84) vs. 0.72 (95% CI, 0.63-0.79) (p = 0.06); and DOR, 35 (95% CI, 13-100) vs. 20 (95% CI, 8-50) (p = 0.16) of pSWE and 2D-SWE. CONCLUSION: LS and SS measured by pSWE and 2D-SWE have good accuracy in predicting HREV. KEY POINTS: • There is modest difference between the diagnostic performance of LS and SS measured by pSWE and 2D-SWE. • LS and SS measured by pSWE and 2D-SWE both have high sensitivity, specificity, and AUSROC for the evaluation of HREV in patients with CLD. • pSWE and 2D-SWE are promising tools for noninvasive monitoring risk of esophageal varices bleeding of CLD patients.

Acoustic radiation force impulse to measure liver stiffness and predict hepatic decompensation in pregnancy with cirrhosis: A cohort study.

BACKGROUND AND STUDY AIMS: Pregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients. PATIENTS AND METHODS: We prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8-12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed. RESULTS: Our cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01-6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32-7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827. CONCLUSION: LS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.

Liver stiffness by two-dimensional shear wave elastography for screening high-risk varices in patients with compensated advanced chronic liver disease.

OBJECTIVES: To investigate the usefulness of the criteria with liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) and platelet count (PLT) for ruling out high-risk varices in patients with compensated advanced chronic liver disease (cACLD). METHODS: A total of 661 patients with cACLD had successfully undergone 2D-SWE and endoscopy screening. We analyzed risk factors for the presence of high-risk varices and compared proportions of patients who were spared endoscopy when used the predicting criteria with LS (ranged from 16 to 25 kPa) and PLT (ranged from 80 × 109/L to 150 × 109/L). RESULTS: PLT, albumin, LS were found to be independent predictors of high-risk varices. The LS values for ruling out and ruling in high-risk varices were 14.0 kPa and 24.8 kPa, respectively. When the Baveno VI criteria LS < 20 kPa and PLT > 150 × 109/L were used, the high-risk varices miss rate was 2.1%, while the saved endoscopy rate only was 19.2%. The new criteria that LS < 16 kPa and PLT > 100 × 109/L saved 30.4-34.6% endoscopy with 0-3.2% high-risk varices miss rate in the subgroup analysis stratified according to the types of underlying liver disease. CONCLUSIONS: The Baveno VI criteria can be applied to LS measurement by 2D-SWE. The new criteria that LS < 16 kPa and PLT > 100 × 109/L could be a potential model to spare more endoscopy screening with < 5% high-risk varices miss rate. KEY POINTS: • LS measured by 2D-SWE is reliable predictive factor for predicting all-size varices and high-risk varices in patients with compensated advanced chronic liver disease. • LS measured by 2D-SWE < 16 kPa and PLT > 100 × 109 /L, which can spare more endoscopy than Baveno VI criteria with < 5% high-risk varices miss rate. • The Baveno VI criteria can be applied to LS measurement by 2D-SWE.

[Risk factors of clinically significant portal hypertension in patients with compensated liver cirrhosis based on hepatic venous pressure gradient].

Objective: The aim of the study is to investigate correlation between HVPG and other clinical parameters and risk factors of clinically significant portal hypertension (CSPH) in patients with compensated cirrhosis based on hepatic vein pressure gradient (HVPG). Methods: 82 patients with compensated cirrhosis were prospectively recruited in the Department of Infectious Diseases of Shulan Hospital from April 2021 to August 2021. Collected the basic data of each patients, laboratory examination results, liver stiffness, gastroscopy, and HVPG. Pearson correlation analysis, univariate logistic regression analysis and multivariate regression analysis are used to find the risk factors of patients with CSPH. Results: The median HVPG of 82 patients were 9.0(8.3)mmHg. There are 31 cases (27.8%) have developed CSPH, and the correlation analysis shown that CSPH was positively correlated with total bilirubin, INR and liver stiffness, but negatively correlated with albumin, hemoglobin and platelet count. According to univariate logistic regression analysis, the factors which can affecting CSPH include male, diabetes, esophageal gastric varices, albumin, hemoglobin, INR, blood sodium, white blood cells, platelet count, liver stiffness and CTP, FIB-4, ALBI, etc. After adjusted by multivariate analysis, only platelet counts, liver stiffness, esophageal gastric varices were independent risk factors for CSPH in patients with compensated cirrhosis. Conclusion: HVPG is the gold criteria for assessment of portal hypertension. The platelet count, liver stiffness, esophageal gastric varices are independently associated with the development of CSPH in patients with compensated cirrhosis, which can help assess PH and give early diagnosis and treatment to improve their prognosis.