The Impact of Portal Hypertension Assessment Method on the Outcomes of Hepatocellular Carcinoma Resection: A Meta-Analysis of Matched Cohort and Prospective Studies.

OBJECTIVE: Examine portal hypertension (PHT) impact on postoperative and survival outcomes in hepatocellular carcinoma (HCC) patients after liver resection (LR), specifically exploring distinctions between indirect signs and invasive measurements of PHT. BACKGROUND: PHT has historically discouraged LR in individuals with HCC due to the elevated risk of morbidity, including liver decompensation (LD). METHODS: A systematic review was conducted using 3 databases to identify prospective-controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and overall survival in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: for aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman-Tukey exact and double arcsine method). RESULTS: Nine studies involving 1124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with hepatic venous pressure gradient (HVPG) ≥10 mm Hg significantly increased the risk of overall complications, PHLF, and LD. Despite elevated risks, the procedure resulted in a 5-year overall survival rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF, and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in minimally invasive LR. CONCLUSIONS: LR in the presence of indirect signs of PHT poses no increased risk of complications. Yet, in HVPG ≥10 mm Hg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. Minimally invasive approach seems to be vital for favorable outcomes, especially in HVPG ≥10 mm Hg patients.

Noninvasive risk assessment of hepatic decompensation in patients with hepatitis B virus-related liver cirrhosis.

BACKGROUND AND AIM: Hepatic decompensation is a major complication of liver cirrhosis. We validated the predictive performance of the newly proposed CHESS-ALARM model to predict hepatic decompensation in patients with hepatitis B virus (HBV)-related cirrhosis and compared it with other transient elastography (TE)-based models such as liver stiffness-spleen size-to-platelet (LSPS), portal hypertension (PH), varices risk scores, albumin-bilirubin (ALBI), and albumin-bilirubin-fibrosis-4 (ALBI-FIB-4). METHODS: Four hundred eighty-two patients with HBV-related liver cirrhosis between 2006 and 2014 were recruited. Liver cirrhosis was clinically or morphologically defined. The predictive performance of the models was assessed using a time-dependent area under the curve (tAUC). RESULTS: During the study period, 48 patients (10.0%) developed hepatic decompensation (median 93 months). The 1-year predictive performance of the LSPS model (tAUC = 0.8405) was higher than those of the PH model (tAUC = 0.8255), ALBI-FIB-4 (tAUC = 0.8168), ALBI (tAUC = 0.8153), CHESS-ALARM (tAUC = 0.8090), and variceal risk score (tAUC = 0.7990). The 3-year predictive performance of the LSPS model (tAUC = 0.8673) was higher than those of the PH risk score (tAUC = 0.8670), CHESS-ALARM (tAUC = 0.8329), variceal risk score (tAUC = 0.8290), ALBI-FIB-4 (tAUC = 0.7730), and ALBI (tAUC = 0.7451). The 5-year predictive performance of the PH risk score (tAUC = 0.8521) was higher than those of the LSPS (tAUC = 0.8465), varices risk score (tAUC = 0.8261), CHESS-ALARM (tAUC = 0.7971), ALBI-FIB-4 (tAUC = 0.7743), and ALBI (tAUC = 0.7541). However, there was no significant difference in the predictive performance among all models at 1, 3, and 5 years (P > 0.05). CONCLUSIONS: The CHESS-ALARM score was able to reliably predict hepatic decompensation in patients with HBV-related liver cirrhosis and showed similar performance to the LSPS, PH, varices risk scores, ALBI, and ALBI-FIB-4.

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis.

BACKGROUND & AIMS: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD. METHODS: A detailed laboratory workup of individuals with cACLD recruited from the Vienna cohort (NCT03267615) was utilised to predict clinically significant portal hypertension (CSPH, i.e., HVPG ≥10 mmHg) and severe PH (i.e., HVPG ≥16 mmHg). The MLMs were then evaluated in individual external datasets and optimised in the merged cohort. RESULTS: Among 1,232 participants with cACLD, the prevalence of CSPH/severe PH was similar in the Vienna (n = 163, 67.4%/35.0%) and validation (n = 1,069, 70.3%/34.7%) cohorts. The MLMs were based on 3 (3P: platelet count, bilirubin, international normalised ratio) or 5 (5P: +cholinesterase, +gamma-glutamyl transferase, +activated partial thromboplastin time replacing international normalised ratio) laboratory parameters. The MLMs performed robustly in the Vienna cohort. 5P-MLM had the best AUCs for CSPH (0.813) and severe PH (0.887) and compared favourably to liver stiffness measurement (AUC: 0.808). Their performance in external validation datasets was heterogeneous (AUCs: 0.589-0.887). Training on the merged cohort optimised model performance for CSPH (AUCs for 3P and 5P: 0.775 and 0.789, respectively) and severe PH (0.737 and 0.828, respectively). CONCLUSIONS: Internally trained MLMs reliably predicted PH severity in the Vienna cACLD cohort but exhibited heterogeneous results on external validation. The proposed 3P/5P online tool can reliably identify individuals with CSPH or severe PH, who are thus at risk of hepatic decompensation. IMPACT AND IMPLICATIONS: We used machine learning models based on widely available laboratory parameters to develop a non-invasive model to predict the severity of portal hypertension in individuals with compensated cirrhosis, who currently require invasive measurement of hepatic venous pressure gradient. We validated our findings in a large multicentre cohort of individuals with advanced chronic liver disease (cACLD) of any cause. Finally, we provide a readily available online calculator, based on 3 (platelet count, bilirubin, international normalised ratio) or 5 (platelet count, bilirubin, activated partial thromboplastin time, gamma-glutamyltransferase, choline-esterase) widely available laboratory parameters, that clinicians can use to predict the likelihood of their patients with cACLD having clinically significant or severe portal hypertension.

[Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension].

Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

Magnetic resonance parametric mapping of the spleen for non-invasive assessment of portal hypertension.

OBJECTIVES: In patients with advanced liver disease, portal hypertension is an important risk factor, leading to complications such as esophageal variceal bleeding, ascites, and hepatic encephalopathy. This study aimed to determine the diagnostic value of T1 and T2 mapping and extracellular volume fraction (ECV) for the non-invasive assessment of portal hypertension. METHODS: In this prospective study, 50 participants (33 patients with indication for trans-jugular intrahepatic portosystemic shunt (TIPS) and 17 healthy volunteers) underwent MRI. The derivation and validation cohorts included 40 and 10 participants, respectively. T1 and T2 relaxation times and ECV of the liver and the spleen were assessed using quantitative mapping techniques. Direct hepatic venous pressure gradient (HVPG) and portal pressure measurements were performed during TIPS procedure. ROC analysis was performed to compare diagnostic performance. RESULTS: Splenic ECV correlated with portal pressure (r = 0.72; p < 0.001) and direct HVPG (r = 0.50; p = 0.003). No significant correlations were found between native splenic T1 and T2 relaxation times with portal pressure measurements (p > 0.05, respectively). In the derivation cohort, splenic ECV revealed a perfect diagnostic performance with an AUC of 1.000 for the identification of clinically significant portal hypertension (direct HVPG ≥ 10 mmHg) and outperformed other parameters: hepatic T2 (AUC, 0.731), splenic T2 (AUC, 0.736), and splenic native T1 (AUC, 0.806) (p < 0.05, respectively). The diagnostic performance of mapping parameters was comparable in the validation cohort. CONCLUSION: Splenic ECV was associated with portal pressure measurements in patients with advanced liver disease. Future studies should explore the diagnostic value of parametric mapping accross a broader range of pressure values. KEY POINTS: • Non-invasive assessment and monitoring of portal hypertension is an area of unmet interest. • Splenic extracellular volume fraction is strongly associated with portal pressure in patients with end-stage liver disease. • Quantitative splenic and hepatic MRI-derived parameters have a potential to become a new non-invasive diagnostic parameter to assess and monitor portal pressure.

Noninvasive imaging assessment of portal hypertension.

Portal hypertension (PH) is a spectrum of complications of chronic liver disease (CLD) and cirrhosis, with manifestations including ascites, gastroesophageal varices, splenomegaly, hypersplenism, hepatic hydrothorax, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. PH can vary in severity and is diagnosed via invasive hepatic venous pressure gradient measurement (HVPG), which is considered the reference standard. Accurate diagnosis of PH and assessment of severity are highly relevant as patients with clinically significant portal hypertension (CSPH) are at higher risk for developing acute variceal bleeding and mortality. In this review, we discuss current and upcoming noninvasive imaging methods for diagnosis and assessment of severity of PH.

Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study.

BACKGROUND & AIMS: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. METHODS: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. RESULTS: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. CONCLUSIONS: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge. LAY SUMMARY: Sudden damage to the kidneys is becoming more common in people who are hospitalized and have cirrhosis. Despite advances in cirrhosis care, those with damage to the kidneys remain at higher risk of dying.

Risk assessment of first upper gastrointestinal bleeding using computerized tomoscanning in esophageal varices patients with cirrhosis and portal hypertension.

To evaluate the risk of first upper gastrointestinal bleeding by computerized tomoscanning (CT) for esophageal varices patients with cirrhotic portal hypertension.One hundred thirty two esophageal varices patients with cirrhotic portal hypertension who are also complicated with gastrointestinal bleeding were recruited as bleeding group, while another 132 patients without bleeding as non-bleeding group. The diameter of esophageal varices, number of vascular sections, and total area of blood vessels were measured by CT scanning. The sensitivity and specificity of these indicators were calculated, and Youden index was adjusted with the critical point.The diameter of esophageal varices was 7.83 ±â€Š2.76 mm in bleeding group, and 6.57 ±â€Š3.42 mm in non-bleeding group. The Youden index was 0.32 with the critical point 5.55 mm. The area under the receiver operating characteristics (AUROC) was 0.72. The number of venous vessels was 4.5 ±â€Š2 in bleeding group, whereas being 4 ±â€Š2 in non-bleeding group. The Youden index was 0.35 with a critical point 4, and the area under the curve (AUC) was 0.68. The blood vessel area was 1.73 ±â€Š1.15 cm in bleeding group, and 1.12 ±â€Š0.89 cm in non-bleeding group. The Youden index was 0.48 with the critical point being 1.03 cm, and corresponding AUC was 0.82.Among all 3 indicators of the total area, diameter, and number of sections of the esophageal varices, the total area of esophageal varices showed more accuracy as a potential and novel indicator for bleeding prediction.

Two-dimensional Shear Wave Elastography with Propagation Maps for the Assessment of Liver Fibrosis and Clinically Significant Portal Hypertension in Patients with Chronic Liver Disease: A Prospective Study.

OBJECTIVES: To investigate the diagnostic performance of liver stiffness (LS) measurements on two-dimensional (2D) shear wave elastography (SWE) for the assessment of hepatic fibrosis using LS measurements on MR elastography (MRE) as the reference standard and the prediction of clinically significant portal hypertension (CSPH). METHODS: In this prospective study, 101 patients with chronic liver disease or cirrhosis underwent both MRE and SWE. After exclusion of technical failure on MRE (n = 5), technical failure/unreliable measurement on SWE (n = 4), LS measurements obtained on SWE with the aid of propagation maps were correlated with those of the MRE using Pearson's correlation analysis. Diagnostic performances for significant fibrosis (≥F2: MRE of ≥2.99 kPa) or cirrhosis (F4: MRE of ≥3.63 kPa) and for the prediction of CSPH were assessed using receiver operating characteristics (ROC) curve analysis. RESULTS: LS values on SWE showed a strong correlation with those on MRE (r = 0.846, P < 0.001). For the diagnosis of significant fibrosis or cirrhosis in patients with hepatitis B virus-related liver disease (n = 75), SWE showed areas under the ROC curves (AUC) of 0.975 and 0.912, respectively (95% confidence interval [CI], 0.910-997, and 0.824-0.965). For the prediction of CSPH, the AUC of SWE was 0.818 (95% CI, 0.712-0.898), and when an LS value of 11.5 kPa was applied as a cut-off, SWE showed a sensitivity of 81.5% and a specificity of 72.9%. CONCLUSION: LS measurements on 2D SWE were demonstrated to be well correlated with those obtained with MRE, and thus, may provide good diagnostic performance for the prediction of hepatic fibrosis and the presence of CSPH.

Novel insights into the assessment of risk of upper gastrointestinal bleeding in decompensated cirrhotic children.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level <150 mg/dL was applied on this cohort. RESULTS: Of 20 enrolled children, 6 had upper gastrointestinal bleeding. Significant differences were observed in fibrinogen level, adenosine diphosphate, and thrombin-dependent platelet aggregation. The model used to compute the upper gastrointestinal bleeding risk had an estimated predictive performance of 81.0%. Platelet aggregation analysis addition improved the estimated predictive performance up to 89.0%. CONCLUSIONS: We demonstrated an association between hemostatic factors and the upper gastrointestinal bleeding risk. A low fibrinogen level and platelet aggregation dysfunction may predict the risk of bleeding in children with decompensated cirrhosis. A predictive model is available to assess the upper gastrointestinal bleeding risk but needs further investigations. Clinicaltrials.gov number: NCT03244332.

Spleen and liver stiffness for noninvasive assessment of portal hypertension in cirrhotic patients with large esophageal varices.

PURPOSE: Noninvasive evaluation of portal hypertension is needed for cirrhotic patients with large esophageal varices. This study was aimed at assessing the diagnostic value of liver/spleen stiffness in predicting hepatic vein pressure gradient (HVPG) in this special population. METHODS: In the present prospective cohort study, liver/spleen stiffness was measured by transient elastography. Patients also underwent HVPG assessment, upper gastrointestinal endoscopy, and other noninvasive serum models. RESULTS: Ninety-nine cirrhotic patients with large esophageal varices were enrolled. Liver/spleen stiffness strongly correlated with HVPG. In regards to significant portal hypertension, area under receiver operating characteristic curves (AUROCs) for liver/spleen stiffness were 0.74 and 0.91. Accuracy for detecting significant portal hypertension was 79% for spleen stiffness of 48.9 kPa (sensitivity: 76%, specificity: 100%, positive predictive value: 100%, negative predictive value: 38%) and 75% for liver stiffness of 16.0 kPa (sensitivity: 78%, specificity: 54%, positive predictive value: 92%, negative predictive value: 27%). Similarly, spleen stiffness had significant higher AUROCs for predicting HVPG ≥16 and ≥20 mm Hg than that of liver stiffness and other noninvasive serum models. CONCLUSION: In cirrhotic patients with large esophageal varices, liver stiffness and spleen stiffness correlate with HVPG, and spleen stiffness is superior to liver stiffness in predicting portal hypertension.

Left gastric vein-based noninvasive test for esophageal varices: a same-day comparison of portal hemodynamic assessment with endoscopic appearance.

OBJECTIVE: To examine the effect of hemodynamic assessment of the left gastric vein (LGV) as a noninvasive test to diagnose esophageal varices (EV) in cirrhosis patients. METHODS: This cross-sectional study consisted of 229 cirrhosis patients (62.7 ± 11.8 years; Child-Pugh score 5-14). One hundred fifty-four patients had EV (67.2%; small, 53; medium, 71; large, 30). All patients underwent a blood test and Doppler ultrasound followed by upper gastrointestinal endoscopy on the same day. The diagnostic ability for EV was compared between LGV-related findings and the platelet count/spleen diameter ratio (Plt/Spl). RESULTS: The detectability of the LGV was higher in patients with EV (129/144, 89.6%) than in those without (35/75, 46.7%; p < 0.0001), and was higher in those with large EV (30/30, 100%) than in those without (134/199, 67.3%; p = 0.0002). The positive detection of the LGV showed 100% sensitivity and negative predictive value (NPV) to identify large EV in the whole cohort and compensated group (n = 127). The best cutoff value in the LGV diameter was 5.35 mm to identify large EV, showing 0.753 area under the receiver operating characteristic curve (AUROC) with 90% sensitivity and 96.5% NPV. The Plt/Spl showed 62.1% sensitivity and 87.1% NPV, and the best cutoff value was 442.9 to identify large EV with 0.658 AUROC, which was comparable to LGV-based assessment (p = 0.162). CONCLUSIONS: This same-day comparison study demonstrated the value of LGV-based noninvasive test to identify large EV with high sensitivity and NPV in cirrhosis patients at a lower cost.

Portal vein thrombosis in liver cirrhosis: incidence, management, and outcome.

BACKGROUND: Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients. METHODS: The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy. RESULTS: Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053). CONCLUSION: We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.

[Disorders of Vasoregulative Endothelial Function, Echocardiographic Assessment of Myocardial Dysfunction and Hemodynamics of Pulmonary Circulation in Cirrhosis of the Liver].

AIM: to study relationship between parameters of intracardiac hemodynamics assessed by Doppler echocardiography and functional activity of endothelium, hepatic blood flow and severity of portal hypertension in patients with cirrhosis of the liver (CL) of different etiology. RESULTS: We found that changes of structural and functional parameters of the heart in LC depended on the stage of compensation of portal hypertension and were accompanied by rearrangement of parameters of intracardiac hemodynamics. Pulmonary arterial hypertension (PAH) was found in 11.1% of patients with LC. PAH was moderate and was more frequent in patients with end-stage disease (Child-Pugh class C) compared with those with initial stage of LC (21.4% and 6.3%, p<0.05, respectively). CONCLUSION: Disorders of vasoregulating endothelial function in patients with CL were related to parameters of cardiopulmonary hemodynamics and functional state of the right ventricle and were more pronounced in patients with PAH.

Assessment of Hepatic Vascular Network Connectivity with Automated Graph Analysis of Dynamic Contrast-enhanced US to Evaluate Portal Hypertension in Patients with Cirrhosis: A Pilot Study.

PURPOSE: To test whether graph analysis of vascular images obtained with hepatic dynamic contrast material-enhanced (DCE) ultrasonography (US) allows calculation of the degree of organization of the liver circulation and whether graph properties are correlated to the severity of portal hypertension. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Fifteen patients with liver cirrhosis (nine men; mean age ± standard deviation, 55 years ± 8) who underwent DCE US and hepatic venous pressure gradient (HVPG) measurement and four healthy subjects (two men and two women; mean age, 34 years ± 4) were included between January 2007 and December 2008. Individual graph models ("vascular connectomes") were computed on the basis of time series analysis of video sequences of DCE US examinations (conducted with the disruption-reperfusion technique). Graph analysis was performed, and the clustering coefficient C was calculated. Correlations between clustering coefficient and HVPG were assessed. RESULTS: Healthy subjects had a high clustering coefficient of vascular connectome (C = 0.4447; interquartile range [IQR], 0.3864-0.4679), suggesting a highly organized hepatic vascular network. Conversely, patients with cirrhosis showed a low clustering coefficient, indicating disruption of normal anatomy (C = 0.0288; IQR, 0.0157-0.0861; P = .001 vs healthy subjects). The clustering coefficient decreased as HVPG increased, with a clustering coefficient of 0.0237 (IQR, 0.0066-0.0378) in patients with HVPG of at least 10 mm Hg versus 0.1180 (IQR, 0.0987-0.1414) in those with HVPG of less than 10 mm Hg (P = .006). The correlation between the best model derived from the distribution of the clustering coefficient (10 bins) of vascular connectome and HVPG had a Pearson correlation of 0.977 (root mean squared error, 1.57 mm Hg; P < .0001). CONCLUSION: This pilot study demonstrates that graph modeling of vascular connectivity based on video processing of liver DCE US examinations and subsequent graph analysis enable calculation of personalized parameters that reflect the degree of organization of the hepatic microvascular network and are correlated to the severity of portal hypertension in cirrhosis.

Sonographic assessment of spleen stiffness before and after transjugular intrahepatic portosystemic shunt placement with or without concurrent embolization of portal systemic collateral veins in patients with cirrhosis and portal hypertension: a feasibility study.

OBJECTIVES: To determine the feasibility of spleen stiffness measurement in the evaluation of portal hemodynamics in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: We prospectively correlated the spleen stiffness as measured by the shear wave velocity with the portal pressure and portosystemic gradient in patients undergoing TIPS procedures. Twenty-three consecutive patients referred for placement of a TIPS were enrolled. Included in our study were 19 patients in whom a spleen stiffness measurement was obtained before, immediately after, and 1 to 3 days after placement. Spleen stiffness was measured by calculating the Young modulus estimated from the shear wave velocity. A 2-tailed nonparametric Mann-Whitney U test was used to assess statistically significant differences in spleen stiffness measurement after TIPS placement, and regression analysis was used to correlate spleen stiffness measurement with portal pressure. RESULTS: After TIPS placement, the spleen stiffness measurement increased, with a mean increase in the Young modulus ± SD of 6.54 ± 6.29 kPa in 42% of patients (8 of 19). In the remaining 58% (11 of 19), the spleens became softer after TIPS placement (Young modulus decreased by 9.57 ± 8.82 kPa). Eight patients, including 5 with concurrent embolization or thrombosis of competitive shunts, had increased spleen stiffness. The mean change in the median spleen stiffness before and after TIPS placement between the patients with and without competitive shunts was statistically significantly different (P < .04, nonparametric Mann-Whitney U test). There was no measurable correlation between spleen stiffness measurement and portal pressure before and after TIPS placement. CONCLUSIONS: This study demonstrates the feasibility of a noninvasive spleen stiffness measurement, which could complement conventional sonography with additional functional information in patients undergoing TIPS procedures.

Cardiac and pulmonary issues in LT assessment candidates.

With the incidence of liver disease increasing worldwide, a growing number of patients are being referred for assessment for liver transplant (LT). Unfortunately, the donor pool is not expanding at the same rate, which consequentially results in increasing demand on a finite resource. It is therefore imperative that the candidate who undergoes an LT gets maximal benefit with a resultant maximal increase in life expectancy. This article addresses some of the main cardiac and pulmonary issues that may occur in LT assessment candidates.

Detection of risky esophageal varices by two-dimensional ultrasound: when to perform endoscopy.

OBJECTIVE: Esophageal varices are a consequence of portal hypertension in cirrhotic patients. Current guidelines recommend that all cirrhotic patients undergo screening endoscopy at diagnosis to identify patients with varices at high risk of bleeding who will benefit from primary prophylaxis. This practice increases costs, involves a degree of invasiveness and discomfort and places a heavy burden on endoscopy units. Several studies have evaluated possible noninvasive predictors of esophageal varices, but most of these studies remain controversial. METHODS: The intra-abdominal portion of the esophagus in 673 patients who presented with liver cirrhosis and portal hypertension was examined using standard 2-dimensional (2D) ultrasound. A direct relationship between the degree of varices observed on upper endoscopy and the intra-abdominal esophageal wall thickness was detected using 2D ultrasound. RESULTS: The mean thicknesses of the esophageal wall were 3.7 ± 0.5 mm (mean ± standard deviation) in normal individuals, 7.3 ± 3.3 mm in those with esophageal varices and 8.65 ± 1.98 mm in those with risky esophageal varices. The overall accuracy of 2D ultrasound was 95%. CONCLUSIONS: The intra-abdominal esophagus should be observed during abdominal ultrasound examination in patients with liver cirrhosis. Two-dimensional ultrasound can play an important role in screening for esophageal varices.

Time trend of medical economic outcomes of endoscopic submucosal dissection for gastric cancer in Japan: a national database analysis.

BACKGROUND: Little information is available on the analysis of chronological changes in medical economic outcomes of endoscopic submucosal dissection (ESD) for gastric cancer. This study aimed to investigate the recent time trend of medical economic outcomes of ESD for gastric cancer based on the Japanese administrative database. METHODS: A total of 32,943 patients treated with ESD for gastric cancer were referred to 907 hospitals from 2009 to 2011 in Japan. We collected patients' data from the administrative database to compare ESD-related complications, risk-adjusted length of stay (LOS), and medical costs during hospitalization. The study periods were categorized into three groups: 2009 (n = 9,727), 2010 (n = 11,052), and 2011 (n = 12,164). RESULTS: No significant difference was observed in ESD-related complications between three study periods (p = 0.496). However, mean LOS and medical costs during hospitalization of patients with ESD were significantly lower in 2011 than in 2009 and 2010 (p < 0.001). Multiple linear regression analysis showed that patients who received ESD in 2011 had a significantly shorter LOS and lower medical costs during hospitalization compared with those in 2009. The unstandardized coefficient of patients with ESD in 2011 for LOS was -0.78 days [95 % confidence interval (CI), -0.89 to -0.65; p ≤ 0.001], while that of those for medical costs during hospitalization was -290.5 US dollars (95 % CI, -392.3 to -188.8; p ≤ 0.001). CONCLUSIONS: This study showed that the complication rate of ESD was stable, whereas the LOS and medical costs of patients were significantly reduced from 2009 to 2011.

Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis.

BACKGROUND: Preoperative measurement of hepatic venous pressure gradient (HVPG) is not performed routinely before hepatectomy in patients with cirrhosis, although it has been suggested to be useful. This study investigated whether preoperative HVPG values and indirect criteria of portal hypertension (PHT) predict the postoperative course in these patients. METHODS: Between January 2007 and December 2009, consecutive patients with resectable hepatocellular carcinoma (HCC) in a cirrhotic liver were included in this prospective study. PHT was assessed by transjugular HVPG measurement and by classical indirect criteria (oesophageal varices, splenomegaly and thrombocytopenia). The main endpoints were postoperative liver dysfunction and 90-day mortality. RESULTS: Forty patients were enrolled. A raised HVPG was associated with postoperative liver dysfunction (median 11 and 7 mmHg in those with and without dysfunction respectively; P = 0·017) and 90-day mortality (12 and 8 mmHg in those who died and survivors respectively; P = 0·026). Oesophageal varices, splenomegaly and thrombocytopenia were not associated with any of the endpoints. In multivariable analysis, body mass index, remnant liver volume ratio and preoperative HVPG were the only independent predictors of postoperative liver dysfunction. CONCLUSION: An increased HVPG was associated with postoperative liver dysfunction and mortality after liver resection in patients with HCC and liver cirrhosis, whereas indirect criteria of PHT were not. This study suggests that preoperative HVPG measurement should be measured routinely in these patients.