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Background: Predicting posthepatectomy liver failure (PHLF) may be a critical requirement for liver disease patients undergoing hepatectomy. This study retrospectively analyzed the impact of the intraoperatively measured portal vein pressure (PVP) prior to hepatectomy on the prediction of PHLF in hepatectomized patients., Methods: A total of 334 hepatectomized patients in whom the PVP was intraoperatively measured before resection at our institution were enrolled in the present study. Outcomes were assessed according to the International Study Group of Liver Surgery definition and the severity of PHLF grading., Results: Thirty-nine of the 334 patients (11.6%) developed grade B/C PHLF. The following factors were significantly associated with grade B/C PHLF in a univariate analysis: indocyanine green retention rate after 15 min, Child-Pugh score, prehepatectomy PVP, and transfusion (each P < 0.0001). A prehepatectomy PVP value of 19.5 cmH 2 O was the optimal cutoff value for predicting grade B/C PHLF. In a multivariate analysis, prehepatectomy PVP (≥ 19.5 cmH 2 O) was selected as the most relevant risk factor for grade B/C PHLF (P = 0.0003, hazard ratio: 5.96, 95% CI: 1.80-19.70)., Conclusions: Prehepatectomy PVP can serve as a useful predictor of the risk of PHLF in patients who have undergone hepatectomy. The results emphasize the possibility of reducing the planned extent of hepatic resection when the prehepatectomy PVP value measured intraoperatively exceeds 19.5 cmH 2 O, and the importance of predicting the PVP before the operation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Portal hypertension-related complications pose a significant risk for liver failure post-transplantation. Thus, accurate monitoring of intraoperative portal venous pressure (PVP) is crucial. However, current PVP monitoring techniques requiring direct percutaneous puncture carry the risk of graft damage. In this study, we present an innovative non-puncture PVP monitoring device (PVPMD) using a 3D-printed prototype. PVPMD design is inspired by the sphygmomanometer principle, and strategically encompasses the portal vein and enables precise PVP measurement through blood flow ultrasonography after temporary occlusion. By a series of mini-pig experiments, the prototype PVPMD demonstrated a strong correlation with invasive catheter measurements in the main trunk of the portal vein ( r s = 0.923, p = 0.000). There was a significant repeatability and reproducibility between the prototype PVPMD- and invasive catheter-measured PVP. This indicates that the PVPMD holds immense potential for direct application in liver transplantation and surgery. Moreover, it has the potential to replace catheter-based central venous pressure (CVP) measurements, thereby mitigating catheter-related complications during many surgeries. In conclusion, our innovative device represents a significant advancement in PVP monitoring during liver transplantation, with comprehensive validation from principle exploration to successful animal experiments. We anticipate that this groundbreaking PVPMD will attract the attention of researchers and clinicians, propelling the noninvasive measurement of PVP or other venous/arterial pressures into a new era of clinical practice.

Background and objectives: Over the last decade our understanding of the pathophysiology of portal hypertension has increased. Novel diagnostic technologies have facilitated and improved the diagnosis and treatment of hepatic fibrosis and cirrhosis. With this review we aim to provide an overview of contemporary diagnostic principles of portal hypertension and indications for measuring portal pressure in cirrhosis. Methods: By review of current literature, we assessed new and old principles of measuring portal hypertension and the diagnostic values of the methods. Results: Invasive measurement of the portal pressure is still the gold standard to quantitate portal hypertension and to assess response to vasoactive treatment. The size of the portal pressure is important to assess since it contains information on the course of the disease and risk of developing hepatic decompensation, hepatocellular carcinoma, and mortality. Reliable non-invasive Elastography techniques are emerging that adequately assess portal pressure, but the available methods are not yet sufficiently accurate. Conclusion: Although elastography techniques provide valuable information and are good monitoring tools, liver vein catheterization remains valuable in diagnosing and monitoring portal hypertension, especially in combination with a trans-jugular liver biopsy.

Background: The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM)., Methods: We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION"., Results: Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process., Conclusions: The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients., Approach and Results: Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components., Conclusions: The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Rationale: Transjugular intrahepatic portosystemic shunt (TIPS) is well established as an effective treatment tool for portal hypertension. However, the effects of TIPS in patients with liver cirrhosis and portal hypertension have not been adequately verified in clinical trials., Patient Concerns: To evaluate the effects of TIPS in patients with liver cirrhosis and portal hypertension with or without portal vein thrombosis (PVT)., Interventions: A total of 55 patients with liver cirrhosis and portal hypertension received TIPS treatment from December 2014 to April 2018 were enrolled. Clinical data, including portal pressure, Child-Pugh score, and relevant complications were recorded., Outcomes: TIPS was successfully performed in 54 patients. The overall technical success rate was 98.19% without serious technical complications. After TIPS treatment, portal pressure was significantly reduced from 38.13 ± 4.00 cmH2O to 24.14 ± 3.84 cmH2O (P < 0.05). In addition, symptoms including gastrointestinal bleeding and ascites were improved after TIPS treatment. During the 6 to 21-month follow up, hepatic encephalopathy in 15 patients (27.8%), shunt dysfunction in 5 patients (9.3%), rebleeding in 12 patients (22.2%) and deterioration of liver function in 2 patients (3.7%) were recorded. Moreover, there were no significant differences in the rates of rebleeding and hepatic encephalopathy between patients with PVT and the non-PVT group, whereas the occurrence rate of TIPS dysfunction was higher in the PVT group, but not statistically significant., Lessons: TIPS treatment could alleviate the symptoms of liver cirrhosis and portal hypertension in individuals with or without PVT. However, complications during follow-up should be appropriately noted and addressed with corresponding treatments., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice., Methods: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH., Results: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies., Discussion: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.

Background: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction., Methods: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13)., Results: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm 3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05)., Conclusions: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

We report here a case of portopulmonary hypertension following transjugular intrahepatic portosystemic shunt., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis., Competing Interests: The authors have declared that no competing interests exist.

Background: In cirrhosis, the nitric oxide-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired, which contributes to increased intrahepatic vascular resistance (IHVR) and fibrogenesis. We investigated if sGC stimulation (riociguat (RIO)), sGC activation (cinaciguat (CINA)) or phosphodiesterase (PDE)-5 inhibition (tadalafil (TADA)) improves portal hypertension (PHT) and liver fibrosis., Methods: Fifty male Sprague-Dawley rats underwent bile-duct ligation (BDL) or sham operation. RIO (0.5 mg/kg), CINA (1 mg/kg), TADA (1.5 mg/kg) or vehicle (VEH) was administered from weeks 2 to 4 after BDL. At week 4, invasive haemodynamic measurements were performed, and liver fibrosis was assessed by histology (chromotrope-aniline blue (CAB), Picro-Sirius red (PSR)) and hepatic hydroxyproline content., Results: Cirrhotic bile duct-ligated rats presented with PHT (13.1 ± 1.0 mmHg) and increased IHVR (4.9 ± 0.5 mmHg⋅min/mL). Both RIO (10.0 ± 0.7 mmHg, p  = 0.021) and TADA (10.3 ± 0.9 mmHg, p  = 0.050) decreased portal pressure by reducing IHVR (RIO: -41%, p  = 0.005; TADA: -21%, p  = 0.199) while not impacting heart rate, mean arterial pressure and portosystemic shunting. Hepatic cGMP levels increased upon RIO (+239%, p  = 0.006) and TADA (+32%, p  = 0.073) therapy. In contrast, CINA dosed at 1 mg/kg caused weight loss, arterial hypotension and hyperlactataemia in bile duct-ligated rats. Liver fibrosis area was significantly decreased by RIO (CAB: -48%, p  = 0.011; PSR: -27%, p  = 0.121) and TADA (CAB: -21%, p  = 0.342; PSR: -52%, p  = 0.013) compared to VEH-treated bile duct-ligated rats. Hepatic hydroxyproline content was reduced by RIO (from 503 ± 20 to 350 ± 30 µg/g, p  = 0.003) and TADA (282 ± 50 µg/g, p = 0.003), in line with a reduction of the hepatic stellate cell activation markers smooth-muscle actin and phosphorylated moesin. Liver transaminases decreased under RIO (AST: -36%; ALT: -32%) and TADA (AST: -24%; ALT: -27%) treatment. Hepatic interleukin 6 gene expression was reduced in the RIO group (-56%, p  = 0.053)., Conclusion: In a rodent model of biliary cirrhosis, the sGC stimulator RIO and the PDE-5 inhibitor TADA improved PHT. The decrease of sinusoidal vascular resistance was paralleled by a reduction in liver fibrosis and hepatic inflammation, while systemic haemodynamics were not affected.

Angiopoietin (Angpt)-2, a permeability-increasing growth factor, is involved in vascular leakage of sepsis and acute lung injury, and could be released from endothelium in response to anaphylaxis-related secretagogues such as histamine and leukotrienes, or cytokines. However, roles of Angpt-2 in the hyperpermeability during systemic anaphylaxis are not known. Thus, we determined plasma levels of Angpt-2 and cytokines and vascular permeability during anaphylactic hypotension in unanesthetized rats. Anaphylaxis was induced by an intravenous injection of ovalbumin antigen. Mean arterial blood pressure (MBP) was measured, and hematocrit (Hct) and plasma levels of Angpt-2 and cytokines were assessed for 24 h after antigen injection. Separately, vascular permeability was measured in various organs using the Evans blue dye method, and Angpt-2 mRNA expression in liver was measured. After antigen injection, MBP decreased to the nadir at 6 min, and returned to baseline at 45 min, and Hct peaked at 20 min and thereafter progressively declined, suggesting that vascular leak and hypotension occurred within 20 min. Plasma Angpt-2 levels began to increase significantly at 1 h after antigen, reaching the peak 2.7-fold baseline at 6 h with a return to baseline at 24 h. Detected cytokines of IL-1α, IL-1β, IL-6, IL-10, and TNF-α peaked 1 or 2 h after antigen. Angpt-2 mRNA increased at 2 h and showed an increasing tendency at 6 h. Vascular permeability in bronchus, trachea, intestines, mesentery and skeletal muscle was increased at 10 min but not at 6 h after antigen. In addition, we confirmed using anesthetized rat anaphylaxis models that plasma Angpt-2 levels increased at 1 h after antigen. In conclusion, plasma Angpt-2 is elevated presumably due to increased cytokines and enhanced gene transcription during anaphylaxis in anesthetized and unanesthetized rats., Competing Interests: The authors have declared that no competing interests exist.

Background: Since the first success in an adult patient, living donor liver transplantation (LDLT) has become an universally used procedure. Small-for-size syndrome (SFSS) is a well-known complication after partial LT, especially in cases of adult-to-adult LDLT. The definition of SFSS slightly varies among transplant physicians. The use of a partial liver graft has risks of SFSS development. Persistent portal vein (PV) hypertension and PV hyper-perfusion after LT were identified as the main factors. Hence, various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome. Herein, the definition, clinical symptoms, pathophysiology, basic research, as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences., Data Sources: The articles were collected through PubMed using search terms "liver transplantation", "living donor liver transplantation", "living liver donation", "partial graft", "small-for-size graft", "small-for-size syndrome", "graft volume", "remnant liver", "standard liver volume", "graft to recipient body weight ratio", "sarcopenia", "porcine", "swine", and "rat". English publications published before March 31, 2020 were included in this review., Results: Many transplant surgeons performed PV flow modulation, including portocaval shunt, splenic artery ligation and splenectomy. With these techniques, patient outcome has been improved even when using a "small" graft. Other factors, such as preoperative recipients' nutritional and skeletal muscle status, graft congestion, and donor factors, were also identified as risk factors which all have been addressed using various strategies., Conclusions: The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients. In the absence of efficacious medications to resolve SFSS, conservative treatments, including aggressive fluid balance correction for massive ascites, anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy, are all required if SFSS could not be prevented., (Copyright © 2020. Published by Elsevier B.V.)

Previously, living donor liver transplantation was considered as a "high-risk, high-return" medical treatment due to the relatively high short-term mortality. It is our task to change "high-risk, high-return" into a "low-risk, high-return" situation. In this review article, the recent evolutions in living donor liver transplantation for both donors and recipients at Kyoto University such as portal vein pressure modulation, hybrid donor operation, and perioperative management considering sarcopenia, focusing on improvement of short-term outcomes are described. Under a paradigm of "marketing and innovation", various innovations and efforts have been made over the last decade aiming at improving the short-term outcomes of both donors and recipients. By doing so, excellent short-term results after living donor liver transplantation have been achieved, along with a potentially epoch-making discoveries., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objectives: We have previously shown that patterns of splenic arterial enhancement on computed tomography scan change following liver transplantation. We suggested that this is related to changes in portal venous pressure. The aim of this study was to see if similar patterns occur in patients with and without portal hypertension and in patients before and after portal systemic shunts (transjugular portosystemic shunts)., Methods: We evaluated contrast enhanced computed tomography scans in patients being evaluated for liver disease and compared those from patients with and without portal hypertension. In addition we evaluated patients who had computed tomography scans before and after transjugular portosystemic shunts shunts. Splenic arterial enhancement was evaluated using Hounsfield units (pixel counts)., Results: Twenty-four patients with clinically significant portal hypertension were compared to 91 without. Mean splenic pixel count was significantly lower in patients with clinically significant portal hypertension (88.2 ± 17.7 vs. 115.2 ± 21.0; m ± SD, P < 0.01). Computed tomography scans were available in 18 patients pre- and post-transjugular portosystemic shunts. Pixel counts were significantly higher in the post-transjugular portosystemic shunts scans (99.7 ± 20.9 vs. 88.9 ± 26.3; P < 0.05)., Conclusion: This study supports the hypothesis that changes in portal venous pressure are related to changes in splenic arterial enhancement. We suggest that this reflects changes in the splenic micro-circulation. This mechanism may be part of the innate immune response and may also be important in the pathogenesis of hypersplenism.

Purpose: Portal venous pressure (PVP) measurement is of clinical significance, especially in patients with portal hypertension. However, the invasive nature and associated complications limits its application. The aim of the study is to propose a noninvasive predictive model of PVP values based on CT-extracted radiomic features., Methods: Radiomics PVP (rPVP) models based on liver, spleen and combined features were established on an experimental cohort of 169 subjects. Radiomics features were extracted from each ROI and reduced via the LASSO regression to achieve an optimal predictive formula. A validation cohort of 62 patients treated for gastroesophageal varices (GOV) was used to confirm the utility of rPVP in predicting variceal recurrence. The association between rPVP and response to treatment was observed., Results: Three separate predictive formula for PVP were derived from radiomics features. rPVP was significantly correlated to patient response to endoscopic treatment for GOV. Among which, the model containing both liver and spleen features has the highest predictability of variceal recurrence, with an optimal cut-off value at 29.102 mmHg (AUC 0.866). A Kaplan Meier analysis further confirmed the difference between patients with varying rPVP values., Conclusion: PVP values can be accurately predicted by a non-invasive, CT derived radiomics model. rPVP serves as a non-invasive and precise reference for predicting treatment outcome for GOV secondary to portal hypertension., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response., Methods: Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events., Results: The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death., Discussion: Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose : Despite refinements in surgical techniques for liver resection, evaluation of hepatic reserve disparity remains one of the most common problems in liver surgery, especially for hepatic malignancies such as hepatocellular carcinoma (HCC). Portal venous pressure (PVP) is regarded one of the important factors in selecting treatment strategy, although its measurement can be invasive and complex. Methods : To establish a formula for calculating PVP preoperatively, intraoperative directly measured PVP was used in 177 patients with preoperative factors and liver function tests such as age, sex, virus status, platelet count, prothrombin time, albumin, total bilirubin, alanine aminotransferase (ALT), Child-Pugh grade, liver damage defined by the Liver Cancer Study Group of Japan, indocyanine green retention rate at 15 min (ICG-R15), and the aspartate transaminase (AST)-platelet ratio index (APRI). Results : Although 90% of the patients were classified as Child-Pugh A, median direct PVP was 16.5 cm H 2 O (5.5-37.0) and the percentage of PVP greater than 20 cm H 2 O was 27.1%, reflecting portal hypertension due to liver damage. After multiple regression analysis, the formula PVP (cmH 2 O) = EXP[2.606 + 0.01 × (ICG-R15) + 0.015 × APRI] was established from the measured data. Conclusion : Considering its simplicity of use, we have adopted this formula for predicting PVP in determining treatment strategy for HCC and other hepatic malignancies.

Background and Aim: The nuclear farnesoid X receptor (FXR) regulates critical pathways of hepatic metabolism, inflammation, and gut mucosal barrier. Thus, we investigated the association of FXR-single nucleotide polymorphism (SNPs) with hepatic decompensation and liver-related mortality in patients with advanced chronic liver disease., Methods: Two FXR-SNPs (rs56163822 G > T and rs35724 G > C) were genotyped in a cohort of 402 prospectively characterized patients with hepatic venous pressure gradient (HVPG) ≥ 6 mmHg., Results: Only 19 patients (4.7%) harbored a rs56163822 T-allele and had less pronounced liver disease as indicated by lower Child-Pugh score (CPS, 6 ± 1 vs 7 ± 2 points, P = 0.034) and higher albumin levels (38.9 ± 4.9 vs 35.9 ± 5.9 g/L, P = 0.026). In contrast, n = 267 (66.4%) patients harbored minor rs35724 allele (G/C or C/C) and had more advanced liver disease, as indicated by a higher model of end-stage liver disease (11 ± 4 vs 10 ± 3, P = 0.016), while other baseline characteristics were similar across FXR-SNP genotypes. In compensated CPS-A patients, the rs35724 minor allele was independently protective for the development of ascites (adjusted hazard ratio [aHR] = 0.411, 95% confidence interval (95% CI): 0.191-0.885; P = 0.023) and tended to reduce the risk of hepatic decompensation (aHR = 0.625, 95% CI: 0.374-1.044, P = 0.072) in multivariate analyses. Of note, transplant-free survival was longer in patients with rs35724 minor allele and HVPG ≥ 10 mmHg (at 5 years: 68.2% vs 55.8%, P = 0.047) and those with HVPG ≥ 16 mmHg (63.3% vs 44.0%, P = 0.021). After adjusting for established risk factors, the rs35724 minor allele was independently associated with reduced liver-related mortality in the overall cohort (aHR = 0.658, 95% CI: 0.434-0.998, P = 0.049), in compensated CPS-A patients (aHR = 0.488, 95% CI: 0.252-0.946, P = 0.034), in patients with HVPG ≥ 10 mmHg (aHR = 0.547, 95% CI: 0.346-0.864, P = 0.010), and in patients with HVPG ≥ 16 mmHg (aHR = 0.519, 95% CI: 0.307-0.878, P = 0.014)., Conclusion: The FXR-SNP rs35724 was associated with a reduced risk for development of ascites and liver-related mortality in patients with advanced chronic liver disease., (© 2019 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Although the well-accepted lower limit of the graft-to-recipient weight ratio (GRWR) for successful living donor liver transplantation (LDLT) remains 0.80%, many believe grafts with lower GRWR may suffice with portal inflow modulation (PIM), resulting in equally good recipient outcomes. This study was done to evaluate the outcomes of LDLT with small-for-size grafts (GRWR <0.80%). Of 1321 consecutive adult LDLTs from January 2012 to December 2017, 287 (21.7%) had GRWR <0.80%. PIM was performed (hemiportocaval shunt [HPCS], n = 109; splenic artery ligation [SAL], n = 14) in 42.9% patients. No PIM was done if portal pressure (PP) in the dissection phase was <16 mm Hg. Mean age of the cohort was 49.3 ± 9.1 years. Median Model for End-Stage Liver Disease score was 14, and the lowest GRWR was 0.54%. A total of 72 recipients had a GRWR <0.70%, of whom 58 underwent HPCS (1 of whom underwent HPCS + SAL) and 14 underwent no PIM, whereas 215 had GRWR between 0.70% and 0.79%, of whom 51 and 14 underwent HPCS and SAL, respectively. During the same period, 1034 had GRWR ≥0.80% and did not undergo PIM. Small-for-size syndrome developed in 2.8% patients. Three patients needed shunt closure at 1 and 4 weeks and 60 months. The 1-year patient survival rates were comparable. In conclusion, with PIM protocol that optimizes postperfusion PP, low-GRWR grafts can be used for appropriately selected LDLT recipients with acceptable outcomes., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background: To examine the incidence of cirrhosis patients with high-risk esophageal varices (EV) who show hepatic venous pressure gradient (HVPG) < 10 mmHg and to identify their hemodynamic features. Methods: This prospective study consisted of 110 cirrhosis patients with EV, all with the candidate for primary or secondary prophylaxis. Sixty-one patients had red sign, and 49 patients were bleeders. All patients underwent both Doppler ultrasound and HVPG measurement. Results: There were 18 patients (16.4%) with HVPG < 10 mmHg. The presence of venous-venous communication (VVC) was more frequent in patients with HVPG < 10 mmHg (10/18) than in those with HVPG ≥ 10 mmHg (19/92; p = 0.0021). The flow volume in the left gastric vein (LGV) and the incidence of red sign were higher in the former (251.9 ± 150.6 mL/min; 16/18) than in the latter (181 ± 100.5 mL/min, p = 0.02; 45/92; p = 0.0018). The patients with red sign had lower HVPG (13.3 ± 4.5) but advanced LGV hemodynamics (velocity 13.2 ± 3.8 cm/s; flow volume 217.5 ± 126.6 mL/min), whereas those without red sign had higher HVPG (16.2 ± 4.6, p = 0.001) but poorer LGV hemodynamics (10.9 ± 2.3, p = 0.002; 160.1 ± 83.1, p = 0.02). Conclusion: Patients with high-risk EV with HVPG < 10 mmHg showed 16.4% incidence. Although low HVPG may be underestimated by the presence of VVC, the increased LGV hemodynamics compensates for the severity of portal hypertension, which may contribute to the development of red sign., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction and Aim: Thromboxane (TX) A 2 was identified as an important vasoconstrictor during Zymosan induced portal perfusion pressure (PP) increase. We aimed at investigating whether hepatic steatosis influences the extent of TXA 2 -induced portal hypertension., Materials and Methods: Sprague-Dawley rats were randomly divided into control and steatosis (induced by the special diet) groups. PP and TXB 2 (stable degradation product of TXA 2 ) in the perfusate were measured after in situ liver perfusion with Zymosan (150μg/ml, 40-46min) or U46619 (TXA 2 analog, 0.1μM/ml, 40-46min). The number of Kupffer cell (KC) was measured by immunohistochemistry with CD163., Results: Zymosan induced more TXB 2 production and a higher PP increase in control group than in steatosis group despite more CD163 positive KCs in fatty livers. PP and TXB 2 efflux revealed a strong correlation in control group and a moderate correlation in steatosis group. Contrary to the effect of Zymosan, U46619 induced a much higher PP increase in steatosis group than in control group., Conclusion: Severe steatosis increased number of KCs, however, PP increase and TXB 2 efflux caused by Zymosan infusion in fatty livers were lower than those in healthy livers. In contrast, TXA 2 analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA 2 in fatty livers might be a potential therapy of severe steatosis., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Introduction: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome., Methods: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment., Results: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h., Conclusion: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

Objective: To observe the immediate and mid-term effects of partial spleen embolization (PSE) in reducing hepatic venous pressure gradient (HVPG) in patients with cirrhotic esophagogastric varices., Methods: Patients diagnosed with cirrhosis and esophagogastric varices in our hospital between July 2016 and March 2018 were consecutively selected. Forty-three patients were selected based on the eligibility criteria to undergo PSE. The change in HVPG 5 minutes before and after embolization, was used to determine the immediate effect of PSE on HVPG reduction. HVPG was retested after 6 months to observe the change in the antihypertensive effect along with time., Results: Forty-three patients successfully underwent PSE and HVPG measurements. The HVPG was 17.7 ± 3.9 mmHg and 13.9 ± 3.1 mmHg before and after PSE, respectively, showing a significant decrease (21.5%, P < .05). Among them, 18 cases were retested for HVPG at 6 months after PSE, and the results showed significant differences in the HVPG levels before, immediately and 6 months after PSE. Compared with preoperative PSE, HVPG was decreased by 22.9% and 17.7% (P < 0.05) immediately and at 6 months after operation, respectively. There was no significant change at 6 months after PSE when compared with immediate postoperative PSE. No serious complications were observed in patients during their postoperative hospital stay., Conclusion: PSE immediately reduced the portal pressure, and HVPG remained stable at 6 months after surgery. PSE is considered as a safe and easy to implement method, and is expected to be one of the treatments for reducing the portal pressure.

Background: Uncontrolled variceal bleeding (VB) remains a great challenge for clinical treatment. Emergency transjugular intrahepatic portosystemic shunt (TIPS) is a salvage procedure, but unsatisfactory clinical outcomes and a high incidence of complications have been reported. This study aimed to investigate the effect and safety of emergency TIPS performed in our institution during recent years., Methods: Fifty-eight consecutive cirrhotic patients with uncontrolled VB who underwent emergency TIPS from March 2009 to November 2017 in our hospital were followed until the last clinical evaluation, liver transplantation (LT), or death., Results: Overall, 5, 36, and 17 patients belonged to Child-Pugh class A, B, and C, respectively. TIPS was successfully performed in 57 (98.3%) patients at 89.5 h (mean) after initial bleeding. After TIPS, bleeding ceased in 52 (91.2%) patients, and 51 (89.5%) patients had a portal pressure gradient below 12 mmHg. Only one (1.8%) major procedure-related complication occurred without any clinical consequences, and no procedure-related deaths occurred. During follow-up, 55 hepatic encephalopathy (HE) episodes occurred in 19 (33.3%) patients, and the median time of the first HE episode was 3.1 months. Seven (12.3%) patients experienced shunt dysfunction after 8.7 months (median). The 6-week, 1-year, and 2-year variceal rebleeding rates were 10.5%, 17.1%, and 20.0%, respectively. The LT-free survival rates at 6 weeks, 1 year, and 2 years were 87.7%, 81.8% and 73.6%, respectively., Conclusion: Our study highlights the fact that emergency TIPS could be effective for patients with liver cirrhosis and uncontrolled VB with few potential complications.

Background: Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome., Aim: To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats., Methods: Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride (CCl 4 ) in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors., Results: No significant difference in portal pressure was observed between integral and castrated male PHT rats (15.2 ± 2.1 mmHg vs 16.7 ± 2.7 mmHg, P > 0.05). The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats (12.7 ± 2.7 mmHg vs 16.5 ± 2.4 mmHg, P < 0.05). In PHT rats, the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right, and the maximal responses (E max ) values were decreased and effective concentrations causing half maximum responses (EC 50 ) values were increased, compared to those of non-PHT rats, both in male and female rats. Compared to non-PHT integral male rats, the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased ( P > 0.05). However, there was no difference between integral and ORX male rats with PHT. In integral female PHT rats, the concentration response curves were shifted to the left ( P < 0.05), and the E max values were increased and EC 50 values were decreased compared to OVX female PHT rats., Conclusion: Clear gender differences were observed in mesenteric vascular reactivity in CCl 4 -induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest to be disclosed., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To analyze the clinical significance of using hepatic transit time (HTT) to evaluate portal vein pressure in gastroesophageal varices patients., Methods: For the observation group, we enrolled 50 gastroesophageal varices patients who had received esophagogastric variceal embolization in our hospital between January 2015 and February 2018. Patients without liver disease populated the control group and were recruited during the same time period. All patients underwent contrast-enhanced sonography. In the observation group, free portal pressure (FPP) was detected during esophagogastric variceal embolization with ultrasound guidance. Differences in hepatic artery-hepatic vein transit time (HA-HVTT), portal vein-hepatic vein transit time (PV-HVTT), and parenchyma-hepatic vein transit time (PA-HVTT) were compared between groups. Correlations between HA-HVTT, PV-HVTT, PA-HVTT, and FPP in the observation group were analyzed using the Pearson coefficient and linear regression analysis., Results: HA-HVTT (t = 5.078; P < .001), PV-HVTT (t = 12.163; P < .001), and PA-HVTT (t = 2.649; P = .009) within the observation group were significantly lower than those of the control group. The areas under the curve of HTT were 0.771 (HA-HVTT), 0.951 (PV-HVTT), and 0.652 (PA-HVTT), and the sensitivity and specificity of PV-HVTT at 7.99 seconds were 86.0% and 88.0%, respectively. The HA-HVTT (r = -0.799; P < .001), PV-HVTT (r = -0.554; P < .001), and PA-HVTT (r = -0.735; P < .001) negatively correlated to FPP in the observation group. Linear regression analysis showed y = -0.410x + 7.254 (HA-HVTT and FPP), y = -0.335x + 4.983 (PV-HVTT and FPP), and y = -0.566x + 4.997 (PA-HVTT and FPP) in the observation group., Conclusion: Compared with the control patients, the HTT of patients with portal hypertension-esophagogastric varices was significantly shorter, and showed an inverse relationship with FPP., (© 2019 by the American Institute of Ultrasound in Medicine.)

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model ( n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control ( n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min -1 ·100 g -1 preoperatively to 240 (48) mL·min -1 ·100 g -1 at 6 h after resection ( P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min -1 ·100 g -1 preoperatively to 7.7 (1.7) mL·min -1 ·100 g -1 8 h after resection ( P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o 2 ) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o 2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection. NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.

Background: Venous congestion might lead to congestive encephalopathy after cardiac surgery. However, objective signs of congestion have yet to be associated with delirium. Portal vein flow pulsatility is a congestion marker that may identify a subgroup of patients at risk., Methods: We performed a retrospective study and a prospective study in patients undergoing cardiac surgery. Adult patients who underwent portal vein Doppler imaging by the attending physician during usual care in the intensive care unit were included in the retrospective cohort. For the prospective cohort, patients had a cognitive and echocardiographic evaluation the day before surgery and daily for 3 days after surgery. Delirium was independently assessed by the nursing staff in the prospective cohort., Results: A total of 237 patients in the retrospective cohort and 145 patients in the prospective cohort were included, for whom 1074 portal Doppler evaluations were performed. An association was found between delirium and portal vein pulsatility in the retrospective cohort (odds ratio [OR], 2.69; confidence interval [CI], 1.47-4.90; P = 0.001). In the prospective cohort, significant associations were found between the presence of portal vein pulsatility and the development of cognitive dysfunction and asterixis assessed by the investigators (OR, 2.10; CI, 1.25-3.53; P = 0.005 and OR, 2.23; CI, 1.13; 4.41; P = 0.02, and delirium detected by the nursing staff (hazard ratio, 2.63; CI, 1.13-6.11; P = 0.025). Higher N-terminal pro-beta natriuretic peptide measurements (OR, 4.03; CI, 1.78-9.15; P = 0.001) and cerebral desaturations (OR, 2.54; CI, 1.12-5.76; P = 0.03) were associated with cognitive dysfunction., Conclusion: These data present an association among hepatic congestion, delirium, and encephalopathy in patients undergoing cardiac surgery. Further studies should explore whether those neurological complications may have a congestive origin in some patients., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Liver structures of a healthy subject are digitised and segmented from computed tomography (CT) images, and hepatic perfusion is modelled in the hepatic artery and portal vein of the healthy subject with structured tree-based outflow boundary conditions. This self-similar structured tree is widely used in the literature, eg, blood flow simulation in larger systemic arteries and cerebral circulation, and is used in this study to model the effect of the smaller hepatic arteries and arterioles, as well as the smaller hepatic portal veins and portal venules. Physiologically reasonable results are obtained. Since the structured tree terminates at the size of the microvasculature system in liver lobules, the structured tree boundary condition will enable the proposed organ-level model of hepatic arterial flow to be easily connected to tissue-level models of liver lobules. Blood flow in the hepatic vein is also modelled in this subject with three-element Windkessel model as outflow boundary conditions. The benefit of integrating the perfusion in all hepatic vascular vessels is that it helps us analyse some complicated clinical phenomenon more efficiently, eg, one possible application is to obtain the portal pressure gradient (PPG) to help examine the reliability of hepatic venous pressure gradient (HVPG) as an indirect measure of portal pressure. Moreover, since four to six generations of hepatic vessels, which are sufficient for liver classification analysis, were employed in the model, this study is setting the computational foundation of a potentially handy surgical tool., (© 2019 John Wiley & Sons, Ltd.)

Background and Aims: Non-invasive assessment of portal hypertension is an area of unmet need. This proof of concept study aimed to evaluate the diagnostic accuracy of a multi-parametric magnetic resonance technique in the assessment of portal hypertension. Comparison to other non-invasive technologies was a secondary aim., Methods: T1 and T2* maps through the liver and spleen were acquired prior to trans-jugular liver biopsy and hepatic vein pressure gradient (HVPG) measurement. T1 measurements reflect changes in tissue water content, but this relationship is confounded by the presence of iron, which in turn can be quantified accurately from T2* maps. Data were analysed using LiverMultiScan (Perspectum Diagnostics, Oxford, UK) which applies an algorithm to remove the confounding effect of iron, yielding the "iron corrected T1" (cT1). Sensitivity, specificity, diagnostic values and area under the curve were derived for spleen cT1, liver cT1, transient elastography, and serum fibrosis scores. HVPG was the reference standard., Results: Nineteen patients (15 men) with median age 57 years were included. Liver disease aetiologies included non-alcoholic fatty liver disease (n = 9; 47%) and viral hepatitis (n = 4; 21%). There was strong correlation between spleen cT1 and HVPG (r = 0.69; p = 0.001). Other non-invasive biomarkers did not correlate with HVPG. Spleen cT1 had excellent diagnostic accuracy for portal hypertension (HVPG >5 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) with an area under the receiver operating characteristic curve of 0.92 for both., Conclusion: Spleen cT1 is a promising biomarker of portal pressure that outperforms other non-invasive scores and should be explored further., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MP, RB, MDR, SN and EB are shareholders in Perspectum Diagnostics (PD). RB, MDR and SN are on the board of directors of PD. RB and MDR are employed by PD. MP, RB, MDR, SKP, SN and EB have filed patent applications, in the field of liver disease assessment using magnetic resonance techniques, including “Medical Imaging” patent with priority application number GB1406304.4, filed on 8th April 2014. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

BACKGROUND We assessed the alterations in portal hemodynamics associated with donor right hepatectomy and its effects on functional regeneration of the remnant liver. MATERIAL AND METHODS This prospective study included 30 adult living donors who underwent right hepatectomy in the Liver Transplantation Unit, Faculty of Medicine, Cairo University from June 2015 to October 2016. During donor surgery, portal venous pressure (PVP) was measured using an antithrombotic catheter inserted into the main portal vein, and was measured before and after clamping of the right portal vein. Postoperatively, liver function tests were done daily until normalization. The outcome measures were the time to normalization of liver function tests and effect of residual volume and steatosis on PVP. RESULTS All donors had normal PVP before clamping and changed significantly after clamping (p<0.001). After clamping, 25 donors (83%) had a PVP above 12 mmHg; i.e. had high portal pressure. The median percentage of change was 55%. There were obvious increases in liver enzymes and bilirubin after surgery, but albumin and international normalized ratio showed progressive decreases postoperatively. The percent change in PVP was positively correlated with the levels of liver enzymes, time to normalization of liver enzymes, albumin, and bilirubin, and with the degree of steatosis, bit it was negatively correlated with residual liver volume. CONCLUSIONS During living donor liver transplantation, PVP increases by over 50% after clamping of the right portal vein of the donor's liver. This increase is associated with temporary delay of normalization of liver function of the donors.

The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG <16 mm Hg or HVPG ≥16 mm Hg) to investigate the correlation between preoperative HVPG and characteristics and surgical outcomes of the patients, including portal vein flow (PVF) and hepatic artery flow (HAF) after graft reperfusion. In total, 35 (46.7%) patients had an HVPG ≥16 mm Hg. These patients had significantly higher international normalized ratio values, serum creatinine levels, and Model for End-Stage Liver Disease scores compared with the 40 patients with HVPG <16 mm Hg. They also had higher rates of variceal bleeding, encephalopathy, and intractable ascites as well as lower serum albumin levels and platelet counts compared with those patients with HVPG <16 mm Hg. Portal inflow modulation (PIM) was frequently performed in the patients with HVPG ≥16 mm Hg compared with those with HVPG <16 mm Hg. No significant differences in surgical outcomes after LDLT were found between these 2 groups except for postoperative ascites. Preoperative HVPG showed a positive correlation with PVF and a negative correlation with HAF after graft reperfusion (false discovery rate [FDR] P = 0.08 and FDR P = 0.08, respectively). In linear regression analyses, preoperative HVPG was independently associated with PVF after graft reperfusion. In conclusion, our findings indicate that preoperative HVPG is associated with hepatic hemodynamics after graft implantation in LDLT. HVPG as a routine preoperative evaluation may be helpful for surgical planning of PIM., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Introduction: Excessive portal venous pressure in the liver remnant is an independent factor in the occurrence of posthepatectomy liver failure and small-for-size syndrome. The baseline portal pressure prior to hepatectomy was not considered previously. The aim of this study is to assess the impact of portal pressure change during hepatectomy on the patient outcome., Material and Methods: Prospective observational study including 30 patients subjected to intraoperative measurement of portal pressure before and after hepatectomy. This variation was related to the patient outcome. Control group evaluation was assessed. Patient, disease and procedure features were considered. The optimal cut-off of portal pressure variation was determined. Linear regression or logistic regression was applied to identify predictors of the outcome., Results: The univariate analysis showed that portal pressure increase after hepatectomy was associated with coagulation impairment in the first 30 postoperative days (p < 0.05), and with the occurrence of major complications (p = 0.01), namely hepatic failure (p = 0.041). The multivariate analysis showed that portal venous pressure increase ≥ 2 mmHg is an independent factor for worse outcomes., Discussion: As in previous studies, this study concludes that, after hepatectomy, in addition to the functional liver remnant, other factors are responsible for deterioration of liver function and patient outcome, such as the portal pressure increase and the exposure to chemotherapy prior to hepatectomy. This work may influence the definition of future indications for portal influx modulation., Conclusion: Patient outcomes are influenced by the portal venous pressure increase: an increment ≥ 2 mmHg after hepatectomy seems to increase the risk of major complications.

Background: Temporary portocaval shunt has a positive impact on short-term outcomes after liver transplantation. An alternative to temporary portocaval shunt is a distal passive decompression through mesenterico-saphenous shunt. The purpose of this study was to compare outcomes of these two types of surgical portosystemic shunt and discuss their respective place during the anhepatic phase., Methods: Patients transplanted with portal decompression during a 4-year period were included. Patients were compared according to two types of surgical decompression techniques: temporary portocaval shunt (n = 44) and mesenterico-saphenous shunt (n = 77). Spontaneous >5-mm portosystemic shunts were described as absent, nonpersistent, distal, or proximal. Intraoperative portal pressure variations and inhospital course were compared between the two groups, with special attention on the impact of competing spontaneous and surgical shunts., Results: Mesenterico-saphenous shunt and temporary portocaval shunt showed a comparable hemodynamic efficiency, with no significant difference in terms of portal pressure variations. We found no significant difference in terms of reperfusion syndrome (P = .956), transfusion rate (P = .575), renal failure (P = .239) nor early allograft dysfunction (P = .976). There was a significantly higher risk of early allograft dysfunction when competing surgical and spontaneous shunts were used (P = .002) with a lesser hemodynamic efficiency (analysis of variance test; P = .04)., Conclusion: Portacaval or mesenterico-saphenous shunts offer similar hemodynamic efficiency without impacting the outcomes after liver transplantation. Their respective place and the place of portal decompression should be discussed regarding the presence of portal thrombosis and pre-existing portosystemic shunts. Evaluation of the anatomy and the efficiency of these shunts may guide tailored portal decompression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Small-for-size-liver grafts (SFSG) in adult transplant recipients have elevated risk of graft failure, limiting its application in clinical liver transplantation. Relevant preclinical model of SFSG is lacking. Relevant to deceased-donor split liver transplant and living-donor liver transplant in adult recipients, in this study, we present our initial characterization of SFSG model using monosegments of a discarded human donor liver., (Copyright © 2019. Published by Elsevier Inc.)

Purpose To develop and validate a computational model for estimating hepatic venous pressure gradient (HVPG) based on CT angiographic images, termed virtual HVPG, to enable the noninvasive diagnosis of portal hypertension in patients with cirrhosis. Materials and Methods In this prospective multicenter diagnostic trial (ClinicalTrials.gov identifier: NCT02842697), 102 consecutive eligible participants (mean age, 47 years [range, 21-75 years]; 68 men with a mean age of 44 years [range, 21-73 years] and 34 women with a mean age of 52 years [range, 24-75 years]) were recruited from three high-volume liver centers between August 2016 and April 2017. All participants with cirrhosis of various causes underwent transjugular HVPG measurement, Doppler US, and CT angiography. Virtual HVPG was developed with a three-dimensional reconstructed model and computational fluid dynamics. Results In the training cohort (n = 29), the area under the receiver operating characteristic curve (AUC) of virtual HVPG in the prediction of clinically significant portal hypertension (CSPH) was 0.83 (95% confidence interval [CI]: 0.58, 1.00). The diagnostic performance was prospectively confirmed in the validation cohort (n = 73), with an AUC of 0.89 (95% CI: 0.81, 0.96). Inter- and intraobserver agreement was 0.88 and 0.96, respectively, suggesting the good reproducibility of virtual HVPG measurements. There was good correlation between virtual HVPG and invasive HVPG (R = 0.61, P < .001), with a satisfactory performance to rule out (7.3 mm Hg) and rule in (13.0 mm Hg) CSPH. Conclusion The accuracy of a computational model of virtual hepatic venous pressure gradient (HVPG) shows significant correlation with invasive HVPG. The virtual HVPG also showed a good performance in the noninvasive diagnosis of clinically significant portal hypertension in cirrhosis. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Malayeri in this issue.

There is a consensus that portal venous pressure (PVP) modulation prevents portal hypertension (PHT) and consequent complications after adult-to-adult living donor liver transplantation (ALDLT). However, PVP-modulation strategies need to be updated based on the most recent findings. We examined our 10-year experience of PVP modulation and reevaluated whether it was necessary for all recipients or for selected recipients in ALDLT. In this retrospective study, 319 patients who underwent ALDLT from 2007 to 2016 were divided into 3 groups according to the necessity and results of PVP modulation: not indicated (n = 189), indicated and succeeded (n = 92), and indicated but failed (n = 38). Graft survival and associations with various clinical factors were investigated. PVP modulation was performed mainly by splenectomy to lower final PVP to ≤15 mm Hg. Successful PVP modulation improved prognosis to be equivalent to that of patients who did not need modulation, whereas failed modulation was associated with increased incidence of small-for-size syndrome (SFSS; P = 0.003) and early graft loss (EGL; P = 0.006). Among patients with failed modulation, donor age ≥ 45 years (hazard ratio [HR], 3.67; P = 0.02) and ABO incompatibility (HR, 3.90; P = 0.01) were independent risk factors for graft loss. Survival analysis showed that PVP > 15 mm Hg was related to poor prognosis in grafts from either ABO-incompatible or older donor age ≥ 45 years (P < 0.001), but it did not negatively affect grafts from ABO-compatible/identical and young donor age < 45 years (P = 0.27). In conclusion, intentional PVP modulation is not necessarily required in all recipients. Although grafts from both ABO-compatible/identical and young donors can tolerate PHT, lowering PVP to ≤15 mm Hg is a key to preventing SFSS and consequent EGL with grafts from either ABO-incompatible or older donors., (© 2018 by the American Association for the Study of Liver Diseases.)

Purpose of Review: The current review aims to explain the different systems available to clinicians for predicting clinical outcomes in patients with cirrhosis., Recent Findings: Cirrhosis is the final stage of chronic liver disease and is associated with high morbidity and mortality. The most commonly utilized tools to predict outcomes in patients with cirrhosis include the following: assessing severity of portal hypertension using hepatic venous pressure gradient (HVPG) measurements, using scoring systems such as the Model for End-stage Liver Disease (MELD) and Child-Pugh-Turcotte (CPT) scores, and recently, clinical staging systems based on cirrhosis-related clinical complications. Assessing portal pressure with HVPG measurements provides valuable prognostic information, yet is costly, time-consuming, and invasive. MELD and CPT scores can be calculated quickly and not only assess liver function, but also yield predictive information. However, they represent only one point in time, and do not take into account the full clinical picture. Clinical staging systems have traditionally been focused on compensated and decompensated stages, with newer models assessing the influence of cirrhosis-related complications. However, these are not commonly utilized., Summary: Predicting clinical outcomes in patients with cirrhosis is challenging, and is likely best accomplished with a combination of objective data (such as MELD and HVPG provide) in addition to the clinical course of cirrhosis.

Hepatic venous pressure gradient (HVPG) is a widely employed surrogate of portal pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little is known about how HVPG measurement is affected by the complex vascular changes associated with PHT. In this study, we employed a computational method to quantitatively evaluate the sensitivity of HVPG measurement to various vascular factors involved in the development of sinusoidal PHT, aiming to provide a theoretical reference to guide the clinical application of HVPG measurement. The method consisted of developing a lumped-parameter model of the hepatic circulation to simulate HVPG measurement, stochastic parameter sampling used to represent a wide range of pathological conditions, and global sensitivity analysis performed to identify factors that dominate the accuracy of HVPG measurement. The major findings included 1) presinusoidal portal vascular resistance (R pxs ) and splanchnic vascular resistance (R spl ) were the major factors determining the relative difference (E HVPG ) between HVPG and PPG; 2) hepatic arteriolar resistance and portosystemic collateral resistance had little influence on E HVPG although they relate closely to the severity of PHT; and 3) postsinusoidal vascular resistance (R pts ) only mildly affected E HVPG , despite its marked influence on HVPG and PPG. Moreover, stochastic simulations calibrated to HVPG/PPG data measured in a patient cohort revealed that misdiagnosis of clinically significant PHT with HVPG was more likely to occur in the presence of high R spl combined with low R pxs and R pts . These findings suggest that understanding patient-specific vascular conditions can help to improve the application or interpretation of HVPG measurement., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Sustained virological response (SVR) improves survival in post-liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension (PH) post-SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after-SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and PH after viral clearance. We evaluated 112 hepatitis C virus-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months post-SVR. Hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and Enhanced Liver Fibrosis (ELF) score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72%-85% in the remaining stages (P = 0.002). HVPG, LSM, and ELF significantly decreased post-SVR. Liver function significantly improved, and survival was significantly better in patients achieving fibrosis regression. Baseline HVPG and LSM as well as decompensations before therapy were independent predictors of fibrosis regression. One year post-SVR, LSM had a high diagnostic accuracy to discard the presence of advanced fibrosis (AF) and clinically significant PH (AUROC, 0.902 and 0.888)., Conclusion: In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: Several studies have defined the optimal portal pressure suitable for adequate graft renewal in liver transplantation (LT) but none have studied an Egyptian population to our knowledge., Objectives: Determine the level of portal venous pressure (PVP) for adequate graft function, and study the effect of PVP modulation on the outcome of LT in an Egyptian population., Design: Cross-sectional, prospectively collected data., Setting: Liver transplantation unit., Patients and Methods: The study included adult cirrhotic pa.tients who underwent right lobe liver donor living transplantation (LDLT) at our transplantation center. Intraoperative Doppler was performed on all LDLT patients. Two PVP measurements were obtained during the recipient operation: before PV clamping and after graft re-perfusion. These PVP measurements were correlated with the results of intraoperative and postoperative Doppler findings and graft function. Mortality in the early postoperative period ( less than 1 month) and development of small-for-size syndrome (SFSS) were recorded., Main Outcome Measures: PVP, graft injury, and the effect of PVP modulation on the outcome of LT were the primary outcome measures. Secondary outcome measures were to correlate PVP to portal vein hemodynamics and intraoperative mean hepatic artery, peak systolic velocity, and also to correlate PVP with the postoperative graft function and mean postoperative platelet count., Sample Size and Characteristics: 69 adult patients with end-stage liver disease., Results: Post-reperfusion PVP was lower than pre-clamping PVP. The mean pre-clamping and post-reperfusion values were higher in patients who experienced early mortality and in patients with smaller grafts. A PVP greater than 16.5 mm Hg at the end of the operation predicted the development of SFSS (sensitivity=91.7% and specificity=50.5%). Cases of high PVP that were modulated to a lower level had a smooth and uneventful postoperative outcome., Conclusion: PVP is a significant hemodynamic factor that influences the functional status of the transplanted liver, including the development of SFSS, in the Egyptian population. PVP modulation may improve the outcome of LDLT., Limitations: Further study with a larger sample is needed to confirm these results., Conflict of Interest: None.

Anaphylactic shock is life-threatening, but pathophysiology of the stomach lesion remains unclear. We determined gastric hemodynamics and gastric functions during anaphylactic hypotension, as compared to hypotension induced by hemorrhage or sodium nitroprusside (SNP) in anesthetized and ovalbumin-sensitized Sprague-Dawley rats. Systemic arterial pressure, portal venous pressure, and gastric arterial blood flow were measured, and gastric vascular resistance (GVR) was determined. Separately, the intragastric pressure (IGP) and gastric effluent, as a measure of gastric flux, were continuously measured. During anaphylaxis, GVR decreased only transiently at 0.5 min, followed by an increase. IGP increased markedly, while gastric flux decreased. During hemorrhage, GVR and IGP increased, while gastric flux did not change. When SNP was injected, both GVR and IGP decreased and gastric flux increased only just after injection. In conclusion, gastric vasodilatation occurs only transiently after antigen injection, and gastric motility increases, but gastric emptying deceases during anaphylactic hypotension in anesthetized rats.

Background: Schistosomiasis is an endemic health problem affecting about four million people. The hepatosplenic form of the disease is characterized by periportal hepatic fibrosis, pre-sinusoidal portal hypertension and splenomegaly. Liver function is preserved, being varices bleeding the main complication of the disease. The surgical treatment used in the majority of centers for the prevention of rebleeding is esophagogastric devascularization and splenectomy. Most authors reported better results with the association of surgical and postoperative endoscopic treatment., Objective: The aim of this study was to compare the intra operative portal pressure decrease and esophageal varices behavior and rebleeding rates in patients submitted to surgical and postoperative endoscopic treatment after long-term follow-up., Methods: A retrospective study of 36 patients with schistosomiasis with, at least, one previous bleeding from esophageal varices rupture submitted to esophagogastric devascularization and splenectomy, added to endoscopic varices postoperative treatment was performed. Patients were stratified according to the intra operative portal pressure decrease in two groups: reduction below and above 30%. Long-term varices presence, size and bleeding recurrence were evaluated., Results: Regarding varices behavior, no significant influence was observed in both groups of portal pressure fall. Regarding bleeding recurrence, despite three times more frequent in the group with lower portal pressure fall, no significant difference was observed. All patients were submitted to postoperative endoscopic treatment., Conclusion: Esophageal varices banding, rather than portal pressure decrease, seems to be the main responsible factor for good results after combination of two therapies (surgery and endoscopy) for patients with portal hypertension due to schistosomiasis; further studies are necessary to confirm this hypothesis.

Background: Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations., Aim: The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO., Results: IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO., Conclusion: This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.

The clinical course of cirrhosis has been typically described by a compensated and a decompensated state based on the absence or, respectively, the presence of any of bleeding, ascites, encephalopathy or jaundice. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. This requires the use of competing risks analysis which investigates the risk of several competing outcomes. In such a situation, the Kaplan-Meier risk estimates and the Cox regression may be not appropriate. Clinical states of cirrhosis presently considered as suitable for a comprehensive multistate model include: in compensated cirrhosis, early (mild) portal hypertension with hepatic venous pressure gradient (HVPG) >5 and <10 mmHg, clinically significant portal hypertension (HVPG ≥ 10 mmHg) without gastro-esophageal varices (GEV), and GEV; in decompensated cirrhosis, a first variceal bleeding without other decompensating events, any first non-bleeding decompensation and any second decompensating event; and in a late decompensation state, refractory ascites, sepsis, renal failure, recurrent encephalopathy, profound jaundice, acute on chronic liver failure, all predicting a very short survival. In this review, we illustrate how competing risks analysis and multistate models may be applied to cirrhosis.

Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.

Measurement of hepatic venous pressure gradient (HVPG) is currently widely adopted to provide an estimate of portal pressure gradient (PPG) in the diagnosis and treatment of portal hypertension associated with liver cirrhosis. Despite the well-documented clinical utility of HVPG, it remains poorly understood how the relationship between HVPG and PPG is affected by factors involved in the pathogenesis and progression of cirrhosis. In the study, a computational model of the hepatic circulation calibrated to in vivo data was developed to simulate the procedure of HVPG measurement and quantitatively investigate the error of HVPG relative to PPG under various pathophysiological conditions. Obtained results confirmed the clinical consensus that HVPG is applicable to the assessment of portal hypertension caused by increased vascular resistance located primarily at the sinusoidal and postsinusoidal sites rather than at the presinusoidal site. On the other hand, our study demonstrated that the accuracy of HVPG measurement was influenced by many factors related to hepatic hemodynamics even in the case of sinusoidal portal hypertension. For instance, varying presinusoidal portal vascular resistance significantly altered the difference between HVPG and PPG, while an enhancement in portosystemic collateral flow tended to improve the accuracy of HVPG measurement. Moreover, it was found that presinusoidal and postsinusoidal vascular resistances interfered with each other with respect to their influence on HVPG measurement. These findings suggest that one should take into account patient-specific pathological conditions in order to achieve a better understanding and utilization of HVPG in the clinical practice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)