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Background: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS)., Methods: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection., Results: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated., Conclusion: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery., (© 2024. Society of Surgical Oncology.)

Background: Cavernous transformation of the portal vein (CTPV) due to portal vein obstruction is a rare vascular anomaly defined as the formation of multiple collateral vessels in the hepatic hilum. This study aimed to investigate the imaging features of intrahepatic portal vein in adult patients with CTPV and establish the relationship between the manifestations of intrahepatic portal vein and the progression of CTPV., Methods: We retrospectively analyzed 14 CTPV patients in Beijing Tsinghua Changgung Hospital. All patients underwent both direct portal venography (DPV) and computed tomography angiography (CTA) to reveal the manifestations of the portal venous system. The vessels measured included the left portal vein (LPV), right portal vein (RPV), main portal vein (MPV) and the portal vein bifurcation (PVB)., Results: Nine males and 5 females, with a median age of 40.5 years, were included in the study. No significant difference was found in the diameters of the LPV or RPV measured by DPV and CTA. The visualization in terms of LPV, RPV and PVB measured by DPV was higher than that by CTA. There was a significant association between LPV/RPV and PVB/MPV in term of visibility revealed with DPV (P = 0.01), while this association was not observed with CTA. According to the imaging features of the portal vein measured by DPV, CTPV was classified into three categories to facilitate the diagnosis and treatment., Conclusions: DPV was more accurate than CTA for revealing the course of the intrahepatic portal vein in patients with CTPV. The classification of CTPV, that originated from the imaging features of the portal vein revealed by DPV, may provide a new perspective for the diagnosis and treatment of CTPV., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

BACKGROUND End-stage hepatic alveolar echinococcosis (AE) can result in cavernous transformation of the portal vein (CTPV) due to extensive invasion of the portal vein. Ex vivo liver resection and autotransplantation (ELRA) is a new treatment option for patients with end-stage hepatic AE combined with CTPV. ELRA can achieve radical resection of HAE lesions and vascular reconstruction, and also effectively controls bleeding, particularly in cases involving multiple tortuous PV collaterals. Unfortunately, postoperative complications related to the portal vein can impede liver blood flow, thereby increasing the risk of portal hypertension and eventual failure of the transplanted liver if not promptly treated through appropriate medical interventions. CASE REPORT We report the case of a 31-year-old woman who underwent ELRA for end-stage hepatic AE combined with CTPV, and early postoperative portal vein anastomotic stenosis occurred. Stenting of the portal vein was performed after clarification of the stenotic segment by portal venography, followed by anticoagulation therapy and close ultrasound follow-up. After the operation, the patient's portal vein anastomosis widened and the blood flow into the liver returned to normal, avoiding graft liver failure. At 3-year follow-up, the portal vein stent was patent and no serious portal vein complications such as thrombosis had occurred. CONCLUSIONS ELRA provides a new therapeutic approach for patients with HAE combined with CTPV, and intraoperative portal vein reconstruction is one of the key procedures. For CTPV patients with early postoperative portal vein stenosis, interventional therapy (IVR) offers fresh perspectives and avoids acute liver failure caused by liver hypoperfusion.

Bleeding events are feared complications in patients with advanced liver diseases and are associated with morbidity and mortality. In this context, gastrointestinal bleeding, particularly upper gastrointestinal bleeding, has a special clinical importance. In addition to endoscopic measures for hemostasis, reducing portal pressure in particular is a key component of treatment. Although the standard coagulation parameters are often altered in patients with liver diseases, optimizing coagulation plays a secondary role. Typically, a bundle of measures are employed in patients with portal hypertensive bleeding, which nowadays in most cases can halt the bleeding and stabilize the situation. The measures include endoscopy, antibiotic treatment, vasopressor treatment and, if necessary, shunt placement (transjugular intrahepatic portosystemic shunt)., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Rationale and Objectives: This meta-analysis aimed to evaluate the performance of different risk assessment models (RAMs) for survival after Transjugular Intrahepatic Portosystemic Shunt (TIPS) in patients with cirrhotic portal hypertension., Materials and Methods: A systematic search of PubMed, WOS, Embase, Cochrane, and CNKI from inception to February 2023 was conducted. We comprehensively reviewed and aggregated data from numerous studies covering prevalent RAMs such as Child-Turcotte-Pugh, the Model for End-Stage Liver Disease (MELD), MELD-Sodium (MELD-Na), the Freiburg Index of Post-TIPS Survival (FIPS), Bilirubin-platelet, Chronic Liver Failure Consortium Acute Decompensation score, and Albumin-Bilirubin grade across different timeframes. For this study, short-term is defined as outcomes within a year while long-term refers to outcomes beyond one year. The area under the receiver operating characteristic (AUC) curve or Concordance Statistics was chosen as the metric to assess predictive capacity for mortality outcomes across six predetermined time intervals. Mean effect sizes at various time points were determined using robust variance estimation., Results: MELD consistently stood out as a primary short-term survival predictor, particularly for 1 month (± 2 weeks) (AUC: 0.72) and 3 months of (± 1 month) survival (AUC: 0.72). MELD-Na showed the best long-term predictive ability, with an AUC of 0.70 at 3.5 years (± 1.5 years). FIPS performed well for 6 months of (± 2 months) survival (AUC: 0.68) and overall transplant-free survival (AUC: 0.75). Efficacy nuances were observed in RAMs when applied to particular subgroups. Meta-regression emphasized the potential predictor overlaps in models like MELD and FIPS., Conclusion: This meta-analysis underscores the MELD score as the premier predictor for short-term survival following TIPS. Meanwhile, the FIPS score and MELD-Na model exhibit potential in forecasting long-term outcomes. The study accentuates the significance of RAM selection for enhancing patient outcomes and advocates for additional research to corroborate these findings and fine-tune risk assessment in TIPS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence., Methods: A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves)., Results: Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03-3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52-3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB., Conclusions: PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks., Methods: In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of Model C-V , we compared it with four previous models, both in discrimination and calibration., Results: The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, Model C-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups., Conclusion: Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies., (© 2024. The Author(s).)

Purpose: To assess the safety and effectiveness of percutaneous transsplenic access (PTSA) for portal vein (PV) interventions among patients with PV disease., Materials and Methods: Adult patients with PV disease were enrolled if they required percutaneous catheterization for PV angioplasty, embolization, thrombectomy, variceal embolization, or transjugular intrahepatic portosystemic shunt (TIPS) placement for a difficult TIPS or recanalization of a chronically occluded PV. The procedures were performed between January 2018 and January 2023. Patients were excluded if they had an active infection, had a chronically occluded splenic vein malignant infiltration of the needle tract, had undergone splenectomy, or were under age 18 years., Results: Thirty patients (15 women, 15 men) were enrolled. Catheterization of the PV through PTSA succeeded for 29 of 30 patients (96.7%). The main adverse effect recorded was flank pain in 5 of 30 cases (16.7%). No bleeding events from the spleen, splenic vein, or percutaneous access point were recorded. Two cases (6.7%) each of hepatic bleeding and rethrombosis of the PV were reported, and a change in hemoglobin levels (mean [SD], - 0.5 [1.4] g/dL) was documented in 14 cases (46.7%)., Conclusion: PTSA as an approach to accessing the PV is secure and achievable, with minimal risk of complications. Minimal to no bleeding is possible by using tract closure methods., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors declare that they have no conflict of interest.

Objectives: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate patients with chronic liver cirrhosis and portal hypertension. Smoking can adversely impact liver function and has been shown to influence liver-related outcomes. This study aimed to examine the impact of smoking on the immediate outcomes of TIPS procedure., Materials and Method: The study compared smokers and non-smokers who underwent TIPS procedures in the National Inpatient Sample (NIS) database from the last quarter of 2015 to 2020. Multivariable analysis was used to compare the in-hospital outcomes post-TIPS. Adjusted pre-procedural variables included sex, age, race, socioeconomic status, indications for TIPS, liver disease etiologies, comorbidities, and hospital characteristics., Results: Compared to non-smokers, smokers had lower risks of in-hospital mortality (7.36% vs 9.88 %, aOR 0.662, p < 0.01), acute kidney injury (25.57% vs 33.66 %, aOR 0.68, p < 0.01), shock (0.45% vs 0.98 %, aOR 0.467, p = 0.02), and transfer out to other hospital facilities (11.35% vs 14.78 %, aOR 0.732, p < 0.01). There was no difference in hepatic encephalopathy or bleeding. Also, smokers had shorter wait from admission to operation (2.76±0.09 vs 3.17±0.09 days, p = 0.01), shorter length of stay (7.50±0.15 vs 9.89±0.21 days, p < 0.01), and lower total hospital cost (148,721± 2,740.7 vs 204,911±4,683.5 US dollars, p < 0.01). Subgroup analyses revealed consistent patterns among both current and past smokers., Conclusion: This study compared the immediate outcomes of smokers and non-smokers after undergoing the TIPS procedure. Interestingly, we observed a smokers' paradox, where smoker patients had better outcomes following TIPS. The underlying causes for this smoker's paradox warrant further in-depth exploration., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

A 52-year-old woman was admitted with a primary complaint of abdominal distension and increased abdominal circumference for more than half a year. There was no evidence of infection or solid tumor on abdominocentesis or laparoscopic surgery. Concurrently, smoldering multiple myeloma was diagnosed. Due to refractory ascites and portal hypertension, a transjugular intrahepatic portosystemic shunt was performed, but the efficacy was not satisfactory. As the anemia progressed, she was finally diagnosed with active multiple myeloma after monoclonal plasma cells were detected in the ascites by flow cytometry. Treated with a triplet regimen that included bortezomib, cyclophosphamide, and dexamethasone (BCD), she achieved a very good partial response and ascites regressed.

Background: Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection., Methods: Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months)., Results: Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant)., Conclusions: Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures., (© 2024. Society of Surgical Oncology.)

Zellweger syndrome or cerebrohepatorenal syndrome is a rare, multisystem disorder occurring due to defect in metabolic pathway within the peroxisomes. Cirrhosis with portal hypertension is an important presentation of these patients. Given its progressive, multisystem nature, the role of liver transplantation (LT) in Zellweger syndrome remains undefined and controversial. An 11-y-old boy diagnosed with Zellweger syndrome presented to the authors with decompensated cirrhosis along with bilateral proptosis. After a meticulous evaluation, he was offered an ABO incompatible liver transplantation with his mother being the donor. He had an uneventful post operative period. After a follow up of 24 mo, he has normal graft function, normal cognition along with resolution of proptosis. Therefore, in a group of carefully selected patients with Zellweger syndrome, a liver transplantation can be offered successfully with an excellent prognosis., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Introduction: Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD)., Materials and Methods: Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups., Results: We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH., Discussion and Conclusion: We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pastrovic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA., Methods: A retrospective cohort study was performed using medical/pharmacy claims from Optum ® Clinformatics ® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May 31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE., Results: In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6 per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0 per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003)., Conclusion: Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted., (© 2024. The Author(s).)

Purpose of Review: Telomere biology disorders (TBD) encompass several illnesses caused by underlying mutations in telomere maintenance leading to premature telomere attrition and telomere dysfunction. These disorders have unique features but share common disease manifestations including pulmonary fibrosis, cirrhosis, and bone marrow failure. The goals of this article are to provide an overview of the gastrointestinal and hepatic manifestations of TBD, focusing on their pathophysiology, clinical disease states, and current management strategies., Recent Findings: Telomere shortening has been observed in patients with chronic liver disease and is associated with a higher risk of progression to cirrhosis and portal hypertension. While the directionality of the association between telomere dysfunction and senescence on liver disease is not fully understood, research in TBD may provide clarity and could lead to future therapies for this increasingly prevalent disease. While treatment options remain limited in TBD-associated liver disease, recent studies point to the safety and efficacy of liver transplantation among patients with end-stage liver disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs., Patient Concerns: We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs)., Diagnoses: The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination., Intervention: With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient., Outcomes: The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge., Lessons: This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Portopulmonary hypertension is a rare condition with a poor prognosis. Prompt management is essential for liver transplantation eligibility, a potentially curative option. This report presents a case of severe portopulmonary hypertension that resolved with a conservative therapeutic regimen of tadalafil, macitentan, and inhaled treprostinil, which ultimately enabled successful liver transplantation. There was no recurrence of pulmonary hypertension after transplantation, and the patient was weaned off most pulmonary arterial hypertension therapies. This case report is the first to provide evidence that inhaled treprostinil is a safe and effective alternative to continuous intravenous prostacyclins in portopulmonary hypertension., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate portal hypertension in patients with decompensated liver cirrhosis. However, the risks and outcomes associated with TIPS in patients with advanced chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the perioperative outcomes of TIPS procedures in patients with advanced CKD using the National Inpatient Sample (NIS) database, a comprehensive all-payer inpatient database in the US., Methods: The study identified patients who underwent TIPS procedures in the NIS database from Q4 2015 to 2020. Patients with advanced CKD were identified using specific ICD-10-CM codes, and they were compared to patients without CKD. Preoperative variables, including demographics, indications for TIPS, comorbidities, APR-DRG subclass, primary payer status, and hospital characteristics, were noted. Perioperative outcomes were examined by multivariable logistic regression., Results: A total of 248 patients with advanced CKD and 5511 patients without CKD undergoing TIPS procedures were identified in the NIS database. Compared to non-CKD, patients with advanced CKD had higher mortality (13.70% vs. 8.60%, aOR = 1.56, P  = 0.03), acute kidney injury (51.21% vs. 29.34, aOR = 1.46, P  < 0.01), transfer out (25.00% vs. 12.84%, aOR = 1.88, P  < 0.01), and length of stay over 7 days (64.11% vs. 38.97%, aOR = 2.34, P  < 0.01). However, there was no difference in hepatic encephalopathy (31.85% vs. 27.19%, aOR = 1.12, P  = 0.42)., Conclusion: Advanced CKD patients undergoing TIPS are at higher risk of mortality and AKI compared to patients without CKD; HE was mildly elevated but NS. Long-term prognosis of patients with advanced CKD who had TIPS is needed in future studies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed., Methods: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66)., Results: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH., Conclusions: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Partial splenic embolization (PSE) has been suggested as an alternative to splenectomy in the treatment of hypersplenism. However, some patients may experience recurrence of hypersplenism after PSE and require splenectomy. Currently, there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications., Aim: To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism., Methods: Between January 2010 and December 2021, 321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department. Based on whether PSE was performed prior to splenectomy, the patients were divided into two groups: PSE group ( n = 40) and non-PSE group ( n = 281). Patient characteristics, postoperative complications, and follow-up data were compared between groups. Propensity score matching (PSM) was conducted, and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding (IB). The receiver operating characteristic curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were employed to evaluate the differentiation, calibration, and clinical performance of the model., Results: After PSM, the non-PSE group showed significant reductions in hospital stay, intraoperative blood loss, and operation time (all P = 0.00). Multivariate analysis revealed that spleen length, portal vein diameter, splenic vein diameter, and history of PSE were independent predictive factors for IB. A nomogram predictive model of IB was constructed, and DCA demonstrated the clinical utility of this model. Both groups exhibited similar results in terms of overall survival during the follow-up period., Conclusion: Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Pregnancy is associated with hyperdynamic circulatory state and increased risk of portal hypertension related complications in patients with extra-hepatic portal vein obstruction (EHPVO). We aim to study the impact of EHPVO on pregnancy-related outcomes with focus on subset of patients with UGIB (upper GI bleed)., Methods: Retrospective analysis of obstetric, maternal and neonatal outcomes of patients with EHPVO registered between January 2006 and December 2022. Forty-five patients were included. Forty-five healthy females with low-risk pregnancies formed the control group., Results: Adverse obstetric and neonatal outcomes were comparable between EHPVO and control group (22% vs. 28.6%; p > .05; low birth weight/ small for gestational age 17.8% vs. 36%, p = .0918 and 14.2% vs. 10%, p = .5698 respectively). Adverse outcomes were similar in patients with and without history of UGIB (26.3% vs. 19.4%, p = .0814; 17.8% vs. 36%, p = .0918; 14.2% vs. 10%, p = .5698). There was no maternal mortality in both the groups. A total of 7% pregnancies in EHPVO patients were complicated by ascites., Conclusions: EHPVO pregnancies have successful obstetric and neonatal outcomes with adequate management of portal hypertension., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary TIPS can be a life-saving procedure for patients with portal hypertensive adverse events. However, success is limited when portal vein occlusion is present, a condition that occurs commonly in patients with cirrhosis, who are a subset of patients who benefit most from this intervention. In this case, the authors used EUS to overcome the relative contraindication of portal vein occlusion before TIPS placement. Under EUS, they visualized and accessed the portal vein occlusion with an FNA needle and then placed a coil into the thrombus. TIPS was then able to use the coil as a marker, directing the TIPS access set to target the direction of the coil and successfully access the portal vein. With widespread acceptance and awareness of this technique, TIPS may be able to be offered to a wider range of in-need patients. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments., (© 2023 Wiley Periodicals LLC.)

Background: Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker., Aims: Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD., Methods: We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients., Results: A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation., Conclusions: Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objective: To identify independent predictors of all-cause and cancer-specific mortality after ablation or surgical resection (SR) for small hepatocellular carcinomas (HCCs), after adjusting for key confounders., Methods: Using Surveillance, Epidemiology, and End Results Program-Medicare, HCCs less than 5 cm treated with ablation or SR in 2009 to 2016 (n = 956) were identified. Univariate and multivariable Cox regression models for all-cause and cancer-specific mortality were performed including demographics, clinical factors (tumor size, medical comorbidities, and liver disease factors), social determinants of health, and treatment characteristics. We also determined the most influential predictors of survival using a random forest analysis., Results: Larger tumor size (3-5 cm) is predictive of all-cause (hazard ratio [HR] 1.31, P = .002) and cancer-specific mortality (HR 1.59, P < .001). Furthermore, chronic kidney disease is predictive of all-cause mortality (HR 1.43, P = .013), though it is not predictive of cancer-specific death. Multiple liver disease factors are predictive of all-cause and cancer-specific mortality including portal hypertension and esophageal varices (HRs > 1, P < .05). Though Asian race is protective in univariate models, in fully adjusted, multivariable models, Asian race is not a significant protective factor. Likewise, other social determinants of health are not significantly predictive of all-cause or cancer-specific mortality. Finally, treatment with SR, in later procedure years or at high-volume centers, is protective for all-cause and cancer-specific mortality. In machine learning models, year procedure was performed, ascites, portal hypertension, and treatment choice were the most influential factors., Discussion: Treatment characteristics, liver disease factors, and tumor size are more important predictors of all-cause and cancer-specific death than social determinants of health for small HCCs., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Aim: To perform a morphometric analysis of the features of vascular remodeling of the arterial bed of the testicles in post-resection portal and pulmonary hypertension., Patients and Methods: Materials and Methods: The testes of 54 white rats were studied, which were divided into groups: 1st included 16 intact animals, 2nd - 20 rats with pulmonary hypertension, 3rd - 18 individuals with post-resection portal hypertension. Postresection pulmonary hypertension was modeled by right-sided pulmonectomy. Postresection portal hypertension was simulated by removing 58.1 % of the liver parenchyma., Results: Results: The outer diameter of the small-caliber arteries of the left testicle increased by 3.4% (p<0.05) in post-resection arterial pulmonary hypertension, and by 2.9% in post-resection portal hypertension. The inner diameter of the small-caliber arteries of the left testicle decreased by 7.7% (p<0.001) in pulmonary heart disease, and by 6.5% (p<0.01) in post-resection portal hypertension. The Kernogan index decreased by 23.0% (p<0.001), the Vogenvoort index increased by 1.26 times. In case of post-resection portal hypertension, the Kernogan index decreased by 19.0% (p<0.001) and the Wogenvoort's index increased by 1.19 times. The relative volume of damaged endotheliocytes in the small-caliber arteries of the left testis increased 20.6 times (p<0.001) in pulmonary heart disease, and increased 16.3 times (p<0.001) in post-resection portal hypertension., Conclusion: Conclusions: Portal and pulmonary hypertension lead to pronounced remodeling of the arterial bed of the testicles, which is characterized by thickening of the arterial wall, narrowing of their lumen, significant changes in Wogenvoort and Kernogan indexes, atrophy, dystrophy, and necrobiosis of endotheliocytes.

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.

Caroli disease is a rare congenital malformation that predisposes to segmental cystic dilatation of the intrahepatic bile ducts. Banti syndrome is characterized by persistent splenomegaly due to chronic congestion, resulting in a low hematocrit and ultimately leading to pancytopenia. In this report, we describe a 29-year-old woman who presented with a >20-year history of hepatitis B surface antigen positivity and a >1-year history of recurrent fatigue and malaise. On examination, the patient had abdominal distension with marked splenomegaly (7 cm below the ribs) and ascites with tenderness of the abdominal muscles to palpation. A complete blood count showed a low white blood cell count, red blood cell count, and hemoglobin concentration. During the course of treatment, the patient developed multiple symptoms of pancytopenia and concomitant splenomegaly, and she was discharged after total splenectomy with good recovery. The combination of Banti syndrome and Caroli disease results in severe symptoms of portal hypertension., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background: Porto-sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life-threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease., Methods: We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium-enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data., Results: All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD-specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model., Conclusions: The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Transjugular intrahepatic portosystemic shunt (TIPS) relieves cirrhotic complications by reducing portacaval pressure gradient (PCG), but it lacks precision in achieving a targeted post-TIPS PCG simply through diameter adjustment of equal diameter stents. This study aimed to present a controlled-expansion, streamlined, and covered tapered stent, and examined its effects on pressure reduction compared with equal- diameter stents. Twenty-four patients who underwent standardized 8-mm stent TIPS implantation at West China Hospital from December 2017 to February 2021 were included in the current study. Virtual equal-diameter stent graft with different diameter and streamlined tapered stents were created in the post-TIPS 3-dimentional models reconstructed based on computed tomography angiography data. The numerical simulation showed that only two patients achieved targeted post-TIPS PCG consistent with the clinical invasive measurement. When 6-mm and 10-mm equal-diameter stents were employed, simulated post-TIPS PCGs for most patients remained outside the safe range, and recirculating flow was observed at the stent-portal vein anastomosis. In contrast, the use of the new streamlined taper stent resulted in post-TIPS PCGs within the 10-12 mmHg range for 17 out of 24 patients, with no recirculating flow observed at the anastomotic sites. In conclusion, the streamlined tapered stent could pose an effective solution to the problem that the big jump depressurization between two different equal-diameter stents and it would improve the hemodynamics in the region near the PV-stent anchorage. Therefore, the streamlined tapered stent may present a superior alternative for TIPS procedure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the impact of pre-transjugular intrahepatic portosystemic shunt (TIPS) hepatic encephalopathy (HE) on developing post-TIPS HE., Materials and Methods: In this retrospective, single center observational study, all patients who underwent successful TIPS placement between January 2005 and May 2020 with data pertaining to HE in their chart were included. Patient demographics and procedural details were recorded. Clinical outcomes post-TIPS, were collected and compared across patients with and without pre-TIPS HE., Results: Of 326 included patients, 159 (159/326, 48.8%) had a history of pre-TIPS HE. In total those without a history of HE were more likely to develop HE during follow up (136 (136/167, 81.4%) vs 107 (107/159, 67.3%), p = 0.001). When evaluating for predictors of developing HE within 3 months of TIPS placement, no significant variables were found on logistic regression, including prior history of HE (HR 1.16 (95% CI 0.73-1.84), p = 0.529). Univariate and multivariate regression analysis, however, showed that a history of HE was predictive of developing HE at any point in the follow-up period (p = 0.002 and p = 0.008, respectively). However, on Kaplan-Meier analysis no significant difference in the development of HE (p = 0.574) or hospital admission for HE (p = 0.554) post-TIPS was seen between patients with and without pre-TIPS HE. Additionally, there was no difference in 3-month survival (p = 0.412) or overall survival post-TIPS survival (p = 0.798)., Conclusion: Pre-TIPS HE did not predict the development of HE within 3 months of TIPS. Outcomes such as hospital admission and survivability were not different between patients with and without prior HE., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose: Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT)., Methods: This study retrospectively reviewed the medical records of pediatric patients aged 0-19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center. The analysis included cases of shunt placement with or without LT., Results: A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement. Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases. A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported., Conclusion: Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

BACKGROUND. The Fontan operation palliates single-ventricle congenital heart disease but causes hepatic congestion with associated progressive hepatic fibrosis. OBJECTIVE. The purpose of this study was to evaluate associations between liver stiffness measured using ultrasound (US) shear-wave elastography (SWE) in patients with Fontan palliation and the occurrence of portal hypertension and Fontan circulatory failure during follow-up. METHODS. This retrospective study included 119 individuals 10 years old or older (median age, 19.1 years; 61 female patients, 58 male patients) with Fontan circulation who underwent liver US with 2D SWE from January 1, 2015, to January 1, 2022, and had 1 year or more of clinical follow-up (unless experiencing earlier outcome-related events). Median liver stiffness from the initial US examination was documented. Varices, ascites, splenomegaly, and thrombocytopenia (VAST) scores (range, 0-4) were determined as a marker of portal hypertension on initial US examination and 1 year or more of follow-up imaging (US, CT, or MRI). Composite clinical outcome for Fontan circulatory failure (death, mechanical circulatory support, cardiac transplant, or unexpected Fontan circulation-related hospitalization) was assessed. Analysis included the Wilcoxon rank sum test, logistic regression analysis with stepwise variable selection, and ROC analysis. RESULTS. Median initial liver stiffness was 2.22 m/s. Median initial VAST score was 0 (IQR, 0-1); median follow-up VAST score was 1 (IQR, 0-2) ( p = .004). Fontan circulatory failure occurred in 37 of 119 (31%) patients (median follow-up, 3.4 years). Initial liver stiffness was higher in patients with a follow-up VAST score of 1 or greater (2.37 m/s) than in those with a follow-up VAST score of 0 (2.08 m/s) ( p = .005), and initial liver stiffness was higher in patients with (2.43 m/s) than without (2.10 m/s) Fontan circulatory failure during follow-up ( p < .001). Initial liver stiffness was the only significant independent predictor of Fontan circulatory failure (OR = 3.76; p < .001); age, sex, Fontan operation type, dominant ventricular morphology, and initial VAST score were not independent predictors. Initial liver stiffness had an AUC of 0.70 (sensitivity, 79%; specificity, 57%; threshold, > 2.11 m/s) for predicting a follow-up VAST score of 1 or greater and an AUC of 0.74 (sensitivity, 84%; specificity, 52%; threshold, > 2.12 m/s) for predicting Fontan circulatory failure. CONCLUSION. In patients with Fontan circulation, increased initial liver stiffness was associated with portal hypertension and circulatory failure during follow-up, although it had moderate performance in predicting these outcomes. CLINICAL IMPACT. US SWE may play a role in post-Fontan surveillance, supporting tailored medical and surgical care.

Rational: The disease of Caroli is a rare congenital disorder, characterized by the dilated intrahepatic bile ducts, resulting from mutations in the PKHD1 gene. Caroli syndrome, characterized by dilated intrahepatic bile ducts with congenital hepatic fibrosis, is linked to autosomal recessive polycystic kidney disease. The clinical manifestations of Caroli disease are not typical, and Caroli disease is easy to be missed and misdiagnosed. Therefore, we reported this case in the hope of raising awareness of the disease among clinicians., Patient Concerns: The clinical manifestation of a 10-year-old girl was subcutaneous hemorrhage., Diagnoses: Magnetic resonance imaging (MRI ) indicates that the person may have Caroli disease, cirrhosis, splenomegaly, portal hypertension, esophagogastric fundal varices, or sponge kidneys., Intervention: The patient was advised for liver transplantation., Outcomes: The patient parents did not take our treatment advice, and they asked to go to a better hospital for further treatment, so we did not give the patient any treatment., Lessons: This case serves as a reminder that if we encounter a patient with hemophilia in our clinic, we should not only consider hematologic diseases and cirrhosis, but also perform an epigastric MRI and magnetic resonance cholangiopancreatography to rule out Caroli disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Common variable immunodeficiency disorder (CVID) manifests with recurrent infections and inflammatory complications, including liver disease. We report the clinical features, natural history, and outcomes of patients with CVID-related liver disease (CVID-rLD) from a tertiary immunology and hepatology center., Methods: Two hundred eighteen patients were identified; CVID-rLD was defined by persistently abnormal liver function tests or evidence of chronic liver disease (CLD) or portal hypertension (PHTN) by radiological or endoscopic investigation, after exclusion of other causes. Patients with CVID-rLD were investigated and managed following a joint pathway between immunology and hepatology services. Data, including clinical parameters, investigations, and outcomes, were retrospectively collected., Results: A total of 91/218 (42%) patients had evidence of CVID-rLD, and 40/91 (44%) had PHTN. Patients with CVID-rLD were more likely to have other noninfectious complications of CVID (85/91, 93.4% vs. 75/127, 59.1%, p<0.001) including interstitial lung disease, gut disease, and autoimmune cytopenias. Nodular regenerative hyperplasia (NRH) was identified in 63.8% of liver biopsies, and fibrosis in 95.3%. Liver stiffness measurements (LSMs) were frequently elevated (median 9.95 kPa), and elevated LSM was associated with PHTN. All-cause mortality was higher in those with CVID-rLD (24/91, 26.4% vs. 14/127, 11%, p=0.003), which was the only organ complication associated with mortality (HR 2.24, 1.06-4.74, p=0.04). Factors predicting mortality in CVID-rLD included PHTN, increasing fibrosis, and LSM., Conclusions: Liver disease is a common complication of CVID as part of complex, multi-organ involvement and is associated with high rates of PHTN and an increased hazard of mortality., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Objective: The aim of this study was to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS., Patients and Methods: This cross-sectional study was conducted in August 2023. A total of 54 healthy volunteers were included in this study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. The relationships between SS and the other variables were investigated., Results: Twenty-nine male and 25 female subjects with a mean age of 54.78 ± 15.40 years were included in the study. Mean craniocaudal diameter was 10.46 ± 1.16 cm, anteroposterior diameter was 9.88 ± 1.29 cm, parenchyma thickness was 4.08 ± 0.67 cm, SS was 3,721.94 ± 709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40 - 311.00) cm3. A significant and strong positive correlation was observed between age and SS (r = 0.779, p < 0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume., Conclusions: Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Aim: To determine risk factors for portal venous system thrombosis (PVST) after partial splenic artery embolisation (PSAE) in cirrhotic patients with hypersplenism., Materials and Methods: Between March 2014 and February 2022, 428 cirrhotic patients with hypersplenism underwent partial splenic artery embolisation and from these patients 208 were enrolled and 220 were excluded. Medical records of enrolled patients were collected. Computed tomography (CT) images were reviewed by two blinded, independent radiologists. Statistical analyses were performed by using SPSS., Results: Progressive PVST was observed in 18.75% (39/208) of cirrhotic patients after PSAE. No significant differences in peripheral blood counts, liver function biomarkers, and renal function were observed between the patients with progressive PVST and the patients without progressive PVST. The imaging data showed significant differences in PVST, the diameters of the portal, splenic, and superior mesenteric veins between the progressive PVST group and non-progressive PVST group. Univariate and multivariate analysis demonstrated portal vein thrombosis, spleen infarction percentage, and the diameter of the splenic vein were independent risk factors for progressive PVST. Seventeen of 173 (9.83%) patients showed new PVST; the growth of PVST was observed in 62.86% (22/35) of the patients with pre-existing PVST. Spleen infarction percentage and the diameter of the splenic vein were independent risk factors for new PVST after PSAE., Conclusion: The present study demonstrated portal vein thrombosis, spleen infarction percentage, and the diameter of the splenic vein were independent risk factors for PVST after PSAE in cirrhotic patients with hypersplenism., (Copyright © 2023. Published by Elsevier Ltd.)

Inflammation plays an essential role in the development liver fibrosis.The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a central cytoplasmic DNA sensor which can recognize cytoplasmic DNA, known to trigger stimulator of interferon genes (STING) and downstream proinflammatory factors. Here, we investigated the role of cGAS-STING signaling pathway in the pathogenesis of liver fibrosis.Differentially expressed genes (DEGs) in human liver tissue were identified using RNA-Seq analysis. As models of liver fibrosis, chronic Carbon tetrachloride (CCl 4 ) exposure were applied in cGAS-knockout mice. LX-2 cells were co-cultured with human liver sinusoidal endothelial cells (LSECs) to explore the underlying mechanisms of hepatic sinusoidal microthrombosis in an inflammatory microenvironment. The endoscopic ultrasound-guided portal vein pressure gradient (EUS-PPG) method was used to analyze the associations between hepatic sinusoidal microthrombosis and PPG in patients with liver fibrosis and portal hypertension (PTH). The RNA-seq analysis results showed that DEGs were enriched in inflammation and endothelial cell activation. The upregulation of the cGAS-STING signaling exacerbated liver fibrosis and intrahepatic inflammation. It also exacerbated LSECs impairment and increased the contribution of hepatic sinusoidal microthrombosis to liver fibrosis in vivo and in vitro. Prothrombotic mediators and proinflammatory factors were associated with PPG in patients with liver fibrosis and portal hypertension. Therefore, activating cGAS-STING signaling pathway promotes liver fibrosis and hepatic sinusoidal microthrombosis, which may lead to increased portal vein pressure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aim: Our primary objective is to report the results of the ultrasound (US)-guided revision technique of transhepatic shunt in patients in whom intrahepatic portosystemic shunt was created by the percutaneous or conventional route. Our secondary objective is to investigate whether there is an association between the indication for a portosystemic shunt and the need for post-shunt revision., Methods: Data from 117 consecutive patients who had a transjugular intrahepatic portosystemic shunt placed percutaneously or conventionally were extracted from hospital electronic medical records and examined those who underwent revision within 11 years and those who did not. US-guided transhepatic shunt revision technique was evaluated in terms of technical success, complications, and patency. In addition, the relationship between etiology and the need for revision was also examined using the chi-square test in three groups., Results: Forty six point two percent of patients who underwent transjugular intrahepatic portosystemic shunt required one or more revisions within 11 years. While patency of the shunt could be established via the transjugular route in 83.3% of revision patients, it was necessary to use the transhepatic route in 16.7%. The technical success rate for the US-guided transhepatic shunt revision method was 100%, and the pressure gradient between the portal and hepatic venous systems decreased below 10 mmHg in all patients at the end of the procedure., Conclusion: US-guided transhepatic shunt revision is a safe and effective method where transjugular revision cannot be performed. In addition, the revision rate is significantly higher in patients who have undergone transjugular intrahepatic portosystemic shunt due to Budd-Chiari syndrome compared with other groups., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Systemic inflammation with elevated inflammatory cytokines is a hallmark in patients with cirrhosis and the main driver of decompensation. There is insufficient data on whether inflammatory cytokine levels differ between hepatic and jugular veins, which may have implications for further immunological studies., Methods: Blood from the hepatic and jugular veins of 40 patients with cirrhosis was collected during hepatic venous pressure gradient (HVPG) measurements. Serum levels of 13 inflammatory cytokines (IL-1 β , Int- α 2, Int- γ , TNF- α , MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33) were quantified by cytometric bead array., Results: Cytokine levels of IFN- α 2, IFN- γ , TNF- α , IL-6, IL-8, IL-10, IL-17A, IL-18, IL-23, and IL-33 were significantly elevated in patients with decompensated cirrhosis compared to patients with compensated cirrhosis. When comparing patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) to patients without CSPH, there were significantly enhanced serum levels of IL-6 and IL-18 in the former group. There was no significant difference between cytokine serum levels between blood obtained from the jugular versus hepatic veins. Even in subgroup analyses stratified for an early cirrhosis stage (Child-Pugh (CP) A) or more decompensated stages (CP B/C), cytokine levels were similar., Conclusion: Cytokine levels increase with decompensation and increasing portal hypertension in patients with cirrhosis. There is no relevant difference in cytokine levels between hepatic and jugular blood in patients with cirrhosis., Competing Interests: The authors declare no competing interests., (Copyright © 2023 Leonard Kaps et al.)

Objective: For transjugular intrahepatic portosystemic shunt (TIPS) creation, ultrasound guidance for portal vein puncture is strongly recommended. However, outside regular hours of service, a skilled sonographer might be lacking. Hybrid intervention suites combine CT imaging with conventional angiography allowing to project 3D information into the conventional 2D imaging and further CT-fluoroscopic puncture of the portal vein. The purpose of this study was to assess whether TIPS using angio-CT facilitates the procedure for a single interventional radiologist., Methods: All TIPS procedures from 2021 and 2022 which took place outside regular working hours were included (n = 20). Ten TIPS procedures were performed with just fluoroscopy guidance and ten procedures using angio-CT. For the angio-CT TIPS, a contrast-enhanced CT was performed on the angiography table. From the CT, a 3D volume was created using virtual rendering technique (VRT). The VRT was blended with the conventional angiography image onto the live monitor and used as guidance for the TIPS needle. Fluoroscopy time, area dose product, and interventional time were assessed., Results: Hybrid intervention with angio-CT did lead to a significantly shorter fluoroscopy time and interventional time (p = 0.034 for both). Mean radiation exposure was significantly reduced, too (p = 0.04). Furthermore, the mortality rate was lower in patients who underwent the hybrid TIPS (0% vs 33%)., Conclusion: TIPS procedure in angio-CT performed by only one interventional radiologist is quicker and reduces radiation exposure for the interventionalist compared to mere fluoroscopy guidance. The results further indicate increased safety using angio-CT., Clinical Relevance Statement: This study aimed to evaluate the feasibility of using angio-CT in TIPS procedures during non-standard working hours. Results indicated that the use of angio-CT significantly reduced fluoroscopy time, interventional time, and radiation exposure, while also leading to improved patient outcomes., Key Points: • Image guiding such as ultrasound is recommended for transjugular intrahepatic portosystemic shunt creation but might be not available for emergency cases outside of regular working hours. • Transjugular intrahepatic portosystemic shunt creation using an angio-CT with image fusion is feasible for only one physician under emergency settings and results in lower radiation exposure and faster procedures. • Transjugular intrahepatic portosystemic shunt creation using an angio-CT with image fusion seems to be safer than using mere fluoroscopy guidance., (© 2023. The Author(s).)

Background and Aims: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients., Methods: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions., Results: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH., Conclusions: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Purpose of Review: This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial changes and progress in this field, including the use of controlled-expansion, covered stents, which has broadened the clinical uses of TIPS., Recent Findings: Recent findings have rapidly expanded the indications for TIPS, including emerging uses in hepatorenal syndrome, hepatopulmonary syndrome and before abdominal surgery. The widespread use of controlled-expansion, covered stents has decreased rates of post-TIPS hepatic encephalopathy, opening TIPS to a larger patient population. Overall, with newer stent technology and more research in this area, the clinical utility and potential of TIPS has rapidly expanded. Going forward, a renewed focus on randomized-control trials and long-term outcomes will be a crucial element to selecting appropriate TIPS recipients and recommending emerging indications for this procedure., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)