Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

BACKGROUND & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

Diagnostic Prediction of portal vein thrombosis in chronic cirrhosis patients using data-driven precision medicine model.

BACKGROUND: Portal vein thrombosis (PVT) is a significant issue in cirrhotic patients, necessitating early detection. This study aims to develop a data-driven predictive model for PVT diagnosis in chronic hepatitis liver cirrhosis patients. METHODS: We employed data from a total of 816 chronic cirrhosis patients with PVT, divided into the Lanzhou cohort (n = 468) for training and the Jilin cohort (n = 348) for validation. This dataset encompassed a wide range of variables, including general characteristics, blood parameters, ultrasonography findings and cirrhosis grading. To build our predictive model, we employed a sophisticated stacking approach, which included Support Vector Machine (SVM), Naïve Bayes and Quadratic Discriminant Analysis (QDA). RESULTS: In the Lanzhou cohort, SVM and Naïve Bayes classifiers effectively classified PVT cases from non-PVT cases, among the top features of which seven were shared: Portal Velocity (PV), Prothrombin Time (PT), Portal Vein Diameter (PVD), Prothrombin Time Activity (PTA), Activated Partial Thromboplastin Time (APTT), age and Child-Pugh score (CPS). The QDA model, trained based on the seven shared features on the Lanzhou cohort and validated on the Jilin cohort, demonstrated significant differentiation between PVT and non-PVT cases (AUROC = 0.73 and AUROC = 0.86, respectively). Subsequently, comparative analysis showed that our QDA model outperformed several other machine learning methods. CONCLUSION: Our study presents a comprehensive data-driven model for PVT diagnosis in cirrhotic patients, enhancing clinical decision-making. The SVM-Naïve Bayes-QDA model offers a precise approach to managing PVT in this population.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT. MATERIALS AND METHODS: Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs. CONCLUSION: RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

Technical Strategy for Pancreatic Body Cancers: A Raison d'etre of Distal Pancreatectomy with Portal Resection.

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.

The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy.

BACKGROUND: Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. METHODS: We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). RESULTS: R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. CONCLUSIONS: Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Comprehensive Review of Future Liver Remnant (FLR) Assessment and Hypertrophy Techniques Before Major Hepatectomy: How to Assess and Manage the FLR.

BACKGROUND: The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR). OBJECTIVE: The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy. METHOD: We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques. RESULTS: The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin-bilirubin [APRI+ALBI] score), concurrent utilization of 99mTc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization). CONCLUSION: There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

Comparison of percutaneous microwave/radiofrequency ablation liver partition and portal vein embolization versus transarterial chemoembolization and portal vein embolization for planned hepatectomy with insufficient future liver remnant.

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.

Evaluation of 4D Flow MRI-Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation. PURPOSE: To explore the relationship between RRT values and the presence of PVT in cirrhotic participants. STUDY TYPE: Prospective. POPULATION: Forty-eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57-73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40-54]). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT-mean], flow velocity, and flow rate) were analyzed. STATISTICAL TESTS: We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT-mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance. RESULTS: The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT-mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 µL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT-mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT-mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT-mean and platelet count) was 0.90. DATA CONCLUSION: Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Natural history of spontaneous pancreatic portal vein fistulae: A systematic review of the literature.

BACKGROUND: Spontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation - varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes. METHODS: A search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria. RESULTS: A total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality. CONCLUSIONS: PPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis.

A case of Crimean-Congo haemorrhagic fever complicated with portal vein thrombosis and hemophagocytosis.

OBJECTIVES: Crimean-Congo haemorrhagic fever (CCHF) is a zoonotic viral infection which is an important public health problem in Turkey. CCHF causes fever and bleeding and can lead to severe health outcomes. The study aims to report a case of a male patient with severe CCHF, hemophagocytic lymphohistiocytosis (HLH) treated with steroids and portal vein thrombosis. CASE REPORT: A 37-year-old man was admitted to the emergency department with complaints of high fever, headache, myalgia and diarrhoea. The patient travelled to the endemic region of Turkey. In laboratory findings, thrombocytopenia, abnormal liver function tests and elevated coagulation parameters were observed. Real-time polymerase chain reaction assay was used for diagnosis of CCHF. Hypofibrinogenemia, hypertriglyceridemia, elevated ferritin and d-dimer levels were observed in the clinical follow-up. Prednisolone treatment was performed due to considered the diagnosis of HLH. Portal vein thrombosis was detected on abdominal computed tomography scan. He was successfully treated with ribavirin, corticosteroids, anticoagulant and supportive therapy. CONCLUSION: The clinical presentation of CCHF can range from self-limiting flu-like to severe symptoms possibly fatal. Acute portal vein embolism is a rare complication that has not been reported before to our knowledge. Corticosteroids may be a life-saving treatment for CCHF patients presenting with HLH.

Transjugular intrahepatic portosystemic shunt in patients with splanchnic vein thrombosis: Prevalence and management of patent foramen ovale.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure for the treatment of several complications of portal hypertension (PH), including non-neoplastic portal vein thrombosis (PVT). Selection criteria for TIPS in PVT are not yet well established. Despite anecdotal, cases of thromboembolic events from paradoxical embolism due to the presence of patent foramen ovale (PFO) after TIPS placement have been reported in the literature. Therefore, we aimed at describing our experience in patients with non-neoplastic splanchnic vein thrombosis (SVT) who underwent TIPS following PFO screening. METHODS: We conducted a single-centre retrospective study, including consecutive patients who underwent TIPS for the complications of cirrhotic and non-cirrhotic portal hypertension (NCPH) and having SVT. RESULTS: Of 100 TIPS placed in patients with SVT, 85 patients were screened for PFO by bubble-contrast transthoracic echocardiography (TTE) with PFO being detected in 22 (26%) cases. PFO was more frequently detected in patients with non-cirrhotic portal hypertension (NCPH) (23% in the PFO group vs. 6% in those without PFO, p = .04) and cavernomatosis (46% in the PFO group vs. 19% in those without PFO, p = .008). Percutaneous closure was effectively performed in 11 (50%) after multidisciplinary evaluation of anatomical and clinical features. No major complications were observed following closure. CONCLUSIONS: PFO screening and treatment may be considered feasible for patients with SVT who undergo TIPS placement.

The Effect of Microvascular Invasion on Hepatocellular Carcinoma With Portal Vein Tumor Thrombus After Hepatectomy: A Retrospective Study.

BACKGROUND: There is no report resolving whether microvascular invasion (MVI) affects the prognosis of hepatectomy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). The present study aimed to investigate the effect of MVI on HCC with PVTT after hepatectomy. METHODS: 362 HCC patients with PVTT were included in this retrospective study. Diagnostic criteria of PVTT in HCC patients were based on typical preoperative radiological features on imaging studies. The log-rank test was utilized to differentiate overall survival (OS) and recurrence-free survival (RFS) rates between the two groups. Univariate and multivariate Cox proportional hazard regression was utilized to detect independent factors. RESULTS: PVTT without MVI accounted for 12.2% (n = 44). PVTT without MVI groups was significantly superior to PVTT with MVI groups in OS (the median survival = 27.1 months vs 13.7 months) and RFS (the median survival = 6.4 months vs 4.1 months). The 1-, 3-, and 5-year OS rates (65.5%, 36.8%, 21.7% vs 53.5%, 18.7%, 10.1%, P = .014) and RFS rates (47.0%, 29.7%, 19.2% vs 28.7%, 12.2%, 6.9%, P = .005) were significant different between two groups. Multivariate analysis showed that MVI was an independent risk factor for OS (hazard ratio (HR) = 1.482; P-value = .045) and RFS (HR = 1.601; P-value = .009). CONCLUSIONS: MVI was an independent prognostic factor closely linked to tumor recurrence and poorer clinical outcomes for HCC patients with PVTT after hepatectomy. MVI should be included in current PVTT systems to supplement to the PVTT type.

Transjugular mesenteric-caval shunt for portal vein cavernous transformation with recurrent variceal bleeding: preliminary results.

OBJECTIVES: This study aimed to evaluate the feasibility, safety, and efficacy of the transjugular mesenteric-caval shunt (TMCS) as a treatment for the cavernous transformation of the portal vein (CTPV) and recurrent variceal bleeding. METHODS: This retrospective case series was conducted with approval from the institutional review board. It involved seven patients diagnosed with CTPV and recurrent variceal bleeding who underwent the TMCS procedure. We analyzed the rate of procedural complications, incidents of rebleeding, stent stenosis, hepatic encephalopathy, and overall survival to assess treatment outcomes. RESULTS: The TMCS was successfully performed in all seven patients without any life-threatening complications. Postoperatively, one patient developed a lung infection and pleural effusion, which resolved with appropriate treatment. Additionally, two patients experienced an increase in total bilirubin levels, but there was no further deterioration in liver function. The median portal pressure gradient significantly decreased from a preoperative value of 27 mmHg (range 20-36 mmHg) to a postoperative value of 6 mmHg (range 4-11 mmHg). A notable improvement was observed in one cirrhotic patient, with liver function progressing from Child-Pugh class B (score 9) to class A (score 6). Over a median follow-up period of 14 months (range 7-18 months), none of the patients encountered rebleeding, stent stenosis, hepatic encephalopathy, or mortality. CONCLUSION: The TMCS appears to be a viable and effective alternative for managing CTPV with recurrent variceal bleeding. Its long-term outcome requires further evaluation. CLINICAL RELEVANCE STATEMENT: TMCS provides a promising treatment for patients with life-threatening CTPV complications when occluded portal vein cannot be recanalized and portal vein recanalization TIPS is not an option. KEY POINTS: Performing TIPS in patients with portal vein cavernoma is complex due to the requirement for recanalization of the occluded portal vein. Creating a mesenteric-caval shunt through a transjugular approach is a feasible technique. Establishing a TMCS provides a means to manage life-threatening complications arising from portal vein cavernoma.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism. METHODS: First, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4-10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity. CONCLUSIONS: A new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

Analysis of factors related to recanalization of portal vein thrombosis in liver cirrhosis: a retrospective cohort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis, yet there are fewer studies about predictors of PVT recanalization. We aimed to further explore the predictors of recanalization in cirrhotic PVT to facilitate accurate prediction of patients' clinical status and timely initiation of appropriate treatment and interventions. To further investigate the benefits and risks of anticoagulant therapy in cirrhotic PVT patients. METHODS: A retrospective cohort study of patients with cirrhotic PVT in our hospital between January 2016 and December 2022, The primary endpoint was to analyze predictors of PVT recanalization by COX regression. Others included bleeding rate, liver function, and mortality. RESULTS: This study included a total of 82 patients, with 30 in the recanalization group and 52 in the non-recanalization group. Anticoagulation therapy was the only independent protective factor for portal vein thrombosis recanalization and the independent risk factors included massive ascites, history of splenectomy, Child-Pugh B/C class, and main trunk width of the portal vein. Anticoagulation therapy was associated with a significantly higher rate of PVT recanalization (75.9% vs. 20%, log-rank P < 0.001) and a lower rate of PVT progression (6.9% vs. 54.7%, log-rank P = 0.002). There was no significant difference between different anticoagulation regimens for PVT recanalization. Anticoagulation therapy did not increase the incidence of bleeding complications(P = 0.407). At the end of the study follow-up, Child-Pugh classification, MELD score, and albumin level were better in the anticoagulation group than in the non-anticoagulation group. There was no significant difference in 2-year survival between the two groups. CONCLUSION: Anticoagulation, massive ascites, history of splenectomy, Child-Pugh B/C class, and main portal vein width were associated with portal vein thrombosis recanalization. Anticoagulation may increase the rate of PVT recanalization and decrease the rate of PVT progression without increasing the rate of bleeding. Anticoagulation may be beneficial in improving liver function in patients with PVT in cirrhosis.

Statin use in cirrhosis and its association with incidence of portal vein thrombosis.

BACKGROUND AND AIM: Statin use has shown a reduction in hepatic decompensation and portal hypertension. Its association with portal vein thrombosis (PVT) incidence is unknown. We aim to compare the incidence of PVT in patients with and without statin use. METHODS: We excluded patients with a history of hepatocellular cancer, liver transplants, Budd-Chiari syndrome, and intra-abdominal malignancies. Patients with cirrhosis were followed from their first hepatologist clinical encounter (January 1, 2016, to January 31, 2021) for 180 days to determine PVT incidence. We tested the association of statin use with PVT using 1:1 propensity score (PS) matching and Cox proportional hazard regression. RESULTS: We analyzed 2785 patients with cirrhosis (mean age:61.0 ± 12.3 years, 44.3% female, 63.8% White, mean MELD-Na score:11.7 ± 6.1, and statin use:23.1%). A total of 89 patients developed PVT during the follow-up, which was lower in patients with statin use as compared to no statin use (1.3% vs 3.8%, P = 0.001, unadjusted HR:0.28, 95% CI: 0.13-0.62, P = 0.001). After matching for demographics, comorbidities, and hepatic decompensation events, patients with statin use had a lower risk of developing PVT in 180-day follow-up as compared to those without statin use (HR:0.24, 95% CI: 0.10-0.55, P = 0.001). Subgroup analysis showed that statin use was associated with lower PVT incidence in non-NASH (HR: 0.20, 95% CI: 0.07-0.54, P = 0.002) and decompensated cirrhosis (HR: 0.12, 95% CI:0.03-0.53, P = 0.005) than no statin use. CONCLUSION: PVT incidence was lower in decompensated cirrhosis patients with statin use than in those with no statin use. However, this finding needs to be further tested in randomized control trials.