Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.

Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

To the Editor: Pathophysiology of Splenic Arteriovenous Fistula.

A splenic arteriovenous fistula causes a "prehepatic" hypertension in the portal venous system with the double mechanism of an increased blood amount and mainly its high pressure inflow. It aggravates for a secondary fibrosis of the portal vein branches and "capillarization" of the hepatic sinusoids, adding a further "intra-hepatic" component. The subsequent development of portosystemic collaterals induces the risk of gastrointestinal hemorrhages All this suggests to perform a close monitoring of every case of splanchnic aneurysm or pseudo-aneurysm, through the current cross-section imaging tools, for their possible evolution in an arteriovenous fistula, and to consider an early therapy, also endovascular, before any secondary damage of the liver parenchyma. In this case the treatment of the portal vein hypertension can be "ethiological" and resolutive.

Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis - a multicentre retrospective cohort study.

OBJECTIVE: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension. DESIGN AND SETTING: Multicentre retrospective cohort study between 2008 and 2021. POPULATION: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis. METHODS AND MAIN OUTCOME MEASURES: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications. RESULTS: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of the 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 were at term (79% of live births and 60% of pregnancies). No maternal deaths were observed; one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention. CONCLUSIONS: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy. Individualised, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population. TWEETABLE ABSTRACT: Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy.

Adaptation of lenvatinib treatment in patients with hepatocellular carcinoma and portal vein tumor thrombosis.

PURPOSE: The aim of this study was to clarify the adaptation of lenvatinib treatment in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHOD: Fifty-three patients with HCC were treated with lenvatinib. Before and after treatment blood sampling, patients were examined by computed tomography and ultrasonography. In patients with portal trunk invasion (Vp4), the analysis focused on the degree of occlusion due to the tumor in the portal trunk. In patients without major PVTT {ie, invasion of the primary branch of the portal vein [Vp3] or Vp4}, portal blood flow volume was measured by Doppler analysis; however, Doppler analysis is difficult to perform in patients with major PVTT, so the time from administration of the contrast agent to when it reached the primary branch of the portal vein (portal vein arrival time) was evaluated with the contrast agent Sonazoid. RESULTS: Patients with Vp4 had a significantly worse prognosis than patients with Vp3 and a significant increase in Child-Pugh score at 2 months. Patients with major PVTT had a poor prognosis if the degree of occlusion of the portal trunk was 70% or more. In patients without major PVTT, portal blood flow was significantly decreased after administration of lenvatinib; and in patients with major PVTT, the hepatic artery and portal vein arrival times were significantly increased. CONCLUSION: Lenvatinib treatment should be avoided in patients with Vp4 with a high degree of portal trunk occlusion because of concerns about decreased portal blood flow.

Multicenter study on recent portal venous system thrombosis associated with cytomegalovirus disease.

BACKGROUND & AIMS: Recent non-malignant non-cirrhotic portal venous system thrombosis (PVT) is a rare condition. Among risk factors for PVT, cytomegalovirus (CMV) disease is usually listed based on a small number of reported cases. The aim of this study was to determine the characteristics and outcomes of PVT associated with CMV disease. METHODS: We conducted a French multicenter retrospective study comparing patients with recent PVT and CMV disease ("CMV positive"; n = 23) to patients with recent PVT for whom CMV testing was negative ("CMV negative"; n = 53) or unavailable ("CMV unknown"; n = 297). RESULTS: Compared to patients from the "CMV negative" and "CMV unknown" groups, patients from the "CMV positive" group were younger, more frequently had fever, and had higher heart rate, lymphocyte count and serum ALT levels (p ≤0.01 for all). The prevalence of immunosuppression did not differ between the 3 groups (4%, 4% and 6%, respectively). Extension of PVT was similar between the 3 groups. Thirteen out of 23 "CMV positive" patients had another risk factor for thrombosis. Besides CMV disease, the number of risk factors for thrombosis was similar between the 3 groups. Heterozygosity for the prothrombin G20210A gene variant was more frequent in "CMV positive" patients (22%) than in the "CMV negative" (4%, p = 0.01) and "CMV unknown" (8%, p = 0.03) groups. Recanalization rate was not influenced by CMV status. CONCLUSIONS: In patients with recent PVT, features of mononucleosis syndrome should raise suspicion of CMV disease. CMV disease does not influence thrombosis extension nor recanalization. More than half of "CMV positive" patients have another risk factor for thrombosis, with a particular link to the prothrombin G20210A gene variant. LAY SUMMARY: Patients with cytomegalovirus (CMV)-associated portal venous system thrombosis have similar thrombosis extension and evolution as patients without CMV disease. However, patients with CMV-associated portal venous system thrombosis more frequently have the prothrombin G20210A gene variant, suggesting that these entities act synergistically to promote thrombosis.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

More Pronounced Hypercoagulable State and Hypofibrinolysis in Patients With Cirrhosis With Versus Without HCC.

In patients with cirrhosis, particularly those with hepatocellular carcinoma (HCC), hypercoagulability may be associated with purported increased risks of portal vein thrombosis and cirrhosis progression. In this study, we extensively investigated hemostatic alterations potentially responsible for the thrombotic tendency in HCC, and evaluated whether such alterations were predictive of hepatic decompensation. Patients with cirrhosis at all stages were prospectively recruited and underwent an extensive hemostatic assessment, including all procoagulant factors and inhibitors, thrombin generation with and without thrombomodulin (TG), profibrinolytic and antifibrinolytic factors, and plasmin-antiplasmin complex. In study part 1 (case control), we compared alterations of coagulation and fibrinolysis in patients with cirrhosis with versus without HCC. In study part 2 (prospective), the subgroup of patients with decompensated cirrhosis was followed for development of further decompensation, and predictors of outcome were assessed by multivariate analysis. One-hundred patients were recruited (50 each with and without HCC). Severity of cirrhosis was comparable between groups. Median HCC volume was 9 cm3 (range: 5-16). Compared with controls, patients with HCC demonstrated a significantly more prothrombotic hemostatic profile due to increased TG and reduced activation of fibrinolysis, independent of cirrhosis stage. During a median follow-up of 175 days, 20 patients with decompensated cirrhosis developed further episodes of decompensation that were predicted by low FVII and high plasminogen activator inhibitor-1 levels, independent of Model for End-Stage Liver Disease score. Conclusion: Patients with cirrhosis with HCC have profound hyper-coagulable changes that can account for their increased thrombotic tendency. In contrast, hypercoagulability in patients with decompensated cirrhosis is more likely a consequence of chronic liver disease rather than a driver for cirrhosis progression.

Indication of Surgical Hepatectomy for the Patients of Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombosis.

The prognosis of hepatocellular carcinoma (HCC) presenting with inferior vena cava tumor thrombus (IVCTT) is extremely poor. The aim of this study was to reveal the postoperative course and to identify patients who have survived surgical hepatectomy among HCC patients with IVCTT. Between January 2006 and December 2018, 643 patients underwent surgical hepatectomy for HCC at Kobe University Hospital. Among them, 20 patients were categorized as Vv3 according to the Japanese staging system. We retrospectively collected detailed data on these patients. The statistical, clinical, and pathological data were recorded prospectively and analyzed retrospectively. The median survival time was 9.8 months. Among all patients, 11 (55%) achieved R0 resection, and only two survivors were from this group. The number of tumors (solitary vs. multiple; p=0.050) and pathological Vp (pVp0 vs. other; p=0.009) were identified as risk factors for overall survival in the univariate analysis. In the multivariate analysis, pathological Vp (pVp0 vs. other; p=0.037) was identified as a significant prognostic factor for survival. Pathological Vp affected overall survival among IVCTT patients; the median survival time was 53.7 months with pVp0, 10.2 months with pVp1, and 8.8 months with pVp2-4 (p=0.035). For patients with IVCTT, surgical hepatectomy should be indicated only for those who do not have portal vein invasion and could achieve R0 resection.

Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.

Comparison of stereotactic body radiation therapy versus fractionated radiation therapy for primary liver cancer with portal vein tumor thrombus.

BACKGROUND: To compare the clinical outcomes of stereotactic body radiation therapy (SBRT) and fractionated radiation therapy (FRT) for primary liver cancer with portal vein tumor thrombus (PVTT). METHODS: This retrospective study included 36 patients who underwent SBRT and 36 patients who underwent FRT from August 2016 to June 2018. Patients were evaluated for short-term efficacy, long-term efficacy, AEs, and quality of life before and after treatment. RESULTS: With a median follow-up of 28.8 months (26-36 months), 27 patients survived in the SBRT group while 19 patients survived in the FRT group. The survival rate in the SBRT group was statistically higher than that of the FRT group after 6 months (80.56% vs. 58.33%; P = 0.041), 12 months (77.78% vs. 55.56%; P = 0.046) and 24 months 75.00% vs. 52.78%; P = 0.049). The median whole survival time of the SBRT group was 13.3 months (95% CI 12.83-13.97), which was statistically longer than 9.8 months in the FRT group (95% CI 8.83-10.97, P < 0.05) based on the Kaplan-Meier method. The SBRT group had better survival quality and fewer adverse events than the FRT group. CONCLUSION: SBRT had better clinical outcomes than FRT for primary liver cancer with PVTT.

The impact of portal vein tumor thrombosis on survival in patients with hepatocellular carcinoma treated with different therapies: A cohort study.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is a frequent complication of hepatocellular carcinoma (HCC), which leads to classification as advanced stage disease (regardless of the degree of PVTT) according to the Barcelona Clinic Liver Cancer Classification. For such patients, systemic therapy is the standard of care. However, in clinical reality, many patients with PVTT undergo different treatments, such as resection, transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or best supportive care (BSC). Here we examined whether patients benefited from such alternative therapies, according to the extent of PVTT. METHODS: This analysis included therapy-naïve patients with HCC and PVTT treated between January 2005 and December 2016. PVTT was classified according to the Liver Cancer study group of Japan as follows: Vp1 = segmental PV invasion; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. Overall survival (OS) was analyzed for each treatment subgroup considering the extent of PVTT. We performed Cox regression analysis with adjustment for possible confounders. To further attenuate selection bias, we applied propensity score weighting using the inverse probability of treatment weights. RESULTS: A total of 278 treatment-naïve patients with HCC and PVTT were included for analysis. The median observed OS in months for each treatment modality (resection, TACE/SIRT, sorafenib, BSC, respectively) was 32.4, 8.1, N/A, and 1.7 for Vp1; 10.7, 6.9, 5.5, and 1.2 for Vp2; 6.6, 7.5, 2.9, and 0.6 for Vp3; and 8.0, 3.6, 5.3, and 0.7 for Vp4. Thus, the median OS in the resection group in case of segmental PVTT (Vp1) was significantly longer compared to any other treatment group (all p values <0.01). CONCLUSIONS: Treatment strategy for HCC with PVTT should not be limited to systemic therapy in general. The extent of PVTT should be considered when deciding on treatment alternatives. In patients with segmental PVTT (Vp1), resection should be evaluated.

Identification of the Most Important Subset of Doppler, Laboratory, and Clinical Parameters for Serial TIPS Evaluation.

OBJECTIVE. The purpose of the present study was to identify the subset of a wide range of serial Doppler, laboratory, and clinical parameters most predictive (both individually and in combination) of TIPS dysfunction in a large patient sample. MATERIALS AND METHODS. The medical records of 189 patients who had undergone TIPS procedures were analyzed. The patients (mean age, 52 years; 62% of whom were men) had undergone 1139 Doppler studies and 323 portovenograms. Laboratory parameters included model for end-stage liver disease (MELD) scores, serum albumin levels, presence of ascites, and time since last intervention. Doppler parameters included intrashunt velocities, temporal change in intrashunt velocities, main portal vein velocity, direction of flow in the left portal hepatic vein, and venous pulsatility index. Statistical analysis used ROC, univariate, and multivariate regression models to assess the parameters both individually and in combination. Shunt dysfunction was defined by a portosystemic gradient of more than 12 mm Hg. RESULTS. The laboratory and clinical parameters of greatest predictive value included the MELD score and the time since the last intervention. The Doppler parameters that were of greatest predictive value included the change in velocity at the hepatic venous end and the left portal vein flow direction. Multivariate models produced an AUC of 0.74. Differences between functional and dysfunctional shunts were also statistically significant for absolute velocity at the hepatic venous end, the change in velocity within the stent, and the temporal change in the mid shunt velocity. CONCLUSION. The subset of serial parameters most predictive of TIPS dysfunction are the temporal change in the velocity at the hepatic venous end, the absolute velocity at the hepatic venous end, the direction of flow in the left portal venous branch, and changes in the MELD score.

Hepatic Artery Embolization for Postoperative Hemorrhage: Importance of Arterial Collateral Vessels and Portal Venous Impairment.

PURPOSE: To investigate the association between hepatic ischemic complications and hepatic artery (HA) collateral vessels and portal venous (PV) impairment after HA embolization for postoperative hemorrhage. MATERIALS AND METHODS: From October 2003 to November 2019, 42 patients underwent HA embolization for postoperative hemorrhage. HA collateral vessels were classified according to visualization after embolization (grade 1, none; grade 2, 1-4 segmental HA; and grade 3, ≥4 segmental HA). Transhepatic portal vein stent placements were performed in the same session for 5 patients (11.9%) with poor HA collateral vessels (grade 1 or 2) and compromised PV flow (>70% stenosis). Hepatic ischemic complications were analyzed for relevance to HA collateral vessels and PV compromise. RESULTS: After HA embolization, HA flow was found to be preserved (grade 3) through intra- and/or extrahepatic collateral vessels in 23 patients (54.8%), and hepatic complications did not occur regardless of PV flow status (0%). Of the 19 patients (45.2%) with poor HA collateral vessels (grade 1 or 2), segmental hepatic infarction occurred in 2 of 15 patients (13.3%) with preserved PV flow (10 naïve and 5 stented). The remaining 4 patients with poor HA collateral vessels and untreated compromised PV flow experienced multisegmental hepatic infarction (n = 3) or hepatic failure (n = 1) (100%) (P < .005). CONCLUSIONS: After HA embolization, preserved HA flow (≥4 segmental HA) lowered the risk of hepatic complications regardless of the PV flow. Based on these findings, transhepatic PV stent placement seems to be an effective intervention for the prevention of hepatic complications in cases of poor HA collateral vessels and compromised PV flow.

Influence of portal vein occlusion on portal flow and liver elasticity in an animal model.

Hepatic fibrosis causes an increase in liver stiffness, a parameter measured by elastography and widely used as a diagnosis method. The concomitant presence of portal vein thrombosis (PVT) implies a change in hepatic portal inflow that could also affect liver elasticity. The main objective of this study is to determine the extent to which the presence of portal occlusion can affect the mechanical properties of the liver and potentially lead to misdiagnosis of fibrosis and hepatic cirrhosis by elastography. Portal vein occlusion was generated by insertion and inflation of a balloon catheter in the portal vein of four swines. The portal flow parameters peak flow (PF) and peak velocity magnitude (PVM) and liver mechanical properties (shear modulus) were then investigated using 4D-flow MRI and MR elastography, respectively, for progressive obstructions of the portal vein. Experimental results indicate that the reduction of the intrahepatic venous blood flow (PF/PVM decreases of 29.3%/8.5%, 51.0%/32.3% and 83.3%/53.6%, respectively) measured with 50%, 80% and 100% obstruction of the portal vein section results in a decrease of liver stiffness by 0.8% ± 0.1%, 7.7% ± 0.4% and 12.3% ± 0.9%, respectively. While this vascular mechanism does not have sufficient influence on the elasticity of the liver to modify the diagnosis of severe fibrosis or cirrhosis (F4 METAVIR grade), it may be sufficient to attenuate the increase in stiffness due to moderate fibrosis (F2-F3 METAVIR grades) and consequently lead to false-negative diagnoses with elastography in the presence of PVT.

Safety and Efficacy of Endovascular Treatment of Portal Vein Stenosis in Liver Transplant Recipients: A Systematic Review.

PURPOSE: To evaluate the efficacy of Angioplasty and Stent Placement for the treatment of Portal Vein Stenosis in Liver Transplant Recipients by performing a systematic review. MATERIALS AND METHODS: The PubMed Database was extensively searched for articles describing Portal Vein Stenosis (PVS) as a complication in Liver Transplant (LT) patients. The initial database search yielded 488 unique records published in the PubMed Database, 19 of which were deemed to meet the inclusion criteria. Outcomes were separated into 2 groups (Group A included patients with primary angioplasty, Group B included patients with primary stent placement), and further subdivided into Adult and Pediatric populations. RESULTS: Group A included a total of 282 LT patients with portal vein stenosis. The population was predominantly pediatric (n = 243). Group B included a total of 111 LT patients with portal vein stenosis. This population was predominantly adult (n = 66). Technical success was significantly higher in both Group B pediatric (100%) and adults (97%) compared to Group A (69.5%) and (66.7%) respectively. Re-stenosis rates were significantly lower in Group B pediatric group compared to Group A (2.3% vs 29.7%, χ2 = 13.9; p < 0.001). Overall major (3.1%) and minor complications rates (1.5%) were low. CONCLUSION: Primary stent placement appears to have higher technical success in both populations and lower re-stenosis rates for treatment of PVS in pediatric populations.

Delayed Splenic Rupture After a Percutaneous Transsplenic Approach to Treat Portal Vein Occlusion.

PURPOSE: To report a case of delayed splenic rupture after percutaneous transsplenic portal vein stent deployment. CASE REPORT: A 72-year-old male patient presented at a medical center with abdominal pain and reduced liver function according to laboratory tests. Due to a history of right hemihepatectomy and left portal vein occlusion, the percutaneous transhepatic approach was considered inappropriate. Instead, percutaneous transsplenic access was selected as a suitable procedure for portal vein catheterization. Eight days following the procedure, the patient developed abdominal pain, and a computed tomography scan showed a small splenic pseudoaneurysm that was underappreciated at the time. Patient suffered acute splenic rupture 32 days post-procedure. Subsequent embolization was performed, achieving complete hemostasis. CONCLUSION: The transsplenic approach should be considered when the transhepatic or transjugular approach is unfeasible or difficult to implement. A careful plugging of the puncture tract is necessary to prevent or minimize hemorrhage from the splenic access tract. In addition, careful serial follow-up computed tomography should be used to evaluate the splenic puncture tract.

Multidisciplinary approach to the complex treatment for non-cirrhotic portal hypertension - case-report-based discussion.

Non-cirrhotic portal vein thrombosis (PVT) in patients with antiphospholipid syndrome (APS) is a rare complication, and the management has to be determined individually based on the extent and severity of the presentation. We report on a 37-year-old male patient with non-cirrhotic chronic PVT related to a severe thrombophilia, comprising APS, antithrombin-, factor V- and factor X-deficiency. Three years after the initial diagnosis of non-cirrhotic PVT, the patient presented with severe hemorrhagic shock related to acute bleeding from esophageal varices, requiring an emergency transjugular intrahepatic portosystemic stent shunt (TIPSS). TIPSS was revised after a recurrent bleeding episode due to insufficient reduction of the portal pressure. Additionally, embolization of the dilated V. coronaria ventriculi led to the regression of esophageal varices but resulted simultaneously in a left-sided portal hypertension (LSPH) with development of stomach wall and perisplenic varices. After a third episode of acute esophageal varices bleeding, a surgical distal splenorenal shunt (Warren shunt) was performed to reduce the LSPH. Despite anticoagulation with low molecular weight heparin and antithrombin substitution, endoluminal thrombosis led to a complete Warren shunt occlusion, aggravating the severe splenomegaly and pancytopenia. Finally, a partial spleen embolization (PSE) was performed. In the postinterventional course, leukocyte and platelet counts increased rapidly and the patient showed no further bleeding episodes. Overall, this complex course demonstrates the need for individual assessment of multimodal treatment options in non-cirrhotic portal hypertension. This young patient required triple modality porto-systemic pressure reduction (TIPSS, Warren shunt, PSE) and involved finely balanced anticoagulation and bleeding control.

Splenic Vein Diameter is a Risk Factor for the Portal Venous System Thrombosis After Partial Splenic Artery Embolization.

PURPOSE: Portal venous system thrombosis is a complication of partial splenic artery embolization, and pre-treatment risk assessment is thus important. The purpose of this study was to identify the risk factors for portal venous system thrombosis after partial splenic artery embolization. MATERIALS AND METHODS: We retrospectively analyzed 67 consecutive patients who underwent contrast-enhanced computed tomography before and after first partial splenic artery embolization between July 2007 and October 2018. As risk factors, we investigated age, sex, hematological data, liver function, steroid use, heparin use, and findings from pre- and post-treatment computed tomography. Uni- and multivariate analyses were performed to evaluate the relationship between thrombus appearance or growth and these factors. Values of p < 0.05 were considered significant. RESULTS: Partial splenic artery embolization was technically successful in all 67 patients. Nine patients showed appearance or growth of thrombus. Univariate analysis showed maximum diameter of the splenic vein before treatment (p = 0.0076), percentage of infarcted spleen (p = 0.017), and volume of infarcted spleen (p = 0.022) as significant risk factors. Multivariate analysis showed significant differences in maximum diameter of the splenic vein before treatment (p = 0.041) and percentage of infarcted spleen (p = 0.023). According to receiver operating characteristic analysis, cutoffs for maximum diameter of the splenic vein and percentage of infarcted spleen for distinguishing the appearance or growth of thrombus were 17 mm and 58.2%. CONCLUSION: Large maximum diameter of the splenic vein before partial splenic artery embolization and high percentage of infarcted spleen after partial splenic artery embolization were identified as risk factors for portal venous system thrombosis. LEVEL OF EVIDENCE: Level 4, Case Series.

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2-12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child-Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.