Emergent TIPS for acute gastroesophageal variceal bleeding in cirrhotic patients with hepatocellular carcinoma.

OBJECTIVES: To estimate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding (AVB) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data of thirty-three patients with AVB and HCC undergoing emergent TIPS creation from January 2016 to January 2022 were enrolled and were retrospectively analyzed. The primary outcomes were the safety of emergent TIPS creation, the bleeding control rate, and the rebleeding rate. The secondary outcomes included overall survival (OS), liver function, overt hepatic encephalopathy (HE), and shunt dysfunction. RESULTS: Emergent TIPS creation was technically successful in 33 patients (100%) and one (3.0%) patient suffered a major procedure-related adverse event. The control rate of bleeding (within 5 days) was 100%. During a median follow-up period of 26.3 months, rebleeding occurred in 6 (18.2%) patients. The median OS was 20.0 months. The 6-week and 1-year survival rates were 87% and 65%, respectively. Laboratory tests showed no significant impairment of liver function following TIPS creation. The incidences of overt HE and shunt dysfunction were 24.2% and 6.1%, respectively. CONCLUSION: Emergent TIPS creation is feasible and effective for treatment of AVB in cirrhotic patients with HCC.

Prognosis Prediction of CRAFITY Score in HCC Undergoing TACE Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapy.

Background: The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy. Methods: Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis. Results: The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1-39.7), 34.5 months (95% CI: 23.1-45.9), and 24.2 months (95% CI: 13.9-39.3), respectively, there were statistical differences among the three groups (p<0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0-18.2), 14.1 months (95% CI: 9.0-19.2), and 9.3 months (95% CI: 7.2-11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p<0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p<0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281-4.564), p = 0.014) and PFS (HR = 2.419(1.281-4.564), p = 0.006). Conclusion: The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.

Feasibility of computed tomography portal venography in the preoperative evaluation of emergent TIPS creation for cirrhotic patients with acute variceal bleeding.

OBJECTIVES: To evaluate the feasibility of computed tomography portal venography (CTPV) in the preoperative evaluation of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for cirrhotic patients with acute variceal bleeding (AVB). METHODS: One hundred and forty-eightcirrhotic patients with AVB undergoing emergent TIPS creation from January 2016 to December 2022 in our institution were enrolled in the retrospective study. The primary outcome was the consistency between CTPV and endoscopy in the classification and grading of gastroesophageal varices (GEVs). The second outcome was extraluminal CTPV findings. The consistency of CTPV and endoscopy in the classification and grading of GEVs was determined by Kappa values. RESULTS: Emergent TIPS creation was technically successful in all patients. Forty-five patients underwent preoperative endoscopy. The results of CTPV diagnosis of GEVs classification were that 112, 28, and 8 patients were classified as gastroesophageal varices type 1 (GOV1), GOV2, and isolated gastric varices type 1 (IGV1), respectively. In diagnosing the classification and grading of GEVs, CTPV showed substantial agreement with preoperative endoscopy, with Kappa values of 0.823 and 0.625, respectively. CTPV provided the afferent and afferent vessels of GEVs for emergent TIPS creation. CONCLUSION: CTPV is feasible and effective to act as an alternative preoperative evaluation method to endoscopy for cirrhotic patients with AVB undergoing emergent TIPS creation.

Emergent Transjugular Intrahepatic Portosystemic Shunt as a First-Line Therapy in Patients with Cirrhosis with Acute Gastroesophageal Variceal Hemorrhage.

PURPOSE: To investigate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) as first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage. MATERIALS AND METHODS: From July 2016 to June 2019, 76 patients with advanced cirrhosis and acute variceal hemorrhage were included in this retrospective study. All patients underwent emergent TIPS as first-line therapy within 24 hours. Gastroesophageal varices in patients with cirrhosis were diagnosed with contrast-enhanced computed tomography because emergent endoscopy has not been routinely performed in this center. The primary outcomes were the control rate of bleeding and the rate of rebleeding. Secondary outcomes were the technical success rate of procedure, transplantation-free survival, the mean hospitalization time, the time of stay in the intensive care unit, and adverse events. RESULTS: All patients underwent TIPS creation successfully and were transferred to general wards. The median follow-up time was 21.7 months (interquartile range, 12.6-28.1 months). The control rate of bleeding (≤5 days) was 100%. The rates of early (>5 days to 6 weeks) and late (>6 weeks to 2 years) rebleeding were 6.6% and 1.3%, respectively. The 6-week, 1-year, and 2-year transplantation-free survival rates were 94.7%, 93.4%, and 84.6%, respectively. The incidences of acute liver failure, hepatic encephalopathy, and shunt dysfunction were 5.3%, 25%, and 5.3%, respectively. CONCLUSIONS: Emergent TIPS as a first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage is safe and effective. This study provides an alternative approach for medical centers without emergent endoscopy facility to manage the condition.

Transarterial Chemoembolization Combined with Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors versus Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Advanced Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Results: Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179-0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. Conclusion: TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

Recent Update on Immunotherapy and Its Combination With Interventional Therapies for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. Approximately, 80% of patients are initially diagnosed at intermediate or advanced stages, which means that curative therapies are unable to be performed. In most cases, systemic treatment is ineffective, especially when conventional cytotoxic agents are used. Sorafenib has been the only systemic agent proven to be effective in treating advanced HCC for over a decade. The rapid development of immunotherapy has remarkably revolutionized the management of advanced HCC. Besides, the combination of immunotherapy with molecular targeted agents or locoregional treatments is emerging as an effective tool for enhancing immunity. In the review, an overview of immunotherapy and its combination therapies for HCC is presented.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. Materials and Methods: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. Results: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5-10.5) and PFS was 8.5 months (95% CI, 5.4-11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. Conclusion: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Single-Centre Retrospective Training Cohort Using Artificial Intelligence for Prognostic Prediction of Encephalopathy, Mortality, and Liver Dysfunction after Early TIPS Creation.

OBJECTIVES: Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. RESULTS: A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. CONCLUSIONS: The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

Performance of artificial intelligence for prognostic prediction with the albumin-bilirubin and platelet-albumin-bilirubin for cirrhotic patients with acute variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt.

PURPOSE: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures. MATERIALS AND METHODS: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS. RESULTS: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability. CONCLUSION: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS.

Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma.

PURPOSE: To explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: From August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan-Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS). RESULTS: In total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively. CONCLUSIONS: TACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

Feasibility and Short-Term Stability of Portal Vein Infusion Port Placement by Transjugular Access.

Six pigs underwent implantation of a portal vein infusion port by transjugular access. The technical success rate was 100% (n = 6), with no surgical complications or deaths. At 1 month after implantation, the catheter tip had moved from the splenic vein to the main portal vein, while the catheter protruded into the right ventricle through the right atrium in all cases. Hence, the infusion port system has not been used in clinical practice due to its obvious displacement after implantation. However, this study provides a new idea for future exploration of portal vein infusion pathways.