Hepatic venous pressure gradient evaluates the Scheuer stage of liver fibrosis by transjugular liver biopsy: a multicenter study.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the criterion for assessing sinusoidal portal hypertension. Using HVPG to assess the degree of liver fibrosis by transjugular liver biopsy (TJLB) is still being explored, as no data has been shown that portal hypertension may already be present in patients with advanced hepatic fibrosis (Scheuer stage ≥ S3). The objective of this study was to observe whether portal hypertension exists before progressing to cirrhosis (Scheuer stage = S4). METHODS: Fifty patients who underwent TJLB and HVPG were enrolled. The correlation between Scheuer stage and HVPG was analyzed using the Pearson correlation coefficient, and the ROC curve predicted the diagnostic value of HVPG in patients with hepatic fibrosis. RESULTS: The Scheuer stage and HVPG significantly correlated (r = 0.654, p < 0.001). The AUC of HVPG in predicting advanced liver fibrosis was 0.896, and of cirrhosis was 0.810. There were 45 patients with portal hypertension (HVPG> 5 mmHg), 12 with S3, 29 with S4; There were 42 patients with CSPH (HVPG≥ 10 mmHg), 11 with S3, and 29 with S4. CONCLUSION: HVPG is valuable in evaluating the Scheuer stage of liver fibrosis in patients with TJLB. Portal hypertension might already exist before the progression to cirrhosis in some patients.

Emergent Transjugular Intrahepatic Portosystemic Shunt Creation for Acute Gastric Variceal Bleeding in Patients with Hepatocellular Carcinoma.

A total of 42 cirrhotic patients (mean age, 51.7 years ± 10.8; 38 men) with hepatocellular carcinoma who underwent emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for controlling acute gastric variceal bleeding (GVB) were included in this multicenter retrospective study. Of these, 37 (88.1%) patients underwent emergent TIPS creation as the first-line treatment to control acute GVB. Five (11.9%) patients underwent emergent TIPS creation as a rescue/salvage treatment to control acute GVB after emergent endoscopic therapy and pharmacotherapy. Emergent TIPS creation was technically successful in 40 (95.2%) patients. Two (4.8%) patients had severe and moderate procedural adverse events. The median follow-up duration was 16.9 months (range, 0.1-100.8 months). Failure to control acute bleeding and failure to prevent rebleeding occurred in 8 (19.0%) patients during follow-up. Eighteen (42.9%) patients died during follow-up. Three (7.1%) patients had shunt dysfunction during follow-up. Overt hepatic encephalopathy occurred in 6 (14.3%) patients during follow-up.

Splenic vein embolization as a feasible treatment for patients with hepatic encephalopathy related to large spontaneous splenorenal shunts.

INTRODUCTION AND OBJECTIVES: Although splenic vein embolization (SVE) has been performed for the management of patients with hepatic encephalopathy (HE) related to large spontaneous splenorenal shunts (SSRS) in recent years, its role remains poorly defined. In this study, we aimed to explore the safety and efficacy of SVE for HE patients with large SSRS. MATERIALS AND METHODS: Data from cirrhotic patients who were confirmed to have recurrent or persistent HE related to large SSRS and underwent SVE from January 2017 to April 2021 were retrospectively collected and analyzed at our center. The primary endpoints were the change of HE severity at 1 week after embolization and the recurrence of HE during the follow-up period. The secondary endpoints were procedure-related complications and changes in laboratory indicators and hepatic function (Child-Pugh score/grade and model for end-stage liver disease score). RESULTS: Of the eight cirrhotic patients included in the study, six were diagnosed with recurrent HE, and the others were diagnosed with persistent HE. Embolization success was achieved for all patients (100%), and no immediate procedure-related complications, de novo occurrence, or aggravation of symptoms related to portal hypertension were observed during the long-term follow-up. HE status was assessed at 1 week after embolization. The results demonstrated that the symptoms were mitigated in three patients and resolved completely in five patients. During the follow-up period, all patients were free of HE within 1 month after embolization, but one patient experienced the recurrence of HE within 6 months and another one experienced the recurrence of HE within 1 year. Compared with the preoperative parameters, the Child-Pugh score and grade were significantly improved at 1 week and 1 month after embolization (all P<0.05), and the serum ammonia level was significantly lower at 1 month after embolization (P<0.05). CONCLUSIONS: SVE could be considered as a feasible treatment for patients with HE related to large SSRS, but further validation is required.

Efficacy and safety of endovascular brachytherapy combined with transarterial chemoembolization for the treatment of hepatocellular carcinoma patients with type III or IV portal vein tumor thrombosis.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of endovascular brachytherapy (EVBT) combined with transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) complicated with type III OR IV portal vein tumor thrombosis (PVTT) and to further analyze the prognostic predictors for the patients with HCC and PVTT. METHODS: We retrospectively analyzed the medical records of 54 patients who were diagnosed with HCC complicated with type III or IV PVTT and received EVBT combined with modified TACE treatment from January 2017 to June 2019. Adverse events, treatment response, overall survival (OS), progression-free survival (PFS), and stent patency were analysed to evaluate the efficacy and safety of this treatment. The independent prognostic predictors of OS were also statistically analyzed by the cox regression model. RESULTS: No adverse events occurred in the enrolled patients receiving EVBT combined with TACE treatment. The objective response and disease control rates were 42.6% and 96.3% respectively within 4 weeks after the treatment. The median OS and PFS were 209 days and 138 days, respectively. Cumulative stent patency rate was 70.4% at the last follow-up. AFP ≥ 400 ng/ml, ECOG PS > 1, Child Pugh grade B, and non-hemihepatic HCC were independent risk predictors to evaluate the OS of HCC patient with type III or IV PVTT. CONCLUSIONS: EVBT combined with TACE was a relatively effective and safe strategy to treat HCC patients with type III or IV PVTT.

Transjugular Intrahepatic Portosystemic Shunt Creation for the Prevention of Gastric Variceal Rebleeding in Patients with Hepatocellular Carcinoma: A Multicenter Retrospective Study.

PURPOSE: To evaluate the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) creation for the prevention of gastric variceal rebleeding in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This multicenter retrospective study included 126 cirrhotic patients (mean age, 54.1 ± 10.2 years; 110 men) with HCC who underwent TIPS creation for the prevention of gastric variceal rebleeding. Of these, 110 (87.3%) patients had gastroesophageal varices and 16 (12.7%) patients had isolated gastric varices. Thirty-five (27.8%) patients had portal vein tumor thrombus. RESULTS: TIPS creation was technically successful in 124 (98.4%) patients. Rebleeding occurred in 26 (20.6%) patients during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 98.3% ± 1.2% and 81.2% ± 3.9%, respectively. Forty-nine (38.8%) patients died during the follow-up period. The 6-week and 1-year actuarial probabilities of survival were 98.4 ± 1.1% and 65.6 ± 4.4%, respectively. Two (1.6%) patients had major procedure-related complications, including acute liver failure (n = 1) and intra-abdominal bleeding (n = 1). Thirty-three (26.2%) patients had at least 1 episode of overt hepatic encephalopathy during the follow-up period. Shunt dysfunction occurred in 15 (11.9%) patients after a median follow-up time of 11.4 months (range, 1.4-41.3 months). Lung metastasis occurred in 3 (2.4%) patients, 3.9-32.9 months after TIPS creation. CONCLUSIONS: TIPS creation may be effective and safe for the prevention of gastric variceal rebleeding in patients with HCC.

Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies.

BACKGROUND: Despite the large number of published papers analyzing the prognostic role of Ki-67 in NSCLC, it is still not considered an established factor for routine use in clinical practice. The present meta-analysis summarizes and analyses the associations between Ki-67 expression and clinical outcome in NSCLC patients. METHODS: PubMed, Cochrane, and Embase databases were searched systematically using identical search strategies. The impacts of Ki-67 expression on survival in patients with NSCLC and NSCLC subtypes were evaluated. Furthermore, the association between Ki-67 expression and the clinicopathological features of NSCLC were evaluated. RESULTS: In total, 32 studies from 30 articles met the inclusion criteria, involving 5600 patients. Meta-analysis results suggested that high Ki-67 expression was negatively associated with overall survival (OS; HR = 1.59, 95 % CI 1.35-1.88, P < 0.001) and disease-free survival (DFS; HR = 2.21, 95 % CI 1.43-3.42, P < 0.001) in NSCLC patients. Analysis of the different subgroups of NSCLC suggested that the negative association between high Ki-67 expression and OS and DFS in Asian NSCLC patients was stronger than that in non-Asian NSCLC patients, particularly in early-stage (Stage I-II) adenocarcinoma (ADC) patients. Additionally, while high expression was more common in males, smokers, and those with poorer differentiation, there was no correlation between high Ki-67 expression and age or lymph node status. Importantly, significant correlations between high Ki-67 expression and clinicopathological features (males, higher tumor stage, poor differentiation) were seen only in Asian NSCLC patients. CONCLUSIONS: The present meta-analysis indicated that elevated Ki-67 expression was associated with a poorer outcome in NSCLC patients, particularly in early-stage Asian ADC patients. Studies with larger numbers of patients are needed to validate our findings.

XPD Functions as a Tumor Suppressor and Dysregulates Autophagy in Cultured HepG2 Cells.

BACKGROUND: Recent clinical studies have linked polymorphisms in the xeroderma pigmentosum group D (XPD) gene, a key repair gene involved in nucleotide excision repair, to increased risk of hepatocellular carcinoma (HCC). However, the cellular effects of XPD expression in cultured HCC cells remain largely uncharacterized. Therefore, the aim of this study was to characterize the in vitro cellular effects of XPD expression on the HCC cell line HepG2. MATERIAL AND METHODS: HepG2 cells were transfected as follows to create four experimental groups: pEGFP-N2/XPD plasmid (XPD) group, EGFP-N2 plasmid (N2) control group, lipofectamine™ 2000 (lipid) control group, and non-transfected (CON) control group. An MTT cell proliferation assay, Annexin V-APC apoptosis assay, colony formation assay, scratch wound migration assay, Transwell migration assay, and Western blotting of the autophagic proteins LC3 and p62 were conducted. RESULTS: XPD expression significantly inhibited HepG2 cell proliferation (p<0.05), significantly promoted HepG2 cell apoptosis (p<0.05), significantly inhibited HepG2 colony formation (p<0.05), significantly decreased HepG2 cells' migratory ability (p<0.05), and significantly lowered HepG2 cells' invasive capacity (p<0.05). Western blotting showed that XPD expression significantly increased LC3 expression (p<0.05) and significantly reduced p62 expression (p<0.05). CONCLUSIONS: XPD expression serves as a tumor suppressor and dysregulates autophagic protein degradation in HepG2 cells in vitro. Further in vivo pre-clinical studies and clinical trials are needed to validate XPD's potential as a tumor-suppressive gene therapy.

Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs. Sorafenib-Everolimus Combination Therapy.

BACKGROUND: Sorafenib-everolimus combination therapy may be more effective than sorafenib monotherapy for hepatocellular carcinoma (HCC). To better understand this effect, we comparatively profiled the metabolite composition of HepG2 cells treated with sorafenib, everolimus, and sorafenib-everolimus combination therapy. MATERIAL AND METHODS: A 2D HRMAS 1H-NMR metabolomic approach was applied to identify the key differential metabolites in 3 experimental groups: sorafenib (5 µM), everolimus (5 µM), and combination therapy (5 µM sorafenib +5 µM everolimus). MetaboAnalyst 3.0 was used to perform pathway analysis. RESULTS: All OPLS-DA models displayed good separation between experimental groups, high-quality goodness of fit (R2), and high-quality goodness of predication (Q2). Sorafenib and everolimus have differential effects with respect to amino acid, methane, pyruvate, pyrimidine, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. The addition of everolimus to sorafenib resulted in differential effects with respect to pyruvate, amino acid, methane, glyoxylate and dicarboxylate, glycolysis or gluconeogenesis, glycerophospholipid, and purine metabolism. CONCLUSIONS: Sorafenib and everolimus have differential effects on HepG2 cells. Sorafenib preferentially affects glycerophospholipid and purine metabolism, while the addition of everolimus preferentially affects pyruvate, amino acid, and glucose metabolism. This phenomenon may explain (in part) the synergistic effects of sorafenib-everolimus combination therapy observed in vivo.

Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts.

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 µmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Interventional embolisation for patients with cirrhosis and recurrent or persistent hepatic encephalopathy related to spontaneous portosystemic shunts: protocol for a prospective, non-randomised controlled study.

INTRODUCTION: The presence of spontaneous portosystemic shunts (SPSS) has been identified to be associated with hepatic encephalopathy (HE) in patients with cirrhosis. Nevertheless, the role of interventional embolisation in managing such patients remains poorly defined. Consequently, this prospective controlled study aims to assess the efficacy and safety of interventional embolisation as a therapeutic approach for patients with cirrhosis and recurrent or persistent HE related to SPSS. METHODS AND ANALYSIS: Cirrhotic patients diagnosed with recurrent or persistent HE associated with SPSS will be recruited for this study, and assigned to either the interventional embolisation group or the standard medical treatment group. The efficacy endpoints encompass the evaluation of postoperative alleviation of HE symptoms and the incidence of overt HE recurrence during the follow-up period, as well as the duration and frequency of hospitalisations for HE, alterations in liver function and volume, and overall survival. The safety endpoints encompass both immediate and long-term postoperative complications. ETHICS AND DISSEMINATION: This study will be conducted in strict adherence to the principles of good clinical practice and the guidelines outlined in the Declaration of Helsinki. Ethical approval for the trial has been obtained from the Ethics Committee of Mengchao Hepatobiliary Hospital of Fujian Medical University (2023_013_02). Written informed consent will be obtained from all the participants by the treating physician for each patient prior to their enrolment. The documented informed consent forms will be retained as part of the clinical trial records for future reference. The study findings will be disseminated through publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300072189.