Search

Background and Aim: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin‐bilirubin (ALBI) grade and low level of des‐gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log‐rank tests with the Kaplan–Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination. [ABSTRACT FROM AUTHOR]

Background and Aim: Molecular‐targeted therapies such as sorafenib and lenvatinib have long been used as first‐line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post‐progression therapy. To investigate the significance of post‐progression therapy, we analyzed the outcomes of aHCC patients following first‐line molecular‐targeted therapy in a real‐world study. Methods: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first‐line therapy between January 2011 and September 2021. Results: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan–Meier analysis revealed no significant differences in progression‐free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis‐4 index, disease control rate, post‐progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post‐progression therapy than in those who did not (log‐rank P < 0.001). Most patients who received an ICI as post‐progression therapy had previously received lenvatinib. Among lenvatinib‐treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post‐progression therapy (P = 0.004). Conclusion: The introduction of newer drugs for post‐progression therapy is expected to prolong survival. ICI‐based regimens appear to be effective after lenvatinib. [ABSTRACT FROM AUTHOR]

Aim: Despite its relevant clinical impact and high prevalence, covert hepatic encephalopathy (HE) still remains underdiagnosed. As patients with liver cirrhosis tend to be older in Japan, more suitable tests for the elderly and cut‐off values based on this attribute are needed. Recently, a Stroop test has been developed and validated for the screening and diagnosis of covert HE in the United States. The present study aims to establish the cut‐off values of the Stroop test to screen covert HE. Methods: This study was a prospective multicenter cross‐sectional endeavor. We undertook a survey of 311 cirrhotic patients, administering the number connection test (NCT)‐A and ‐B and the Stroop‐off and ‐on test. Results: We determined the cut‐off values of Stroop test results for cirrhotic patients in a variety of age ranges. The cut‐off value of the Stroop test was strongly correlated with age. There was a significant correlation between the results of NCT‐B and age, and Stroop‐on test results showed a correlation with serum albumin (Alb) levels. Serum Alb ≤3.2 g/dl could have the potential to be an objective biomarker of covert HE. In addition, stepwise logistic regression analysis revealed a relationship between the results of the Stroop‐on test and plasma ammonia levels. Conclusions: We established the cut‐off values of Stroop test results and confirmed the efficacy of the Stroop test as a simple tool for assessing cognitive alterations. The Stroop test could be suitable as a necessary minimum for the diagnosis of covert HE. [ABSTRACT FROM AUTHOR]

Background: Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE. Methodology/Principal Findings: We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ) (7 days after/before TACE) and Cancer of Liver Italian Program (CLIP) score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively). Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph. Conclusions: The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio) and time-fixed (CLIP score) prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease. [ABSTRACT FROM AUTHOR]

Reduction and glycosylation of benzophenone, which is an endocrine disrupting chemical, were investigated using immobilized marine microalga and plant cells from the viewpoint of bioremediation of benzophenone. Immobilized marine microalga of Chrysocampanulla spinifera reduced benzophenone to diphenylmethanol. Immobilized marine microalga of Amphidinium crassum glucosylated diphenylmethanol to the corresponding glucoside. The sequential biotransformation with C. spinifera and A. crassum effectively converted benzophenone into diphenylmethyl glucoside. On the other hand, immobilized plant cells of Catharanthus roseus transformed benzophenone to diphenylmethanol, diphenylmethyl glucoside, and diphenylmethyl primeveroside, which was a new compound, by one-step biotransformation. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) can develop in patients who are negative for the hepatitis B surface antigen (HBsAg) in serum but positive for hepatitis B virus (HBV) DNA in the liver, referred to as occult HBV infection (OBI). Previous reports showed that HBV variants in OBI-related HCC are different from those in HBsAg-positive HCC. In the present study, HBV quasispecies based on the pre-S/S gene in OBI-related HCC patients were examined by high throughput sequencing and compared with those in HBsAg-positive HCC. Methods: Nineteen tissue samples (9 OBI-related and 10 HBsAg-positive non-cancerous tissues) were collected at the time of surgery at Kobe University Hospital. The quasispecies with more than 1% variation in the pre-S/S region were isolated and analysed by ultra-deep sequencing. Results: There were no significant differences in the major HBV populations, which exhibit more than 20% variation within the entire pre-S/S region, between OBI-related HCC and HBsAg-positive HCC. However, the prevalences of major populations with pre-S2 region mutations and of minor populations with polymerized human serum albumin-binding domain mutations were significantly higher in OBI-related HCC than in HBsAg-positive HCC. Moreover, the major variant populations associated with the B-cell epitope, located within the pre-S1 region, and the a determinant domain, located in the S region, were detected frequently in HBsAg-positive HCC. The minor populations of variants harbouring the W4R, L30S, Q118R/Stop, N123D and S124F/P mutations in the pre-S region and the L21F/S and L42F/S mutations in the S region were detected more frequently in OBI-related HCC than in HBsAg-positive HCC. Conclusions: Ultra-deep sequencing revealed that the B-cell epitope domain in the pre-S1 region and alpha determinant domain in the S region were variable in HBsAg-positive HCC, although the quasispecies associated with the pre-S2 region were highly prevalent in OBI-related HCC. Trial registration: Ref: R000034382/UMIN000030113 ; Retrospectively registered 25 November 2017. [ABSTRACT FROM AUTHOR]

Background: Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. Objectives: We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. Patients and Methods: We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. Results: Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). Conclusions: NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis. [ABSTRACT FROM AUTHOR]