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Abstract Background and Objective Durvalumab plus tremelimumab (Durva/Treme) has recently been approved as a first-line or later-line treatment for patients with unresectable hepatocellular carcinoma (u-HCC) in Japan. We assessed the real-world outcomes of Durva/Treme for u-HCC, with a focus on treatment efficacy and safety. Methods We retrospectively evaluated 22 patients with u-HCC treated with Durva/Treme at Iwate Medical University during the period from 2023 to 2024, with a comparison of the clinical outcomes between patients who received Durva/Treme as first-line and later-line treatments. We further evaluated changes in the modified albumin-bilirubin (mALBI) grade during treatment. Results There were 10 patients in the first-line group and 12 patients in the later-line treatment group. During the follow-up with a median duration of 7.6 months, the median progression-free survival (first-line versus later-line: 4.7 months versus 2.9 months, p = 0.85), the objective response rate (0.0% versus 16.7%, p = 0.48), the disease control rate (60.0% versus 58.4%, p = 1.00), and the incidence of any adverse event (50.0% versus 75.0%, p = 0.38) were not statistically different between the two groups. The changes in the mALBI scores were not statistically significant (p = 0.75). Conclusions Durva/Treme may be effective and safe for patients with u-HCC, even in patients who receive Durva/Treme as a later-line treatment.

Background & Aims: Radiofrequency ablation (RFA) is the standard treatment for small hepatocellular carcinoma (HCC), specifically for tumors

Purpose The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)–derived proton density fat fraction (MRI-derived PDFF) as the reference standard. Methods Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. Results AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P

Abstract Aim This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. Methods We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity‐score‐matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed‐effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow‐up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. Results Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were −2.41 ± 0.40 and −2.44 ± 0.42 at baseline, and −2.17 ± 0.56 and −2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p

Abstract It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (− 0.0086253) × age + (− 0.34667) × (naïve/recurrence) + (− 0.034962) × (number of nodules) + (− 0.079447) × (the size of the largest nodule) + (− 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (− 0.00014741) × (α-fetoprotein)) × (− natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.

Abstract Aim Multiple studies have revealed the correlation between gut microbiome and the response to checkpoint inhibitors (CPIs) in patients with cancer, and oral administration of butyrate‐producing enterobacteria has been reported to enhance the efficacy of CPIs. However, the effects of enterobacteria on patients with hepatocellular carcinoma (HCC) are not well understood. Methods In this retrospective multicenter study, we enrolled 747 patients with advanced HCC, treated with atezolizumab and bevacizumab combination therapy. Tumor response, survival, and adverse effects were compared between 99 patients who ingested drugs containing butyric acid‐producing enterobacteria (butyric acid group) and the remaining patients (control group). Results Objective response and disease control rates in butyric acid group (29.7% and 77.8%, respectively) were higher than those in the control group (26.4% and 72.7%, respectively). However, the differences were not statistically significant (p = 0.543 and p = 0.222, respectively). No difference in median survival time was observed between the two groups (20.0 months and 21.4 months, respectively; p = 0.789), even after matching the backgrounds of the patients with propensity scores (p = 0.714). No adverse effects occurred upon the administration of butyrate‐producing bacteria. However, proteinuria (41.4% vs. 30.9%; p = 0.041), fever (17.2% vs. 10.2%, p = 0.036), and diarrhea (15.2% vs. 6.2%; p = 0.001) occurred more frequently in the butyric acid group. Conclusion Butyrate‐producing bacteria does not enhance the efficacy of atezolizumab–bevacizumab combination therapy in patients with HCC.

Abstract Aims The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. Methods A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression‐free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c‐index) and Akaike information criterion (AIC) results. Results Cox‐hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI‐De) scoring system. For IMABALI‐De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p

Background and Aims: Acute liver injury (ALI) due to autoimmune hepatitis (AIH) can be treated by immunosuppression. In contrast, idiosyncratic drug-induced liver injury (DILI) had a poor prognosis. DILI thus needs to be distinguished from non-DILI. Methods: Twenty-nine patients with DILI and 77 with non-DILI (42 of AIH and 35 with undetermined cause) diagnosed during 2005–2017 comprised the derivation cohort. 110 patients with ALI due to either AIH, DILI, or obscure causes at 6 liver centers during 2010–2015 were the validation cohort. Revised international AIH group scores (IAIHGs) and the Roussel-Uclaf Causality Assessment Method (RUCAM) were modified to calculate results using medical interviews and laboratory data without chronological changes. Diagnostic accuracy for the distinction of DILI and non-DILI was evaluated by receiver operating characteristic analysis and results were expressed as the area under the curve (AUC). This study received institutional institutional review board approval (MH2020-205). Results: The AUCs of modified IAIHGs and RUCAM scores for the diagnosis of DILI were 0.96 and 1.00 when cut-off values were set at 3 for the modified RUCAM and 5 for the modified IAIHGs in the derivation cohort. In the validation cohort, the AUCs of modified IAIHGs and RUCAM scores for the diagnosis of DILI were 0.95 and 0.97, respectively. The accuracy of the combination of the modified scores was 81% (89/110). Conclusion: Modified diagnostic scores based on detailed medical interviews and routine laboratory data can distinguish DILI from non-DILI in patients with ALI.

Abstract Sarcopenia is a common complication in patients with chronic liver disease (CLD); however, the progression of sarcopenia over the course of CLD is unclear. The present study therefore determined the natural course of the progression of sarcopenia in patients with CLD and the effect of liver cirrhosis (LC) on this progression. This observational study analyzed patients with chronic hepatitis (CH) (n = 536) and LC (n = 320) who underwent evaluations of the grip strength and skeletal muscle mass of the arms, trunk, and legs for sarcopenia between 2016 and 2021. A bioelectrical impedance analysis was used to evaluate skeletal muscle mass. The annual rate of change (%/year) in two tests were compared between patients with CH and LC. The annual rates of change in grip strength and skeletal muscle of arms, trunk, and legs of patients with CH and LC were − 0.84% vs. − 2.93%, − 0.54% vs. − 1.71%, − 0.43% vs. − 1.02%, and − 0.76% vs. − 1.70% for men and − 0.12% vs. − 1.71%, − 0.66% vs. − 1.71%, − 0.49% vs. − 1.31%, and − 0.76% vs. − 1.54% for women, respectively. The progression of sarcopenia was greater in LC patients than in CH patients and that the decrease in grip strength was most prominent in the progression of sarcopenia in patients with LC.

Abstract Sarcopenia is associated with poor prognosis of patients with hepatocellular carcinoma (HCC). We investigated the association of skeletal muscle volume (SMV) and its change in HCC patients taking lenvatinib. In 130 HCC patients, psoas mass index (PMI) was calculated as the left–right sum of the major × minor axis of psoas muscle at the third lumbar vertebra, divided by height squared. Patients were classified into two groups (low and normal PMI) based on indices of

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or super selective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, super selective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and three patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Discussion/Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

Objective: There is limited information regarding the benefits of Lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for unresectable hepatocellular carcinoma (u-HCC). We compared the efficacy and safety of LEN-TACE sequential therapy to LEN monotherapy and investigated the factors contributing to the LEN-TACE sequential therapy deep response. Methods: We enrolled a multi-center cohort of 247 patients with u-HCC treated with LEN between 2018 and 2020. Propensity score matching identified sixty-three matching pairs of patients with well-balanced characteristics. We retrospectively compared the clinical outcomes, including overall survival (OS), progression-free survival (PFS), and incidence of adverse events (AEs), between the LEN-TACE and LEN monotherapy groups. Additionally, we evaluated the tumor response, change in albumin-bilirubin (ALBI) score, factors affecting PFS and OS, and independent predictors contributing to the LEN-TACE sequential therapy deep response. In this study, at eight weeks after resumption of LEN after initial TACE, "deep response" was defined as achieving CR or PR on mRECIST, and at least a 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters as the reference. Results: The OS and PFS in the LEN-TACE group were significantly higher than those in the LEN monotherapy group (P = 0.002 and P = 0.037, respectively). The incidence of AEs related to LEN was not significantly different between the two groups. In LEN-TACE sequential therapy, the objective response rate was 61.9%, and the disease control rate was 74.6%, according to the mRECIST criteria. No significant change in the ALBI score was observed during sequential LEN-TACE therapy. Multivariable analyses revealed that deep response was independently associated with the outcome of the initial response to LEN by mRECIST: PR (odds ratio: 13.75, 95% CI: 0.41–1.32, P

AimWe aimed to analyze the dispersion slope (DS) using shear wave dispersion (SWD) in patients with Fontan-associated liver disease (FALD) and to investigate its utility as a biomarker of disease progression.MethodsThis cross-sectional study enrolled 27 adults with FALD who underwent SWD, two-dimensional shear wave elastography (2D-SWE), transthoracic echocardiography, cardiac catheterization, or abdominal computed tomography (CT) from April 2019 to April 2021. According to CT findings, patients were divided into two groups: significant fibrosis and non-significant fibrosis.ResultsThe median DS in the control (n = 10), non-significant fibrosis (n = 12), and significant fibrosis (n = 15) was 9.35, 12.55, and 17.64 (m/s)/kHz, respectively. The significant fibrosis group showed a significantly higher DS than non-significant fibrosis group (P = 0.003). DS showed a significant correlation with central venous pressure (r = 0.532, P = 0.017) and liver stiffness measurements using 2D-SWE (r = 0.581, P = 0.002). The areas under the receiver operating characteristic curve for the diagnosis of significant fibrosis were 0.903 and 0.734 for SWD and 2D-SWE, respectively (P = 0.043).ConclusionsDS measured by SWD reflects the severity of liver damage in patients with FALD. SWE may be valuable for the therapeutic management of patients with FALD.

Background & Aims: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. Methods: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. Results: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF >5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF ≥-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). Conclusions: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa). [ABSTRACT FROM AUTHOR]