Hironori Tanaka

Aim: Patients with chronic liver disease often experience significant physical, psychological, and financial burdens. These burdens result from repeated long‐term hospital visits or admissions caused by progression to decompensated cirrhosis or hepatocellular carcinoma. Patients with viral liver disease may fear discrimination or social prejudice. This study aimed to clarify the employment status of patients with liver disease in Japan and provide basic data to promote support for balancing treatment and work responsibilities. Methods: A cross‐sectional questionnaire survey on employment was conducted among patients attending 22 hospitals across Japan. Results: Of the 4022 respondents, 2183 were analyzed, including 1694 (77.6%) participants with liver disease. Patients with liver disease were predominantly male and in their 60 s. Disclosure of health information to the workplace was significantly lower among patients with viral liver disease (80.8%) than among those without liver disease or with nonviral liver disease. The intention to continue working after diagnosis was significantly higher among patients with malignancies than among those without. However, this intention did not significantly differ between liver disease and non‐liver disease groups. The awareness rate of the support system for balancing treatment and work program was 27.1%, with no significant difference observed between the liver disease and malignancy groups. Awareness was significantly higher in large workplaces, where full‐time occupational health physicians are mandated. Conclusion: Workers with viral liver disease may hesitate to disclose their condition owing to fear of discrimination or prejudice. Therefore, raising awareness of support systems that protect all workers with illnesses, while considering stigma and discrimination, is essential.

Aim: This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real‐world clinical practice, characterize “stable disease (SD),” and identify SD responders (SD‐R) who benefit from Dur + Tre treatment.Methods: This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u‐HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first‐line and 117 later‐line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression‐free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.Results: Disease control rate (DCR) and PFS were significantly better in the first‐line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤–10% were classified as SD‐R, as they had long‐term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD‐R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD‐R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).Conclusions: In real‐world clinical practice, Dur + Tre is highly effective as a first‐line treatment for u‐HCC. Additionally, patients with SD who met the SD‐R criteria (PFS ≥84 days or RECIST DOR ≤−10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.

Aim: This study aimed to evaluate the prognostic impact of muscle volume changes during atezolizumab‐bevacizumab (AB) combination therapy (AB therapy) for unresectable hepatocellular carcinoma (u‐HCC). Additionally, we evaluated whether changes in muscle volume relate to prognosis based on treatment response. Methods: The present retrospective, multicenter study included 165 patients with u‐HCC treated with AB therapy at eight institutions. Results: The median albumin–bilirubin score in the entire cohort was −2.42. The objective response rate was 31.5%, and the disease control rate was 80.6%. The median overall survival (OS) was not reached, whereas the median progression‐free survival (PFS) was 6.9 months (95% confidence interval [CI]: 5.3–8.5). At the first post‐treatment computed tomography scan, patients were categorized into two groups: those with a nondecreased psoas muscle area index (PI) (group A) and those with a decreased PI (group B). The median OS was not reached in either group ( p = 0.059). The median PFS was 10.5 months in group A and 5.5 months in group B ( p = 0.025). Multivariate analysis using the Cox proportional hazards model identified alpha‐fetoprotein ≥400 ng/mL (hazard ratio [HR]: 1.68; 95% CI: 1.11–2.54; p = 0.01) and decreased PI (HR: 1.59; 95% CI: 1.07–2.36; p = 0.02) as factors associated with PFS. Conclusions: Nondecreased muscle volume after initiating AB therapy was associated with improved treatment efficacy and prognosis in patients with u‐HCC.

Background and Aims: We aimed to evaluate the efficacy and safety of durvalumab plus tremelimumab (Dur + Tre) combination therapy in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice.Methods: We retrospectively evaluated 37 patients with uHCC from our institutions between April 2023 and January 2024. Patients were divided into first‐ and later‐line groups for analysis of antitumor efficacy, adverse events (AEs), and transition rate to second‐line treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST).Results: The disease control rate (DCR) for the first‐line group was 80.9%, which was significantly higher than that for the later‐line group (50%). The incidence of immune‐related AEs (irAEs) was 24.3%, with grade 3 or higher irAEs including increased transaminase (8.1%), diarrhea (8.1%), and adrenal insufficiency (2.7%). The rates of drug withdrawal and discontinuation owing to AEs were 23.8% and 19%, respectively, in the first‐line treatment and 31.2% and 12.5%, respectively, in the later‐line treatment, with no significant difference. Analysis of changes in liver reserve using the albumin–bilirubin (ALBI) score showed no obvious loss of liver reserve for up to 12 weeks. The transition rate from first‐ to second‐line therapy after progressive disease (PD) was as high as 94.7%.Conclusion: The efficacy and safety of Dur + Tre in clinical practice were comparable to those reported in a recent phase III trial. The first‐line Dur + Tre therapy had a higher DCR than that of the later lines, and the transition rate to second‐line therapy was considerably high, suggesting that Dur + Tre therapy would be more beneficial in first‐line treatment.

This retrospective multicenter study analyzed 244 patients with unresectable hepatocellular carcinoma treated with lenvatinib (LEN) and atezolizumab + bevacizumab (Atezo + Bev) to examine the characteristics, treatment courses, and prognoses. The cases of patients who could achieve HCC downstaging from Barcelona Clinic Liver Cancer (BCLC) stage B or C to A or zero indicated the need for conversion therapy. The patients’ prognoses with and without conversion therapy were compared. Of the 244 patients, 12 (4.9%) underwent conversion therapy, six out of 131 (4.6%) were treated with LEN, and six out of 113 (5.3%) were treated with Atezo + Bev. Eleven patients (91.7%) with a modified albumin bilirubin (mALBI) grade 1 or 2a and BCLC-B stage showed significantly higher rates of transition during conversion therapy (p < 0.05). The patients undergoing conversion therapy had a significantly longer median overall survival rate than those receiving chemotherapy alone (1208 [1064–NA] vs. 569 [466–704] days, p < 0.01). A comparison of the patients who achieved a partial response with and without conversion was evaluated using propensity score matching to reduce the confounding factors, showing a significant survival benefit in the conversion group (1208 [1064–NA] vs. 665 days, p < 0.01). Among the patients with u-HCC who were treated with LEN and Atezo + Bev, those with mALBI 1 + 2a and BCLC-B were likely to achieve conversion therapy with downstaging.

Purpose In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause. Methods The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia. Results The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy (p < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37–3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy (p < 0.01, HR 2.73, 95% CI 1.29–5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy (p = 0.01, HR 3.44, 95% CI 1.25–9.48). Conclusions Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy.

The influence of changes in alcohol consumption on erosive esophagitis (EE) development in both sexes is unclear. This observational study investigated sex differences in the influence of alcohol consumption on EE development, and included 2582 patients without EE at baseline from 13,448 patients who underwent >2 health check-ups over >1 year. The rates of non-drinkers who started drinking, and drinkers who abstained from drinking, who increased, and who decreased their weekly alcohol consumption were 7.2%, 9.7%, 14.7%, and 24.1% and 7.3%, 17.8%, 12.8%, and 39.0% in men and women, respectively. In the final cohort, 211/1405 (15.0%) men and 79/1177 (6.7%) women newly developed EE. The odds ratio (OR) for drinking in EE development was 1.252 (95% confidence interval (CI), 0.907–1.726) among men and 1.078 (95% CI, 0.666–1.747) among women. Among men aged <50 years, the OR for drinking ≥70 g/week in EE development was 2.825 (95% CI, 1.427–5.592), whereas among women, the OR for drinking ≥140 g/week in EE development was 3.248 (95% CI, 1.646–6.410). Among participants aged <50 years, the OR for daily drinking in EE development was 2.692 (95% CI, 1.298–5.586) among men and 4.030 (95% CI, 1.404–11.57) among women. The influence of alcohol consumption on EE development differed between the sexes. We recommend no alcohol consumption for individuals aged <50 years to avoid EE development. Daily drinkers should be assessed for EE development.

Aim: Cabozantinib (CAB), a multiple kinase inhibitor, has been approved for use in patients with previously treated unresectable hepatocellular carcinoma (uHCC). However, real‐world clinical data are lacking, particularly clinical data regarding dose modifications of CAB. We analyzed the clinical outcomes of CAB in uHCC and compared treatment outcomes between the full‐ and reduced‐dose groups.Methods: This multicenter, observational study included patients with uHCC who were treated with CAB from March 2021 to April 2022. Patient characteristics, efficacy, and safety were compared between the full‐ and reduced‐dose groups.Results: Twenty‐six patients from eight institutes were analyzed. Cabozantinib was administered as a third‐line or later treatment in 25 (96.2%) patients and postimmunotherapy in 21 (80.5%) patients. There were 15 patients in the full‐dose group (60 mg CAB) and 11 in the reduced‐dose group (40 or 20 mg CAB). The objective response rate (ORR) and disease control rate (DCR) were not significantly different between the two groups. The ORR was 6.7% for the full‐dose group and 9.1% for the reduced‐dose group, and the DCR was 53.4% and 81.8%, respectively. Progression‐free survival analysis showed no significant differences between the two groups. The incidence of decreased appetite, fatigue, and diarrhea, and the rate of discontinuation and dose reduction, was significantly higher in the full‐dose group.Conclusions: Our study suggests that the efficacy and safety of CAB in real‐world clinical practice are comparable to those of the phase III trial (CELESTIAL), and that dose reduction of CAB may be a safer treatment option.

Aim: We analyzed the association between the modified albumin–bilirubin (mALBI) grade and therapeutic efficacy of atezolizumab plus bevacizumab (Atezo+Bev) for the treatment of unresectable hepatocellular carcinoma (u‐HCC).Methods: In this retrospective observational study, we included 71 u‐HCC patients treated with Atezo+Bev between September 2020 and September 2021. Patients were grouped corresponding to the mALBI grade at the start of treatment (mALBI 1+2a or mALBI 2b+3) and analyzed for therapeutic effect and the transition rate to secondary treatment.Results: According to the Response Evaluation Criteria in Solid Tumors, the overall response rate was significantly higher for the mALBI 1+2a group, than for the mALBI 2b+3 group, with 26.2% and 3.4%, respectively. The progression‐free survival (PFS) was significantly longer in the mALBI 1+2a group (10.5 months) than in the mALBI 2b+3 group (3.0 months). In the multivariate analysis, an mALBI of 1+2a was found to be an independent factor of PFS. The rate of second‐line treatment with multi‐targeted agents was also significantly higher in the mALBI 1+2a group.Conclusions: In real‐world practice, Atezo+Bev treatment might have higher therapeutic efficacy in u‐HCC patients with mALBI 1+2a.

Aim: To investigate the therapeutic effect of lenvatinib (LEN) in liver disease etiology, especially nonviral hepatocellular carcinoma (HCC).Methods and Results: Sixty‐seven patients with unresectable advanced HCC (u‐HCC) treated with LEN and consisting of 26 hepatitis C virus (HCV), 19 hepatitis B virus (HBV), 11 alcohol, and 11 nonalcoholic steatohepatitis (NASH) cases were retrospectively recruited. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for survival. The objective response rate in the nonviral (alcohol and NASH) group was higher than that in the viral group (59.1% [13/22] vs. 46.7% [21/45]). Progression‐free survival was significantly longer in the nonviral group than in the viral group (13.7 vs. 6.6 months; hazard ratio [HR] 0.324; 95% confidence interval [CI] 0.174–0.602; P < 0.01). Similarly, median overall survival (OS) was significantly longer in the nonviral group than in the viral group (not evaluable vs. 15.9 months; HR = 0.277; 95% CI = 0.116–0.662; P < 0.01). Multivariate analysis revealed that portal vein invasion (HR = 5.327, P = 0.0025), treatment line (HR = 0.455, P = 0.023), and etiology (HR = 0.180, P = 0.00055) were significant independent factors associated with OS in u‐HCC patients treated with LEN.Conclusion: Our results suggest that LEN is more effective against nonviral u‐HCC than against viral u‐HCC.