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.

We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09–1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04–2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.

Cabozantinib (CAB) causes a high incidence of adverse events in unresectable hepatocellular carcinoma (u-HCC) and requires dose adjustments. We evaluated the efficacy and safety of the 7-on/7-off regimen composed of 7 consecutive days’ administration of CAB followed by a 7-day rest period. This was a retrospective analysis of 35 patients with u-HCC, who were treated with CAB in a multicenter cohort in Japan from 2020 to 2024. The clinical outcomes of 12 patients treated with the 7-on/7-off regimen and 23 patients treated with daily dosing were compared. There were significant differences in overall survival (12.4 months vs. 6.3 months, p = 0.03), median progression-free survival (4.8 months vs. 3.2 months, p < 0.01), objective response rate (16.7% vs. 0.0%, p = 0.04), and incidence of any adverse events (75.0% vs. 100.0%, p = 0.03) between the 7-on/7-off regimen group and daily dosing group. The median duration of drug exposure (122 days vs. 42 days, p < 0.01) and median duration of dose reduction (100 days vs. 23 days, p < 0.01) were prolonged significantly in the 7-on/7-off group than in the daily dosing group. CAB in a 7-on/7-off regimen may improve the tolerability and treatment response in patients with u-HCC.