Background: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. Methods: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. Results: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin–bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child–Pugh C. Conclusions: The long-term rifaximin treatment was effective and safe for patients with HE, including Child–Pugh C.

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

Background/Aim: Surgical resection remains the only curative treatment for combined hepatocellular-cholangiocarcinoma; however, systemic therapy is the primary treatment option for unresectable cases. This multicenter retrospective study aimed to assess the efficacy of systemic therapy for unresectable combined hepatocellular-cholangiocarcinoma. Patients and Methods: Twenty-one patients with histologically confirmed or clinically diagnosed combined hepatocellular-cholangiocarcinoma who received systemic therapy were included. First-line regimens consisted of lenvatinib (n=14) and atezolizumab plus bevacizumab (n=7) and their therapeutic efficacy was evaluated. Results: The objective response and disease control rates were 42.9% and 92.9% for lenvatinib, and 14.3% and 100% for atezolizumab plus bevacizumab, respectively. Median overall survival for all treatments was 14.9 months and median progression-free survival was 6.5 months. By regimen, median overall and progression-free survival was 14.9 and 6.1 months for lenvatinib, and “not reached” and 7.9 months for atezolizumab plus bevacizumab, respectively. Conclusion: Lenvatinib and atezolizumab plus bevacizumab exhibited potential activity in patients with combined hepatocellular-cholangiocarcinoma.

Background/Objectives: Rifaximin is a therapeutic agent for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Japanese patients with cirrhosis. The effects and safety of 3-year rifaximin treatment on HE was investigated in Japan. Methods: A total of 190 Japanese patients with cirrhosis who were continuously administered rifaximin for more than 1 year suffered overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative overt HE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occurrence of adverse events was also assessed. Results: The levels of ammonia improved significantly after 3 months of rifaximin administration, which continued for 3 years. Serum albumin and prothrombin activity also significantly improved 3 years after initiation of rifaximin treatment. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin administration. Only three (1.6%) patients discontinued rifaximin therapy because of severe diarrhea after 1 year of rifaximin administration. No other serious adverse events were observed. Conclusions: Three years of continuous rifaximin (RFX) treatment was both effective and safe for patients with hepatic encephalopathy. Liver function improved and did not worsen during treatment.

Previous studies have reported prognostic factors for hepatocellular carcinoma (HCC) patients receiving lenvatinib; however, no studies have evaluated the effects of both handgrip strength and skeletal muscle mass on the clinical outcomes. Therefore, this retrospective study investigated the individual effect of handgrip strength, skeletal muscle mass, and sarcopenia on clinical outcomes of 53 HCC patients treated with lenvatinib. Before receiving lenvatinib, handgrip strength and skeletal muscle index (SMI) were measured. Low handgrip strength and muscle depletion were defined as <26 and <18 kg and SMI <42 and SMI <38 cm²/m² in men and women, respectively. Sarcopenia was defined as having low handgrip strength and muscle depletion. Multivariate analysis identified modified albumin–bilirubin grade 1–2a (p = 0.010), Barcelona Clinic Liver Cancer stage A–B (p = 0.011), and absence of low handgrip strength (p = 0.015) as favorable prognostic factors for survival. Furthermore, sarcopenia was an independent significant prognostic factor for survival. Time to treatment failure was associated with handgrip strength and sarcopenia. Our findings suggest that handgrip strength may be a useful marker of clinical outcomes in HCC patients treated with lenvatinib.

Background & Aims: Despite the advances in systemic therapy for unresectable hepatocellular carcinoma (HCC), patients with Child–Pugh class B (CP‐B) liver function face a significant unmet need. This study evaluated the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) in patients with unresectable HCC and CP‐B. Methods: This retrospective study included 796 patients who received Atez/Bev between October 2020 and July 2024 from 10 institutions in Japan. The median observation period was 14.6 months. The liver function was assessed using the CP classification and modified ALBI (mALBI) grade. The progression‐free survival (PFS), overall survival (OS) and median survival time (MST) were evaluated. Results: Patients with CP‐B had significantly shorter PFS and OS than those with CP‐A (median PFS, 4.6 months vs. 7.0 months; MST, 10.3 months vs. 23.2 months) (PFS, p = 0.009; OS, p < 0.001). Although CP‐B was associated with a higher incidence of bleeding‐related events, the discontinuation rate due to adverse events did not differ from that of CP‐A. As a factor for stratifying CP‐B outcomes, significant differences in the PFS, OS and response rate were observed between mALBI grades ≤ 2b and 3 (PFS, p = 0.004; OS, p = 0.024; response rate, p = 0.001). In multivariate analysis, the mALBI grade (hazard ratio [95% CI]: 2.388 [1.186–4.810]; p = 0.014) was extracted as a factor contributing to OS in patients with CP‐B. Conclusion: Atez/Bev therapy demonstrated efficacy and safety in patients with CP‐B, especially when hepatic reserve is maintained within mALBI grade 2b.