Hung-Wei Wang

Introduction: Atezolizumab plus bevacizumab (Atezo+Bev) is the most widely used first-line treatment for unresectable hepatocellular carcinoma (HCC), while lenvatinib remains a standard alternative. Previous studies suggest limited efficacy of Atezo+Bev in patients with HCC exhibiting a CRAFITY score of 2 (CRP ≥1 mg/dL and AFP ≥100 ng/mL). We conducted an international collaborative study to compare the efficacy of Atezo+Bev and lenvatinib stratified by the baseline CRAFITY score. Methods: We retrospectively analyzed 994 patients who initiated Atezo+Bev or lenvatinib as first-line therapy for unresectable HCC between September 2017 and March 2024 across 11 hospitals in Japan and 13 hospitals in Taiwan. Patients were categorized by baseline CRAFITY score, and progression-free survival (PFS) and overall survival (OS) were compared between treatment groups. Results: The median age of the patients was 71 years, and 770 (77.5%) were male. The baseline CRAFITY score was 0 in 375 patients (37.7%), 1 in 402 patients (40.4%), and 2 in 217 patients (21.8%). In patients with a CRAFITY-0 score, median PFS (10.8 vs. 9.4 months; p = 0.548) and OS (21.1 vs. 29.3 months; p = 0.074) did not differ significantly between Atezo+Bev and lenvatinib. Similar findings were observed in CRAFITY-1 patients, with median PFS of 6.0 vs. 6.1 months (p = 0.943) and OS of 12.7 vs. 15.1 months (p = 0.168). In contrast, among CRAFITY-2 patients, lenvatinib was associated with significantly longer PFS (2.3 vs. 4.4 months; hazard ratio, 0.66; p = 0.017), while OS did not differ significantly between treatments (5.7 vs. 9.1 months; hazard ratio, 0.90; p = 0.586). A significant interaction was observed between CRAFITY score (0/1 vs. 2) and treatment regimen (Atezo+Bev vs. lenvatinib) for PFS (p = 0.002). Consistent findings were observed in adjusted analyses. Conclusion: Lenvatinib was associated with significantly longer PFS than Atezo+Bev in patients with a baseline CRAFITY score of 2. The CRAFITY score may be useful for identifying patients in whom lenvatinib could be considered as a first-line option, and prospective validation is warranted.

Introduction: Evidence supporting the combination of immunotherapy with intra-arterial therapy (IAT) for unresectable hepatocellular carcinoma (HCC) remains limited. This study aimed to evaluate whether the addition of IAT to first-line immunotherapy improves survival outcomes. Methods: Using the Taiwan Liver Cancer Association (TLCA) Research Group database, we identified patients with unresectable HCC who initiated first-line immunotherapy between May 2017 and January 2024. Patients with Barcelona Clinic Liver Cancer (BCLC) stage A or D disease, prior liver transplantation, or follow-up of 1 (aHR 1.58, 95% CI: 1.11–2.27; p = 0.012), tumor burden beyond the up-to-7 criteria (aHR 1.67, 95% CI: 1.02–2.74; p = 0.043), and portal vein invasion (aHR 1.67; 95% CI: 1.19–2.35; p = 0.003). Five-year OS was higher in the IAT group than in the control group (28.7% [95% CI: 17.8–46.2] vs. 16.4% [95% CI: 10.7–25.2]; p = 0.007). Landmark and subgroup analyses consistently supported the OS benefit of IAT. Conclusion: In unresectable HCC, the addition of IAT to first-line immunotherapy improves response rates, prolongs the duration of response, and enhances OS.

Chronic hepatitis B (CHB) is a major cause of hepatocellular carcinoma (HCC). In patients receiving CHB treatment, coexistence of steatotic liver disease (SLD) and cardiometabolic risk factors (CMRFs) markedly influence HCC risk. This study explored hepatic and metabolic profiles, HCC predictors, and the modifying roles of SLD and CMRFs in CHB. This study included 1012 patients receiving nucleos(t)ide analogs between 2004 and 2022. They were stratified into SLD (N = 702) or non-SLD (N = 310) groups. Over a 5.5-year follow-up period, 73 patients developed HCC. At baseline, the SLD group had younger age, higher body mass index values, lower fibrosis indices, and more severe metabolic dysregulation than did the non-SLD group. SLD conferred protection against HCC (adjusted hazard ratio: 0.43; p = 0.001). However, the presence of ≥2 CMRFs significantly increased HCC risk (adjusted hazard ratio: 1.93; p = 0.009). The highest HCC risk was observed in patients without SLD having ≥2 CMRFs (5-year incidence rate: 21.4%). The protective effect of SLD persisted after inverse probability of treatment weighting. It was most pronounced in older, cirrhotic, and high-metabolic-risk subgroups. Hepatitis B virus DNA suppression, hepatitis B surface antigen decline, and fibrosis score improvement during treatment were similar between the two groups. Among patients with CHB receiving nucleos(t)ide analogs, those without SLD having ≥2 CMRFs had the highest risk of HCC. Thus, steatosis and metabolic burden should be incorporated into precision risk stratification.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of hepatocellular carcinoma (HCC). Whether structured, incentive-based diabetes care programmes reduce HCC incidence remains uncertain. We examined the association between participation in Taiwan’s nationwide diabetes pay-for-performance (P4P) programme and incident HCC among patients with T2DM.Methods: We conducted a nationwide, retrospective cohort study using Taiwan’s National Health Insurance Research Database (2008–2021). Adults with newly diagnosed T2DM were classified by P4P participation. P4P participants were propensity score–matched 1:1 with non-participants by age, sex, comorbidities, medications, and index year. The primary outcome was incident HCC. Associations were estimated using Cox proportional hazards models, Fine–Gray competing risk models, and inverse probability of treatment weighting (IPTW).Findings: The study included 1 931 750 adults with newly diagnosed T2DM (965 875 P4P participants and 965 875 matched non-participants). Over a mean follow-up of 4·77 years, 22 877 HCC cases were identified. HCC incidence was lower among P4P participants than non-participants (2·18 vs 2·88 per 1000 person-years). P4P participation was consistently associated with reduced HCC risk across analytic approaches (aHR 0·70, 95% CI 0·68–0·72; aSHR 0·70, 0·68–0·72; IPTW aHR 0·70, 0·68–0·71; all p<0·001).Interpretation: Participation in a nationwide diabetes P4P programme was associated with a lower risk of hepatocellular carcinoma among patients with T2DM, supporting the potential role of structured, performance-based diabetes care in liver cancer prevention.