AIM:Evidence regarding the optimal first-line immune checkpoint inhibitor (ICI) regimen for treating unresectable hepatocellular carcinoma (uHCC) with Child-Pugh class B (CP-B) liver function remains limited. This study compared atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre group) in real-world settings. METHODS:In this multicenter retrospective study, 211 consecutive patients with uHCC and CP-B liver function who underwent ICI-based therapy as a first-line therapy were analyzed. Treatment responses, survival outcomes, albumin-bilirubin (ALBI) score changes, and adverse events were evaluated. Survival analyses were adjusted using inverse probability weighting (IPW). RESULTS:The median progression-free survival associated with the Atez/Bev and Dur/Tre regimens was 5.0 and 3.5 months, respectively; the median corresponding overall survival was 10.5 and 12.4 months. After IPW adjustment, no significant differences were observed in progression-free or overall survival. The Atez/Bev regimen-associated disease control rate was significantly higher (75.2% vs. 55.0%, p = 0.02). The Dur/Tre regimen, meanwhile, was associated with a significantly higher immune-related adverse event incidence (10.5% vs. 32.7%, p < 0.01) and a greater need for high-dose corticosteroid treatment. In contrast, the Atez/Bev regimen resulted in a progressive decrease in ALBI scores, whereas the Dur/Tre regimen maintained the hepatic functional reserve. CONCLUSIONS:The Atez/Bev and Dur/Tre regimens afforded comparable survival outcomes but differed substantially in safety and effects on the hepatic functional reserve. Given the trade-off between immunotoxicity and liver function preservation, treatment selection for CP-B liver function should be individualized, considering baseline hepatic reserve, tolerability, and anticipated treatment trajectory.
BACKGROUND/AIM:In hepatocellular carcinoma (HCC), portal hypertension (PHT) during the advanced stages of cirrhosis leads to splenomegaly. Additionally, the immune environment is an important factor in HCC treatment. Splenectomy and partial splenic embolization (PSE) are expected to improve this condition; however, data on the effects of PSE on immune function are limited. Therefore, we investigated the effects of PSE on the immune environment and hepatic function in patients with PHT-related cirrhosis. PATIENTS AND METHODS:The study included 117 of 238 patients who underwent PSE for PHT at our Department between 2011 and 2024 and were followed-up for more than 12 months, excluding those who underwent additional procedures concurrent with PSE. Changes in blood cell counts, hepatic function and immunological parameters including the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio, were examined. RESULTS:The mean splenic volume, mean splenic infarction volume, and splenic infarction rate were 396.64 ml, 222.8 ml, and 58.6%, respectively. The preoperative splenic volume was inversely correlated with platelet and lymphocyte counts. The platelet count increased from 7.3 to 10.4 at 1 year; the platelet-albumin-bilirubin score improved from -2.38 to -2.49 (p<0.01); the fibrosis-4 index improved from 6.02 to 4.69 (p<0.01); the albumin-bilirubin score improved from -2.10 to -2.27 (p<0.01); and the NLR improved from 2.49 to 2.25 (p=0.028). Additionally, analysis of the background liver revealed improvements in platelet count and NLR. CONCLUSION:PSE not only improved platelet counts, but also increased lymphocyte counts and improved the NLR. PSE-induced improvements in the immune environment may be useful for introducing combination immunotherapy for HCC.
AimThis study aimed to compare the prognostic performance of the risk models for patients with hepatocellular carcinoma (HCC) receiving atezolizumab and bevacizumab (Atez/Bev) as first-line treatment.MethodsAmong 449 patients included in this retrospective multicenter study, we compared the prognostic performance of 13 risk models for the 12-month and 18-month survival status using area under the curve (AUC), net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) analysis. We also constructed a calibration plot to assess the fitness of each model.ResultsRegarding the analysis of the 12-month survival status, none of the risk models demonstrated AUC values higher than the modified albumin-bilirubin (mALBI) grade. In the NRI analysis, only the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De score) exhibited a statistically significant improvement compared with the mALBI grade (p = 0.009). While the modified albumin-bilirubin grade (mALF) score and prognostic nutritional index (PNI) did not exhibit significant differences compared to the mALBI grade (p = 0.3 and 0.2, respectively), the remaining risk models were inferior to the mALBI grade. In the relative IDI analysis, none of the risk models showed a significant improvement compared with the mALBI grade. The calibration plot of the PNI was unsatisfactory. The results for the 18-month survival status were consistent with those for the 12-month survival status. A time-dependent ROC analysis demonstrated that both the mALBI grade and the mALBI-based model showed consistent performance over time.ConclusionsThe mALBI grade, as well as the IMABALI-De and mALF scores (both of which are risk models based on mALBI grade), exhibited reliable performance in predicting the prognosis of patients with HCC.
Achieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study. This retrospective multicenter study included child–pugh class A patients with unresectable HCC without extrahepatic spread or macrovascular invasion who received atezolizumab plus bevacizumab as first-line therapy. Modified clinical CR (mCCR) was defined as CR per mRECIST with sustained normal alpha-fetoprotein (AFP) levels (< 10.0 ng/dl). Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on the “drug-off” criteria defined by following: (1) mRECIST CR with locoregional therapies, (2) sustained normalization of AFP/AFP-L3/ des-gamma-carboxy prothrombin (DCP) for 12–24 weeks, and (3) complete tumor vascularity disappearance by contrast-enhanced ultrasonography (CEUS) or pathological curative resection. The median follow-up was 16.5 months (95
Background/Aim: The combination of atezolizumab and bevacizumab is the standard treatment for hepatocellular carcinoma (HCC). However, cases of portal hypertension (PHT) have been reported with atezolizumab/bevacizumab combination therapy. Splenomegaly caused by PHT may disrupt the immune environment and increase the risk of therapeutic failure with this combination therapy. Partial splenic embolization (PSE) is a treatment option for splenomegaly; however, the usefulness of PSE for PHT during atezolizumab/bevacizumab combination therapy is unclear. This study investigated the effect of PSE on the immune environment in a patient with splenomegaly caused by exacerbation of PHT during atezolizumab/bevacizumab combination therapy for HCC. Patients and Methods: Of the 56 patients with unresectable HCC treated with atezolizumab/bevacizumab, four with splenomegaly and progressive disease (PD) underwent PSE. Results: PHT during atezolizumab/bevacizumab combination therapy led to a mean enlargement of the splenic size of 142.7%, an increase in the neutrophil-lymphocyte ratio (NLR), a decrease in lymphocyte counts, and a decrease in platelet counts. PSE increased platelet counts and lymphocyte counts, and decreased the NLR compared with pre-PSE levels. Atezolizumab/bevacizumab combination therapy, which caused PD due to PHT, resulted in a non-PD state with continued treatment after PSE. Conclusion: In patients with PHT receiving atezolizumab/bevacizumab combination therapy, PSE promotes recovery from leukopenia and thrombocytopenia. Furthermore, PSE treatment may also induce host immune activation and boost immunity.
