Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

Progression pattern and post-progression survival following atezolizumab and bevacizumab treatment in advanced hepatocellular carcinoma.

BACKGROUND: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished. METHODS: We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. RESULTS: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 33, 55 and 22 showing the BCLCp-B, BCLCp-C1 and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B stage of the disease showed better overall survival than those with the BCLCp-C1 and BCLCp-C2 stages (hazard ratios: 1.93 [95% confidence interval, CI, 1.06-3.51] and 2.64 [95% CI, 1.32-5.30] for HCC stages BCLCp-C1 and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class and alpha-fetoprotein as poor prognostic factors for PPS. CONCLUSIONS: BCLCp-B1 stage was identified as a better prognostic factor for PPS following ATZ + BEV treatment compared with BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

Transluminal antegrade drill dilation technique for hepaticojejunostomy stricture with cholangioscopic evaluation (with video).

Background and study aims Balloon dilation and plastic stent deployment have been performed as hepaticojejunostomy stricture (HJS) treatment techniques under endoscopic ultrasound guidance (EUS). Although these techniques have shown favorable clinical results, the treatment period can be long because stent deployment is required. In addition, HJS may recur even after treatment because the scar tissue itself remains. To overcome these challenges, we developed an EUS-guided antegrade drill dilation technique for treating HJS. The aim of this study was to evaluate the technical feasibility and safety of this technique in terms of the pre- and post-cholangioscopic findings. Patients and methods This retrospective study included consecutive patients whose conditions were complicated with symptomatic HJS between November 2022 and February 2023. Transluminal antegrade drill dilation (TAD) using a novel drill dilator was attempted within 14 days after EUS-guided hepaticogastrostomy (HGS). HJS was diagnosed with cholangioscopy before TAD, and resolution was evaluated after TAD using cholangioscopy. Results TAD was attempted at approximately 11 days after EUS-HGS. The cholangioscope was inserted successfully in all patients after this procedure. Cholangioscopy revealed stricture without evidence of malignancy in 19 patients. In the remaining three patients, stricture was not observed and these patients underwent stent exchange rather than TAD. Among the 19 patients, passage of the guidewire across the HJS into the intestine was unsuccessful in four patients, and the technical success rate for this procedure was 78.9%. TAD was successful in all 15 patients in whom passage of the guidewire was achieved. Conclusions In conclusion, TAD appears to be technically feasible and safe.

Evaluation of exclusive internal endoscopic drainage for complex biloma with transluminal and transpapillary stenting.

Background and study aims Biloma is treated endoscopically with endoscopic retrograde cholangiography (ERCP) or endoscopi ultrasound-guided transluminal biloma drainage (EUS-TBD). However, almost all previous studies have used both internal and external drainage. External drainage has the disadvantages of poor cosmetic appearance and self-tube removal. The aim of the present study was to evaluate the internal endoscopic drainage for complex biloma after hepatobiliary surgery with an ERCP- or EUS-guided approach, without external drainage. Patients and methods This retrospective study included consecutive patients who had bilomas. A 7F plastic stent was deployed from the biloma to the duodenum in the ERCP group and the metal stent was deployed from the biloma to the stomach in the EUS-TBD group. Results Forty-seven patients were enrolled. The technical success rate was similar between the groups (ERCP 94% vs EUS-TBD 100%, P =0.371); however, mean procedure time was significantly shorter in the EUS-TBD group (16.9 minutes) than in the ERCP group (26.6 minutes) ( P =0.009). The clinical success rate was 87% (25 of 32 patients) in the ERCP group and 84% (11 of 13 patients) in the EUS-TBD group ( P =0.482). The duration of median hospital stay was significantly shorter in the EUS-TBD group (22 days) than in the ERCP group (46 days) ( P =0.038). There was no significant difference in procedure-associated adverse events between the groups. Conclusions In conclusion, ERCP and EUS-TBD are complementary techniques, each with its own merits in specific clinical scenarios. If both techniques can be performed, EUS-TBD should be considered because of the short times for the procedure, hospital stay. and biloma resolution.

Moving scope technique improves technical success rate of device insertion during EUS-guided hepaticogastrostomy (with video).

Background: Technical tips for device insertion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) have not been reported. To improve the technical success rate of device insertion without unnecessary tract dilation, the pushing force should be transmitted directly from the channel of the echoendoscope to the intrahepatic bile duct. Objectives: We developed a novel technique, termed the 'moving scope technique', the feasibility of which during EUS-HGS is described. Design: Retrospective study. Methods: The primary outcome of this study was the technical success rate of dilation device insertion without electrocautery dilation after the moving scope technique. The initial technical success rate of dilation device insertion was defined as successful insertion into the biliary tract. If dilation device insertion failed, the moving scope technique was attempted. Results: A total of 143 patients were enrolled in this study. The initial technical success rate for device insertion was 80.4% (115/143). The moving scope technique was therefore attempted in 28 patients. The mean angle between the intrahepatic bile duct and the guidewire was improved to 141.0° and resulted in a technical success rate of 100% (28/28). The area under the ROC curve (AUC) was 0.88, and 120° predicted successful dilation device insertion with sensitivity of 88.0% and specificity of 78.8%. Bile peritonitis (n = 8) and cholangitis (n = 2) were observed as adverse events, but were not severe. Conclusion: In conclusion, the moving scope technique may be helpful during EUS-HGS to achieve successful insertion of the dilation device into the biliary tract. These results should be evaluated in a prospective randomized controlled trial.

Liver impaction technique improves technical success rate of guidewire insertion during EUS-guided hepaticogastrostomy (with video).

Background: If the guidewire becomes kinked by the needle, guidewire manipulation may be difficult, and can cause complications such as guidewire shearing or injury during endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). To overcome this matter, we have previously described a technical tip for preventing guidewire injury, termed 'liver impaction technique'. However, its technical feasibility has been not reported in the setting of a large patient cohort. Objectives: The aim of study was to evaluate the clinical usefulness of the liver impaction technique during EUS-HGS. Design: Retrospective, single-center study. Methods: This retrospective study included consecutive patients who underwent EUS-HGS between April 2018 and September 2022. The primary outcome of this study was the technical success rate of guidewire insertion using the liver impaction technique. Results: A total of 166 patients were enrolled in this study. Initial successful guidewire insertion without using liver impaction technique was obtained in 108 patients (65.1%). Among 58 patients in whom guidewire insertion failed initially, guidewire advancement into the periphery of the bile duct was observed in 32 patients (55.2%) and into a non-interest bile duct branch was observed in 26 patients (44.8%). Liver impaction technique contributed to increasing the technical success rate of guidewire insertion from 65.1% to 95.8%. Overall, adverse events were observed in 12 patients (7.2%; bile peritonitis n = 9, cholangitis n = 3), and these adverse events were Grade I. Among patients who underwent liver impaction technique (n = 58), adverse events were observed in two patients (3.4%; bile peritonitis). Also, guidewire sharing was not observed in any patients during liver impaction technique. Conclusions: In conclusion, the liver impaction technique may be helpful during EUS-HGS to obtain successful guidewire insertion into the biliary tract of interest.

Impact of body composition for patients with hepatocellular carcinoma who received atezolizumab plus bevacizumab therapy.

OBJECTIVE: To investigate the association between body composition and prognosis in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab. METHODS: This cohort study analysed 119 patients who received atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. We investigated the association between body composition and progression-free survival and overall survival. Body composition was quantified by the visceral fat index, subcutaneous fat index, and skeletal muscle index. A high or low index score was defined as that above or below the median of these indices. RESULTS: Poor prognosis was observed in the low visceral fat index and low subcutaneous fat index groups. The mean progression-free survival in the low visceral fat index and low subcutaneous fat index groups vs. the other groups were 194 and 270 days, respectively [95% confidence interval (CI), 153-236 and 230-311 days, respectively; P = 0.015], while the mean overall survival was 349 vs. 422 days, respectively (95% CI, 302-396 and 387-458 days, respectively; P = 0.027). In the multivariate analysis, both a low subcutaneous fat index and low visceral fat index were statistically associated with lower progression-free and overall survival rates [hazard ratio (HR) 1.721; 95% CI, 1.101-2.688; P = 0.017; and HR 2.214; 95% CI, 1.207-4.184; P = 0.011, respectively]. CONCLUSION: Low visceral fat index and subcutaneous fat index scores were independent predictors of poor prognosis in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Association Between Immune-Related Adverse Events and Survival in Patients with Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. PATIENTS AND METHODS: We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). RESULTS: Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis. CONCLUSION: The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.

Clinical evaluation of a novel drill dilator as the first-line tract dilation technique during EUS-guided biliary drainage by nonexpert hands (with videos).

BACKGROUND AND AIMS: In cases in which tract dilation fails using the initially selected dilation device during EUS-guided hepaticogastrostomy (EUS-HGS), dilation should be re-attempted using another device. However, switching from one device to another during the procedure is often associated with prolonged procedure time and deviation from the correct axis. Therefore, it is highly desired that the initial tract dilation succeeds on the first attempt. Recently, a novel drill dilator has become available in Japan. Because there have been no previous studies comparing this novel device versus others as an initial dilation device, this article reports on the technical feasibility of this novel device for use during EUS-HGS and compares it with a balloon catheter. METHODS: This retrospective study included patients who underwent EUS-HGS using a self-expandable metal stent between October 2021 and October 2022. Excluded from the study were patients who underwent EUS-HGS using a plastic stent or stent deployment without tract dilation. The primary outcome in this study was the technical success rate of initial tract dilation using the drill dilator. This dilator has been available at our hospital since June 2022. Thus, EUS-HGS was performed using this device as the primary dilation device from June 2022 to October 2022. As the control group, we corrected patients who underwent EUS-HGS using a 4-mm balloon catheter as the primary dilation device from October 2021 to May 2022. RESULTS: A total of 49 patients were included: 19 underwent EUS-HGS using the drill dilator and 30 underwent EUS-HGS using a balloon catheter. EUS-HGS using the drill dilator initially was performed mainly by nonexpert hands (n = 19), whereas only some procedures in the balloon catheter group were performed by nonexpert hands (n = 2). Although the initial tract dilation was successful in all patients in the drill dilator group (19 of 19 [100%]) and in 29 (97%) of 30 in the balloon catheter group, additional tract dilation was needed in 73.7% (14 of 19) of the drill dilator group upon insertion of the 8.5F stent delivery system. In contrast, the stent delivery system insertion was successful without additional tract dilation in all patients in the balloon catheter group. CONCLUSIONS: The novel drill dilator might be useful as a dilation device; however, the balloon dilation technique should be selected first upon deploying a dedicated metal stent with an 8.5F stent delivery system.

Risk factors for liver-related mortality of patients with hepatitis C virus after sustained virologic response to direct-acting antiviral agents.

Background and Aim: The aim of this study was to identify the factors associated with liver-related and non-liver-related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct-acting antiviral agents (DAAs). Methods: We conducted a retrospective, single-center cohort study of HCV patients cured by DAAs. Results: A total of 330 patients with SVR to DAAs were eligible. The median follow-up period was 3.38 years (inter-quartile range: 2.03-4.58). The cumulative liver-related or non-liver-related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver-related deaths, 9 of the 10 were from liver cancer. Among the non-liver-related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81-61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76-59.2), independently predicted liver-related death. No variables were associated with non-liver-related death. Conclusion: Our findings suggest that DM and a history of HCC are risk factors for liver-related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.

Effects of endoscopic injection sclerotherapy for esophagogastric varices on portal hemodynamics and liver function.

OBJECTIVES: To identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function. METHODS: We selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS. RESULTS: Low value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence. CONCLUSIONS: Patients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS.

A prospective observational cohort study of lenvatinib as initial treatment in patients with BCLC-defined stage B hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial. We therefore aimed to evaluate the efficacy and safety of LEN as a first-line treatment for the patients with HCC at BCLC substage B2. METHODS: This prospective observational study used LEN in TACE-naïve patients with HCC at BCLC substage B2 and preserved hepatic function. The primary endpoint was overall survival. A one-year survival rate threshold of 60% and an expected survival rate of 78%, based on previous reports of TACE, was assumed for setting the sample size. With a one-sided α-type error of 5% and 70% detection power, 25 patients were required over a 2-year enrollment period and 10-month follow-up period. RESULTS: Thirty-one patients were enrolled in this study from June 2018 to June 2020. The 1-year survival rate was 71.0% (90% confidence interval, 68.4-73.6%). Median overall and progression-free survival periods were 17.0 and 10.4 months, and the objective response rates according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and modified RECIST criteria were 22.6% and 70.0%, respectively. Common adverse events (AEs) were fatigue (68%), hypertension (65%), anorexia (61%), palmar-plantar erythrodysesthesia (39%), and thrombocytopenia (32%) of any grade; aspartate aminotransferase increased (23%), alanine aminotransferase increased (16%), and grade ≥ 3 proteinuria (13%). Treatment interruption and dose reduction were required in 61% and 81% of patients, respectively. LEN was discontinued in 29 patients due to disease progression (n = 17), AEs (n = 9), conversion to curative treatments (n = 2), and sudden death (n = 1), whereas post-LEN treatments were administered in 18 patients, including systemic chemotherapy (n = 11), TACE (n = 6), transarterial infusion (n = 1) and clinical trial (n = 1). CONCLUSIONS: The results suggest that LEN provides treatment benefits as an initial therapeutic in patients with BCLC substage B2 HCC with a safety profile comparable to that previously reported.

Identification of CT Values That Could Be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma after Lenvatinib Treatment.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (<30.6%) N30-CTav group (p < 0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Comparative study between sorafenib and lenvatinib as the first-line therapy in the sequential treatment of unresectable hepatocellular carcinoma in a real-world setting.

AIMS: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. METHODS AND RESULTS: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). CONCLUSION: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.

Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: A multicenter analysis.

PURPOSE: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC). METHOD: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. RESULTS: The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST. CONCLUSION: In real-world practice, ATZ + BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR.