Introduction: Biannual ultrasound (US) is recommended for HCC surveillance, although its sensitivity for early-stage HCC is low. This study aims to compare the performance of annual dynamic abbreviated MRI (D-AMRI) and biannual US for HCC detection.Methods: This prospective, two-center cohort study enrolled participants eligible for HCC surveillance according to Korean guidelines between November 2018 and December 2021. Participants underwent four rounds of surveillance at 6-month intervals: both D-AMRI and US at the first and third rounds and only US at the second and fourth rounds. The diagnostic yield (DY) and false referral rate (FRR) were compared between the two modalities. The scan time of D-AMRI was measured using a stopwatch.Results: Of the 257 enrolled participants, 213 participants completed the protocol and were included in the analysis. Primary liver cancers were found in 32 participants, including 31 HCCs (22 very early-stage, eight early-stage, and one advanced-stage) and one intrahepatic cholangiocarcinoma. The DY of annual D-AMRI was higher than biannual US for all (6.4% [26/405] vs. 2.2% [9/405]), early-stage (6.2% [25/405] vs. 2.0% [8/405]), and very early-stage HCCs (4.7% [19/405] vs. 1.2% [5/405]) (P <0.001 for all). No significant difference in the FRR was observed for all (2.5% [10/405] for both), early-stage (2.7% [11/405] for both) (P >0.999 for both), and very early-stage HCCs (4.2% [17/405] vs. 3.5% [14/405], P = 0.564). The median scan time of D-AMRI was 13 min. Conclusion: Annual D-AMRI showed a higher DY than biannual US for detecting HCCs, without increasing the FRR.

Introduction: Biannual ultrasound (US) is recommended for HCC surveillance, although its sensitivity for early-stage HCC is low. This study aims to compare the performance of annual dynamic abbreviated MRI (D-AMRI) and biannual US for HCC detection.Methods: This prospective, two-center cohort study enrolled participants eligible for HCC surveillance according to Korean guidelines between November 2018 and December 2021. Participants underwent four rounds of surveillance at 6-month intervals: both D-AMRI and US at the first and third rounds and only US at the second and fourth rounds. The diagnostic yield (DY) and false referral rate (FRR) were compared between the two modalities. The scan time of D-AMRI was measured using a stopwatch.Results: Of the 257 enrolled participants, 213 participants completed the protocol and were included in the analysis. Primary liver cancers were found in 32 participants, including 31 HCCs (22 very early-stage, eight early-stage, and one advanced-stage) and one intrahepatic cholangiocarcinoma. The DY of annual D-AMRI was higher than biannual US for all (6.4% [26/405] vs. 2.2% [9/405]), early-stage (6.2% [25/405] vs. 2.0% [8/405]), and very early-stage HCCs (4.7% [19/405] vs. 1.2% [5/405]) (P <0.001 for all). No significant difference in the FRR was observed for all (2.5% [10/405] for both), early-stage (2.7% [11/405] for both) (P >0.999 for both), and very early-stage HCCs (4.2% [17/405] vs. 3.5% [14/405], P = 0.564). The median scan time of D-AMRI was 13 min. Conclusion: Annual D-AMRI showed a higher DY than biannual US for detecting HCCs, without increasing the FRR.

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment.Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment. Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis.Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment.Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment. Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis.Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.

IntroductionDespite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry.Methods Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin–bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade.Results Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2, 7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stage C, and 968 stage D. The median OS for all patients was 3.1 years (95% CI: 3.0–3.2) and significantly differed with the inclusion of ALBI grade and GNRI (P < 0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all P < 0.001), except for stage D (P = 0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk. Conclusion The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC.

IntroductionDespite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry.Methods Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin–bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade.Results Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2, 7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stage C, and 968 stage D. The median OS for all patients was 3.1 years (95% CI: 3.0–3.2) and significantly differed with the inclusion of ALBI grade and GNRI (P < 0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all P < 0.001), except for stage D (P = 0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk. Conclusion The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC.

Background: Despite the emergence of atezolizumab and bevacizumab (A+B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A+B treatment.Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A+B regimen from September 2020 to December 2022. Patients were categorised into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs, classified as grade 3 or higher.Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: Group 1 (n = 84) had no irAEs, Group 2 (n = 37) had mild irAEs (grade 1–2), and Group 3 (n = 29) had severe irAEs (grade ≥ 3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to Group 1 (9.5 months) and Group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, Group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both Group 1 and Group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS.Conclusions: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A+B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

Background: Despite the emergence of atezolizumab and bevacizumab (A+B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A+B treatment.Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A+B regimen from September 2020 to December 2022. Patients were categorised into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs, classified as grade 3 or higher.Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: Group 1 (n = 84) had no irAEs, Group 2 (n = 37) had mild irAEs (grade 1–2), and Group 3 (n = 29) had severe irAEs (grade ≥ 3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to Group 1 (9.5 months) and Group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, Group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both Group 1 and Group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS.Conclusions: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A+B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

Background: Despite the emergence of atezolizumab and bevacizumab (A+B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A+B treatment.Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A+B regimen from September 2020 to December 2022. Patients were categorised into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs, classified as grade 3 or higher.Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: Group 1 (n = 84) had no irAEs, Group 2 (n = 37) had mild irAEs (grade 1–2), and Group 3 (n = 29) had severe irAEs (grade ≥ 3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to Group 1 (9.5 months) and Group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, Group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both Group 1 and Group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS.Conclusions: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A+B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

Background: Despite the emergence of atezolizumab and bevacizumab (A+B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A+B treatment.Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A+B regimen from September 2020 to December 2022. Patients were categorised into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs, classified as grade 3 or higher.Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: Group 1 (n = 84) had no irAEs, Group 2 (n = 37) had mild irAEs (grade 1–2), and Group 3 (n = 29) had severe irAEs (grade ≥ 3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to Group 1 (9.5 months) and Group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, Group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both Group 1 and Group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS.Conclusions: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A+B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.