Simplified BALAD (BALAD‐S) Score as a Guide for First‐Line Immune Checkpoint Inhibitor Selection for Unresectable Hepatocellular Carcinoma

BACKGROUND AND AIM: Atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are widely used first-line immune checkpoint inhibitor (ICI)-based regimens for unresectable hepatocellular carcinoma (uHCC). However, reliable biomarkers to inform treatment choice remain limited. This study evaluated whether the simplified BALAD-based score (BALAD-S) is associated with differential treatment outcomes. MATERIALS AND METHODS: This multicenter retrospective study included 752 Japanese patients with uHCC who received first-line Atez/Bev (n = 645) or Dur/Tre (n = 107) between October 2020 and March 2026. BALAD-S was calculated using bilirubin, albumin, AFP, AFP-L3, and des-γ-carboxy prothrombin, and patients were stratified into BALAD-S low (≤ 2) and high (≥ 3) groups. Treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: In the BALAD-S low group, Atez/Bev showed longer PFS than Dur/Tre (10.5 vs. 4.3 months; p < 0.001), with longer OS also observed (28.3 vs. 19.4 months; p = 0.049). In the BALAD-S high group, PFS did not differ significantly (7.0 vs. 5.3 months with Dur/Tre and Atez/Bev, respectively, p = 0.210), whereas OS was longer with Dur/Tre than with Atez/Bev (27.3 vs. 16.4 months; p = 0.022). Treatment effects differed by BALAD-S category (HR for Dur/Tre vs. Atez/Bev: 1.50 in BALAD-S low and 0.55 in BALAD-S high; p for interaction = 0.005). In patients treated from 2023 onward, similar treatment-effect heterogeneity was observed (HR 1.61 in BALAD-S low and 0.59 in BALAD-S high; p for interaction = 0.007). CONCLUSION: Outcomes with Atez/Bev and Dur/Tre differed according to BALAD-S score. BALAD-S may help identify patients with differential outcomes between first-line ICI-based regimens and represents a candidate stratification marker requiring validation.

Authors

Institutions

Publication Details

Journal
Hepatology Research
Published
2026-07-16
DOI
https://doi.org/10.1111/hepr.70239
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Simplified BALAD (BALAD‐S) Score as a Guide for First‐Line Immune Checkpoint Inhibitor Selection for Unresectable Hepatocellular Carcinoma

Takanori Matsuura, Yoshihide Ueda, Hideko Ohama, Tamami Abe et al.
Hepatology Research
Hepatocellular Carcinoma Treatment and Prognosis
article

Simplified BALAD (BALAD‐S) Score as a Guide for First‐Line Immune Checkpoint Inhibitor Selection for Unresectable Hepatocellular Carcinoma

Takanori Matsuura, Yoshihide Ueda, Hideko Ohama, Tamami Abe, Norio Itokawa, Joji Tani, Kazunari Tanaka, Yuki Kanayama, Hidenao Noritake, Kazuhito Kawata, Jumpei Okamura, Kazuya Kariyama, Hidenori Toyoda, Hirayuki Enomoto, Kazuhiro Nouso, Hideyuki Tamai, Takeshi Hatanaka, Masatoshi Kudo, Yoichi Hiasa, Kunihiko Tsuji, Atsushi Hiraoka, Takashi Kumada, Takuya Nagano, Ei Itobayashi, Masaki Kaibori, Masashi Hirooka, Chikara Ogawa, Hisashi Kosaka, Kazuto Tajiri, Shohei Komatsu, Takashi Nishimura, Toshifumi Tada, Atsushi Naganuma, Akemi Tsutsui, Hidekatsu Kuroda, Toru Ishikawa, Yutaka Yata, Masanori Atsukawa, Yuichi Koshiyama, Tomoko Aoki, Fujimasa Tada, Asahiro Morishita, Koichi Takaguchi, Satoru Kakizaki, Kosuke Matsui, Shinichiro Nakamura, Osamu Yoshida, Soo Ki Kim, Shintaro Takaki, Tomomitsu Matono, Taeang Arai, Hironori Ochi, Tomomi Okubo, Yoshiko Nakamura, Hiroki Nishikawa, the RELPEC Group and the HCC 48 Group, Michitaka Imai, Hironori Tanaka
article en

Abstract

BACKGROUND AND AIM: Atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are widely used first-line immune checkpoint inhibitor (ICI)-based regimens for unresectable hepatocellular carcinoma (uHCC). However, reliable biomarkers to inform treatment choice remain limited. This study evaluated whether the simplified BALAD-based score (BALAD-S) is associated with differential treatment outcomes. MATERIALS AND METHODS: This multicenter retrospective study included 752 Japanese patients with uHCC who received first-line Atez/Bev (n = 645) or Dur/Tre (n = 107) between October 2020 and March 2026. BALAD-S was calculated using bilirubin, albumin, AFP, AFP-L3, and des-γ-carboxy prothrombin, and patients were stratified into BALAD-S low (≤ 2) and high (≥ 3) groups. Treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: In the BALAD-S low group, Atez/Bev showed longer PFS than Dur/Tre (10.5 vs. 4.3 months; p < 0.001), with longer OS also observed (28.3 vs. 19.4 months; p = 0.049). In the BALAD-S high group, PFS did not differ significantly (7.0 vs. 5.3 months with Dur/Tre and Atez/Bev, respectively, p = 0.210), whereas OS was longer with Dur/Tre than with Atez/Bev (27.3 vs. 16.4 months; p = 0.022). Treatment effects differed by BALAD-S category (HR for Dur/Tre vs. Atez/Bev: 1.50 in BALAD-S low and 0.55 in BALAD-S high; p for interaction = 0.005). In patients treated from 2023 onward, similar treatment-effect heterogeneity was observed (HR 1.61 in BALAD-S low and 0.59 in BALAD-S high; p for interaction = 0.007). CONCLUSION: Outcomes with Atez/Bev and Dur/Tre differed according to BALAD-S score. BALAD-S may help identify patients with differential outcomes between first-line ICI-based regimens and represents a candidate stratification marker requiring validation.

Hepatology Research
Hiroshima University (JP), Kansai Medical University (JP), Hamamatsu University (JP), Iwate Medical University (JP), Kagawa University (JP), Hamamatsu University School of Medicine (JP), Wakayama Rosai Hospital (JP), Niigata Cancer Center Hospital (JP), Takamatsu Red Cross Hospital (JP), Kindai University Hospital (JP), Saiseikai Niigata Daini Hospital (JP), National Hospital Organization Takasaki Medical Center (JP), Matsuyama Red Cross Hospital (JP), Ogaki Municipal Hospital (JP), Himeji Medical Center (JP), Hanwa Memorial Hospital (JP), Gunma Saiseikai Maebashi Hospital (JP), Himeji Red Cross Hospital (JP), Teine Keijinkai Hospital (JP), Asahi General Hospital (JP), Toyama University Hospital (JP), Ehime Prefectural Central Hospital (JP), Kobe Asahi Hospital (JP), Kagawa Prefectural Central Hospital (JP), Takarazuka City Hospital (JP), Kure Medical Center (JP), Ehime University (JP), Gifu Kyoritsu University (JP), Kobe University (JP), Nippon Medical School (JP), Hyogo University (JP), Osaka University of Pharmaceutical Sciences (JP), Kindai University (JP)
Good health and well-being
Openalex Percentile: Top 11%
Hepatocellular Carcinoma Treatment and Prognosis
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.