C-reactive protein–bilirubin–albumin (CBA) index: a novel and simplified prognostic marker in hepatocellular carcinoma

Öz

Aim: Hepatocellular carcinoma (HCC) prognosis is influenced by both tumor biology and hepatic functional reserve. Existing prognostic indices, such as the albumin–bilirubin (ALBI) grade and inflammation-based scores such as the C-reactive protein/albumin ratio (CAR) and the C-reactive protein–albumin–lymphocyte (CALLY) index, have clinical relevance but may be limited by the complexity of calculation or hematologic variability. To our knowledge, the C-reactive protein–Bilirubin–Albumin (CBA) index has not been previously described in the literature. This study aimed to evaluate the prognostic value of the CBA index in patients with HCC. Material and Methods: This retrospective study included 69 patients diagnosed with HCC between 2015 and 2023. Baseline demographic, clinical, and laboratory variables were recorded. The CBA index was calculated as (CRP × Total Bilirubin) / Albumin. Overall survival (OS) was estimated using the Kaplan–Meier method, and the prognostic impact of variables was evaluated using the log-rank test and multivariate Cox proportional hazards regression analysis. Results: The median OS for the cohort was 14.03 months. Patients with CBA < 0.47 had significantly longer survival than those with CBA ≥ 0.47 (median OS: 23.30 vs. 7.30 months; p = 0.005). ALBI grade was also associated with OS (p < 0.001), whereas the CALLY score did not demonstrate significant prognostic discrimination (p = 0.110). In multivariate analysis, CBA ≥ 0.47 remained an independent predictor of mortality (HR = 2.07, 95% CI: 1.08–3.97, p = 0.027), along with ALBI Grade 3 (HR = 6.37, 95% CI: 1.80–25.05, p = 0.004). Conclusion: The CBA index is a simple and practical prognostic marker in HCC. It integrates inflammation and liver function parameters and independently predicts overall survival. Larger studies are needed for validation.

Anahtar Kelimeler

• hepatocellular carcinoma
• prognostic index
• C-reactive protein
• albumin
• bilirubin

Hepatosellüler karsinomda yeni ve basitleştirilmiş bir prognostik belirteç: C-reaktif protein–bilirubin–albümin (CBA) indeksi

Öz

Amaç: Hepatoselüler karsinomda prognoz; tümör yükü, karaciğer fonksiyon rezervi ve sistemik inflamatuar yanıtın etkileşimi ile belirlenmektedir. Albumin–bilirubin (ALBI) skoru, CALLY (C-reaktif protein-albümin-lenfosit) ve CAR (C-reaktif protein/albümin oranı) gibi inflamasyon temelli indeksler prognostik değer taşımakla birlikte, hesaplama zorlukları veya hematolojik parametrelerdeki değişkenlik nedeniyle rutin klinik kullanımda sınırlılık gösterebilmektedir. Bu çalışmada literatürde daha önce tanımlanmamış yeni bir belirteç olan CBA (C-reaktif protein–Bilirubin–Albumin) indeksinin hepatoselüler karsinomdaki prognostik değerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: 2015–2023 yılları arasında hepatoselüler karsinom tanısı alan 69 hasta retrospektif olarak incelendi. Klinik, demografik ve laboratuvar değişkenler kaydedildi. CBA indeksi (CRP × Total bilirubin) / Albumin formülüyle hesaplandı. Genel sağkalım Kaplan–Meier yöntemi ile değerlendirildi ve gruplar arası karşılaştırmalar log-rank testi ile yapıldı. Bağımsız prognostik faktörler çok değişkenli Cox regresyon analizi ile belirlendi. Bulgular: Kohortun medyan genel sağkalımı 14,03 ay idi. CBA < 0,47 olan hastalarda sağkalım belirgin olarak daha uzun olup medyan genel sağkalım 23,30 ay, CBA ≥ 0,47 olan grupta ise 7,30 ay olarak bulundu (p = 0,005). ALBI skoru sağkalımı anlamlı olarak farklılaştırırken (p < 0,001), CALLY skorunun prognostik katkısı anlamlı bulunmadı (p = 0,110). Çok değişkenli analizde CBA ≥ 0,47 bağımsız mortalite belirteci olarak saptandı (HR = 2,07; %95 GA: 1,08–3,97; p = 0,027). Ayrıca ALBI Grade 3 yüksek mortalite riski ile ilişkiliydi (HR = 6,37; %95 GA: 1,80–25,05; p = 0,004). Sonuç: CBA indeksi, HCC'de basit ve pratik bir prognostik belirteçtir. İnflamasyon ve karaciğer fonksiyon parametrelerini entegre eder ve genel sağkalımı bağımsız olarak tahmin eder. Doğrulama için daha geniş çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• hepatoselüler karsinom
• prognoz
• C-reaktif protein
• bilirubin
• albumin

Kaynakça

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229-63.
2. Tada T, Kumada T, Hiraoka A, Atsukawa M, Hirooka M, Tsuji K et al. Impact of modified albumin–bilirubin grade on survival in patients with HCC who received lenvatinib. Sci Rep 2021; 11: 14474.
3. Kudo M. Systemic therapy for hepatocellular carcinoma: latest advances and future perspectives. J Clin Oncol 2023; 41: e16135.
4. Bruix J, Reig M, Sherman M. Hepatocellular carcinoma: clinical frontiers and perspectives. Hepatology 2021; 73: 52-68.
5. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-90.
6. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-73.
7. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382: 1894-905.
8. Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid 2023; 388: 889-901.

9. Dirim MG, Cifcibasi Ormeci A, Cavus B, Poyanli A, Serin KR, Akyuz F et al. Inflammation and Immune-Based Scores Predict Prognosis for Patients with Hepatocellular Carcinoma: A Pilot Single-Center Study. Turk J Gastroenterol 2025; 34: 413-20.
10. Mai RY, Lu TL, Lu RJ, Zeng C, Lian F, Li LQ et al. C-reactive protein–albumin ratio (CAR): a more promising inflammation-based prognostic marker for patients undergoing curative hepatectomy for hepatocellular carcinoma. J Inflamm Res 2024; 17: 919-31.
11. Wang S, Xu S, Wang J, Ye H, Zhang K, Fan X et al. Preoperative C-reactive protein to albumin ratio may be a good prognostic marker in patients undergoing hepatectomy for hepatocellular carcinoma: a meta-analysis. Front Nutr 2024; 11: 1444352.
12. Hiraoka A, Kumada T, Michitaka K, Toyoda H, Tada T, Ueki H et al. Usefulness of albumin-bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2016; 31: 1031-6.
13. Kim KP, Kim KM, Ryoo BY, Choi WM, Cha WC, Kang M et al. Prognostic Efficacy of the Albumin-Bilirubin Score and Treatment Outcomes in Hepatocellular Carcinoma: A Large-Scale, Multi-Center Real-World Database Study. Liver Cancer 2024; 13: 610-28.
14. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K et al. The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol 2015; 22: 803-10.
15. Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 2015; 33: 550-8.
16. Hiraoka A, Tanizawa Y, Huang YJ, Cai Z, Sakaguchi S. Association of Albumin-Bilirubin Grade and Sequential Treatment with Standard Systemic Therapies for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study Using a Japanese Administrative Database. Drugs Real World Outcomes 2021; 8: 301-14.
17. Feng H, Xu F, Zhao Y, Jin T, Liu J, Li R et al. Prognostic value of combined inflammatory and nutritional biomarkers in HCC within the Milan criteria after hepatectomy. Front Oncol 2022; 12: 947302.
18. Müller L, Hahn F, Mähringer-Kunz A, Stoehr F, Gairing SJ, Michel M et al. Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index. Cancers (Basel) 2021; 13: 5018.