Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment

被引：20

作者：

Celsa, Ciro ^{[1
,2
]}

Cabibbo, Giuseppe ^{[2
]}

Fulgenzi, Claudia Angela Maria ^{[1
]}

Battaglia, Salvatore ^{[3
]}

Enea, Marco ^{[4
]}

Scheiner, Bernhard ^{[5
]}

D'Alessio, Antonio ^{[1
,6
]}

Manfredi, Giulia F. ^{[1
,6
]}

Stefanini, Bernardo ^{[1
,7
]}

Nishida, Naoshi ^{[8
]}

Galle, Peter R. ^{[9
]}

Schulze, Kornelius ^{[10
]}

Wege, Henning ^{[10
]}

Ciccia, Roberta ^{[2
]}

Hsu, Wei-Fan ^{[11
]}

Vivaldi, Caterina ^{[12
]}

Wietharn, Brooke ^{[13
]}

Lin, Ryan Po-Ting ^{[14
,15
]}

Pirozzi, Angelo ^{[16
,17
]}

Pressiani, Tiziana ^{[17
]}

Dalbeni, Andrea ^{[18
,19
,20
]}

Natola, Leonardo A. ^{[19
,20
]}

Auriemma, Alessandra ^{[19
,21
]}

Rigamonti, Cristina ^{[6
]}

Burlone, Michela ^{[6
]}

Parisi, Alessandro ^{[22
]}

Huang, Yi-Hsiang ^{[23
,24
,25
]}

Lee, Pei-Chang ^{[24
,26
]}

Ang, Celina ^{[27
]}

Marron, Thomas U. ^{[28
]}

Pinter, Matthias ^{[5
]}

Cheon, Jaekyung ^{[28
]}

Phen, Samuel ^{[29
]}

Singal, Amit G. ^{[29
]}

Gampa, Anuhya ^{[30
]}

Pillai, Anjana ^{[30
]}

Roehlen, Natascha ^{[31
]}

Thimme, Robert ^{[31
]}

Vogel, Arndt ^{[32
,33
]}

Soror, Noha ^{[34
]}

Ulahannan, Susanna ^{[34
]}

Sharma, Rohini ^{[1
]}

Sacerdoti, David ^{[19
,20
]}

Pirisi, Mario ^{[6
]}

Rimassa, Lorenza ^{[16
,17
]}

Lin, Chun-Yen ^{[14
,15
]}

Saeed, Anwaar ^{[35
]}

Masi, Gianluca ^{[12
]}

Schoenlein, Martin ^{[36
]}

von Felden, Johann ^{[10
]}

机构：

[1] Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Du Cane Rd, London W12 0HS, England

[2] Univ Palermo, Dept Hlth Promot Mother & Child Care Internal Med, Gastroenterol & Hepatol Unit, Palermo, Italy

[3] Univ Palermo, Dept Econ Business & Stat, Palermo, Italy

[4] Univ Palermo, Dept Hlth Promot Mother & Child Care Internal Med, Palermo, Italy

[5] Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Vienna, Austria

[6] Univ Piemonte Orientale, Dept Translat Med, Novara, Italy

[7] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy

[8] Kindai Univ, Dept Gastroenterol & Hepatol, Osaka, Japan

[9] Univ Med Ctr Mainz, Dept Internal Med 1, Mainz, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Dept Med, Hamburg, Germany

[11] China Med Univ Hosp, Ctr Digest Med, Dept Internal Med, Taichung, Taiwan

[12] Azienda Osped Univ Pisana, Unit Med Oncol 2, Translat Res & New Technol Med & Surg, Pisa, Italy

[13] Kansas Univ, Div Med Oncol, Dept Med, Ctr Canc, Kansas City, KS USA

[14] Chang Gung Mem Hosp, Linkou Med Ctr, Dept Gastroenterol & Hepatol, Taoyuan, Taiwan

[15] Chang Gung Univ, Coll Med, Taoyuan, Taiwan

[16] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[17] IRCCS Humanitas Res Hosp, Med Oncol & Hematol Unit, Humanitas Canc Ctr, Milan, Italy

[18] Univ Verona, Dept Med, Sect Gen Med C, Verona, Italy

[19] Univ & Hosp Trust AOUI Verona, Verona, Italy

[20] Univ Verona, Dept Med, Liver Unit, Verona, Italy

[21] Univ Verona, Dept Engn Innovat Med DIMI, Sect Innovat Biomed Oncol Area, Verona, Italy

[22] Univ Politecn Marche, Dept Oncol, Azienda Osped Univ Marche, Ancona, Italy

[23] Taipei Vet Gen Hosp, Healthcare & Serv Ctr, Dept Med, Taipei, Taiwan

[24] Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol & Hepatol, Taipei, Taiwan

[25] Natl Yang Ming Chiao Tung Univ, Inst Clin Med, Dept Med, Taipei, Taiwan

[26] Natl Yang Ming Chiao Tung Univ, Dept Med, Taipei, Taiwan

[27] Mt Sinai Hosp, Tisch Canc Inst, Div Hematol Oncol, Dept Med, New York, NY USA

[28] CHA Univ, Dept Internal Med, CHA Bundang Med Ctr, Med Oncol, Seongnam, South Korea

[29] Univ Texas Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA

[30] Univ Chicago Med, Sect Gastroenterol Hepatol & Nutr, Chicago, IL USA

[31] Univ Freiburg, Freiburg Univ Med Ctr, Dept Med Gastroenterol Hepatol Endocrinol & Infec, Freiburg, Germany

[32] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany

[33] Toronto Gen Hosp, Div Gastroenterol & Hepatol, Dept Med,Schwartz Reisman Liver Res Ctr,Med Oncol, Princess Margaret Canc Ctr,Longo Family Chair Liv, Toronto, ON, Canada

[34] Univ Oklahoma, Dept Internal Med, Stephenson Canc Ctr, Med Oncol TSET Phase 1 Program, Oklahoma City, OK USA

[35] Univ Pittsburgh, Div Hematol & Oncol, Dept Med, Pittsburgh, PA USA

[36] Univ Med Ctr Hamburg Eppendorf, Sect Pneumol, Dept Oncol Hematol & Bone Marrow Transplantat, Hamburg, Germany

[37] Fdn Policlin Univ Campus Biomed, Operat Res Unit Oncol, Rome, Italy

来源：

HEPATOLOGY | 2025年 / 81卷 / 03期

关键词：

HEPATOCELLULAR-CARCINOMA; CIRRHOSIS; SURVIVAL; EFFICACY; SAFETY;

D O I：

10.1097/HEP.0000000000001026

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and Aims: Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients. Approach and Results: From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95% CI: 5.1-19.7), 293 patients (51.3%) developed tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma progression (HR: 9.91, 95% CI: 5.85-16.78), albumin-bilirubin (ALBI) grade 2/3 (HR: 2.16, 95% CI: 1.69-2.77), and number of nodules >3(HR: 1.63, 95% CI: 1.28-2.08) were independently associated with OS. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93). Conclusions: Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.

引用

页码：837 / 852

页数：16

共 41 条

[1]

Abou-Alfa Ghassan K, 2022, NEJM Evid, V1, pEVIDoa2100070, DOI 10.1056/EVIDoa2100070

[2] Evaluating the risk-benefit ratio of immunotherapy according to liver-functional reserve in advanced HCC: the dark side of the moon [J].

Cabibbo, Giuseppe ;

Celsa, Ciro ;

Alimenti, Eleonora ;

Iavarone, Massimo .

HEPATOLOGY, 2023, 77 (04) :1074-1077

[3] Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients [J].

Cabibbo, Giuseppe ;

Celsa, Ciro ;

Calvaruso, Vincenza ;

Petta, Salvatore ;

Cacciola, Irene ;

Cannavo, Maria Rita ;

Madonia, Salvatore ;

Rossi, Margherita ;

Magro, Bianca ;

Ini, Francesca ;

Distefano, Marco ;

Larocca, Licia ;

Prestileo, Tullio ;

Malizia, Giuseppe ;

Bertino, Gaetano ;

Benanti, Francesco ;

Licata, Anna ;

Scalisi, Ignazio ;

Mazzola, Giovanni ;

Di Rosolini, Maria Antonietta ;

Alaimo, Giuseppe ;

Averna, Alfonso ;

Cartabellotta, Fabio ;

Alessi, Nicola ;

Guastella, Salvatore ;

Russello, Maurizio ;

Scifo, Gaetano ;

Squadrito, Giovanni ;

Raimondo, Giovanni ;

Trevisani, Franco ;

Craxi, Antonio ;

Di Marco, Vito S. ;

Camma, Calogero .

JOURNAL OF HEPATOLOGY, 2019, 71 (02) :265-273

[4] Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma [J].

Cabibbo, Giuseppe ;

Petta, Salvatore ;

Barbara, Marco ;

Attardo, Simona ;

Bucci, Laura ;

Farinati, Fabio ;

Giannini, Edoardo G. ;

Negrini, Giulia ;

Ciccarese, Francesca ;

Rapaccini, Gian Lodovico ;

Di Marco, Maria ;

Caturelli, Eugenio ;

Zoli, Marco ;

Borzio, Franco ;

Sacco, Rodolfo ;

Virdone, Roberto ;

Marra, Fabio ;

Mega, Andrea ;

Morisco, Filomena ;

Benvegnu, Luisa ;

Gasbarrini, Antonio ;

Svegliati-Baroni, Gianluca ;

Foschi, Francesco Giuseppe ;

Olivani, Andrea ;

Masotto, Alberto ;

Nardone, Gerardo ;

Colecchia, Antonio ;

Persico, Marcello ;

Craxi, Antonio ;

Trevisani, Franco ;

Camma, Calogero .

JOURNAL OF HEPATOLOGY, 2017, 67 (01) :65-71

[5] Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours [J].

Celsa, Ciro ;

Cabibbo, Giuseppe ;

Fulgenzi, Claudia A. M. ;

Scheiner, Bernhard ;

D'Alessio, Antonio ;

Manfredi, Giulia F. ;

Nishida, Naoshi ;

Ang, Celina ;

Marron, Thomas U. ;

Saeed, Anwaar ;

Wietharn, Brooke ;

Pinter, Matthias ;

Cheon, Jaekyung ;

Huang, Yi-Hsiang ;

Lee, Pei -Chang ;

Phen, Samuel ;

Gampa, Anuhya ;

Pillai, Anjana ;

Vivaldi, Caterina ;

Salani, Francesca ;

Masi, Gianluca ;

Roehlen, Natascha ;

Thimme, Robert ;

Vogel, Arndt ;

Schoenlein, Martin ;

von Felden, Johann ;

Schulze, Kornelius ;

Wege, Henning ;

Galle, Peter R. ;

Kudo, Masatoshi ;

Rimassa, Lorenza ;

Singal, Amit G. ;

El Tomb, Paul ;

Ulahannan, Susanna ;

Parisi, Alessandro ;

Chon, Hong Jae ;

Hsu, Wei-Fan ;

Stefanini, Bernardo ;

Verzoni, Elena ;

Giusti, Raffaele ;

Veccia, Antonello ;

Catino, Annamaria ;

Aprile, Giuseppe ;

Guglielmini, Pamela Francesca ;

Di Napoli, Marilena ;

Ermacora, Paola ;

Antonuzzo, Lorenzo ;

Rossi, Ernesto ;

Verderame, Francesco ;

Zustovich, Fable .

JOURNAL OF HEPATOLOGY, 2024, 80 (03) :431-442

[6] Four-year overall survival (OS) update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC) [J].

Chan, S. L. ;

Sangro, B. ;

Kelley, R. K. ;

Lau, G. ;

Kudo, M. ;

Sukeepaisarnjaroen, W. ;

De Toni, E. N. ;

Furuse, J. ;

Kang, Y-K. ;

Galle, P. R. ;

Rimassa, L. ;

Heurgue, A. ;

Tam, V. C. ;

Dao, T. V. ;

Thungappa, S. Chiradoni ;

Breder, V. ;

Ostapenko, Y. V. ;

Reig Monzon, M. E. ;

Gupta, C. ;

Abou-Alfa, G. K. .

ANNALS OF ONCOLOGY, 2023, 34 :S1530-S1531

[7]

Cheng AL, 2022, J HEPATOL, V76, P862, DOI [10.1016/j.jhep.2021.11.030, 10.1016/j.jceh.2022.07.003]

[8] Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer [J].

Cortellini, Alessio ;

D'Alessio, Antonio ;

Cleary, Siobhan ;

Buti, Sebastiano ;

Bersanelli, Melissa ;

Bordi, Paola ;

Tonini, Giuseppe ;

Vincenzi, Bruno ;

Tucci, Marco ;

Russo, Alessandro ;

Pantano, Francesco ;

Russano, Marco ;

Stucci, Luigia Stefania ;

Sergi, Maria Chiara ;

Falconi, Martina ;

Zarzana, Maria Antonietta ;

Santini, Daniele ;

Spagnolo, Francesco ;

Tanda, Enrica T. ;

Rastelli, Francesca ;

Giorgi, Francesca Chiara ;

Pergolesi, Federica ;

Giusti, Raffaele ;

Filetti, Marco ;

Lo Bianco, Francesca ;

Marchetti, Paolo ;

Botticelli, Andrea ;

Gelibter, Alain ;

Siringo, Marco ;

Ferrari, Marco ;

Marconcini, Riccardo ;

Vitale, Maria Giuseppa ;

Nicolardi, Linda ;

Chiari, Rita ;

Ghidini, Michele ;

Nigro, Olga ;

Grossi, Francesco ;

De Tursi, Michele ;

Di Marino, Pietro ;

Queirolo, Paola ;

Bracarda, Sergio ;

Macrini, Serena ;

Inno, Alessandro ;

Zoratto, Federica ;

Veltri, Enzo ;

Spoto, Chiara ;

Vitale, Maria Grazia ;

Cannita, Katia ;

Gennari, Alessandra ;

Morganstein, Daniel L. .

CLINICAL CANCER RESEARCH, 2023, 29 (14) :2714-2724

[9] We Have to Be Discrete About This: A Non-Parametric Imputation Technique for Missing Categorical Data [J].

Cranmer, Skyler J. ;

Gill, Jeff .

BRITISH JOURNAL OF POLITICAL SCIENCE, 2013, 43 :425-449

[10] Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study [J].

D'Alessio, Antonio ;

Fulgenzi, Claudia Angela Maria ;

Nishida, Naoshi ;

Schoenlein, Martin ;

von Felden, Johann ;

Schulze, Kornelius ;

Wege, Henning ;

Gaillard, Vincent E. ;

Saeed, Anwaar ;

Wietharn, Brooke ;

Hildebrand, Hannah ;

Wu, Linda ;

Ang, Celina ;

Marron, Thomas U. ;

Weinmann, Arndt ;

Galle, Peter R. ;

Bettinger, Dominik ;

Bengsch, Bertram ;

Vogel, Arndt ;

Balcar, Lorenz ;

Scheiner, Bernhard ;

Lee, Pei-Chang ;

Huang, Yi-Hsiang ;

Amara, Suneetha ;

Muzaffar, Mahvish ;

Naqash, Abdul Rafeh ;

Cammarota, Antonella ;

Personeni, Nicola ;

Pressiani, Tiziana ;

Sharma, Rohini ;

Pinter, Matthias ;

Cortellini, Alessio ;

Kudo, Masatoshi ;

Rimassa, Lorenza ;

Pinato, David J. .

HEPATOLOGY, 2022, 76 (04) :1000-1012

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