Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours

被引：31

作者：

Celsa, Ciro ^{[1
,2
]}

Cabibbo, Giuseppe ^{[2
,3
]}

Fulgenzi, Claudia A. M. ^{[1
]}

Scheiner, Bernhard ^{[1
,4
,30
]}

D'Alessio, Antonio ^{[1
,5
]}

Manfredi, Giulia F. ^{[1
,5
,6
]}

Nishida, Naoshi ^{[6
]}

Ang, Celina ^{[7
]}

Marron, Thomas U. ^{[7
]}

Saeed, Anwaar ^{[8
]}

Wietharn, Brooke ^{[9
]}

Pinter, Matthias ^{[4
]}

Cheon, Jaekyung ^{[10
]}

Huang, Yi-Hsiang ^{[11
,12
,13
]}

Lee, Pei -Chang ^{[12
,14
]}

Phen, Samuel ^{[15
]}

Gampa, Anuhya ^{[16
]}

Pillai, Anjana ^{[17
]}

Vivaldi, Caterina ^{[18
]}

Salani, Francesca ^{[17
,18
]}

Masi, Gianluca

Roehlen, Natascha ^{[19
]}

Thimme, Robert ^{[19
]}

Vogel, Arndt ^{[20
,21
]}

Schoenlein, Martin ^{[22
]}

von Felden, Johann ^{[23
]}

Schulze, Kornelius ^{[23
]}

Wege, Henning

Galle, Peter R. ^{[24
]}

Kudo, Masatoshi

Rimassa, Lorenza ^{[25
,26
]}

Singal, Amit G.

El Tomb, Paul ^{[27
]}

Ulahannan, Susanna ^{[27
]}

Parisi, Alessandro ^{[28
]}

Chon, Hong Jae

Hsu, Wei-Fan ^{[29
]}

Stefanini, Bernardo ^{[30
]}

Verzoni, Elena ^{[31
]}

Giusti, Raffaele ^{[32
]}

Veccia, Antonello ^{[33
]}

Catino, Annamaria ^{[34
]}

Aprile, Giuseppe ^{[35
]}

Guglielmini, Pamela Francesca ^{[36
]}

Di Napoli, Marilena ^{[37
]}

Ermacora, Paola ^{[38
]}

Antonuzzo, Lorenzo ^{[26
,39
]}

Rossi, Ernesto ^{[40
]}

Verderame, Francesco ^{[41
]}

Zustovich, Fable ^{[42
]}

机构：

[1] Hammersmith Hosp, Imperial Coll London, Dept Surg & Canc, Du Cane Rd, London W120HS, England

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

[3] Fdn Policlin Univ Campus Biomed, Operat Res Unit Oncol, Via Alvaro del Portillo 200, I-00128 Rome, Italy

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

[5] Univ Piemonte Orientale, Dept Translat Med, Div Oncol, Novara, Italy

[6] Kindai Univ, Fac Med, Dept Gastroenterol & Hepatol, Osaka, Japan

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

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

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

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

[11] Taipei Vet Gen Hosp, Healthcare & Serv Ctr, Taipei, Taiwan

[12] Taipei Vet Gen Hosp, Div Gastroenterol & Hepatol, Taipei, Taiwan

[13] Natl Yang Ming Chiao Tung Univ, Inst Clin Med, Fac Med, Taipei, Taiwan

[14] Natl Yang Ming Chiao Tung Univ, Fac Med, Taipei, Taiwan

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

[16] Univ Chicago Med, Sect Gastroenterol Hepatol & Nutr, 5841 S Maryland Ave, Chicago, IL 60637 USA

[17] Azienda Osped Univ Pisana, Unit Med Oncol 2, Pisa, Italy

[18] Interdisciplinary Res Ctr Hlth Sci, Scuola Super St Anna Pisa, Pisa, Italy

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

[20] Hannover Med Sch, Hannover, Germany

[21] Toronto Gen Hosp, Longo Family Chair Liver Canc Res, Princess Margaret Canc Ctr, Princess Margaret Canc Ctr,Div Gastroenterol & He, Toronto, ON, Canada

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

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

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

[25] Humanitas Univ, Dept Biomed Sci, Via Rita Levi Montalcini 4, I-20072 Milan, Italy

[26] IRCCS Humanitas Res Hosp, Humanitas Canc Ctr, Med Oncol & Hematol Unit, Via Manzoni 56, I-20089 Milan, Italy

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

[28] Univ Politecn Marche, Dept Oncol, I-60126 Ancona, Italy

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

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

[31] Fdn IRCCS Ist Nazl Tumori, SS Oncol Genitourinaria, Milan, Italy

[32] St Andrea Hosp, Med Oncol Unit, Rome, Italy

[33] Santa Chiara Hosp, Med Oncol, Trento, Italy

[34] IRCCS Ist Tumori Giovanni Paolo II, Med Thorac Oncol Unit, Bari, Italy

[35] San Bortolo Gen Hosp, Dept Oncol, Vicenza, Italy

[36] SC Oncol, AO SS Antonio & Biagio & C Arrigo, Alessandria, Italy

[37] Ist Nazl Tumori Fdn G Pascale, UC Oncol Med Uro Ginecolog, UC Oncol Med Uroginecol, Naples, Italy

[38] Presidio Osped Univ Santa Maria Misericordia, Dipartimento Oncol, Azienda Sanit Univ Integrata Friuli Cent, Udine, Italy

[39] Univ Hosp Careggi, Med Oncol Unit, Florence, Italy

[40] Fdn Policlin Univ A Gemelli IRCCS, Med Oncol, Rome, Italy

[41] Osped Riuniti Villa Sofia Cervello, Ospedali Riuniti Villa Sofia Cervello, Palermo, Italy

[42] Osped San Martino Genova, Dipartimento Oncol Clin, UOC Oncol Belluno, AULSS 1 Dolomiti, Belluno, Italy

[43] Univ Aquila, St Salvatore Hosp, Dept Biotechnol & Appl Clin Sci, Laquila, Italy

[44] Ist Dermopat Immacolata IDI, UOC Oncol, IRCCS, Rome, Italy

[45] Osped Gen Prov Macerata, UOC Oncol, ASUR Area Vasta 3, Macerata, Italy

[46] Papa Giovanni XXIII Hosp, Med Oncol Unit, Bergamo, Italy

[47] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Med Oncol Unit, Milan, Italy

[48] Med Oncol Unit, ARNAS Garibaldi, Catania, Italy

[49] Univ Hosp Modena & Reggio Emilia, Med Oncol Unit, Modena, Italy

[50] Med Oncol Unit, AUSL IRCCS Reggio Emilia, Reggio Emilia, Italy

来源：

JOURNAL OF HEPATOLOGY | 2024年 / 80卷 / 03期

基金：

英国惠康基金; 新加坡国家研究基金会;

关键词：

immune-related liver injury; hepatocellular carcinoma; immunotherapy; atezolizumab plus bevacizumab; hepatotoxicity; ATEZOLIZUMAB PLUS BEVACIZUMAB; ADVERSE EVENTS; TOXICITY; SAFETY; CTLA-4; HCC;

D O I：

10.1016/j.jhep.2023.10.040

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & aims: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours. Methods: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure. Results: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96). Conclusions: Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumours), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes.

引用

页码：431 / 442

页数：13

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