Pub Date : 2024-07-03DOI: 10.1007/s12072-024-10690-6
Mengxuan Zuo, Yuzhe Cao, Yi Yang, Guanglei Zheng, Da Li, Hongyan Shao, Qiaoyun Ma, Peng Song, Chao An, Wang Li
Background and aims: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC.
Methods: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated.
Results: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively.
Conclusion: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety.
Trail registration: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).
{"title":"Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.","authors":"Mengxuan Zuo, Yuzhe Cao, Yi Yang, Guanglei Zheng, Da Li, Hongyan Shao, Qiaoyun Ma, Peng Song, Chao An, Wang Li","doi":"10.1007/s12072-024-10690-6","DOIUrl":"https://doi.org/10.1007/s12072-024-10690-6","url":null,"abstract":"<p><strong>Background and aims: </strong>There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC.</p><p><strong>Methods: </strong>From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated.</p><p><strong>Results: </strong>After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively.</p><p><strong>Conclusion: </strong>The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety.</p><p><strong>Trail registration: </strong>The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1007/s12072-024-10688-0
Nan Zhang, Zhaohui Li, Yutao Liu, Xiaohua Shi, Di Shi, Yue Li, Xiaoyan Si, Ziyu Xun, Jing Shao, Haitao Zhao, Hanping Wang
Background: The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge.
Methods: This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics.
Results: Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36 days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3 months.
Conclusion: irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.
{"title":"Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.","authors":"Nan Zhang, Zhaohui Li, Yutao Liu, Xiaohua Shi, Di Shi, Yue Li, Xiaoyan Si, Ziyu Xun, Jing Shao, Haitao Zhao, Hanping Wang","doi":"10.1007/s12072-024-10688-0","DOIUrl":"https://doi.org/10.1007/s12072-024-10688-0","url":null,"abstract":"<p><strong>Background: </strong>The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge.</p><p><strong>Methods: </strong>This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics.</p><p><strong>Results: </strong>Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36 days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3 months.</p><p><strong>Conclusion: </strong>irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1007/s12072-024-10701-6
Mohammad Alarabi, Ziyan Pan, Manuel Romero-Gómez, Jacob George, Mohammed Eslam
Background and aims: Healthy weight (lean) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) have a more favorable metabolic and histological profile in cross-sectional studies compared with their non-lean counterparts. Paradoxically, they also have higher overall mortality. The underpinning pathophysiology of this paradox is not understood. Telomere attrition is associated with increased mortality in various diseases.
Methods: We investigated the role of telomere length in the pathogenesis of lean MAFLD in cohorts with biopsy-proven MAFLD (n = 303). We measured serum malondialdehyde (MDA) levels and hepatic 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) expression (reactive oxygen species (ROS) markers), growth/differentiation factor-15 (GDF-15) and tested the effect of H2O2 on telomere length and activity in hepatocyte cell lines. The association between leukocyte telomere length and mortality was examined.
Results: Telomere length was significantly lower in patients with lean MAFLD (p < 0.001). They also demonstrated an increase in ROS levels and decreases in GDF-15. H2O2 induced telomere shortening and reducing telomere activity in hepatocyte cell lines. We subsequently confirmed that telomere length shortening at baseline is associated with increased hazards of all-cause mortality; the deleterious effect was more profound in lean people.
Conclusion: Differences in telomere length in part explain the increased mortality of lean compared to non-lean patients with MAFLD. The effect is in part mediated through ROS activation and provide opportunities for therapy.
{"title":"Telomere length and mortality in lean MAFLD: the other face of metabolic adaptation.","authors":"Mohammad Alarabi, Ziyan Pan, Manuel Romero-Gómez, Jacob George, Mohammed Eslam","doi":"10.1007/s12072-024-10701-6","DOIUrl":"https://doi.org/10.1007/s12072-024-10701-6","url":null,"abstract":"<p><strong>Background and aims: </strong>Healthy weight (lean) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) have a more favorable metabolic and histological profile in cross-sectional studies compared with their non-lean counterparts. Paradoxically, they also have higher overall mortality. The underpinning pathophysiology of this paradox is not understood. Telomere attrition is associated with increased mortality in various diseases.</p><p><strong>Methods: </strong>We investigated the role of telomere length in the pathogenesis of lean MAFLD in cohorts with biopsy-proven MAFLD (n = 303). We measured serum malondialdehyde (MDA) levels and hepatic 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) expression (reactive oxygen species (ROS) markers), growth/differentiation factor-15 (GDF-15) and tested the effect of H<sub>2</sub>O<sub>2</sub> on telomere length and activity in hepatocyte cell lines. The association between leukocyte telomere length and mortality was examined.</p><p><strong>Results: </strong>Telomere length was significantly lower in patients with lean MAFLD (p < 0.001). They also demonstrated an increase in ROS levels and decreases in GDF-15. H<sub>2</sub>O<sub>2</sub> induced telomere shortening and reducing telomere activity in hepatocyte cell lines. We subsequently confirmed that telomere length shortening at baseline is associated with increased hazards of all-cause mortality; the deleterious effect was more profound in lean people.</p><p><strong>Conclusion: </strong>Differences in telomere length in part explain the increased mortality of lean compared to non-lean patients with MAFLD. The effect is in part mediated through ROS activation and provide opportunities for therapy.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-07DOI: 10.1007/s12072-024-10639-9
Ibrahim Ayada, Jiajing Li, Willem Pieter Brouwer, Robert J de Knegt, Qiuwei Pan
{"title":"Impact of chronic hepatitis B and concurrent steatosis on the risk of hepatocellular carcinoma.","authors":"Ibrahim Ayada, Jiajing Li, Willem Pieter Brouwer, Robert J de Knegt, Qiuwei Pan","doi":"10.1007/s12072-024-10639-9","DOIUrl":"10.1007/s12072-024-10639-9","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-13DOI: 10.1007/s12072-024-10646-w
Pedro David Wendel-Garcia, Rea Andermatt, Christian Bode, Sascha David, Klaus Stahl
{"title":"\"Dosis sola facit venenum\"-Evidence for causality in the association between ketamine and cholestatic liver injury.","authors":"Pedro David Wendel-Garcia, Rea Andermatt, Christian Bode, Sascha David, Klaus Stahl","doi":"10.1007/s12072-024-10646-w","DOIUrl":"10.1007/s12072-024-10646-w","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-08DOI: 10.1007/s12072-024-10676-4
Shiye Yang, Huoqi Liang, Xing Li, Jiayi Qian, Zhibing Ming
{"title":"Is the TAE score a promising prognostic predictor for unresectable hepatocellular carcinoma treated with TACE plus lenvatinib with PD‑1 inhibitors? Further validation should be performed.","authors":"Shiye Yang, Huoqi Liang, Xing Li, Jiayi Qian, Zhibing Ming","doi":"10.1007/s12072-024-10676-4","DOIUrl":"10.1007/s12072-024-10676-4","url":null,"abstract":"","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-09DOI: 10.1007/s12072-023-10637-3
Tao Chen, Guang Chen, Guiqiang Wang, Sombat Treeprasertsuk, Cosmas Rinaldi Adithya Lesmana, Han-Chieh Lin, Mamun Al-Mahtab, Yogesh K Chawla, Soek-Siam Tan, Jia-Horng Kao, Man-Fung Yuen, Guan-Huei Lee, Diana Alcantara-Payawal, Nobuaki Nakayama, Zaigham Abbas, Wasim Jafri, Dong-Joon Kim, Ashok Choudhury, Rakhi Mahiwall, Jinlin Hou, Saeed Hamid, Jidong Jia, J S Bajaj, Fusheng Wang, Shiv K Sarin, Qin Ning
End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.
{"title":"Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.","authors":"Tao Chen, Guang Chen, Guiqiang Wang, Sombat Treeprasertsuk, Cosmas Rinaldi Adithya Lesmana, Han-Chieh Lin, Mamun Al-Mahtab, Yogesh K Chawla, Soek-Siam Tan, Jia-Horng Kao, Man-Fung Yuen, Guan-Huei Lee, Diana Alcantara-Payawal, Nobuaki Nakayama, Zaigham Abbas, Wasim Jafri, Dong-Joon Kim, Ashok Choudhury, Rakhi Mahiwall, Jinlin Hou, Saeed Hamid, Jidong Jia, J S Bajaj, Fusheng Wang, Shiv K Sarin, Qin Ning","doi":"10.1007/s12072-023-10637-3","DOIUrl":"10.1007/s12072-023-10637-3","url":null,"abstract":"<p><p>End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.</p>","PeriodicalId":12901,"journal":{"name":"Hepatology International","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}