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Matono T, Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Nishikawa H, Tanaka K, Tsuji K, Ishikawa T, Tajiri K, Koshiyama Y, Toyoda H, Ogawa C, Hatanaka T, Kakizaki S, Kawata K, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Nishimura T, Imai M, Kosaka H, Naganuma A, Aoki T, Kuroda H, Yata Y, Tamai H, Matsuura T, Komatsu S, Ueda Y, Nakamura Y, Yoshida O, Nakamura S, Enomoto H, Kaibori M, Fukumoto T, Hiasa Y, Kudo M, Real‐life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group. Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab. Hepatol Res 2025. [PMID: 40515751 DOI: 10.1111/hepr.14224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 05/23/2025] [Accepted: 06/02/2025] [Indexed: 06/16/2025]
Abstract
AIM To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut-off values for predicting overall survival (OS). RESULTS The median progression-free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7-4.4), whereas the median OS was not reached (95% CI: 12.1 months-not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second-line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230-2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033-3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months-not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months-not reached) in those with an NLR of ≥ 2.56 (p = 0.016). A Sankey diagram illustrating post-treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care (p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3-3.0 represents an appropriate cut-off for predicting OS. CONCLUSIONS The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.
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Affiliation(s)
- Tomomitsu Matono
- Department of Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Japan
| | - Toshifumi Tada
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Chiba, Japan
| | - Shinya Fukunishi
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Hyogo, Japan
| | - Hiroki Nishikawa
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Kazunari Tanaka
- Center of Gastroenterology, Teine Keijinkai Hospital, Hokkaido, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Hokkaido, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Yuichi Koshiyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Kagawa, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, NHO Takasaki General Medical Center, Gunma, Japan
| | - Kazuhito Kawata
- Department of Hepatology, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Hyogo, Japan
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, NHO Takasaki General Medical Center, Gunma, Japan
| | - Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
| | - Yutaka Yata
- Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
| | - Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshihide Ueda
- Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Yoshiko Nakamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Shinichiro Nakamura
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Hyogo, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
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Guzel Dirim M, Cifcibasi Ormeci A, Cavus B, Poyanli A, Rahmi Serin K, Akyuz F, Demir K, Fatih Besisik S, Kaymakoglu S. Inflammation and Immune-Based Scores Predict Prognosis for Patients with Hepatocellular Carcinoma: A Pilot Single-Center Study. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2025; 36:219-228. [PMID: 40181742 PMCID: PMC12001462 DOI: 10.5152/tjg.2025.24407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 11/15/2024] [Indexed: 04/05/2025]
Abstract
Background/Aims Hepatocellular carcinoma (HCC) ranks as a major contributor to cancer-related deaths. Systemic inflammation plays a pivotal role in HCC development and progression. Thus, we aimed to determine the impact of inflammation- and immune-based scores in predicting the prognosis of HCC. Materials and Methods In this retrospective study, patients with HCC were enrolled between 2010 and 2020. The purpose of this retrospective study was to evaluate the impact of various biomarkers, including baseline alpha-fetoprotein (AFP) levels, C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, neutrophil-to-CRP (N/CRP) ratio, systemic immune-inflammation index (SII), albumin-bilirubin (ALBI) score, neutrophil-to-lymphocyte ratio (NLR), and aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) (AST/ALT) ratio (AAR), on survival, invasion of vascular tracts, metastasis, and treatment responses. Results A total of 199 patients with complete (n = 44) and non-complete (n = 145) treatment response groups were enrolled in the study. All scores for the non-complete response group were statistically significant (P < .05). The areas under the curves for predicting a non-complete response group were 0.651, 0.649, 0.636, 0.625, 0.613, 0.609, and 0.600 for AFP, CALLY index, AAR, SII, N/CRP ratio, ALBI score, and NLR, respectively. These results are consistent with the assessment of mortality and HCC progression. Conclusion Our results indicate that these biomarkers could serve as powerful prognostic tools for HCC.
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Affiliation(s)
- Merve Guzel Dirim
- Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Asli Cifcibasi Ormeci
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Bilger Cavus
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Arzu Poyanli
- Department of Radiology, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Kursat Rahmi Serin
- Department of General Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Filiz Akyuz
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Kadir Demir
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Selman Fatih Besisik
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
| | - Sabahattin Kaymakoglu
- Division of Gastroenterohepatology, Department of Internal Medicine, İstanbul University İstanbul Faculty of Medicine, İstanbul, Türkiye
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Zhang YY, Liu FH, Wang YL, Liu JX, Wu L, Qin Y, Zheng WR, Xing WY, Xu J, Chen X, Xu HL, Bao Q, Wang JY, Wang R, Chen XY, Wei YF, Zou BJ, Liu JC, Yin JL, Jia MQ, Gao S, Luan M, Wang HH, Gong TT, Wu QJ. Associations between peripheral whole blood cell counts derived indexes and cancer prognosis: An umbrella review of meta-analyses of cohort studies. Crit Rev Oncol Hematol 2024; 204:104525. [PMID: 39370059 DOI: 10.1016/j.critrevonc.2024.104525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/15/2024] [Accepted: 09/24/2024] [Indexed: 10/08/2024] Open
Abstract
Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.
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Affiliation(s)
- Ying-Ying Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ya-Li Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Information Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Jia-Xin Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Ying Qin
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wen-Rui Zheng
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei-Yi Xing
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jin Xu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xing Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi Bao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Yi Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ran Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xi-Yang Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing-Jie Zou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Cheng Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Li Yin
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ming-Qian Jia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Meng Luan
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Hui-Han Wang
- Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China.
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Wang HW, Lai HC, Su WP, Kao JT, Hsu WF, Chen HY, Chang CW, Huang GT, Peng CY. Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma. J Gastrointest Oncol 2024; 15:2216-2229. [PMID: 39554567 PMCID: PMC11565097 DOI: 10.21037/jgo-24-351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/05/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND Given the significant advancements in the management of hepatocellular carcinoma (HCC) and the emergence of novel treatment approaches, establishing reliable predictors has become crucial for optimizing patient selection and therapeutic sequencing in HCC. In this study, we aimed to investigate the prognostic factors and treatment efficacy associated with lenvatinib-based therapy. METHODS We retrospectively enrolled 53 patients receiving lenvatinib monotherapy, and 19 patients receiving lenvatinib plus immune checkpoint inhibitor combination therapy as their first-line systemic treatment for unresectable HCC at a single medical center. We employed univariate and multivariate Cox regression analyses to ascertain the factors influencing survival in these cohorts. RESULTS For lenvatinib monotherapy and the combination therapy, the objective response rates were 30.2% and 63.2%, respectively (P=0.03); the median progression-free survival (PFS) durations were 7 months [95% confidence interval (CI): 4.5-9.5] and 12 months (95% CI: 6.4-17.6), respectively (P=0.74); and the median overall survival (OS) was not reached in either group (P=0.93). Although patients receiving the combination therapy had a greater treatment response, no significant survival differences were observed between the lenvatinib monotherapy and combination therapy subgroups, even after inverse probability of treatment weighting (IPTW). Patients who received lenvatinib monotherapy could be stratified based on a combination of albumin-bilirubin (ALBI) grade (either grade 1 or 2a) and a neutrophil-lymphocyte ratio (NLR) of ≤5.8. Compared to the other subgroups combined, those who met both of these criteria exhibited PFS with a hazard ratio (HR) of 0.382 (95% CI: 0.168-0.871; P=0.02), corresponding to 11 and 5 months, respectively; and an OS (HR: 0.198, 95% CI: 0.043-0.920; P=0.04) of not reached versus 12 months, respectively, according to multivariate Cox regression analysis. CONCLUSIONS In our study cohort, there were no statistically significant differences observed in the survival rates between patients treated with lenvatinib monotherapy and those treated with a combination of lenvatinib and immunotherapy. The incorporation of ALBI grade and NLR facilitates the stratification of survival outcomes in patients with unresectable HCC undergoing lenvatinib monotherapy.
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Affiliation(s)
- Hung-Wei Wang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- School of Medicine, China Medical University, Taichung
- Graduate Institute of Biomedical Science, China Medical University, Taichung
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- School of Chinese Medicine, China Medical University, Taichung
| | - Wen-Pang Su
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Jung-Ta Kao
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- School of Medicine, China Medical University, Taichung
| | - Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- Graduate Institute of Biomedical Science, China Medical University, Taichung
- School of Chinese Medicine, China Medical University, Taichung
| | - Hung-Yao Chen
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Che-Wei Chang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Guan-Tarn Huang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- School of Medicine, China Medical University, Taichung
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung
- School of Medicine, China Medical University, Taichung
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Liu J, Xia S, Zhang B, Mohammed DM, Yang X, Zhu Y, Jiang X. Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives. Discov Oncol 2024; 15:259. [PMID: 38960980 PMCID: PMC11222362 DOI: 10.1007/s12672-024-01110-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 06/18/2024] [Indexed: 07/05/2024] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.
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Affiliation(s)
- Jianzhong Liu
- Clinical Laboratory, Wuhan No.7 Hospital, Zhong Nan 2nd Road, Wuhan, 430071, China
| | - Shuai Xia
- Department of Biochemistry and Molecular Biology, Jining Medical University, Jining, 272067, Shandong, China
| | - Baoyi Zhang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Cairo, Egypt
| | - Xiangliang Yang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Yanhong Zhu
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Xinnong Jiang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
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Chen D, Mao P, Sun C, Fan X, Zhu Q, Chen Z, He Z, Lou Y, Sun H. Prognostic Value of Combined Neutrophil-to-Lymphocyte Ratio and Imaging Tumor Capsule in Solitary Hepatocellular Carcinoma Patients after Narrow-Margin Hepatectomy. J Clin Med 2024; 13:351. [PMID: 38256485 PMCID: PMC10816149 DOI: 10.3390/jcm13020351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/15/2023] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND The study aimed to investigate the clinical value and prognostic patterns of the neutrophil-to-lymphocyte ratio (NLR) and imaging tumor capsule (ITC) in solitary hepatocellular carcinoma (HCC) patients undergoing narrow-margin hepatectomy. METHODS Data for solitary HCC patients treated with narrow-margin surgery were extracted from Shanghai General Hospital. Clinical features of recurrence-free survival (RFS), overall survival (OS), and early recurrence were investigated by Cox/logistic regression. The significant variables were subsequently incorporated into the nomogram pattern. Survival analysis stratified by NLR and ITC was also performed. RESULTS The study included a cohort of 222 patients, with median RFS and OS of 24.083 and 32.283 months, respectively. Both an NLR ≥ 2.80 and incomplete ITC had a significant impact on prognosis. NLR and ITC independently affected RFS and OS, whereas alpha-fetoprotein (AFP) and ITC were identified as independent factors for early relapse. The RFS and OS nomogram, generated based on the Cox model, demonstrated good performance in validation. The combination of NLR and ITC showed greater predictive accuracy for 5-year RFS and OS. Subgroups with an NLR ≥ 2.80 and incomplete ITC had the worst prognosis. CONCLUSIONS Both NLR and ITC significantly affected RFS, OS, and early recurrence among solitary HCC patients who underwent narrow-margin hepatectomy. The combination of NLR and ITC has the potential to guide rational clinical treatment and determine the prognosis.
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Affiliation(s)
- Desheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
| | - Pengjuan Mao
- Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
| | - Chen Sun
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
| | - Xuhui Fan
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
| | - Qi Zhu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
| | - Zeping Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
| | - Zeping He
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
| | - Yichao Lou
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
| | - Hongcheng Sun
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; (D.C.); (Q.Z.); (Z.C.); (Z.H.); (Y.L.)
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Heshmat-Ghahdarijani K, Sarmadi V, Heidari A, Falahati Marvasti A, Neshat S, Raeisi S. The neutrophil-to-lymphocyte ratio as a new prognostic factor in cancers: a narrative review. Front Oncol 2023; 13:1228076. [PMID: 37860198 PMCID: PMC10583548 DOI: 10.3389/fonc.2023.1228076] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 09/18/2023] [Indexed: 10/21/2023] Open
Abstract
The increasing incidence of cancer globally has highlighted the significance of early diagnosis and improvement of treatment strategies. In the 19th century, a connection was made between inflammation and cancer, with inflammation recognized as a malignancy hallmark. The neutrophil-to-lymphocyte ratio (NLR), calculated from a complete blood count, is a simple and accessible biomarker of inflammation status. NLR has also been proven to be a prognostic factor for various medical conditions, including mortality classification in cardiac patients, infectious diseases, postoperative complications, and inflammatory states. In this narrative review, we aim to assess the prognostic potential of NLR in cancer. We will review recent studies that have evaluated the association between NLR and various malignancies. The results of this review will help to further understand the role of NLR in cancer prognosis and inform future research directions. With the increasing incidence of cancer, it is important to identify reliable and accessible prognostic markers to improve patient outcomes. The study of NLR in cancer may provide valuable insights into the development and progression of cancer and inform clinical decision-making.
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Affiliation(s)
- Kian Heshmat-Ghahdarijani
- Cardiac Rehabilitation, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vida Sarmadi
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Afshin Heidari
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Sina Neshat
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Biostatistics and Epidemiology, University of California, San Francisco, San Francisco, CA, United States
| | - Sina Raeisi
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Motomura K, Kuwano A, Tanaka K, Koga Y, Masumoto A, Yada M. Potential Predictive Biomarkers of Systemic Drug Therapy for Hepatocellular Carcinoma: Anticipated Usefulness in Clinical Practice. Cancers (Basel) 2023; 15:4345. [PMID: 37686621 PMCID: PMC10486942 DOI: 10.3390/cancers15174345] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 08/21/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
In the systemic drug treatment of hepatocellular carcinoma, only the tyrosine kinase inhibitor (TKI) sorafenib was available for a period. This was followed by the development of regorafenib as a second-line treatment after sorafenib, and then lenvatinib, a new TKI, proved non-inferiority to sorafenib and became available as a first-line treatment. Subsequently, cabozantinib, another TKI, was introduced as a second-line treatment, along with ramucirumab, the only drug proven to be predictive of therapeutic efficacy when AFP levels are >400 ng/mL. It is an anti-VEGF receptor antibody. More recently, immune checkpoint inhibitors have become the mainstay of systemic therapy and can now be used as a first-line standard treatment for HCC. However, the objective response rate for these drugs is currently only 30% to 40%, and there is a high incidence of side effects. Additionally, there are no practical biomarkers to predict their therapeutic effects. Therefore, this review provides an overview of extensive research conducted on potential HCC biomarkers from blood, tissue, or imaging information that can be used in practice to predict the therapeutic efficacy of systemic therapy before its initiation.
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Affiliation(s)
- Kenta Motomura
- Department of Hepatology, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka 820-8505, Japan; (A.K.); (K.T.); (Y.K.); (A.M.); (M.Y.)
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9
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Zhang L, Zhang W, Wang J, Jin Q, Ma D, Huang R. Neutrophil-to-lymphocyte ratio predicts 30-, 90-, and 180-day readmissions of patients with hepatic encephalopathy. Front Med (Lausanne) 2023; 10:1185182. [PMID: 37457569 PMCID: PMC10348710 DOI: 10.3389/fmed.2023.1185182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 06/12/2023] [Indexed: 07/18/2023] Open
Abstract
Introduction Hepatic encephalopathy (HE) is a significant complication of cirrhosis, known to be associated with hospital readmission. However, few new serological indicators associated with readmission in HE patients have been identified and reported. The objective of our study was to identify simple and effective predictors reated to readmission in HE patients. Materials and methods We conducted a retrospective study at a single center on adult patients admitted with HE from January 2018 to December 2022. The primary endpoint was the first liver-related readmission within 30, 90, and 180 days, and we collected electronic medical records from our hospital for sociodemographic, clinical, and hospitalization characteristics. We utilized logistic regression analysis and multiple linear regression analysis to determine the predictors that were associated with the readmission rate and the length of the first hospitalization. Results A total of 424 patients were included in the study, among whom 24 (5.7%), 63 (14.8%), and 92 (21.7%) were readmitted within 30, 90, and 180 days, respectively. Logistic regression analysis showed that insurance status, alcoholic liver disease (ALD), ascites, the model for end-stage liver disease (MELD) score, and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with 30-, 90-, and 180-day readmissions. Age and hepatocellular carcinoma (HCC) were predictors of 90- and 180-day readmissions. ALD was identified as a unique predictor of readmission in men, while hypertension was a predictor of 180-day readmission in women. Variceal bleeding, chronic kidney disease, and MELD score were associated with the length of the first hospitalization. Conclusions NLR at discharge was identified as a significant predictor of 30-, 90- and 180-day readmissions in patients with HE. Our findings suggest that incorporating NLR into routine clinical assessments could improve the evaluation of the prognosis of liver cirrhosis.
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Tsai MC, Yong CC, Lin CC, Lee WC, Wang CC, Hung CH, Chen IH, Cheng YF, Hsiao CC, Hu TH, Chen CL. Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma. Hepatobiliary Surg Nutr 2023; 12:169-182. [PMID: 37124687 PMCID: PMC10129878 DOI: 10.21037/hbsn-21-196] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 08/26/2021] [Indexed: 11/06/2022]
Abstract
Background Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Results Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. Conclusions LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.
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Affiliation(s)
- Ming Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - I-Hsuan Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yu-Fan Cheng
- Liver Transplantation Center and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chang-Chun Hsiao
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
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Lee DS, Kim CW, Kim HY, Ku YM, Won YD, Lee SL, Sun DS. Association between Posttreatment Serum Platelet-to-Lymphocyte Ratio and Distant Metastases in Patients with Hepatocellular Carcinoma Receiving Curative Radiation Therapy. Cancers (Basel) 2023; 15:cancers15071978. [PMID: 37046639 PMCID: PMC10092989 DOI: 10.3390/cancers15071978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/07/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Background: We sought to investigate whether serum immune and inflammatory parameters can help to predict distant metastasis (DM) in patients with unresectable hepatocellular carcinoma (HCC) undergoing curative radiation therapy (RT). Methods: A total of 76 RT courses were analyzed. The following variables were included in the analysis: systemic inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), absolute lymphocyte count, lymphocyte-to-monocyte ratio, albumin, albumin-to-alkaline phosphatase ratio, RT-related parameters, and levels of total protein, hemoglobin, α-fetoprotein, and PIVKA-II. Distant control (DC) and overall survival (OS) rates were calculated and compared. Results: The mean age was 61.4 years, and most patients were men (n = 62, 81.6%). The median RT fraction number and fractional doses were 12 (range, 4–30) and 5 (range, 2–12) Gy, respectively. With a median follow-up of 12 (range, 3.1–56.7) months, the 1-year DC and OS rates were 64.4% and 55.2%, respectively. The development of DM significantly deteriorated OS (p = 0.013). In the multivariate analysis, significant independent prognostic indicators for DC and OS rates were the highest posttreatment PLR (≤235.7 vs. >235.7, p = 0.006) and the lowest posttreatment PNI (≤25.4 vs. >25.4, p < 0.001), respectively. Conclusions: Posttreatment serum PLR might be helpfully used as a predictive biomarker of DM in unresectable HCC patients undergoing RT. Future research is necessary to confirm our findings.
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Affiliation(s)
- Dong Soo Lee
- Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
- Correspondence:
| | - Chang Wook Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (C.W.K.); (H.Y.K.)
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (C.W.K.); (H.Y.K.)
| | - Young-Mi Ku
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (Y.-M.K.); (Y.D.W.); (S.-L.L.)
| | - Yoo Dong Won
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (Y.-M.K.); (Y.D.W.); (S.-L.L.)
| | - Su-Lim Lee
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (Y.-M.K.); (Y.D.W.); (S.-L.L.)
| | - Der Sheng Sun
- Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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Lin Z, Li H, He C, Yang M, Chen H, Yang X, Zhuo J, Shen W, Hu Z, Pan L, Wei X, Lu D, Zheng S, Xu X. Metabolomic biomarkers for the diagnosis and post-transplant outcomes of AFP negative hepatocellular carcinoma. Front Oncol 2023; 13:1072775. [PMID: 36845695 PMCID: PMC9947281 DOI: 10.3389/fonc.2023.1072775] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 01/26/2023] [Indexed: 02/11/2023] Open
Abstract
Background Early diagnosis for α-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) remains a critical problem. Metabolomics is prevalently involved in the identification of novel biomarkers. This study aims to identify new and effective markers for AFP negative HCC. Methods In total, 147 patients undergoing liver transplantation were enrolled from our hospital, including liver cirrhosis patients (LC, n=25), AFP negative HCC patients (NEG, n=44) and HCC patients with AFP over 20 ng/mL (POS, n=78). 52 Healthy volunteers (HC) were also recruited in this study. Metabolomic profiling was performed on the plasma of those patients and healthy volunteers to select candidate metabolomic biomarkers. A novel diagnostic model for AFP negative HCC was established based on Random forest analysis, and prognostic biomarkers were also identified. Results 15 differential metabolites were identified being able to distinguish NEG group from both LC and HC group. Random forest analysis and subsequent Logistic regression analysis showed that PC(16:0/16:0), PC(18:2/18:2) and SM(d18:1/18:1) are independent risk factor for AFP negative HCC. A three-marker model of Metabolites-Score was established for the diagnosis of AFP negative HCC patients with an area under the time-dependent receiver operating characteristic curve (AUROC) of 0.913, and a nomogram was then established as well. When the cut-off value of the score was set at 1.2895, the sensitivity and specificity for the model were 0.727 and 0.92, respectively. This model was also applicable to distinguish HCC from cirrhosis. Notably, the Metabolites-Score was not correlated to tumor or body nutrition parameters, but difference of the score was statistically significant between different neutrophil-lymphocyte ratio (NLR) groups (≤5 vs. >5, P=0.012). Moreover, MG(18:2/0:0/0:0) was the only prognostic biomarker among 15 metabolites, which is significantly associated with tumor-free survival of AFP negative HCC patients (HR=1.160, 95%CI 1.012-1.330, P=0.033). Conclusion The established three-marker model and nomogram based on metabolomic profiling can be potential non-invasive tool for the diagnosis of AFP negative HCC. The level of MG(18:2/0:0/0:0) exhibits good prognosis prediction performance for AFP negative HCC.
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Affiliation(s)
- Zuyuan Lin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Huigang Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Chiyu He
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Modan Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Hao Chen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Xinyu Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Jianyong Zhuo
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
| | - Wei Shen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Zhihang Hu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Linhui Pan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Di Lu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China,Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China,Zhejiang University School of Medicine, Hangzhou, China,*Correspondence: Xiao Xu,
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Kaibori M, Yoshii K, Kosaka H, Ota M, Komeda K, Ueno M, Hokutou D, Iida H, Matsui K, Sekimoto M. Preoperative Serum Markers and Risk Classification in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Study. Cancers (Basel) 2022; 14:5459. [PMID: 36358877 PMCID: PMC9658667 DOI: 10.3390/cancers14215459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 10/29/2022] [Accepted: 11/02/2022] [Indexed: 11/10/2022] Open
Abstract
Accurate risk stratification selects patients who are expected to benefit most from surgery. This retrospective study enrolled 225 Japanese patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent hepatectomy between January 2009 and December 2020 and identified preoperative blood test biomarkers to formulate a classification system that predicted prognosis. The optimal cut-off values of blood test parameters were determined by ROC curve analysis, with Cox univariate and multivariate analyses identifying prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. CART analysis revealed decision trees for recurrence-free survival (RFS) and overall survival (OS) and created three risk classifications based on machine learning of preoperative serum markers. Five-year rates differed significantly (p < 0.001) between groups: 60.4% (low-risk), 22.8% (moderate-risk), and 4.1% (high-risk) for RFS and 69.2% (low-risk), 32.3% (moderate-risk), and 9.2% (high-risk) for OS. No difference in OS was observed between patients in the low-risk group with or without postoperative adjuvant chemotherapy, although OS improved in the moderate group and was prolonged significantly in the high-risk group receiving chemotherapy. Stratification of patients with ICC who underwent hepatectomy into three risk groups for RFS and OS identified preoperative prognostic factors that predicted prognosis and were easy to understand and apply clinically.
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Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Kansai Medical University, Osaka 573-1191, Japan
| | - Kengo Yoshii
- Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University, Osaka 573-1191, Japan
| | - Masato Ota
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki 569-8686, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki 569-8686, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Daisuke Hokutou
- Department of Surgery, Nara Medical University, Kashihara 634-8521, Japan
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan
| | - Kosuke Matsui
- Department of Surgery, Kansai Medical University, Osaka 573-1191, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Osaka 573-1191, Japan
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Preoperative inflammatory markers as prognostic predictors after hepatocellular carcinoma resection: data from a western referral center. BMC Surg 2022; 22:329. [PMID: 36056350 PMCID: PMC9440527 DOI: 10.1186/s12893-022-01779-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 08/26/2022] [Indexed: 12/23/2022] Open
Abstract
Background Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown. Aim To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5–10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.
Methods Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS. Results In total, 161 consecutive adult patients were included. A high NLR (> 1.715) was associated with worse OS (P = 0.018). High NLR (> 2.475; P = 0.047) and PLR (> 100.25; P = 0.028) were predictors of short DFS. In HCC < 5 cm, MLR (> 1.715) was associated with worse OS (P = 0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS [hazard ratio (HR) 3.029; 95%CI 1.499–6.121; P = 0.002]. Conclusion Inflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12893-022-01779-6.
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Llovet JM, Singal AG, Villanueva A, Finn RS, Kudo M, Galle PR, Ikeda M, Callies S, McGrath LM, Wang C, Abada P, Widau RC, Gonzalez-Gugel E, Zhu AX. Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials. Clin Cancer Res 2022; 28:2297-2305. [PMID: 35247922 PMCID: PMC9662930 DOI: 10.1158/1078-0432.ccr-21-4000] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/19/2022] [Accepted: 03/02/2022] [Indexed: 01/07/2023]
Abstract
PURPOSE Ramucirumab is an effective treatment for patients with advanced hepatocellular carcinoma (aHCC) and baseline alpha-fetoprotein (AFP) ≥400 ng/mL. We aimed to identify prognostic and predictive factors of response to ramucirumab in patients with aHCC with AFP ≥400 ng/mL from the phase III REACH and REACH-2 randomized trials. PATIENTS AND METHODS Patients with aHCC, Child-Pugh class A with prior sorafenib treatment were randomized in REACH and REACH-2 (ramucirumab 8 mg/kg or placebo, biweekly). Meta-analysis of individual patient-level data (pooled population) from REACH (AFP ≥400 ng/mL) and REACH-2 was performed. A drug exposure analysis was conducted for those with evaluable pharmacokinetic data. To identify potential prognostic factors for overall survival (OS), multivariate analyses were performed using a Cox proportional hazards regression model. To define predictors of ramucirumab benefit, subgroup-by-treatment interaction terms were evaluated. RESULTS Of 542 patients (316 ramucirumab, 226 placebo) analyzed, eight variables had independent prognostic value associated with poor outcome (geographical region, Eastern Cooperative Oncology Group performance score ≥1, AFP >1,000 ng/mL, Child-Pugh >A5, extrahepatic spread, high neutrophil-to-lymphocyte ratio, high alkaline phosphatase and aspartate aminotransferase). Ramucirumab survival benefit was present across all subgroups, including patients with very aggressive HCC [above median AFP; HR: 0.64; 95% confidence interval (CI): 0.49-0.84] and nonviral aHCC (HR: 0.56; 95% CI: 0.40-0.79). While no baseline factor was predictive of a differential OS benefit with ramucirumab, analyses demonstrated an association between high drug exposure, treatment-emergent hypertension (grade ≥3), and increased ramucirumab benefit. CONCLUSIONS Ramucirumab provided a survival benefit irrespective of baseline prognostic covariates, and this benefit was greatest in patients with high ramucirumab drug exposure and/or those with treatment-related hypertension.
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Affiliation(s)
- Josep M. Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Augusto Villanueva
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Richard S. Finn
- Division of Hematology/Oncology, University of California, Los Angeles, California
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Peter R. Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | | | | | | | - Paolo Abada
- Eli Lilly and Company, Indianapolis, Indiana
| | | | | | - Andrew X. Zhu
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts
- Jiahui International Cancer Center, Jiahui Health, Shanghai, P.R. China
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Bae BK, Park HC, Yoo GS, Choi MS, Oh JH, Yu JI. The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment. Cancers (Basel) 2022; 14:2081. [PMID: 35565210 PMCID: PMC9102776 DOI: 10.3390/cancers14092081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/11/2022] [Accepted: 04/18/2022] [Indexed: 12/21/2022] Open
Abstract
Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.
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Affiliation(s)
- Bong Kyung Bae
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Joo Hyun Oh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
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The Impact of a Preoperative Staging System on Accurate Prediction of Prognosis in Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2022; 14:cancers14051107. [PMID: 35267414 PMCID: PMC8909481 DOI: 10.3390/cancers14051107] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Non-invasive biomarkers detected preoperatively are still inadequate for treatment decision making for patients with intrahepatic cholangiocarcinoma (ICC). In this study, we analyzed preoperative findings to establish a novel preoperative staging system (PRE-Stage) for patients with ICC. Methods: The clinical data of 227 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals were analyzed. Results: Cox proportional hazards regression analysis of survival revealed that a CRP−albumin−lymphocyte index < 3, central tumor location, and CA19-9 level > 40 U/mL were prognostic factors among the preoperatively obtained clinical findings (hazard ratios (HRs) of all three factors for disease-specific survival (DSS) and disease-free survival (DFS: 2.4−3.3 and 1.7−2.9; all p < 0.05). The PRE-Stage was developed using these three prognostic factors, and it was able to significantly predict DSS and DFS when the patients were stratified into four stages (p < 0.05). In addition, the PRE-Stage resulted in similar HRs as those of the Liver Cancer Study Group of Japan (LCSGJ) stage (HRs for DSS: PRE-Stage, 1.985; LCSGJ stage, 1.923; HRs for DFS: LCSGJ stage, 1.909, and PRE-Stage, 1.623, all p < 0.05). Conclusion: The PRE-Stage demonstrated similar accuracy in predicting the prognosis of ICC as that of the LCSGJ stage, which is based on postoperative findings. The PRE-Stage may contribute to appropriate treatment decision making.
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Hasan I, Lutfie L, Rinaldi I, Kurniawan J, Loho IM. Comparison Between Neutrophil-Lymphocyte Ratio and Systemic Immune-Inflammation Index as Predictors of One-Year Survival in Patients with Untreated Advanced Hepatocellular Carcinoma. J Gastrointest Cancer 2022; 54:135-146. [PMID: 35099753 DOI: 10.1007/s12029-021-00796-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) generally only come for treatment when cancer has reached an advanced stage, with very limited treatment options. There has not been an accurate predictor marker to be able to identify which group of patients may have better survival. This study wanted to analyze the role of the inflammatory status indices as predictors of 1-year survival in patients with advanced HCC who did not undergo therapy. METHODS This study has a retrospective cohort design using secondary data on subjects with advanced HCC who did not undergo therapy at Cipto Mangunkusumo Hospital and Dharmais Hospital. The neutrophil-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) were evaluated for their role as predictors of 1-year survival based on the area under receiving operator curve (AUROC). The best optimal cut-off for NLR and SII was decided based on the Youden index, followed by survival analysis based on those cut-offs. Confounding factors were analyzed with multivariate cox regression analysis. RESULTS A total of 196 subjects were included in the data analysis. One-year survival was 6.6%, with a median survival of 56 days (95% CI: 46-67). The NLR had a discriminatory ability based on AUROC of 0.667 (95% CI: 0.536-0.798; p = 0.044), with the optimal cut-off point to differentiate survival was 3.7513. The SII has a discriminatory ability based on AUROC of 0.766 (95% CI: 0.643-0.889; p = 0.001), with the optimal cut-off point to distinguish survival was 954.4782. SII had superiority in discriminatory ability (p = 0.0415). CONCLUSIONS The discriminatory ability based on AUROC of SII was better than that of NLR in predicting 1-year survival in patients with advanced HCC who did not undergo therapy.
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Affiliation(s)
- Irsan Hasan
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/ Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia
| | - Lutfie Lutfie
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia.
| | - Ikhwan Rinaldi
- Division of Medical Oncology Hematology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia
| | - Juferdy Kurniawan
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/ Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia
| | - Imelda Maria Loho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Dharmais National Cancer Center Hospital, Jakarta, Indonesia
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Development and internal validation of laboratory prognostic score to predict 14-day mortality in terminally ill patients with gastrointestinal malignancy. Support Care Cancer 2022; 30:4179-4187. [PMID: 35083539 DOI: 10.1007/s00520-021-06746-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 12/07/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Few studies have developed an easy scoring system for the short-term survival of patients with gastrointestinal (GI) malignancy. METHODS A total of 816 terminally ill patients with GI malignancy were admitted to our palliative care unit. They were randomly divided into the investigation (n = 490) and validation (n = 326) groups. A total of 19 laboratory blood parameters were analyzed. Receiver-operating characteristic analysis was performed for each blood factor, and the area under the curve was calculated to determine the predictive value for 14-day survival after the blood test. Multivariable logistic regression analysis was performed to identify significant independent prognostic factors for 14-day mortality. To develop a scoring system for 14-day mortality, the laboratory prognostic score for gastrointestinal malignancy (GI-LPS) was calculated using the sum of indices of the independent prognostic factors. RESULTS Multivariable analysis showed that 5 of 19 indices, namely total bilirubin ≥ 2.1 mg/dL, blood urea nitrogen ≥ 28 mg/dL, eosinophil percentage ≤ 0.5%, neutrophil-to-lymphocyte ratio ≥ 9.2, and platelet count ≤ 194 × 103/μL, were significant independent factors of 14-day survival. GI-LPS showed acceptable accuracy for 14-day mortality in the investigation and validation groups. GI-LPS 3 (including any three factors) predicted death within 14 days, with a sensitivity of 56-58%, a specificity of 82-87%, a positive predictive value of 48-50%, and a negative predictive value of 87-90%. CONCLUSIONS GI-LPS showed an acceptable ability to predict 14-day survival and can provide additional information to conventional prognostic scores.
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20
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Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma. HPB (Oxford) 2022; 24:101-115. [PMID: 34244053 DOI: 10.1016/j.hpb.2021.06.414] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 04/25/2021] [Accepted: 06/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. METHODS Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). RESULTS The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. CONCLUSION The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.
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Sugama Y, Miyanishi K, Osuga T, Tanaka S, Hamaguchi K, Ito R, Sakamoto H, Kubo T, Ohnuma H, Murase K, Takada K, Kobune M, Kato J. Combination of psoas muscle mass index and neutrophil/lymphocyte ratio as a prognostic predictor for patients undergoing nonsurgical hepatocellular carcinoma therapy. JGH Open 2021; 5:1335-1343. [PMID: 34950776 PMCID: PMC8674551 DOI: 10.1002/jgh3.12676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 08/07/2021] [Accepted: 11/04/2021] [Indexed: 12/25/2022]
Abstract
Background and Aim Reliable predictors for hepatocellular carcinoma (HCC) are urgently needed. The psoas muscle index (PMI) is a simple and rapid method for evaluating muscle atrophy. Furthermore, the neutrophil/lymphocyte ratio (NLR) is a prognostic factor that is easy to calculate in everyday clinical practice. We aimed to investigate the value of the PMI and NLR as prognostic factors for patients receiving nonsurgical HCC therapy, hepatic arterial infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), or molecular targeted drugs such as sorafenib (SOR) and lenvatinib (LEN). Methods We enrolled 87 patients with HCC who were treated with HAIC, TACE, SOR, or LEN. The primary endpoint was overall survival (OS) with variable PMI or NLR status. For Barcelona Clinic Liver Cancer (BCLC)‐B patients, useful prognostic factors were examined by comparing the OS between stratified groups. Prognostic factors including PMI and NLR were evaluated by univariate and multivariate analysis. Results Analysis of HAIC or TACE (HAIC/TACE) and SOR or LEN (SOR/LEN) patients showed significant differences in OS between low and high PMI. In patients treated with TACE, there was a significant difference in OS between low and high NLR. For BCLC‐B and low PMI, the prognosis was significantly worse for SOR/LEN than for TACE, although there was no difference for high PMI, suggesting that PMI may be useful for treatment selection. In addition, the prognostic formula composed of PMI, NLR, and up‐to‐seven criteria developed in the present study may be useful. Conclusion PMI and NLR are considered to be independent prognostic factors for HCC.
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Affiliation(s)
- Yusuke Sugama
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Koji Miyanishi
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Takahiro Osuga
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Shingo Tanaka
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan.,Department of Infection Control and Laboratory Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Kota Hamaguchi
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Ryo Ito
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Hiroki Sakamoto
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Tomohiro Kubo
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Hiroyuki Ohnuma
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Kazuyuki Murase
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Kohich Takada
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
| | - Masayoshi Kobune
- Department of Hematology Sapporo Medical University School of Medicine Sapporo Japan
| | - Junji Kato
- Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan
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Mouchli M, Reddy S, Gerrard M, Boardman L, Rubio M. Usefulness of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor after treatment of hepatocellular carcinoma." Review article. Ann Hepatol 2021; 22:100249. [PMID: 32896610 DOI: 10.1016/j.aohep.2020.08.067] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023]
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker which has been investigated as a prognostic indicator in post-therapeutic recurrence and survival of patients with HCC. Our aim was to review all studies that assessed the prognostic value of pre-treatment NLR in predicting patient survival, cancer recurrence, and graft survival in patients undergoing various therapies for HCC. We searched the database of PubMed and Google Scholar to review all studies that have the word "NLR" and the word "HCC." We included all studies that assessed pre-treatment NLR as a prognostic factor in predicting outcomes in HCC patients. We excluded studies that assessed the correlation between post-treatment NLR or dynamic changes in NLR after treatment and HCC outcomes in an effort to minimize the confounding effect of each treatment on NLR. We reviewed 123 studies that studied the correlation between pre-treatment NLR and patient survival, 72 studies that evaluated the correlation between pre-treatment NLR and tumor recurrence, 21 studies that evaluated the correlation between NLR and tumor behavior, and 4 studies that assessed the correlation between NLR and graft survival. We found a remarkable heterogeneity between the methods of the studies, which is likely responsible for the differences in outcomes. The majority of the studies suggested a correlation between higher levels of pre-treatment NLR and poor outcomes. We concluded that NLR is a reliable and inexpensive biomarker and should be incorporated into other prognostic models to help determine outcomes following HCC treatment.
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Affiliation(s)
- Mohamad Mouchli
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States; Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States; Cleveland Clinic Foundation, Division of Gastroenterology & Hepatology, Cleveland, OH, United States.
| | - Shravani Reddy
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
| | - Miranda Gerrard
- Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
| | - Lisa Boardman
- Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States
| | - Marrieth Rubio
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
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Tsai MC, Wang CC, Lee WC, Lin CC, Chang KC, Chen CH, Hung CH, Lin MT, Hsiao CC, Chen CL, Chien RN, Hu TH. Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection. Liver Cancer 2021; 11:22-37. [PMID: 35222505 PMCID: PMC8820175 DOI: 10.1159/000518940] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 08/09/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. AIMS The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. METHODS From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. RESULT After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027-2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763-12.558, p = 0.002), but not in early recurrence. CONCLUSIONS TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Che Lin
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chang-Chun Hsiao
- Division of Pulmonary and Critical Care Medicine, Graduate Institute of Clinical Medical Sciences, College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Linko Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,*Tsung-Hui Hu,
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Johnson PJ, Dhanaraj S, Berhane S, Bonnett L, Ma YT. The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study. Br J Cancer 2021; 125:714-716. [PMID: 34127809 PMCID: PMC8405698 DOI: 10.1038/s41416-021-01445-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 04/13/2021] [Accepted: 05/17/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND The neutrophil-lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). METHODS In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. RESULTS On entry into the study ('baseline'), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. CONCLUSION NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.
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Affiliation(s)
- Philip J. Johnson
- grid.10025.360000 0004 1936 8470Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Sofi Dhanaraj
- Liver Services, University Hospitals NHS Foundation Trust, Birmingham, UK
| | - Sarah Berhane
- grid.6572.60000 0004 1936 7486Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Laura Bonnett
- grid.10025.360000 0004 1936 8470Department of Health Data Science, University of Liverpool, Liverpool, UK
| | - Yuk Ting Ma
- grid.6572.60000 0004 1936 7486Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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Choi GH, Jang ES, Kim JW, Jeong SH. Prognostic role of plasma level of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor in hepatocellular carcinoma. World J Gastroenterol 2021; 27:4453-4467. [PMID: 34366616 PMCID: PMC8316901 DOI: 10.3748/wjg.v27.i27.4453] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/16/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Most hepatocellular carcinomas (HCCs) are hypervascular, with characteristic features of hepatic arterial supply to the tumor. The factors involved in tumor angiogenesis include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF).
AIM To investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival (OS) and progression-free survival (PFS).
METHODS Plasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1, Ang-2, and VEGF. Their associations with clinical characteristics, OS, and PFS were analyzed.
RESULTS The median plasma levels of Ang-1, Ang-2, and VEGF were 3216 pg/mL, 1684 pg/mL, and 26.5 pg/mL, respectively. The plasma level of Ang-2 showed a significant increase from early stage [Barcelona clinic liver cancer (BCLC) A] to intermediate (BCLC B) and advanced stage HCC (BCLC C/D), whereas Ang-1, VEGF, and alpha-fetoprotein (AFP) levels in the plasma did not show any such changes. Multivariable analysis, propensity score-matched analysis, and time-dependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and PFS. Neither Ang-1 nor VEGF was significantly associated with OS or PFS. The neutrophil-to-lymphocyte ratio was an independent factor for OS and PFS.
CONCLUSION The plasma levels of Ang-2 correlated with liver function, tumor stage, and tumor invasiveness, showing better performance in predicting OS and PFS than AFP, Ang-1, or VEGF.
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Affiliation(s)
- Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
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Harding-Theobald E, Yao FYK, Mehta N. Neutrophil-to-Lymphocyte Ratio Predicts High-Risk Explant Features and Waitlist Survival But Is Not Independently Associated With Recurrence or Survival Following Liver Transplantation for Hepatocellular Carcinoma. Liver Transpl 2021; 27:818-829. [PMID: 33570786 DOI: 10.1002/lt.26010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 01/28/2021] [Accepted: 01/31/2021] [Indexed: 12/11/2022]
Abstract
We assessed the prognostic significance and the clinical stability of the neutrophil-to-lymphocyte ratio (NLR) before liver transplantation (LT) in a large cohort of patients with hepatocellular carcinoma (HCC) from a region with a long waitlist time. A high preoperative NLR ≥5 has been reported to predict poor outcomes following LT for HCC, and the NLR has been incorporated into several prognostic models. We evaluated 758 patients with HCC with Model for End-Stage Liver Disease exceptions and listed for LT from 2002 to 2015 at a single LT center, of which 505 underwent LT and 253 dropped out before LT. The NLR was collected in all patients at LT and, if available, between 15 and 90 days before LT (NLR2) or at dropout. An NLR ≥5 was associated with microvascular invasion (MVI), poorer tumor differentiation, and more advanced pathology on explant. Patients with an NLR ≥5 exhibited no differences in alpha-fetoprotein, tumor burden at listing, or number of locoregional therapies compared with patients with an NLR <5. After a median post-LT follow-up of 4.7 years, overall survival and recurrence rates were similar for patients with an NLR ≥5 versus patients with an NLR <5. The NLR changed frequently, and 47% of patients whose NLR2 was ≥5 had an NLR <5 by LT. The NLR was ≥5 in 47.6% of patients at dropout compared with 14.9% of patients undergoing LT. Although the NLR at LT correlated with MVI and tumor stage at explant, the NLR did not predict post-LT survival or HCC recurrence. The NLR appeared to be a relatively unstable inflammatory marker during the immediate 3 months before LT for HCC.
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Affiliation(s)
| | - Francis Y K Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA.,Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
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Chen H, Song S, Li A, Ma D, Lin C, Qian X, Gao X, Shen X. Presurgical platelet-lymphocyte ratio for prognosis in advanced hypopharyngeal squamous cell carcinoma in individuals undergoing radical resection. Acta Otolaryngol 2021; 141:537-543. [PMID: 33872102 DOI: 10.1080/00016489.2021.1891456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Patient prognosis in hypopharyngeal carcinoma remains difficult to predict, necessitating new, readily available biomarkers. OBJECTIVE Platelet-lymphocyte ratio (PLR)'s effects on recurrence-free survival (RFS) and overall survival (OS) were evaluated in individuals undergoing radical resection for advanced hypopharyngeal squamous cell carcinoma (HSCC). METHODS A total of 89 patients were retrospectively assessed. PLR, and derived neutrophil-lymphocyte (dNLR) and neutrophil-lymphocyte (NLR) ratios were determined based on complete blood count. Then, the prognostic values of PLR, dNLR and NLR were assessed by univariate and multivariate Cox regression analyses adjusted for disease-specific prognostic factors. Endpoints of interest were RFS and OS. RESULTS The optimal cutoff of PLR was 98.815, based on which individuals were categorized into the high- (PLR ≥98.815) and low- (PLR <98.815) PLR groups. High PLR (p = .022) had a significant association with reduced RFS, which still showed significance in multivariable analysis (HR = 2.020, 95%CI: 1.076-3.794, p = .029). In univariate analysis, PLR (p = .046) and positive surgical margin (p = .021) also had significant associations with OS. CONCLUSION Elevated PLR has associations with increased risk of recurrence and reduced survival in advanced HSCC cases undergoing radical resection. High presurgical PLR may independently predict RFS. Therefore, further multi-institutional prospective studies are needed to better characterize the role of pre-operative blood PLR as prognostic factors in HSCC.
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Affiliation(s)
- Hong Chen
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Shenghua Song
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Ao Li
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Dengbin Ma
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Chuanyao Lin
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Xiaoyun Qian
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Xia Gao
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
| | - Xiaohui Shen
- Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, China
- Research Institution of Otolaryngology, Nanjing, China
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Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation. Mediators Inflamm 2021; 2021:6656996. [PMID: 33628115 PMCID: PMC7899762 DOI: 10.1155/2021/6656996] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 02/07/2023] Open
Abstract
Background It was reported that systemic immune inflammation index (SII) was related to poor prognosis in a variety of cancers. We aimed to investigate the ability of the prognostic predictors of SII in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing liver transplantation (LT). Methods The 28 iCCA patients who underwent LT at our hospital between 2013 and 2018 were reviewed. Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of SII. Patients were divided into the high and low SII groups according to the cut-off value. Results The 1-, 3-, and 5-year OS rates were significantly lower in the high SII group (85.7%, 28.6%, and 21.4%, respectively) than in the low SII group (92.9%, 71.4%, and 57.2%, respectively; P = 0.009). The 1-, 3-, and 5-year RFS rates were, respectively, 57.1%, 32.7%, and 21.8% in the high SII group and 85.7%, 61.1%, and 61.1% in the low SII group (P = 0.021). SII ≥ 447.48 × 109/L (HR 0.273, 95% CI 0.082–0.908; P = 0.034) was an independent prognostic factor for OS. Conclusions Our results showed that SII can be used to predict the survival of patients with iCCA who undergo LT.
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Hyperprogression in hepatocellular carcinoma: Illusion or reality? J Hepatol 2021; 74:269-271. [PMID: 33109354 DOI: 10.1016/j.jhep.2020.09.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 09/17/2020] [Indexed: 12/29/2022]
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Clinical importance of the absolute count of neutrophils, lymphocytes, monocytes, and platelets in newly diagnosed hepatocellular carcinoma. Sci Rep 2021; 11:2614. [PMID: 33510378 PMCID: PMC7844216 DOI: 10.1038/s41598-021-82177-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 01/18/2021] [Indexed: 02/08/2023] Open
Abstract
Although several studies have confirmed the clinical significance of the systemic inflammation markers in hepatocellular carcinoma (HCC), evaluating the clinical significance of each blood cell remains to be conducted. We aimed to evaluate the clinical importance of absolute counts of blood cells in the overall survival (OS) of patients with newly diagnosed HCC. We recruited patient cohorts from the prospective registry of newly diagnosed and previously untreated HCC at Samsung Medical Center, which included a training set of 6619 patients (2005–2013) and a validation set of 2084 patients (2014–2016). More than three-quarters of all patients had hepatitis B virus (HBV)-related HCC in both training and validation sets. The optimal cutoff values of the absolute counts of neutrophils, lymphocytes, monocytes, and platelets were 3917, 488, 1379, and 22,100, respectively, which correlated significantly with OS. The absolute blood cell counts categorized by each optimal cutoff value significantly correlated with liver function status determined by Child–Pugh class/albumin-bilirubin (ALBI) grade and the HCC burden determined by several staging systems/portal vein tumor thrombosis. Although the prognostic model based on these blood cells (ABC model) showed a lower prognostic ability than the Japan Integrated Staging or ALBI-T staging systems, it provided significant discrimination of survival in the subgroups of ALBI-T and showed the highest prognostic ability in the present study in the training and validation sets. Absolute counts of blood cells are independently associated with OS, though it is also significantly associated with liver function and tumor burden in newly diagnosed HCC.
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31
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Wang R, Silva-Junior G, Guo X, Qi X. Prognostic Assessment of Variceal Bleeding in Liver Cirrhosis. VARICEAL BLEEDING IN LIVER CIRRHOSIS 2021:161-169. [DOI: 10.1007/978-981-15-7249-4_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome. Adv Cancer Res 2020; 149:171-255. [PMID: 33579424 DOI: 10.1016/bs.acr.2020.10.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.
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Sun L, Jin Y, Hu W, Zhang M, Jin B, Xu H, Du S, Xu Y, Zhao H, Lu X, Sang X, Zhong S, Yang H, Mao Y. The Impacts of Systemic Immune-Inflammation Index on Clinical Outcomes in Gallbladder Carcinoma. Front Oncol 2020; 10:554521. [PMID: 33194617 PMCID: PMC7645045 DOI: 10.3389/fonc.2020.554521] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 09/14/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Systemic immune-inflammation index (SII) is considered to be a prognostic marker in several cancers. However, the prognostic value of baseline pre-operative SII in gallbladder carcinoma (GBC) has not been evaluated. This study aimed to determine the prognostic significance of SII and generate a predictive nomogram. Methods: We retrospectively studied 142 GBC patients who underwent surgical resection at the Peking Union Medical College Hospital between 2003 and 2017. SII, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were evaluated for their prognostic values. A multivariate Cox proportional hazards model was used for the recognition of significant factors. Then, the cohort was randomly divided into the training and the validation set. A nomogram was constructed using SII and other selected indicators in the training set. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram's clinical utility in both the training and the validation set. Results: The predictive accuracy of SII (Harrell's concordance index [C-index]: 0.624), NLR (C-index: 0.626), and LMR (C-index: 0.622) was evaluated. The multivariate Cox model showed that SII was a superior independent predictor than NLR and LMR. SII level (≥600) (hazard ratio [HR]: 1.694, 95% confidence interval [CI]: 1.069–2.684, p = 0.024), carbohydrate antigen (CA) 19-9 level (≥37 U/ml) (HR: 2.407, 95% CI: 1.472–3.933, p < 0.001), and TNM stage (p = 0.026) were selected to construct a nomogram for predicting overall survival (OS). The predictive ability of this model was assessed by C-index (0.755 in the training set, 0.754 in the validation set). Good performance was demonstrated by the calibration plot. A high net benefit was proven by decision curve analysis (DCA). Conclusion: SII is an independent prognostic indicator in GBC patients after surgical resection, and the nomogram based on it is a useful tool for predicting OS.
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Affiliation(s)
- Lejia Sun
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yukai Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Wenmo Hu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Mengyuan Zhang
- Peking Union Medical College (PUMC), PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Shouxian Zhong
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
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Yoneoka G, Bozhilov K, Wong LL. Prognostic ability of inflammation-based markers in radioembolization for hepatocellular carcinoma. ACTA ACUST UNITED AC 2020; 6. [PMID: 33134551 PMCID: PMC7597831 DOI: 10.20517/2394-5079.2020.57] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Aim: Inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have recently been used as prognostic indicators in hepatocellular carcinoma (HCC). We aimed to determine whether NLR and PLR may predict response to yttrium-90 transarterial radioembolization (TARE) as primary treatment for HCC. Methods: We performed a retrospective review of a prospectively collected database of HCC cases (1994–2019) and selected patients who received TARE as primary treatment (n = 42). Laboratory studies were used to calculate NLR and PLR. Response to TARE was determined using the modified response evaluation criteria in solid tumors (mRECIST). Patients were classified as non-responders (stable or progressive disease) or responders (partial or complete response) to treatment based on mRECIST. Results: Receiver operating characteristic curves identified a pre-treatment NLR cutoff of ≥ 2.83 and a pre-treatment PLR cutoff of ≥ 83 for predicting non-response to treatment. Pre-treatment NLR ≥ 2.83 was the only significant predictor of non-response to TARE in multivariate logistic regression analysis (odds ratio 7.83, P = 0.036). On time to progression analysis, both pre-treatment NLR ≥ 2.83 and pre-treatment PLR ≥ 83 were associated with a higher proportion of tumor progression at 6 months post-treatment (43.6% vs. 10.0%, P = 0.014, log-rank) and (38.6% vs. 0%, P = 0.010, log-rank), respectively. Conclusion: NLR confers prognostic value and may be superior to PLR in determining response to TARE as primary treatment for HCC. Future studies are necessary to validate these findings in a larger cohort.
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Affiliation(s)
- Grant Yoneoka
- Transplant Center, The Queen's Medical Center, Honolulu, HI 96813, USA
| | - Kliment Bozhilov
- Transplant Center, The Queen's Medical Center, Honolulu, HI 96813, USA.,Department of Surgery, University of Hawaii, John A. Burns School of Medicine, Honolulu, HI 96813, USA
| | - Linda L Wong
- Transplant Center, The Queen's Medical Center, Honolulu, HI 96813, USA.,Department of Surgery, University of Hawaii, John A. Burns School of Medicine, Honolulu, HI 96813, USA
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Finotti M, Vitale A, Volk M, Cillo U. A 2020 update on liver transplant for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:885-900. [PMID: 32662680 DOI: 10.1080/17474124.2020.1791704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 07/01/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma is the most frequent liver tumor and is associated with chronic liver disease in 90% of cases. In selected cases, liver transplantation represents an effective therapy with excellent overall survival. AREA COVERED Since the introduction of Milan criteria in 1996, numerous alternative selection systems to LT for HCC patients have been proposed. Debate remains about how best to select HCC patients for transplant and how to prioritize them on the waiting list. EXPERT OPINION The selection of the best scoring system to propose in the context of LT for HCC is far to be identified. In this review, we analyze and categorize the various selection systems, assessing their roles in the different decisional phases.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health , Loma Linda, California, USA
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
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Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
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Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
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Fu XT, Tang Z, Chen JF, Shi YH, Liu WR, Gao Q, Ding GY, Song K, Wang XY, Zhou J, Fan J, Ding ZB. Laparoscopic hepatectomy enhances recovery for small hepatocellular carcinoma with liver cirrhosis by postoperative inflammatory response attenuation: a propensity score matching analysis with a conventional open approach. Surg Endosc 2020; 35:910-920. [PMID: 32748270 DOI: 10.1007/s00464-020-07710-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 06/09/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND The concurrent presence of liver cirrhosis and hepatocellular carcinoma (HCC) poses a challenge for laparoscopic surgeons to establish a routine practice. The aim of this study was to gather evidence and produce recommendations on the safe and effective practice of laparoscopic hepatectomy for patients with solitary HCC (≤ 5 cm) and liver cirrhosis. METHODS Between October 2013 and October 2014, 356 curative hepatectomies were performed for patients pathologically diagnosed with solitary HCC (≤ 5 cm) accompanied by cirrhosis (stage 4 fibrosis). To overcome selection bias, a 1:2 match using propensity score matching analysis was conducted between laparoscopic and open hepatectomy. Perioperative outcomes were compared between the groups, including hospitalization, operation time, blood loss, and surgical complications. Perioperative inflammation-based markers, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were collected from medical records and analyzed. RESULTS There were 43 and 77 patients in the laparoscopic and open groups, respectively. The laparoscopic group had less hepatic inflow occlusion (16.3% vs. 61%; P < 0.001), shorter operation time (155 vs. 170 min; P = 0.004), and shorter postoperative hospital stay (4 vs. 7 days; P < 0.001). Although the difference was not significant (P = 0.154), the rate of postoperative complications tended to be lower in the laparoscopic group (2.3%) compared with the open group (9.1%). The increase in postoperative SII, NLR, and LMR for laparoscopic hepatectomy were significantly lower than for open hepatectomy. NLR < 5.8 on postoperative day 3 was significantly correlated with shorter hospital stay (P < 0.001). CONCLUSIONS Compared with open hepatectomy, laparoscopic hepatectomy for selected HCC patients, even in the presence of cirrhosis, might result in better perioperative outcomes and postoperative inflammatory response attenuation, and ultimately promote faster recovery. This provides evidence for considering routine laparoscopic hepatectomy through careful selection of patients with HCC.
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Affiliation(s)
- Xiu-Tao Fu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Zheng Tang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Jia-Feng Chen
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Ying-Hong Shi
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Wei-Ren Liu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Qiang Gao
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Guang-Yu Ding
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Kang Song
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China
| | - Xiao-Ying Wang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China.
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China.,Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China. .,Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, China.
| | - Zhen-Bin Ding
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 1609 Xietu Road, Shanghai, 200032, China.
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Abdallah MA, Wongjarupong N, Hassan MA, Taha W, Abdalla A, Bampoh S, Onyirioha K, Nelson M, Glubranson LA, Wiseman GA, Fleming CJ, Andrews JC, Mahipal A, Roberts LR. The efficacy, safety, and predictors of outcomes of transarterial radioembolization for hepatocellular carcinoma: a retrospective study. Expert Rev Gastroenterol Hepatol 2020; 14:619-629. [PMID: 32490691 DOI: 10.1080/17474124.2020.1777856] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy. METHODS A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS). RESULTS The median OS and the median PFS were12.9 (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS. CONCLUSION In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.
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Affiliation(s)
- Mohamed A Abdallah
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA.,Department of Internal Medicine, University of South Dakota Sanford School of Medicine , Sioux Falls, SD, USA
| | - Nicha Wongjarupong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Mohamed A Hassan
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Wesam Taha
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Abubaker Abdalla
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Sally Bampoh
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Kristeen Onyirioha
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Morgan Nelson
- Department of Internal Medicine, University of South Dakota Sanford School of Medicine , Sioux Falls, SD, USA
| | - Lyn A Glubranson
- Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Gregory A Wiseman
- Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Chad J Fleming
- Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - James C Andrews
- Division of Vascular and Interventional Radiology, Department of Radiology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Amit Mahipal
- Division of Hematology and Oncology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
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Chen Q, Li F, Zhong C, Zou Y, Li Z, Gao Y, Zou Q, Xia Y, Wang K, Shen F. Inflammation Score System using Preoperative Inflammatory Markers to Predict Prognosis for Hepatocellular Carcinoma after Hepatectomy: A Cohort Study. J Cancer 2020; 11:4947-4956. [PMID: 32742442 PMCID: PMC7378936 DOI: 10.7150/jca.45274] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/29/2020] [Indexed: 02/07/2023] Open
Abstract
Background: This study developed a novel inflammation score system to predict survival outcomes using preoperational inflammatory markers in hepatocellular carcinoma (HCC) after surgery. Materials and Methods: An inflammation score system was developed using five preoperative inflammatory markers based on the clinical data of 455 HCC patients (training cohort) receiving radical resection in the Eastern Hepatobiliary Surgery Hospital. The system was validated using a cohort from a different hospital (external validation). Kaplan-Meier curves and log-rank test were used to compare the survival of patients with different inflammation scores. A nomogram including inflammation scores for survival prediction was created to exhibit the risk factors of overall survival (OS). Results: The patients in the low-score group showed better OS and recurrence-free survival (RFS) in the training and external validation cohorts than those from the high-score group. Subgroup analysis showed that compared with patients in the training cohort from the high-score group, stage I (eighth TNM stage) patients in the low-score group exhibited better prognosis results, whereas the findings for Stage II and III patients were different. Multivariate Cox analysis revealed that high inflammation score is an independent risk factor of OS and RFS. The nomogram established using the inflammation score with the C-index value of 0.661 (95% confidence interval=0.624-0.698) revealed a good three- and five-year calibration curves. Conclusions: The inflammation score system based on five preoperative inflammatory markers well predicted the survival of HCC patients after surgery, especially in those at the early stage (Stage I).
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Affiliation(s)
- Qinjunjie Chen
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fengwei Li
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.,Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chengqian Zhong
- Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, China
| | - Yiran Zou
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zheng Li
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yuzhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, Jiangsu, China
| | - Qifei Zou
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yong Xia
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kui Wang
- Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Yu JI, Park HC, Yoo GS, Paik SW, Choi MS, Kim HS, Sohn I, Nam H. Clinical Significance of Systemic Inflammation Markers in Newly Diagnosed, Previously Untreated Hepatocellular Carcinoma. Cancers (Basel) 2020; 12:cancers12051300. [PMID: 32455607 PMCID: PMC7281027 DOI: 10.3390/cancers12051300] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/15/2020] [Accepted: 05/19/2020] [Indexed: 02/07/2023] Open
Abstract
This study aimed to investigate the clinical significance of systemic inflammation markers (SIMs)-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-in patients with newly diagnosed, previously untreated hepatocellular carcinoma (HCC). The present study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC from a single institution. The training set included 6619 patients from 2005 to 2013 and the validation set included 2084 patients from 2014 to 2016. The SIMs as continuous variables significantly affected the overall survival (OS), and the optimal cut-off value of NLR, PLR, and LMR was 3.0, 100.0, and 3.0, respectively. There were significant correlations between SIMs and the albumin-bilirubin grade/Child-Turcotte-Pugh class (indicative of liver function status) and the staging system/portal vein invasion (indicative of the tumor burden). The OS curves were well stratified according to the prognostic model of SIMs and validated using the bootstrap method (1000 times, C-index 0.6367, 95% confidence interval (CI) 0.6274-0.6459) and validation cohort (C-index 0.6810, 95% CI 0.6570-0.7049). SIMs showed significant prognostic ability for OS, independent of liver function and tumor extent, although these factors were significantly correlated with SIMs in patients with newly diagnosed, previously untreated HCC.
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Affiliation(s)
- Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.I.Y.); (G.S.Y.)
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.I.Y.); (G.S.Y.)
- Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
- Correspondence: ; Tel.: +82-2-3410-2612; Fax: +82-2-3410-2619
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.I.Y.); (G.S.Y.)
| | - Seung Woon Paik
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (S.W.P.); (M.S.C.)
| | - Moon Seok Choi
- Departments of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (S.W.P.); (M.S.C.)
| | - Hye-Seung Kim
- Statistics and Data Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (H.-S.K.); (I.S.)
| | - Insuk Sohn
- Statistics and Data Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (H.-S.K.); (I.S.)
| | - Heerim Nam
- Department of Radiation Oncology, Gangbook Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul 03181, Korea;
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Tada T, Kumada T, Hiraoka A, Michitaka K, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T, Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N, Shibata H, Ochi H, Yasuda S, Toyoda H, Fukunishi S, Ohama H, Kawata K, Nakamura S, Nouso K, Tsutsui A, Nagano T, Itokawa N, Hayama K, Arai T, Imai M, Joko K, Koizumi Y, Hiasa Y. Neutrophil-to-lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib. Liver Int 2020; 40:968-976. [PMID: 32064740 DOI: 10.1111/liv.14405] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/09/2020] [Accepted: 02/09/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. METHODS A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves. RESULTS Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival. CONCLUSIONS NLR can be associated with outcomes in patients with HCC treated with lenvatinib.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine, Himeji Red Cross Hospital, Himeji, Japan
| | - Takashi Kumada
- Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Hiroshi Shibata
- Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan
| | - Hironori Ochi
- Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Hideko Ohama
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | | | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Korenobu Hayama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kouji Joko
- Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
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Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma. Ann Surg 2020; 271:616-624. [PMID: 30870180 DOI: 10.1097/sla.0000000000003253] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Dai T, Lin G, Deng M, Zhu S, Li H, Yao J, Li H, Liu W, Yang Y, Chen G, Wang G. The prognostic significance of neutrophil-to-lymphocyte ratio at different time points in patients with hepatocellular carcinoma receiving liver resection. Transl Cancer Res 2020; 9:441-457. [PMID: 35117389 PMCID: PMC8798615 DOI: 10.21037/tcr.2019.11.29] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 11/05/2019] [Indexed: 11/25/2022]
Abstract
BACKGROUND Neutrophil-to-lymphocyte ratio (NLR) has been demonstrated a significant association with the prognosis of hepatocellular carcinoma (HCC). The current study aimed to evaluate the prognostic value of NLR at different time points in HCC patients receiving liver resection. METHODS Data were retrospectively collected from 195 HCC patients receiving liver resection. The preoperative NLR (pre-NLR), postoperative NLR (post-NLR) and corresponding changes of NLR (NLRc) at different time points were calculated. The disease-free survival (DFS) and overall survival (OS) was calculated by the Kaplan-Meier method and compared by the log-rank test. Both univariate and multivariate analyses were performed to evaluate their prognostic values for DFS and OS. And the prognostic significance of pre-NLR, post-NLRs, and NLRcs were further evaluated with subgroup analysis and with early and late recurrence of HCC. RESULTS Pre-NLR was not significantly correlated with DFS or OS (both P>0.05), whereas higher post-NLR at 4-8 weeks [NLR (4-8 w)] and 3-6 months [(NLR (3-6 m)] predicted worse DFS (P=0.023 and P<0.001, respectively) and OS (P=0.012 and P=0.001, respectively). The value of area under the curve (AUC) of NLR (3-6 m) were higher than NLR (4-8 w) for DFS (0.656 vs. 0.572) and OS (0.650 vs. 0.621). Multivariate analyses showed that NLRc (4-8 w) was not a significant predictor of DFS (P=0.369) or OS (P=0.173), while the NLRc (3-6 m) with 25% increase was found to be an independent factor for adverse DFS in patients with HCC (P=0.041). The AUC of NLRc (3-6 m) for DFS was 0.600. Subgroup analysis showed NLR (3-6 m) was significantly corrected to DFS (P<0.001) and OS (P=0.001) in patients with cirrhosis. And NLR (3-6 m) also showed with significant correlation with early recurrence (P<0.001), while NLR (4-8 w) was found with significant association both with early and late recurrence (P=0.037 and P=0.027, respectively). CONCLUSIONS The post-NLRs are significant predictors of clinical outcome in HCC patients receiving liver resection, and post-NLR and NLRc with a relatively long-term interval after operation have better prognostic values.
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Affiliation(s)
- Tianxing Dai
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Guozhen Lin
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Mingbin Deng
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Shuguang Zhu
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
| | - Haibo Li
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
| | - Jia Yao
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
| | - Guihua Chen
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen University, Guangzhou 510630, China
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Liu L, Gong Y, Zhang Q, Cai P, Feng L. Prognostic Roles of Blood Inflammatory Markers in Hepatocellular Carcinoma Patients Taking Sorafenib. A Systematic Review and Meta-Analysis. Front Oncol 2020; 9:1557. [PMID: 32064238 PMCID: PMC7000550 DOI: 10.3389/fonc.2019.01557] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 12/23/2019] [Indexed: 12/24/2022] Open
Abstract
Objective: The purpose of this meta-analysis is to investigate the effectiveness of the prognostic roles of blood inflammatory markers in hepatocellular carcinoma (HCC) patients receiving sorafenib. Methods: We carried out a comprehensive literature search in four databases. Study endpoints, hazard ratios (HRs) and the associated 95% confidence intervals (CI) for clinical outcomes, which were to assess therapeutic efficacy, were extracted. This meta-analysis was conducted by Review Manager 5.3. Results: We summarized the available evidence from 18 studies with a total of 2,745 cases. The pooled results showed that the synthesized HR favored patients with low pretreatment NLR (neutrophil-to-lymphocyte ratio), which also indicated that HCC patients with a lower baseline NLR may have a better response to sorafenib than those with higher NLR (HR = 1.76, 95% CI [1.44, 2.15], P < 0.00001, I2 = 68%). Significance was also observed for the prognostic function of the PLR (platelet-to-lymphocyte ratio) of HCC patients treated with sorafenib (HR = 1.49, 95% CI [1.16, 1.93], P = 0.002, I2 = 0%, P = 0.65). The subgroup analysis revealed that different gene backgrounds play a prominent role in the source of heterogeneity. Interestingly, the predictive effect on OS (overall survival) was more pronounced as the NLR cutoff value increased. Notably, a significant predictive effect of NLR on the clinical outcome was detected in HCC patients treated with sorafenib compared to those treated with tivantinib. Conclusion: In conclusion, the present study reported promising predictive biomarkers for HCC patients and notably indicated that HCC patients with a lower baseline NLR and PLR may have a better response to sorafenib than those with higher ones. Further large-scale prospective studies are required to determine the optimal NLR and PLR cutoff values, which are important for identifying the dominant populations for sorafenib treatment.
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Affiliation(s)
- Lixing Liu
- Department of Chinese Medicine, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Gong
- The General Hospital of Shenyang Military Region, Shenyang, China
| | - Qinglin Zhang
- Department of Chinese Medicine, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Panpan Cai
- Department of Chinese Medicine, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Feng
- Department of Chinese Medicine, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis. J Transl Med 2019; 17:390. [PMID: 31771612 PMCID: PMC6880547 DOI: 10.1186/s12967-019-02138-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 11/13/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably changed genes, and to find out better diagnostic and prognostic markers for HCC. METHODS A systematic review was performed by searching publications indexed in Pubmed from March 1, 2001 to July 1, 2016. Studies that reporting cDNA microarray profiles in HCC, containing both tumor and nontumor data and published in English-language were retrieved. The differentially expressed genes from eligible studies were summarized and ranked according to the frequency. High frequency genes were subjected to survival analyses. The expression and prognostic value of alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) was further evaluated in HCC datasets in Oncomine and an independent HCC tissue array cohort. The role of AGXT in HCC progression was evaluated by proliferation and migration assays in a human HCC cell line. RESULTS A total of 43 eligible studies that containing 1917 HCC patients were included, a list of 2022 non redundant abnormally expressed genes in HCC were extracted. The frequencies of reported genes were ranked. We finally obtained a list of only five genes (AGXT; ALDOB; CYP2E1; IGFBP3; TOP2A) that were differentially expressed in tumor and nontumor tissues across studies and were significantly correlated to HCC prognosis. Only AGXT had not been reported in HCC. Reduced expression of AGXT reflected poor differentiation of HCC and predicts poor survival. Knocking down of AGXT enhanced cell proliferation and migration of HCC cell line. CONCLUSIONS The present study supported the feasibility and necessity of systematic review on discovering new and reliable biomarkers for HCC. We also identified a list of high frequency prognostic genes and emphasized a critical role of AGXT deletion during HCC progression.
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Pu N, Yin H, Zhao G, Nuerxiati A, Wang D, Xu X, Kuang T, Jin D, Lou W, Wu W. Independent effect of postoperative neutrophil-to-lymphocyte ratio on the survival of pancreatic ductal adenocarcinoma with open distal pancreatosplenectomy and its nomogram-based prediction. J Cancer 2019; 10:5935-5943. [PMID: 31762803 PMCID: PMC6856566 DOI: 10.7150/jca.35856] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023] Open
Abstract
Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor. Open distal pancreatosplenectomy (ODPS) is prevalent in the patients of early PDAC located in pancreatic body or tail. However, the models for relapse or survival prediction in those patients are still limited. Postoperative neutrophil-to-lymphocyte rate (poNLR), a novel inflammation-based score, has been formulated to analyze the prognostic significance in PDAC patients with ODPS. Therefore, this study aims to generate a valuable prognostic nomogram for PDAC following ODPS. Methods: We retrospectively enrolled 97 patients of PDAC undergoing ODPS in this study. The Cox proportional hazards regression methodology was used in univariate and multivariate survival analyses to identify significant independent prognostic factors. The prognostic nomograms integrating poNLR into the American Joint Commission on Cancer (AJCC) staging system (8th edition) for predicting overall survival (OS) and relapse free survival (RFS) were established to achieve superior discriminatory abilities. Further, these prognostic nomograms were verified according to concordance index (C-index), calibrations and decision curve analyses (DCA). Results: The optimal cut-off value of poNLR for assessing OS determined by X-tile program was 14.1. Higher poNLR was associated with higher postoperative neutrophil (poNeutrophil), lower postoperative lymphocyte (poLymphocyte), lower preoperative lymphocyte-to-monocyte rate (preLMR) and higher △NLR (postoperative-preoperative NLR). In the univariate and multivariate analysis, poNLR was identified as an independent prognostic indicator for OS and RFS (P=0.044 and 0.028, respectively) and patients with higher poNLR level were probable to have shorter OS and RFS. Compared with the TNM staging system of the AJCC 8th edition, the nomogram comprising of poNLR and AJCC 8th edition exhibited superior predictive accuracy for OS and RFS. Conclusions: poNLR can be a proven, inexpensive and novel survival predictor of PDAC patients with ODPS. One more advanced and accurate predictive model will be achieved to assist in risk stratification via the incorporation of poNLR into nomograms.
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Affiliation(s)
- Ning Pu
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Hanlin Yin
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Guochao Zhao
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Abulimiti Nuerxiati
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Dansong Wang
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Xuefeng Xu
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Tiantao Kuang
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Dayong Jin
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
| | - Wenchuan Wu
- Department of General Surgery, Zhongshan Hospital, Institute of General Surgery and Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
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Predictive Effects of Inflammatory Scores in Patients with BCLC 0-A Hepatocellular Carcinoma after Hepatectomy. J Clin Med 2019; 8:jcm8101676. [PMID: 31614976 PMCID: PMC6832545 DOI: 10.3390/jcm8101676] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 10/01/2019] [Accepted: 10/10/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Inflammatory markers are regarded as prognostic factors of the outcomes of hepatocellular carcinoma (HCC). Examples include the neutrophil-to-lymphocyte ratio (NLR); platelet to lymphocyte ratio (PLR); the albumin and lymphocyte counts used in the prognostic nutritional index (PNI); and the neutrophil, lymphocyte, and platelet counts used in the systemic immune-inflammation index (SII). This study evaluates the effects of PNI, NLR, PLR, and SII to predict recurrence and survival in patients with Barcelona Clinic Liver Cancer (BCLC) stages 0-A of HCC after hepatectomy. Methods: This retrospective study was conducted at Kaohsiung Chung-Gung Memorial Hospital, Taiwan. The study enrolled 891 patients (77.9% males; mean age 58.53 ± 11.60 years) with BCLC stage 0/A HCC undergoing hepatectomy between 2001 and 2016. PNI, NLR, PLR and SII were measured before hepatectomy. Results: High NLR (>1.8) was adversely associated with overall survival (p = 0.032). Low PNI (≤45) was adversely associated with overall survival and disease-free survival (p < 0.001). Low SII (≤45) also had an adverse association with overall survival (p = 0.008) and disease-free survival (p < 0.001). Diabetes mellitus, cirrhosis, microvascular invasion, low PNI (≤45), and low SII (≤160) were independently associated with poor overall survival in a multivariate analysis. HCV infection, diabetes mellitus, cirrhosis, microvascular invasion, low PNI, and low SII were independent prognostic factors of recurrent HCC. The combined use of PNI and SII provided improved prognostic information. Conclusions: Low PNI and low SII are significantly poor prognostic factors for overall survival and recurrence in patients with BCLC 0-A hepatocellular carcinoma after hepatectomy.
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Changes in the neutrophil-to-lymphocyte ratio predict the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib. Eur J Gastroenterol Hepatol 2019; 31:1250-1255. [PMID: 30925530 DOI: 10.1097/meg.0000000000001405] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Although sorafenib is the first systemic therapy to show survival benefit for advanced hepatocellular carcinoma (HCC), its survival benefit is variable for HCC. Systemic inflammation may be associated with survival in HCC. We investigated the use of systemic inflammation markers, including neutrophil-to-lymphocyte ratio (NLR), in the prognosis of sorafenib-treated HCC patients. PATIENTS AND METHODS We retrospectively analyzed data of 82 patients with advanced HCC who received sorafenib as the first-line treatment. Data on pretreatment and post-treatment (2-3 months after initiating sorafenib therapy, first tumor response evaluation day) clinical, laboratory, and tumor characteristics were collected. Survival-related prognostic factors were analyzed. RESULTS Patients were mostly in the intermediate (12.2%) or advanced (87.8%) Barcelona Clinic Liver Cancer stages. Fifty-six (68.3%) patients had vascular invasion and 34 (41.5%) patients had extrahepatic disease. The median progression-free survival (PFS) and overall survival (OS) were 4.7 months [95% confidence interval (CI): 2.8-6.5 months] and 4.7 months (95% CI: 2.8-6.5 months). In multivariate analysis for OS, diarrhea (hazard ratio: 0.588; 95% CI: 0.348-0.993) and NLR decline (decreased compared with pretreatment) (hazard ratio: 0.479; 95% CI: 0.300-0.765) were independent factors of good OS. In the NLR decline group, the median PFS and OS were 7.1 and 7.3 months, respectively. In the NLR nondecline group, the median PFS and OS were 3.0 and 3.2 months, respectively. The difference in OS between the two groups was significant (P = 0.004). CONCLUSION A change in NLR after sorafenib therapy was associated with a better prognosis in patients with advanced HCC.
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Utility of Prognostic Prediction Models in the Terminal Stage of Gastrointestinal Cancer. J Gastrointest Cancer 2019; 51:515-519. [PMID: 31256333 DOI: 10.1007/s12029-019-00270-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE For patients receiving palliative care, information about prognosis is important to help them set priorities and expectations for care and to assist clinicians in decision-making. The purpose of this study was to investigate prognostic models applicable to the terminal stage of gastrointestinal cancer, especially in terms of accuracy of prediction regarding 3-week survival. METHODS We validated retrospectively the accuracy of a prognosis prediction model for 354 end-stage gastrointestinal cancer patients who underwent palliative care at our hospital. Using receiver operating characteristic analysis and the area under the curve (AUC), we selected the cut-off value for 3-week survival and evaluated the predictive ability using sensitivity, specificity, positive predictive value, negative predictive value, and accurate diagnosis rate. RESULTS In our analysis of various models, Palliative Prognostic Index (PPI) and Biological Prognostic Score (BPS) version 3 showed excellent predictive performance with AUCs of 0.85 and 0.83, respectively, and accurate diagnosis rates of 80.0 and 79.0, respectively. BPS version 2 showed fair predictive performance with an AUC of 0.76 and an accurate diagnosis rate of 72.0. Using these models, stratification of prognostic prediction was possible. CONCLUSIONS PPI and BPS were found to be accurate prediction models for short-term survival of terminal gastrointestinal cancer patients.
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Meischl T, Rasoul-Rockenschaub S, Györi G, Sieghart W, Reiberger T, Trauner M, Soliman T, Berlakovich G, Pinter M. C-reactive protein is an independent predictor for hepatocellular carcinoma recurrence after liver transplantation. PLoS One 2019; 14:e0216677. [PMID: 31141535 PMCID: PMC6541257 DOI: 10.1371/journal.pone.0216677] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Serum C-reactive protein (CRP) is a prognostic factor for overall survival (OS) and recurrence of hepatocellular carcinoma (HCC) in patients treated with resection or non-surgical treatment. Here, we investigated the association of elevated CRP (≥1 vs. <1 mg/dL) with (i) recurrence of HCC and (ii) OS after liver transplantation (LT). METHODS Adult HCC patients undergoing orthotopic deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed. RESULTS Among 216 patients included, 132 (61.1%) were transplanted within the Milan criteria and forty-two patients (19.4%) had microvascular invasion on explant histology. Seventy patients (32.4%) showed elevated CRP (≥ 1 mg/dL). On multivariate analysis, a CRP ≥ 1 mg/dL was an independent risk factor for HCC recurrence with a 5-year recurrence rate of 27.4% vs. 16.4% (HR 2.33; 95% CI 1.13-4.83; p = 0.022). OS was similar in patients with normal vs. elevated CRP levels. CONCLUSIONS Elevated serum CRP is associated with HCC recurrence after LT and may be a marker for more aggressive tumor biology. Future studies should evaluate whether patients with elevated pre-transplant CRP levels benefit from closer monitoring for HCC recurrence.
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Affiliation(s)
- Tobias Meischl
- Division of Gastroenterology und Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | | | - Georg Györi
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology und Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology und Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology und Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Soliman
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Gabriela Berlakovich
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology und Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
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