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Liu G, Tang F, Wang T, Yan JQ, Li FH, Ha FS, Zhang X, Jing L, Liang J. Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study. World J Gastroenterol 2025; 31:105004. [PMID: 40248371 PMCID: PMC12001200 DOI: 10.3748/wjg.v31.i14.105004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/24/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Patients with acute-on-chronic liver failure (ACLF) have a high mortality rate, poor prognosis, and often experience concurrent thrombocytopenia and bleeding events. AIM To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in patients with ACLF with concomitant severe thrombocytopenia. METHODS This was a prospective, open-label study. We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group, with 35 patients in each group. Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days, while patients in the control group did not receive rhTPO treatment. The primary endpoint was the proportion of patients with platelet count > 50 × 109/L on day 14. RESULTS The proportion of patients with platelet count > 50 × 109/L on day 14 was 60.7% in the rhTPO group, which was significantly higher than that (12.0%) in the control group (P < 0.001). The platelet count in the rhTPO group on day 14 was 64 × 109/L, exceeding the baseline of 28 × 109/L. Compared to the control group, the rhTPO group exhibited a significant increase in platelet count from baseline (P < 0.05). Model for end-stage liver disease score, albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection. The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL, respectively, showing a significant increase from baseline (P < 0.05). Eight (22.9%) patients had bleeding events in the control group compared with four (11.4%) in the rhTPO group. The incidence of 90-day mortality was also higher in the control group (6, 17.1%) than that in the rhTPO group (3, 8.6%). CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events, with a good safety profile.
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Affiliation(s)
- Gang Liu
- Department of Internal Medicine, The Third Central Clinical College of Tianjin Medical University, Tianjin 300300, China
- Department of Internal Medicine, Tianjin Dongli Hospital, Tianjin 300300, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Tao Wang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Jun-Qing Yan
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Feng-Hui Li
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Fu-Shuang Ha
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Xu Zhang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Li Jing
- Department of Medical Laboratory, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
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Nelaturi P, Kademani SP, Siva Subramanian V, Ravikumar S. Noninvasive Biomarkers for Alcohol-Related Liver Disease-A Proteomic Related Preliminary Report. Indian J Clin Biochem 2024; 39:392-400. [PMID: 39005863 PMCID: PMC11239637 DOI: 10.1007/s12291-023-01120-9] [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: 08/22/2022] [Accepted: 02/20/2023] [Indexed: 03/06/2023]
Abstract
Increased alcohol intake over decades leads to progressive alcohol-related liver disease (ALD) and contributes to increased mortality. It is characterized by reduced platelet count. Platelets have a role in protecting vascular integrity and involved in liver regeneration. Alcohol affects the platelet count and its function. Platelet function is regulated by their proteins, released during pathophysiological conditions. Therefore, platelet proteome plays a vital role during ALD. This preliminary study consists of 10 patients with ALD. It includes the preparation of human platelets for the proteomic approach. We performed liquid chromatography-mass spectrometry for the samples. A total of 536 proteins were identified in patients with ALD of which 31 proteins were mentioned as a candidate based on their clinical significance. The advancement of diagnostic or therapeutic tools based on the application of platelet proteins in ALD is still far off. Platform for platelet and its proteome research may give diagnostic and prognostic insights into ALD. Platelet proteomes could possibly be concluded as therapeutic and potential diagnostic or prognostic markers in ALD. Supplementary Information The online version contains supplementary material available at 10.1007/s12291-023-01120-9.
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Affiliation(s)
- Prabhudas Nelaturi
- Multi-Disciplinary Center for Biomedical Research, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (Deemed to Be University), Kirumampakkam, Puducherry, 607402 India
| | - Sangeetha P Kademani
- Multi-Disciplinary Center for Biomedical Research, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (Deemed to Be University), Kirumampakkam, Puducherry, 607402 India
| | - Vithiavathi Siva Subramanian
- Department of General Medicine, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (Deemed to Be University), Kirumampakkam, Puducherry, 607402 India
| | - Sambandam Ravikumar
- Multi-Disciplinary Center for Biomedical Research, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (Deemed to Be University), Kirumampakkam, Puducherry, 607402 India
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Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges. JOURNAL OF ONCOLOGY 2022; 2022:9138195. [PMID: 36405248 PMCID: PMC9668468 DOI: 10.1155/2022/9138195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/28/2022] [Accepted: 10/11/2022] [Indexed: 11/10/2022]
Abstract
Background Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 109/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown. Methods Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled. Avatrombopag dose, peak and absolute platelet count increase, combination treatment with other thrombopoietic agents, responder (peak count ≥50 × 109/L with absolute increase ≥20 × 109/L) rate, and anticancer treatment effect were analyzed. Thrombosis and bleeding events were assessed. Results In total, 93 patients were enrolled, with 72 and 21 in the CLD and non-CLD groups, respectively. Patients with CLD had hepatitis B or C, larger spleen volume, and a higher cirrhosis degree. Baseline platelet counts were similar between two groups (median, 37.0 × 109/L vs. 39.0 × 109/L; P=0.594), while patients without CLD had higher peak platelet (median, 134.0 × 109/L vs. 74.0 × 109/L; P=0.015) and absolute increase (median, 101.0 × 109/L vs. 41.0 × 109/L; P=0.020) after avatrombopag treatment. The responder rate was higher in patients without CLD (100% vs. 76.4%; P=0.010). Combined avatrombopag with other thrombopoietic agents significantly increased platelet count; repeated use of avatrombopag produced similar effects with that of initial treatment. Concerning anticancer treatment effect, patients who responded to avatrombopag had a higher disease control rate. No thrombosis or hemorrhagic events were observed, even in patients with portal vein tumor thrombosis. Conclusion Avatrombopag was safe and effective and ensured successful implementation of anticancer treatment in liver cancer patients with severe thrombocytopenia, accompanied with or without CLD.
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Ding Z, Wu H, Zeng Y, Kuang M, Yang W, Meng Z, Chen Y, Hao C, Zou S, Sun H, Liu C, Lin K, Shi G, Wang X, Fu X, Chen R, Chen Y, Liang R, Kano T, Pan H, Yang S, Fan J, Zhou J. Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures. Hepatol Int 2022; 17:180-189. [PMID: 36258065 PMCID: PMC9895009 DOI: 10.1007/s12072-022-10421-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 09/09/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.
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Affiliation(s)
- Zhenbin Ding
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Hong Wu
- Department of Liver Surgery and Liver Transplantation, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan China
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025 Fujian China
| | - Ming Kuang
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat Sen University, Guangzhou, 510080 Guangdong China
| | - Wei Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061 Shanxi China
| | - Zhiqiang Meng
- Minimally Invasive Therapy Center, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
| | - Yajin Chen
- Department of Hepatobiliary Surgery, Sun Yat Sen Memorial Hospital of Sun Yat Sen University, Guangzhou, 510120 Guangdong China
| | - Chunyi Hao
- Department of Hepatobiliary Surgery, Beijing Cancer Hospital, Beijing, 100142 China
| | - Shubing Zou
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006 Jiangxi China
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Chang Liu
- Department of Liver Surgery and Liver Transplantation, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan China
| | - Kecan Lin
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025 Fujian China
| | - Guoming Shi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Xiaoying Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Xiutao Fu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Rongxin Chen
- Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, 200032 China
| | - Yi Chen
- Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, 200032 China
| | - Ruifang Liang
- Eddingpharm Co, Ltd, Unit 122-129, Building A3, No. 700, Wanrong Road, Shanghai, China
| | - Takeshi Kano
- Shionogi & Co, Ltd, 3-13, Imabashi 3-chome, Chuou-ku, Osaka, 541-0042 Japan
| | - Huiyan Pan
- Shionogi & Co, Ltd, 3-13, Imabashi 3-chome, Chuou-ku, Osaka, 541-0042 Japan
| | - Suna Yang
- Eddingpharm Co, Ltd, Unit 122-129, Building A3, No. 700, Wanrong Road, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China ,Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032 China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China ,Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032 China
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