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Nanizawa E, Tamaki Y, Yakura T, Otsuka S, Hatayama N, Naito M. The impact of a short-term high-fat diet on coagulation function in a mouse model and its role in exacerbating concanavalin A-induced liver injury. BMC Nutr 2024; 10:158. [PMID: 39696700 DOI: 10.1186/s40795-024-00966-3] [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: 08/13/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Recently, the number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced condition, metabolic dysfunction-associated steatohepatitis (MASH), has been increasing. These patients are at a higher risk of cardiovascular events and thromboembolism. However, the direct impact of high-fat diet (HFD), a cause of MASLD, on liver coagulation function is not well understood. Previously, we demonstrated that a short-term, 4-day intake of a HFD exacerbates concanavalin A (Con A)-induced acute liver injury in mice by promoting coagulation and inflammation. This model demonstrates that the liver exposed to a short-term HFD is vulnerable even before disease onset. In this study, using this model, we elucidated the detailed mechanisms by which short-term HFD intake promotes coagulation, considering primary and secondary hemostasis. METHODS C57BL/6 mice normally fed a normal diet (ND) were subjected to a HFD for 4 days. Liver tissue and blood samples were collected before and 4 and 24 h after Con A administration. Histological analysis, flow cytometry for platelet analysis, and blood coagulation tests related to secondary hemostasis were performed. RESULTS Even with short-term consumption of a HFD alone, platelet and fibrinogen levels increased in the peripheral blood and liver. Additionally, when Con A was administered to mice on a short-term HFD, an increase in P-selectin expression was observed in the liver, with no upregulation in peripheral blood platelets. Furthermore, in mice subjected to a short-term HFD and treated with Con A, prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed. CONCLUSIONS Consuming a HFD in short-term can enhance primary and secondary hemostasis, thereby increasing the risk of thrombosis. These conditions are presumed to be a risk factor that exacerbates Con A-induced liver injury. The findings provide insight into early intervention strategies for chronic liver diseases, such as MASLD and MASH.
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Affiliation(s)
- Eri Nanizawa
- Department of Anatomy, Aichi Medical University, 1-1, Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan.
| | - Yuki Tamaki
- Department of Anatomy, Aichi Medical University, 1-1, Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan
| | - Tomiko Yakura
- Department of Anatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-Ku, Tokyo, 160-8402, Japan
| | - Shun Otsuka
- Department of Anatomy, Aichi Medical University, 1-1, Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan
| | - Naoyuki Hatayama
- Department of Anatomy, Aichi Medical University, 1-1, Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan
| | - Munekazu Naito
- Department of Anatomy, Aichi Medical University, 1-1, Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan
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Liu ZW, Song T, Wang ZH, Sun LL, Zhang S, Yu YZ, Wang WW, Li K, Li T, Hu JH. Predicting Portal Pressure Gradient in Patients with Decompensated Cirrhosis: A Non-invasive Deep Learning Model. Dig Dis Sci 2024; 69:4392-4404. [PMID: 39466491 DOI: 10.1007/s10620-024-08701-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 10/18/2024] [Indexed: 10/30/2024]
Abstract
BACKGROUND A high portal pressure gradient (PPG) is associated with an increased risk of failure to control esophagogastric variceal hemorrhage and refractory ascites in patients with decompensated cirrhosis. However, direct measurement of PPG is invasive, limiting its routine use in clinical practice. Consequently, there is an urgent need for non-invasive techniques to assess PPG. AIM To develop and validate a deep learning model that predicts PPG values for patients with decompensated cirrhosis and identifies those with high-risk portal hypertension (HRPH), who may benefit from early transjugular intrahepatic portosystemic shunt (TIPS) intervention. METHODS Data of 520 decompensated cirrhosis patients who underwent TIPS between June 2014 and December 2022 were retrospectively analyzed. Laboratory and imaging parameters were used to develop an artificial neural network model for predicting PPG, with feature selection via recursive feature elimination for comparison experiments. The best performing model was tested by external validation. RESULTS After excluding 92 patients, 428 were included in the final analysis. A series of comparison experiments demonstrated that a three-parameter (3P) model, which includes the international normalized ratio, portal vein diameter, and white blood cell count, achieved the highest accuracy of 87.5%. In two distinct external datasets, the model attained accuracy rates of 85.40% and 90.80%, respectively. It also showed notable ability to distinguish HRPH with an AUROC of 0.842 in external validation. CONCLUSION The developed 3P model could predict PPG values for decompensated cirrhosis patients and could effectively distinguish HRPH.
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Affiliation(s)
- Zi-Wen Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Tao Song
- Peking University, 5, Yiheyuan Road, Haidian District, Beijing, China
| | - Zhong-Hua Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Lin-Lin Sun
- Department of Interventional Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Shuai Zhang
- Department of Interventional Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Yuan-Zi Yu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Wen-Wen Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Kun Li
- Department of Gastroenterology, The First Hospital Affiliated With Shandong First Medical University, 16766, Jingshi Road, Ji'nan, Shandong Province, China
| | - Tao Li
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China
| | - Jin-Hua Hu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Rd, Ji'nan, Shandong Province, China.
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Liu L, Huang C, Nie Y, Zhang Y, Zhou J, Zhu X. Low platelet to high-density lipoprotein ratio predicts poor short-term prognosis in hepatitis B-related acute-on-chronic liver failure. BMC Infect Dis 2024; 24:888. [PMID: 39210311 PMCID: PMC11363422 DOI: 10.1186/s12879-024-09769-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is characterized by a systemic inflammatory response, predominantly associated with hepatitis B virus in the Asia-Pacific region, with a high short-term mortality rate. The platelet to high-density lipoprotein ratio (PHR) has been used to predict the prognosis of patients with various inflammatory diseases. We aim to is to use the PHR to predict the short-term prognosis of patients with HBV-ACLF. METHOD In this study, we retrospectively analyzed clinical data from 270 HBV-ACLF patients. Using logistic regression, we identified independent risk factors for short-term mortality and developed a prognostic model. This model was then validated, compared, and its clinical utility assessed via decision curve analysis (DCA). RESULTS Among the 270 HBV-ACLF patients, 98 patients died within 28 days. The deceased group exhibited a higher proportion of severe hepatic encephalopathy and ascites. Additionally, there was a statistically significant difference (P = 0.046) in the novel inflammation scoring system, PHR, between the two groups. Following stringent variable selection, PHR was identified as a predictive factor for short-term mortality in HBV-ACLF patients using logistic regression analysis (OR: 0.835 (0.756-0.999), P = 0.009), and it exhibited a synergistic effect with certain traditional scores. The prognostic model constructed based on PHR demonstrated a superior ability to predict short-term mortality compared to traditional scores such as Child-Turcotte-Pugh (AUC: 0.889). Evaluation using calibration curves and decision curve analysis (DCA) suggested its practical utility. CONCLUSION PHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death.
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Affiliation(s)
- Linxiang Liu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China
| | - Chenkai Huang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China
| | - Yuan Nie
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China
| | - Yue Zhang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China
| | - Juanjuan Zhou
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China.
| | - Xuan Zhu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, Yongwaizhengjie Road, Donghu District Nanchang 330006, Nanchang, Jiangxi, China.
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Zanetto A, Toffanin S, Campello E, Radu CM, Gavasso S, Burra P, Russo FP, Senzolo M, Simioni P. Reticulated platelets are increased and hyper-activated in patients with cirrhosis, especially those with poor outcome. Dig Liver Dis 2024; 56:1327-1334. [PMID: 38553338 DOI: 10.1016/j.dld.2024.03.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/26/2024] [Accepted: 03/11/2024] [Indexed: 07/29/2024]
Abstract
BACKGROUND Reticulated platelets (RePLT) are emergency circulating platelets released to contrast peripheral platelet destruction. AIM We conducted a prospective study to [a] characterize RePLT in cirrhosis; [b] evaluate the association between RePLT and hepatic decompensation/death. METHODS Cirrhosis patients without hepatocellular carcinoma were prospectively recruited and underwent assessment of RePLT and thrombopoietin (TPO). RePLT were evaluated by cytofluorimetry and immuno-fluorescence microscopy. Twenty healthy subjects were included as controls. Patients were followed for 6 months for hepatic decompensation and further decompensation/ACLF. RESULTS Forty-five patients were included (Child-Pugh [CP] A/B/C 18/11/16). Compared to controls, RePLT in cirrhosis were significantly increased (0.82% vs. 0.05%; p < 0.001) and hyperactivated (4.35% vs. 0.17%; p = 0.004). No correlation was observed between RePLT and CP, platelet count, TPO, MELD score, and C-reactive protein. TPO was lower in cirrhosis than controls (28 pg/mL vs. 52 pg/mL; p = 0.005), decreasing significantly with CP stage. In CP B/C patients (n = 27), RePLT were significantly higher in those who progressed towards further decompensation/ACLF (2.11 [0.56-2.95] vs. 0.69 [0.02-1.22]; p < 0.01). A proportion of RePLT >2% accurately identified high-risk patients (AUROC 0.818; 95%CI: 0.639-0.997; sensitivity 94%, specificity 73%). CONCLUSION RePLT in cirrhosis are increased and hyper-activated. In decompensated patients, higher RePLT appear to be associated with worse outcomes.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Serena Toffanin
- Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine (DIMED), University of Padova, Italy
| | - Elena Campello
- Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine (DIMED), University of Padova, Italy; General Internal Medicine Unit, Azienda Ospedale - Università Padova, Padova, Italy
| | - Claudia Maria Radu
- Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine (DIMED), University of Padova, Italy
| | - Sabrina Gavasso
- Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine (DIMED), University of Padova, Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Paolo Simioni
- Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine (DIMED), University of Padova, Italy; General Internal Medicine Unit, Azienda Ospedale - Università Padova, Padova, Italy.
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Wang X, Wang J, Peng H, Zuo L, Wang H. Role of immune cell interactions in alcohol-associated liver diseases. LIVER RESEARCH 2024; 8:72-82. [DOI: 10.1016/j.livres.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang Y, Ye Q, Li P, Huang L, Qi Z, Chen W, Zhan Q, Wang C. Renal Replacement Therapy as a New Indicator of Voriconazole Clearance in a Population Pharmacokinetic Analysis of Critically Ill Patients. Pharmaceuticals (Basel) 2024; 17:665. [PMID: 38931333 PMCID: PMC11206427 DOI: 10.3390/ph17060665] [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: 04/24/2024] [Revised: 05/16/2024] [Accepted: 05/17/2024] [Indexed: 06/28/2024] Open
Abstract
AIMS The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile. METHODS Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. RESULTS A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CLCR), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. CONCLUSIONS We found that qCRP, CRRT, CLCR, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.
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Affiliation(s)
- Yuqiong Wang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China; (Y.W.); (C.W.)
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
| | - Qinghua Ye
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
| | - Pengmei Li
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China;
| | - Linna Huang
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
| | - Zhijiang Qi
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
| | - Wenqian Chen
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China;
| | - Qingyuan Zhan
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China; (Y.W.); (C.W.)
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
| | - Chen Wang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China; (Y.W.); (C.W.)
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; (Q.Y.); (L.H.); (Z.Q.)
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Kasirer Y, Shchors I, Hammerman C, Bin-Nun A. Platelet Indices: Universally Available Clinical Adjunct for Diagnosing Necrotizing Enterocolitis. Am J Perinatol 2024; 41:e1575-e1580. [PMID: 36918160 DOI: 10.1055/a-2053-7759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
OBJECTIVE Platelet function parameters can be predictive of several adult diseases and their severity. However, few studies report on the association between platelet indices and neonatal diseases, specifically necrotizing enterocolitis (NEC). The objective of this study is to investigate whether platelet indices are associated with NEC diagnosis and NEC-related mortality. STUDY DESIGN We retrospectively examined records from infants admitted to the neonatal intensive care unit with a diagnosis of NEC, verified by the presence of pneumatosis on X-ray or pathology at surgery. We compared them with an age-matched group of prematures without NEC. We investigated platelet count, mean platelet volume (MPV), platelet distribution width and red cell distribution width to platelet ratio (RPR) and delta platelets from birth to the time of NEC diagnosis or day of life 14 in the control group. RESULTS Sixty-nine infants with NEC and 78 control infants were studied. Basic sociodemographic data were similar in both groups. All platelet parameters measured-except for MPV-were significantly associated with NEC diagnosis. Although MPV was not associated with the diagnosis of NEC (p = 0.800), it was significantly associated with NEC-related mortality (p < 0.001). Only total platelet count and RPR were significantly associated with both NEC diagnosis (p < 0.0001) and mortality (p = 0.04 and 0.01, respectively). On multivariable analysis only the change in platelet count from birth to time of diagnosis remained significant. CONCLUSION While not definitive, this study demonstrates that these routinely available, inexpensive, and easily calculated platelet indices can provide a clinical adjunct in the often-elusive attempts to definitively diagnose NEC in preterm neonates. KEY POINTS · Platelet indices were associated with NEC diagnosis.. · MPV was predictive of NEC-related mortality.. · Delta platelet count from birth was significantly related to NEC diagnosis..
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Affiliation(s)
- Yair Kasirer
- Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Irina Shchors
- Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Cathy Hammerman
- Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Department of Pediatrics, The Hebrew University, Jerusalem, Israel
| | - Alona Bin-Nun
- Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Department of Pediatrics, The Hebrew University, Jerusalem, Israel
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Wang J, Wang X, Peng H, Dong Z, Liangpunsakul S, Zuo L, Wang H. Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils. Cell Mol Gastroenterol Hepatol 2024; 18:41-52. [PMID: 38461963 PMCID: PMC11127035 DOI: 10.1016/j.jcmgh.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 02/29/2024] [Accepted: 03/01/2024] [Indexed: 03/12/2024]
Abstract
Alcohol-associated liver disease (ALD) is a major contributor to liver-related mortality globally. An increasing body of evidence underscores the pivotal role of platelets throughout the spectrum of liver injury and recovery, offering unique insights into liver homeostasis and pathobiology. Alcoholic-associated steatohepatitis is characterized by the infiltration of hepatic neutrophils. Recent studies have highlighted the extensive distance neutrophils travel through sinusoids to reach the liver injury site, relying on a platelet-paved endothelium for efficient crawling. The adherence of platelets to neutrophils is crucial for accurate migration from circulation to the inflammatory site. A gradual decline in platelet levels leads to diminished neutrophil recruitment. Platelets exhibit the ability to activate neutrophils. Platelet activation is heightened upon the release of platelet granule contents, which synergistically activate neutrophils through their respective receptors. The sequence culminates in the formation of platelet-neutrophil complexes and the release of neutrophil extracellular traps intensifies liver damage, fosters inflammatory immune responses, and triggers hepatotoxic processes. Neutrophil infiltration is a hallmark of alcohol-associated steatohepatitis, and the roles of neutrophils in ALD pathogenesis have been studied extensively, however, the involvement of platelets in ALD has received little attention. The current review consolidates recent findings on the intricate and diverse roles of platelets and neutrophils in liver pathophysiology and in ALD. Potential therapeutic strategies are highlighted, focusing on targeting platelet-neutrophil interactions and activation in ALD. The anticipation is that innovative methods for manipulating platelet and neutrophil functions will open promising avenues for future ALD therapy.
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Affiliation(s)
- Juan Wang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Xianda Wang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Haodong Peng
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; The First School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China
| | - Zijian Dong
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Li Zuo
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China.
| | - Hua Wang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China.
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Gemery JM, Forauer AR, Hoffer EK. Platelet Count after Transjugular Intrahepatic Portosystemic Shunt: Response to Wong et al, JVIR, August 2023. J Vasc Interv Radiol 2024; 35:469. [PMID: 38043706 DOI: 10.1016/j.jvir.2023.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/17/2023] [Accepted: 11/25/2023] [Indexed: 12/05/2023] Open
Affiliation(s)
- John M Gemery
- Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Giesel School of Medicine, Dartmouth College, Hanover, NH.
| | - Andrew R Forauer
- Department of Radiology, Pennsylvania State University, Hershey, PA; College of Medicine, Pennsylvania State University, Hershey, PA
| | - Eric K Hoffer
- Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Giesel School of Medicine, Dartmouth College, Hanover, NH
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10
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Zanetto A, Campello E, Senzolo M, Simioni P. Assessment of whole blood platelet aggregation in patients with cirrhosis: challenges and opportunities. Platelets 2023; 34:2178823. [PMID: 36803379 DOI: 10.1080/09537104.2023.2178823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy.,Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy, and
| | - Elena Campello
- General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale - Università Padova, Padova, Italy.,Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy, and
| | - Paolo Simioni
- General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
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11
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Suja L, Logithasan N, Senthil N, Anil AA. Spontaneous muscle haematoma in a patient with cirrhosis. BMJ Case Rep 2023; 16:e254525. [PMID: 37923333 PMCID: PMC10626913 DOI: 10.1136/bcr-2022-254525] [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] [Indexed: 11/07/2023] Open
Abstract
Decompensated liver disease is associated with alterated haemostasis that can either lead to spontaneous bleeding or development of thrombosis. Alcohol consumption coupled with advanced liver disease favours spontaneous bleeding. There have been only few documented cases of spontaneous muscle haematoma (SMH) in patients with cirrhosis. The pathogenesis of SMH is hypothesised to be multifactorial and it has been seen in patients on anticoagulation or with haemostatic disorders. We report a case of alcohol-related cirrhosis presenting with an expanding, voluminous haematoma in the intermuscular plane between the trapezius and the teres major muscles. This patient also had a retroperitoneal haemorrhage, clinically evidenced by the Grey Turner's and Cullen's signs. Haemorrhage was confirmed radiologically by CT. The patient was managed in an intensive care facility and treated with multiple blood products, including packed red blood cells, fresh frozen plasma and cryoprecipitates. However, as his clinical condition deteriorated, he required surgical intervention by incision and drainage, followed by evacuation. Early identification of coagulopathy and aggressive treatment are essential in these cases of cirrhosis to avoid unfavourable outcomes.
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Affiliation(s)
- Lakshmanan Suja
- General Medicine, Sri Ramachandra University Medical College, Chennai, Tamil Nadu, India
| | - Nanthakumar Logithasan
- General Medicine, Sri Ramachandra University Medical College, Chennai, Tamil Nadu, India
| | - Narayanasamy Senthil
- General Medicine, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, Tamil Nadu, India
| | - Archa Anna Anil
- General Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
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12
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Zhou J, Li X, Wang M, Gu C, Liu J. Platelet-to-Monocyte Ratio as a Novel Promising Agent for the Prognosis of Hepatitis B Virus-Associated Decompensated Cirrhosis. Can J Gastroenterol Hepatol 2023; 2023:6646156. [PMID: 37485072 PMCID: PMC10361825 DOI: 10.1155/2023/6646156] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 06/02/2023] [Accepted: 07/04/2023] [Indexed: 07/25/2023] Open
Abstract
Aim The present study aimed at investigating associations of the platelet-to-monocyte ratio (PMR), a novel hematological indicator of inflammatory responses with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). Methods We recruited 329 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Receiver operating characteristic curve analysis was performed to compare the predictive values of prognostic markers. Results During the 30-day follow-up period, 21 (6.4%) patients died. The PMR was significantly different between nonsurvivors and survivors. Lower PMR was found to be associated with an increased risk of 30-day mortality, and PMR (odds ratio: 1.011; 95% CI: 1.003-1.019; P=0.005) was found to be an independent predictor of 30-day mortality in patients with HBV-DeCi with a significant predictive value (AUC = 0.826, 95% CI: 0.781-0.865). The combination of PMR and MELD score could improve prognostic accuracy in these patients (AUC = 0.911, 95% CI: 0.876-0.940). Conclusions Our results demonstrate that low PMR may be an independent predictor of 30-day mortality in patients with HBV-DeCi, and combined with the MELD score, it may be useful to complement other conventional measures to enable effective management of these patients.
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Affiliation(s)
- Jun Zhou
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Xin Li
- Department of Laboratory Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, China
| | - Min Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Chunrong Gu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Jingping Liu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
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13
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Zhang Q, Mao W, He X, Yuan M. High red cell distribution width-to-platelet ratio indicates adverse outcomes for hepatitis B virus-associated decompensated cirrhosis. Biomark Med 2023; 17:189-196. [PMID: 37158064 DOI: 10.2217/bmm-2023-0123] [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] [Indexed: 05/10/2023] Open
Abstract
Background: This work was designed to determine the association between red cell distribution width-to-platelet ratio (RPR) and 30-day prognosis in hepatitis B virus-associated decompensated cirrhosis (HBV-DC) patients. Methods: A total of 168 HBV-DC patients were included. Independent risk factors for poor prognosis were determined by logistic regression analyses. Results: A total of 21 (12.5%) patients died within 30 days. RPR was higher in nonsurvivors than in survivors. Multivariate analysis identified RPR and Model for End-Stage Liver Disease (MELD) score as independent prognostic predictors, and the predictive value of RPR was similar to that of the MELD score. Moreover, combining RPR with the MELD score further improved the predictive value for mortality. Conclusion: RPR has potential as a reliable tool for the prediction of poor prognosis in HBV-DC patients.
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Affiliation(s)
- Qiu Zhang
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
| | - WeiLin Mao
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
| | - ManChun Yuan
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
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14
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Gîrleanu I, Trifan A, Huiban L, Muzica CM, Petrea OC, Sîngeap AM, Cojocariu C, Chiriac S, Cuciureanu T, Stafie R, Zenovia S, Stratina E, Rotaru A, Nastasa R, Sfarti C, Costache II, Stanciu C. Anticoagulation for Atrial Fibrillation in Patients with Decompensated Liver Cirrhosis: Bold and Brave? Diagnostics (Basel) 2023; 13:1160. [PMID: 36980468 PMCID: PMC10047341 DOI: 10.3390/diagnostics13061160] [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: 02/11/2023] [Revised: 03/07/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.
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Affiliation(s)
- Irina Gîrleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Oana Cristina Petrea
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Sîngeap
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
| | - Irina Iuliana Costache
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Cardiology Department, “Saint Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” University Hospital, 700111 Iasi, Romania
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15
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Yuan X. Chinese expert consensus on managing thrombocytopenia in patients with cancer and liver injury. ONCOLOGY AND TRANSLATIONAL MEDICINE 2023; 9:1-14. [DOI: 10.1007/s10330-023-0628-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 01/20/2023] [Indexed: 01/04/2025]
Abstract
Abstract
Thrombocytopenia and liver injury are serious clinical problems in patients with cancer. The etiology of thrombocytopenia in patients with cancer and liver injury (TCLI) is complicated. Managing cancer therapy-induced thrombocytopenia has gradually become standardized, and managing liver injury-associated thrombocytopenia has become more effective with the approval and marketing of relevant drugs. However, the optimal strategy for managing thrombocytopenia in patients with cancer and liver injury remains unclear, and the superposition of thrombocytopenia and liver injury further increases the difficulty of cancer treatment. Therefore, the Committee of Cancer Support Therapy of the Chinese Anti-Cancer Association has organized experts to analyze and discuss relevant literature to form a Chinese expert consensus on managing thrombocytopenia in patients with cancer and liver injury (2022 Edition) to guide clinical practice.
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Affiliation(s)
- Xianglin Yuan
- Committee of neoplastic supportive-care (CONS), China Anti-Cancer Association
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16
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Wu Y, Peng W, Shen J, Zhang X, Li C, Wen TF. Prognostic nomograms for HBV-related BCLC 0-a stage hepatocellular carcinoma incorporating aspartate aminotransferase to albumin ratio. Scand J Gastroenterol 2023:1-9. [PMID: 36620916 DOI: 10.1080/00365521.2023.2165417] [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] [Indexed: 01/10/2023]
Abstract
BACKGROUND Curative hepatectomy is currently the first-line treatment for hepatocellular carcinoma (HCC), but the prognosis is still not optimistic. The prediction model for prognosis of hepatitis B virus (HBV)-related BCLC 0-A stage HCC has not been well established. Therefore, we aimed to develop new nomograms to predict recurrence and survival in these patients. METHODS A total of 982 patients with HBV-related BCLC 0-A stage HCC who underwent curative hepatectomy at West China Hospital from February 2007 to February 2016 were retrospectively collected and randomly allocated to a training set and a validation set in a ratio of 4:1. Prognostic nomograms using data from the training set were developed using a Cox regression model and validated on the validation set. RESULTS We constructed nomograms based on independent factors for recurrence-free survival (RFS) (tumor size, satellite, microvascular invasion, capsular invasion, differentiation and aspartate aminotransferase to albumin ratio (ASAR)) and overall survival (OS) (gender, tumor size, satellite, microvascular invasion, differentiation, lymphocyte count, and ASAR). Compared with conventional HCC staging systems and other nomograms reported by previous literature, our ASAR integrated nomograms predicted RFS and OS with the highest C-indexes (0.682 (95%CI: 0.646-0.709), 0.729 (95%CI: 0.691-0.766), respectively) and had well-fitted calibration curves in the training set. Concurrently, the nomograms also obtained consistent results in the validation set. DCA revealed that our nomograms provided the largest clinical net benefits. CONCLUSION We first constructed ASAR integrated nomograms to predict the prognosis of HBV-related BCLC 0-A stage HCC patients after curative hepatectomy with good performance.
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Affiliation(s)
- Youwei Wu
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Junyi Shen
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Tian-Fu Wen
- Department of Liver Surgery and Liver Transplantation Centre, West China Hospital, Sichuan University, Chengdu, China
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17
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Huang CE, Chang JJ, Wu YY, Huang SH, Chen WM, Hsu CC, Lu CH, Hung CH, Shi CS, Lee KD, Chen CC, Chen MC. Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection. Biomed J 2022; 45:788-797. [PMID: 34508913 PMCID: PMC9661505 DOI: 10.1016/j.bj.2021.09.001] [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: 03/08/2021] [Revised: 07/21/2021] [Accepted: 09/01/2021] [Indexed: 10/25/2022] Open
Abstract
BACKGROUND Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP. METHODS We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts <100 × 109/L and <50 × 109/L, respectively) by Cox proportional hazards models. Moreover, we prospectively enrolled 63 HCV-TP patients, 11 HBV-TP patients, and 27 HCV controls to detect specific antiplatelet antibodies by enzyme-linked immunosorbent assay and analyze their effects. RESULTS Prevalence of platelet <100 × 109/L was 11.86% and 6.35% in HCV and HBV patients without cancer history, respectively. HCV-to-HBV incidence rate ratio for thrombocytopenia was 6.95. Initial thrombocytopenia was the most significant risk factor for HCV-TP and HBV-TP regardless of thrombocytopenia severity. Splenomegaly and cirrhosis were significant risk factors for moderate, but not severe HCV-TP. Hyperbilirubinemia was an important moderate and severe HBV-TP risk factor. Antiplatelet antibodies were correlated with HCV-TP severity, of which anti-glycoprotein IIb/IIIa antibody being associated with smaller spleen size. The antiplatelet autoantibody might contribute to thrombocytopenia either independently or with splenomegaly as the important risk in HCV-TP patients without advanced cirrhosis. CONCLUSION HCV was associated with higher thrombocytopenia incidence than HBV. Thrombocytopenia risk factors varied with virus type and severity. Different management for HCV-TP and HBV-TP was suggested.
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Affiliation(s)
- Cih-En Huang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Jung-Jung Chang
- Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Yu-Ying Wu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Shih-Hao Huang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; Department of Public Health and Biostatistics Consulting Center, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Ming Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chia-Chen Hsu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Chang-Hsien Lu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Chao-Hung Hung
- Division of Gastroenterology and Hepatology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Sheng Shi
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Kuan-Der Lee
- Division of Hematology and Oncology, Department of Internal Medicine, and Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan; International Ph.D. Program for Cell Therapy and Regeneration Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chih-Cheng Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Min-Chi Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; Department of Public Health and Biostatistics Consulting Center, Chang Gung University, Taoyuan, Taiwan.
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18
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Liao MJ, Li J, Dang W, Chen DB, Qin WY, Chen P, Zhao BG, Ren LY, Xu TF, Chen HS, Liao WJ. Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China. World J Gastroenterol 2022; 28:3503-3513. [PMID: 36158257 PMCID: PMC9346453 DOI: 10.3748/wjg.v28.i27.3503] [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: 02/14/2022] [Revised: 03/23/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.
AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.
METHODS With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.
RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively.
CONCLUSION The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.
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Affiliation(s)
- Min-Jun Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Jun Li
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
- Genetics and Precision Medicine Laboratory, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Wei Dang
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Dong-Bo Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Wan-Ying Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Pu Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Bi-Geng Zhao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Li-Ying Ren
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Ting-Feng Xu
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Hong-Song Chen
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
| | - Wei-Jia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
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19
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Feng R, Liu Y, Zhu XL, Zhai WY, He Y, Fu HX, Jiang Q, Jiang H, Lu J, Liu H, Wang JW, Wang H, Xie YD, Ma H, Huang XJ, Zhang XH. Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: Multicentre real-world observational study. J Viral Hepat 2022; 29:306-316. [PMID: 35152507 DOI: 10.1111/jvh.13655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 11/25/2021] [Accepted: 02/03/2022] [Indexed: 12/23/2022]
Abstract
Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.
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Affiliation(s)
- Ru Feng
- Department of Hematology, National Center of Gerontology, Beijing Hospital, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Yi Liu
- Department of Hematology, the Sixth Medical Center of PLA General Hospital, Beijing, China
| | - Xiao-Lu Zhu
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Wan-Yi Zhai
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Yun He
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Hai-Xia Fu
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Qian Jiang
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Hao Jiang
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Jin Lu
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Hui Liu
- Department of Hematology, National Center of Gerontology, Beijing Hospital, Beijing, China
| | - Jing-Wen Wang
- Department of Hematology, Beijing Tongren Hospital, Beijing, China
| | - Hao Wang
- Institute of Hepatic Diseases, Peking University People's Hospital, Beijing, China
| | - Yan-Di Xie
- Institute of Hepatic Diseases, Peking University People's Hospital, Beijing, China
| | - Hui Ma
- Institute of Hepatic Diseases, Peking University People's Hospital, Beijing, China
| | - Xiao-Jun Huang
- Institute of Hematology, Peking University People's Hospital, Beijing, China
| | - Xiao-Hui Zhang
- Institute of Hematology, Peking University People's Hospital, Beijing, China
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Shettar SS, Vandyck K, Tanaka KA. Coagulation Management in End-Stage Liver Disease. CURRENT ANESTHESIOLOGY REPORTS 2022. [DOI: 10.1007/s40140-022-00524-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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21
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Driever EG, Lisman T. Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease. Semin Thromb Hemost 2022; 48:596-606. [PMID: 35135033 DOI: 10.1055/s-0042-1742438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.
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Affiliation(s)
- Ellen G Driever
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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22
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B. Riahi E, Adelborg K, Pedersen L, Kristensen SR, Hansen AT, Sørensen H. Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding: A Danish population-based cohort study. Res Pract Thromb Haemost 2022; 6:e12668. [PMID: 35229067 PMCID: PMC8867136 DOI: 10.1002/rth2.12668] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 12/28/2021] [Accepted: 01/05/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVES We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). METHODS This population-based cohort study used data from Danish health registries. We identified all patients with a first-time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA2DS2VASc score, and Charlson Comorbidity Index score. RESULTS We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow-up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1-1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2-2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7-1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1-2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1-4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3-2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7-3.9). CONCLUSION In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications.
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Affiliation(s)
- Emil B. Riahi
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
- Department of SurgeryRanders Regional HospitalRandersDenmark
| | - Kasper Adelborg
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
- Department of Clinical BiochemistryAarhus University HospitalAarhusDenmark
| | - Lars Pedersen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
| | - Søren R. Kristensen
- The Atrial Fibrillation Study GroupAalborg University HospitalAalborgDenmark
- Department of Clinical BiochemistryAalborg University HospitalAalborgDenmark
| | - Anette T. Hansen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
| | - Henrik T. Sørensen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
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23
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Xu X, Li C, Chen J, Liu X, Su H, Tong J, Hu J. Relationship Between Platelet to White Blood Cell Ratio and 30-Day Prognosis of Patients with Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.118640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
Background: Acute-on-chronic liver failure (ACLF) is always associated with thrombocytopenia or leukocytosis. Therefor the platelet to white blood cell ratio (PWR) in ACLF patients is always reduced. Objectives: Here, we assessed the relationship between PWR and prognosis in ACLF patients. Methods: A retrospective cohort of 415 patients, including 100 patients that were diagnosed of chronic hepatitis B, 104 patients suffered of HBV-related liver cirrhosis and 211 patients suffered of HBV-related ACLF, was investigated. Univariate and multivariate COX models were used to investigate the relationship between PWR and 30-day survival in patients with ACLF. Factors affecting PWR in ACLF patients were also analysed using logistic regression analysis. Results: At baseline, the platelet count in patients with HBV-related ACLF was significantly lower than that in patients with CHB and patients suffered of HBV-related cirrhosis. The PWR value was much higher in the survivors of ACLF than in ACLF patients who died. PWR, age, total bilirubine, prothrombin activity, and aspartate transaminase were independent predictors of the 30-day survival rate of ACLF patients. We also found that ascites and infection were independent factors related to the decrease of PWR in ACLF patients. Conclusions: The PWR value was significant declined in ACLF patients. And it was independent risk factors for the survival rate of those patients.
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24
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An J, Kim HD, Kim SO, Kim HI, Song GW, Lee HC, Shim JH. Cervicocerebral atherosclerosis and its hepatic and coronary risk factors in patients with liver cirrhosis. Clin Mol Hepatol 2021; 28:67-76. [PMID: 34637612 PMCID: PMC8755468 DOI: 10.3350/cmh.2021.0202] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 10/11/2021] [Indexed: 11/16/2022] Open
Abstract
Background/Aims We aimed to investigate the silent atherosclerotic burden of cervicocephalic vessels in cirrhotic patients compared with the general population, as well as the relevant risk factors including coronary parameters. Methods This study included 993 stroke-free patients with liver cirrhosis (LC) who underwent magnetic resonance angiography (MRA) of the head and neck as a pre-liver transplant assessment and 6,099 health checkup participants who underwent MRA examination. The two cohorts were matched for cerebrovascular risk factors, and the prevalence of atherosclerosis in major intracranial and extracranial arteries was compared in 755 matched pairs. Moreover, traditional, hepatic, and coronary variables related to cerebral atherosclerosis were assessed in cirrhotic patients. Results Overall, intracranial atherosclerosis was significantly less prevalent in the LC group than in the matched control group (2.3% vs. 5.4%, P=0.002), whereas the prevalence of extracranial atherosclerosis was similar (4.4% vs. 5.8%, P=0.242). These results were maintained in multivariate analyses of the pooled samples, with corresponding adjusted odds ratios [ORs] of LC of 0.56 and 0.77 (95% confidence intervals [CIs], 0.36–0.88 and 0.55–1.09). In the LC group, lower platelet count was inversely correlated with intracranial atherosclerosis (adjusted OR, 0.31; 95% CI, 0.13–0.76). Coronary artery calcium (CAC) score ≥100 was the only predictive factor for both intracranial and extracranial atherosclerosis (adjusted ORs, 4.06 and 5.43, respectively). Conclusions LC confers protection against intracranial atherosclerosis, and thrombocytopenia may be involved in this protective effect. High CAC score could serve as a potential surrogate for cervicocerebral vascular screening in asymptomatic cirrhotic patients.
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Affiliation(s)
- Jihyun An
- Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Gyeonggi, Republic of Korea
| | - Hyung-Don Kim
- Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seon-Ok Kim
- Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ha Il Kim
- Gastroenterology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
| | - Gi-Won Song
- Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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25
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Han S. Possible roles of platelets in liver transplantation: regeneration and cancer recurrence. Anesth Pain Med (Seoul) 2021; 16:225-231. [PMID: 34352964 PMCID: PMC8342825 DOI: 10.17085/apm.21063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 07/03/2021] [Indexed: 12/28/2022] Open
Abstract
When tissue injury results in breakage, platelets are not only involved in plug formation and wound sealing, but they also play an important role throughout the tissue recovery process. Specifically, platelets accumulate at the site of injury and release a large number of biologically active mediators at injury sites, which initiate or modulate damaged tissue regeneration. Moreover, extensive experimental evidence has elucidated the involvement of platelets in tumor growth and metastasis. As such, this mini-review aimed to highlight the relatively lesser known functions of platelets.
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Affiliation(s)
- Sangbin Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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26
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Ding JN, Zhao WF. Mechanism, diagnosis, and treatment of portal vein thrombosis in cirrhosis. Shijie Huaren Xiaohua Zazhi 2021; 29:670-676. [DOI: 10.11569/wcjd.v29.i12.670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Jing-Nuo Ding
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215000, JiangSu Province, China
| | - Wei-Feng Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215000, JiangSu Province, China
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27
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Rangaswamy C, Mailer RK, Englert H, Konrath S, Renné T. The contact system in liver injury. Semin Immunopathol 2021; 43:507-517. [PMID: 34125270 PMCID: PMC8202222 DOI: 10.1007/s00281-021-00876-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/27/2021] [Indexed: 01/18/2023]
Abstract
Coagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma coagulation factors and their inhibitors that, in addition to thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both hypercoagulability and bleeding disorders due to a pathologic balance of pro- and anticoagulant plasma factors. At sites of vascular injury, thrombus propagation that finally may occlude the blood vessel depends on negatively charged biopolymers, such as polyphosphates and extracellular DNA, that provide a physiological surface for contact activation of coagulation factor XII (FXII). FXII initiates the contact system that drives both the intrinsic pathway of coagulation, and formation of the inflammatory mediator bradykinin by the kallikrein–kinin system. Moreover, FXII facilitates receptor-mediated signalling, thereby promoting mitogenic activities, angiogenesis, and neutrophil stimulation with implications for liver diseases. Here, we summarize current knowledge on the FXII-driven contact system in liver diseases and review therapeutic approaches to target its activities during impaired liver function.
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Affiliation(s)
- Chandini Rangaswamy
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Reiner K Mailer
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Hanna Englert
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Sandra Konrath
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Thomas Renné
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
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Thrombocytopenia and Hemostatic Changes in Acute and Chronic Liver Disease: Pathophysiology, Clinical and Laboratory Features, and Management. J Clin Med 2021; 10:jcm10071530. [PMID: 33917431 PMCID: PMC8038677 DOI: 10.3390/jcm10071530] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/22/2021] [Accepted: 03/24/2021] [Indexed: 12/12/2022] Open
Abstract
Thrombocytopenia, defined as a platelet count <150,000/μL, is the most common complication of advanced liver disease or cirrhosis with an incidence of up to 75%. A decrease in platelet count can be the first presenting sign and tends to be proportionally related to the severity of hepatic failure. The pathophysiology of thrombocytopenia in liver disease is multifactorial, including (i) splenomegaly and subsequently increased splenic sequestration of circulating platelets, (ii) reduced hepatic synthesis of thrombopoietin with missing stimulation both of megakaryocytopoiesis and thrombocytopoiesis, resulting in diminished platelet production and release from the bone marrow, and (iii) increased platelet destruction or consumption. Among these pathologies, the decrease in thrombopoietin synthesis has been identified as a central mechanism. Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures. This review summarizes recent advances in the understanding of defective but at low level rebalanced hemostasis in stable cirrhosis, discusses clinical consequences and persistent controversial issues related to the inherent bleeding risk, and is focused on a risk-adapted management of thrombocytopenia in patients with chronic liver disease, including a restrictive transfusion regimen.
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29
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Soliman Z, El Kassas M, Elsharkawy A, Elbadry M, Hamada Y, ElHusseiny R, M El-Nahaas S, Fouad R, Esmat G, Abdel Alem S. Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome. Platelets 2021; 32:383-390. [PMID: 32250721 DOI: 10.1080/09537104.2020.1742313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/21/2020] [Indexed: 12/11/2022]
Abstract
Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84-127) × 103/mm3 vs. 120 (87-153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn't reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.
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Affiliation(s)
- Zeinab Soliman
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Elbadry
- Tropical Medicine and Gastroenterology Department, Aswan University, Aswan, Egypt
| | - Yasser Hamada
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ramy ElHusseiny
- Internal Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Saeed M El-Nahaas
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of research development, Badr University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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30
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Ramzy I, Fouad R, Salama R, Abdellatif Z, Elsharkawy A, Zayed N, Elsharkawy M, El Akel W, Bakheet N. Evaluation of red cell distribution width to platelet ratio as a novel non-invasive index for predicting hepatic fibrosis in patients with chronic hepatitis C. Arab J Gastroenterol 2021; 22:6-11. [PMID: 33664008 DOI: 10.1016/j.ajg.2020.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/03/2020] [Accepted: 12/28/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND STUDY AIMS Assessing the extent of fibrosis is an essential part of therapeutic decisions in patients with chronic hepatitis C (CHC). Liver biopsies are the "gold standard" for evaluating liver fibrosis but have many limitations. Thus, noninvasive predictors of fibrosis have been developed. This study aimed to determine the effectiveness of red cell distribution width (RDW) to platelet ratio as a simple noninvasive method for predicting the hepatic fibrosis stage in patients with CHC. PATIENTS AND METHODS This cross-sectional study included 197 Egyptian patients with CHC. A routine pretreatment reference needle liver biopsy was performed. Fib-4, transient elastography (TE) by Fibroscan, AST to Platelet Ratio Index (APRI), and RDW to platelet ratio (RPR) were measured. Predictors of significant fibrosis (Metavir score ≥ F2) and advanced fibrosis (Metavir score ≥ F3) were identified. RESULTS Fib-4, TE, APRI, and RPR values differed significantly when comparing different stages of fibrosis (p < 0.01). Fib-4, TE, APRI, and RPR were reliable diagnostic tools at cutoff values of 1.17, 7.75, 0.18, and 0.07, respectively, for predicting significant fibrosis and cutoff values of 1.99, 8, 1.77, and 0.08, respectively, for predicting advanced fibrosis. Using logistic regression analysis, TE was identified as an independent predictor associated with significant and advanced fibrosis. Fib-4 was significantly associated with advanced fibrosis only. CONCLUSION The use of Fib-4, TE, APRI, and RPR measurements may decrease the need for liver biopsies for predicting significant and advanced fibrosis. RPR showed fair sensitivity, specificity, positive and negative predictive values, and overall accuracy for predicting significant fibrosis in patients with CHC.
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Affiliation(s)
- Iman Ramzy
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Salama
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Naglaa Zayed
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Marwa Elsharkawy
- Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nader Bakheet
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Baseline thrombopoietin level is associated with platelet count improvement in thrombocytopenic chronic hepatitis C patients after successful direct-acting antiviral agent therapy. BMC Gastroenterol 2021; 21:30. [PMID: 33478399 PMCID: PMC7818549 DOI: 10.1186/s12876-021-01606-x] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 01/12/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. METHODS From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO. RESULTS This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32-149) × 103/µL at BL to 116.5 (40-196) and 118.0 (35-275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P < 0.001; P12 vs. BL, P < 0.001). BL TPO was positively correlated with significant platelet count improvement (P < 0.001), platelet count improvement ratio at EOT (P = 0.004), and P12 (P < 0.001). The area under the receiver operating characteristic curve and optimal cutoffs (pg/ml) were 0.77 (95% confidence interval, 0.67-0.86) and 120, respectively, for significant platelet count improvement prediction. The sensitivity, specificity, and accuracy were 88.6%, 71.7%, and 78.8%, respectively. CONCLUSIONS BL TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic patients after successful DAA therapy.
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Liu LX, Zhang Y, Nie Y, Zhu X. Assessing the Prediction Effect of Various Prognosis Model for 28-Day Mortality in Acute-on-Chronic Liver Failure Patients. Risk Manag Healthc Policy 2021; 13:3155-3163. [PMID: 33402854 PMCID: PMC7778450 DOI: 10.2147/rmhp.s281999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 12/10/2020] [Indexed: 12/13/2022] Open
Abstract
Background Acute-on-chronic liver failure (ACLF) is an extremely clinical entity associated with short-term high mortality. The CLIF-SOFA score measures both hepatic and extrahepatic organ dysfunction and can discriminate significantly better between survivors and nonsurvivors compared to other methods. The MELD score is widely used for organ allocation in liver transplantation. Recent reports indicate that the PWR is a potential biomarker for predicting clinical outcomes. The ALBI score is a new score model for evaluating the severity of liver dysfunction. We aimed to compare these prognosis models to predict short-term mortality in ACLF patients. Methods A retrospective analysis of 89 ACLF patients between 2015 and 2018 was performed. The receiver operating characteristic (ROC) curve was used to assess the power of four prognosis models for predicting 28-day mortality in patients with ACLF. Results The ALBI score, MELD score and CLIF-SOFA score were significantly higher, and the PWR was slightly lower in nonsurviving ACLF patients than in surviving patients. The MELD score and ALBI score were positively correlated with the CLIF-SOFA score, while the PWR was inversely related to the CLIF-SOFA score. The area under the ROC curves (AUROCS) of the CLIF-SOFA score, PWR, ALBI score and MELD score were 0.804, 0.759, 0.710 and 0.670, respectively. Conclusion The CLIF-SOFA score, PWR and ALBI score can better predict 28-day mortality in ACLF patients, but the MELD score has worse predictability. The CLIF-SOFA score is the best prognosis model among these models. PWR may be a simple and useful tool that can predict 28-day outcome.
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Affiliation(s)
- Lin Xiang Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China
| | - Yue Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China
| | - Yuan Nie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China
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Translational insight into prothrombotic state and hypercoagulation in nonalcoholic fatty liver disease. Thromb Res 2020; 198:139-150. [PMID: 33340925 DOI: 10.1016/j.thromres.2020.12.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/17/2020] [Accepted: 12/07/2020] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an emerging and threatening pathological condition, ranging from fatty liver (FL) to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma (HCC). Recent findings suggest that patients with NAFLD have a higher risk of cardiovascular events and thromboembolism and that this risk is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidaemia, and obesity. The vascular involvement of NAFLD might be considered its systemic burden, conditioning higher mortality in patients affected by the disease. These clinical findings suggested the existence of a prothrombotic state in NAFLD, which is partially unexplored and whose underlying mechanisms are to date not completely understood. Here, we review the mechanisms involved in the pathogenesis of the prothrombotic state in NAFLD across the progression from the healthy liver through the different stages of the disease. We focused on the possible role of several metabolic features of NAFLD possibly leading to hypercoagulation other than endothelial and platelet activation, such as insulin-resistance, nitric oxide production regulation, and gut microbiota homeostasis. Also, we analysed the involvement of plasminogen activator inhibitor-1 (PAI-1) and thromboinflammation taking place in NAFLD. Finally, we described factors striking a prothrombotic imbalance in NASH cirrhosis, with a particular focus on the pathogenesis of portal vein thrombosis.
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Zhang H, Zhang S, Zhang J, Zhou R, Nie Y, Ren S, Li J, Feng K, Ji F, Kong G, Li Z. Improvement of human platelet aggregation post-splenectomy with paraesophagogastric devascularization in chronic hepatitis B patients with cirrhotic hypersplenism. Platelets 2020; 31:1019-1027. [PMID: 31851564 DOI: 10.1080/09537104.2019.1704715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 12/05/2019] [Accepted: 12/09/2019] [Indexed: 12/13/2022]
Abstract
Thrombocytopenia is a common hematological abnormality in patients with cirrhotic hypersplenism. Splenectomy with paraesophagogastric devascularization (SPD) is a conventional surgical therapy which can reverse pancytopenia in these patients. Platelets are traditionally recognized for their central role in hemostasis. However, the status of platelet aggregation in chronic hepatitis B patients with cirrhotic hypersplenism before and after SPD has not been reported yet. A total of 41 cirrhotic patients and 31 healthy controls were included in this study. Platelet aggregation was detected by AggRAM® Advanced Modular System (Helena Laboratories, USA). ELISA was used to detect the cytokines closely related to platelet aggregation. Expressions of platelet membrane glycoproteins (GPs) were evaluated by flow cytometric analysis. Platelet aggregation was found to be decreased distinctly in the cirrhotic patients, and to be restored to normal level after SPD. The cirrhotic patients showed higher plasma levels of the cytokines HMGB1, PEDF, vWF, cAMP and cGMP, which also improved partially after SPD. Moreover, the cirrhotic patients had much lower expression of GPIIb/IIIa, GPIbα and P-selectin than either the healthy controls or SPD patients at basal or activated level. Generally, SPD benefits cirrhotic patients with bleeding tendencies by improving platelet counts and aggregation. GPIIb/IIIa may be the key membrane protein responsible for the change in platelet aggregation before and after SPD.
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Affiliation(s)
- Hui Zhang
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Shaoying Zhang
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Jian Zhang
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Rui Zhou
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an, Shaanxi Province, People's Republic of China
| | - Song Ren
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Jun Li
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Keping Feng
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
| | - Fanpu Ji
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
| | - Guangyao Kong
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
| | - Zongfang Li
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic and Splenic Diseases, Xi'an, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, People's Republic of China
- Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Ministry of Education of China , Xi'an, Shaanxi Province, People's Republic of China
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Ollivier-Hourmand I, Nguyen N, De Gottardi A, Valla D, Hillaire S, Dutheil D, Bureau C, Hernandez-Gea V, De Raucourt E, Plessier A. Management of anticoagulation in adult patients with chronic parenchymal or vascular liver disease: Vascular liver diseases: Position papers from the francophone network for vascular liver diseases, the French Association for the Study of the Liver (AFEF), and ERN-rare liver. Clin Res Hepatol Gastroenterol 2020; 44:438-446. [PMID: 32278777 DOI: 10.1016/j.clinre.2020.03.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Isabelle Ollivier-Hourmand
- Department of gastroenterology and hepatology, university hospital of Caen, Côte de la Nacre hospital, avenue de la Côte de Nacre, 14033 Caen cedex 9, France; French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Nga Nguyen
- Department of gastroenterology and hepatology, university hospital of Caen, Côte de la Nacre hospital, avenue de la Côte de Nacre, 14033 Caen cedex 9, France; French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Andrea De Gottardi
- Department of gastroenterology and hepatology, Cantonal Hospital Authority, Direzione generale, Viale Officina 3, 6500 Bellinzona, Switzerland
| | - Dominique Valla
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
| | - Sophie Hillaire
- Department of internal medicine, Foch hospital, 40, rue Worth, 92150 Suresnes, France
| | - Danielle Dutheil
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Association of patients with vascular liver diseases (AMVF), Beaujon hospital, 100, boulevard du Général Leclerc, 92118 Clichy, France
| | - Christophe Bureau
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of gastroenterology and hepatology, university hospital of Toulouse, Rangueil hospital, 1, avenue du Professeur Jean-Poulhès, 31400 Toulouse, France
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd). Health Care Provider of the European Reference Network onRare Liver Disorders (ERN-Liver), Spain
| | - Emmanuelle De Raucourt
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of laboratory hematology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
| | - Aurélie Plessier
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
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Nie Y, Lan Y, Deng XZ, Li LH, Cai WP, Li F, Hu FY. Assessing the association between platelets and immune recovery in HIV/HBV co-infected patients: A long-term cohort in Asia. INFECTION GENETICS AND EVOLUTION 2020; 84:104480. [PMID: 32736042 DOI: 10.1016/j.meegid.2020.104480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/22/2020] [Accepted: 07/23/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Previous studies have reported that platelet count is associated with the progression of liver disease caused by hepatitis B virus (HBV), but there have been no reports on whether platelet count is associated with immune recovery in HIV/HBV co-infected patients. METHODS A retrospective analysis was conducted on 167 HIV-infected patients whose continuously highly active antiretroviral therapy (HAART) strategy was lamivudine +tenofovir+ efavirenz, of which 75 were HIV/HBV co-infected patients and 92 were HIV mono-infected patients. The biochemical examination results and demographic characteristics of all patients before HAART were collected, and routine blood test results (including platelet count) and immune cell count (including CD4 cells count) after all time points of HAART were obtained. All patients were observed until 72 months. CD4 cells count of 350 or 500 cells/μl 72 months after HAART served as the boundary for judging the immune reconstruction effect. RESULTS The basic characteristics of HIV/HBV co-infected patients and HIV mono-infected patients were matched. All patients had a good viral response (HIV RNA <20 copies/ml, HBV DNA < 100 copies/mL) and immune response during HAART. The platelets with poor immune recovery in HIV/HBV co-infected patients were also maintained at an apparent lower level than that in patients with good immune recovery. However, this phenomenon was not found in HIV mono-infected patients. The platelet level at many time points after HAART therapy in HIV/HBV co-infected patients can predict the effect of immune recovery at 72 months after HAART. CONCLUSION The platelet counts of HIV/HBV co-infected patients were correlated with CD4 counts during the follow-up of HAART. These results suggest that the mechanisms associated with thrombocytopenia may be involved in the regulation of immune recovery after treatment in HIV/HBV co-infected patients.
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Affiliation(s)
- Yuan Nie
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yun Lan
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xi-Zi Deng
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lin-Hua Li
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Wei-Ping Cai
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Feng Li
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Feng-Yu Hu
- Research institute, Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China.
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37
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Rawi S, Wu GY. Pathogenesis of Thrombocytopenia in Chronic HCV Infection: A Review. J Clin Transl Hepatol 2020; 8:184-191. [PMID: 32832399 PMCID: PMC7438357 DOI: 10.14218/jcth.2020.00007] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/25/2020] [Accepted: 03/31/2020] [Indexed: 12/12/2022] Open
Abstract
A large proportion of patients with chronic hepatitis C have associated thrombocytopenia (TCP). Due to bleeding risks, TCP, when severe, can limit diagnostic and therapeutic procedures, treatments, and increases risk of complications, especially excessive bleeding. It is important to understand the mechanisms that cause TCP in order to manage it. In general, TCP can be due to increased destruction or decreased production. Proposed mechanisms of increased destruction include autoantibodies to platelets and hypersplenism with sequestration. Proposed mechanisms of decreased production include virus-induced bone marrow suppression and decreased TPO production. Autoantibodies directed against platelet surface antigens have demonstrated an inverse correlation with platelet counts. Hypersplenism with sequestration involves the interaction of portal hypertension, splenomegaly, and platelet destruction. Decreased production mechanisms involve appropriate and inappropriate levels of TPO secretion. There is limited evidence to support viral-induced bone marrow suppression. In contrast, there is strong evidence to support low levels of TPO in liver failure as a major cause of TCP. TPO-agonists, specifically eltrombopag, have been shown in hepatitis C patients to increase platelet counts without reducing portal hypertension or splenomegaly. We conclude that TCP in hepatitis C virus-induced liver disease is often multifactorial, but an understanding of the mechanisms can lead to judicious use of new drugs for treatment.
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Affiliation(s)
- Sarah Rawi
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Sarah Rawi, Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06032, USA. Tel: +1-858-692-2372, E-mail:
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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38
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Zermatten MG, Fraga M, Moradpour D, Bertaggia Calderara D, Aliotta A, Stirnimann G, De Gottardi A, Alberio L. Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis. Hepatology 2020; 71:2135-2148. [PMID: 32090357 DOI: 10.1002/hep.31201] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 01/20/2020] [Accepted: 02/11/2020] [Indexed: 12/11/2022]
Abstract
In the setting of liver cirrhosis (LC), profound hemostatic changes occur, which affect primary hemostasis, coagulation, and fibrinolysis. They involve prohemorrhagic and prothrombotic alterations at each of these steps. Patients with cirrhosis exhibit multifactorial thrombocytopenia and in vitro thrombocytopathy, counterbalanced by increased von Willebrand factor. The resultant shift is difficult to assess, but overall these changes probably result in a rebalanced primary hemostasis. Concerning coagulation, the reduced activity of coagulation factors is counterbalanced by an increase in factor VIII (produced by liver sinusoidal endothelial cells), a decrease of the natural anticoagulants, and complex changes, including changes in circulating microparticles, cell-free DNA, and neutrophil extracellular traps. Overall, these alterations result in a procoagulant state. As for fibrinolysis, increased tissue-type and urokinase-type plasminogen activators, a relatively decreased plasminogen activator inhibitor 1, and decreased levels of thrombin-activatable fibrinolysis inhibitor and α2-antiplasmin are counterbalanced by decreased plasminogen and a decreased fibrin clot permeability. Whether and how these changes shift fibrinolysis remains to be determined. Overall, the current consensus is that in patients with cirrhosis, the hemostasis is shifted toward a procoagulant state. We review the published evidence for the concept of LC as a prothrombotic state, discuss discordant data, and highlight the impact of the underlying cause of LC on the resultant imbalance.
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Affiliation(s)
- Maxime G Zermatten
- Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Montserrat Fraga
- Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Debora Bertaggia Calderara
- Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Alessandro Aliotta
- Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Guido Stirnimann
- University Clinic for Visceral Surgery and Medicine, University Hospital Inselspital and University of Bern, Bern, Switzerland
| | - Andrea De Gottardi
- University Clinic for Visceral Surgery and Medicine, University Hospital Inselspital and University of Bern, Bern, Switzerland.,Gastroenterology and Hepatology, Ente Ospedaliero Cantonale, Università della Svizzera Italiana, Lugano, Switzerland
| | - Lorenzo Alberio
- Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
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39
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Chen YC, Tseng CW, Tseng KC. Rapid platelet count improvement in chronic hepatitis C patients with thrombocytopenia receiving direct-acting antiviral agents. Medicine (Baltimore) 2020; 99:e20156. [PMID: 32384505 PMCID: PMC7220127 DOI: 10.1097/md.0000000000020156] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The effect of direct-acting antiviral agents (DAAs) on short-term platelet improvement in chronic hepatitis C (CHC) patients with thrombocytopenia is unclear.From December 2015 to March 2018, a total of 249 CHC patients receiving DAA treatment with baseline thrombocytopenia (platelet count <150 × 10 /μL) at Dalin Tzu Chi Hospital were enrolled in this retrospective study. Blood examinations were conducted at baseline (BL), week 4 (W4) after DAA initiation, end of treatment (EOT), and 12 weeks after EOT (P12).Hepatitis C virus (HCV) genotyping revealed that 184 patients (73.9%) carried HCV genotype 1. Of the patients in the cohort, 87 (34.9%) were interferon (IFN)-experienced, and 213 (85.5%) had advanced fibrosis. All but 1 patient achieved SVR12 (sustained virologic response (SVR) rate, 99.6%; 248/249). The platelet count recovered significantly in 104 patients (41.7%; 104/249). The mean baseline platelet count was 102 × 10/μL before DAA, increasing to 116 × 10/μL, 114 × 10/μL, and 113 × 10/μL at W4, EOT, and P12, respectively. Comparison of the mean platelet count at baseline with that at W4, EOT, and P 12 showed statistically significant increases at all time points (W4 vs BL, P < .001; EOT vs BL, P < .001; P12 vs BL, P < .001). Multivariate analyses revealed moderate or severe fatty liver (P = .024) and lower baseline platelet count (P = .005) was significantly associated with platelet count improvement.In conclusion, thrombocytopenia associated with CHC rapidly improves with the administration of DAA. Moderate or severe fatty liver and lower baseline platelet count predict significant improvement of platelet count.
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Affiliation(s)
- Yen-Chun Chen
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi
| | - Chih-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi
- School of Medicine, Tzuchi University, Hualien, Taiwan
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40
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Reshetnyak VI, Maev IV, Reshetnyak TM, Zhuravel SV, Pisarev VM. Liver Diseases and the Hemostasis (Rewiew) Part 1. Non-Cholestatic Diseases of the Liver and Hemostasis. GENERAL REANIMATOLOGY 2019; 15:74-87. [DOI: 10.15360/1813-9779-2019-5-74-87] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
In liver diseases, most commonly in the terminal stage of liver failure, a variety of hemostatic defects affecting almost all parts of the blood coagulation system are developing. This leads to diminishing the capabilities of patients with liver diseases to correctly maintain the hemostatic balance.The severity of hemostatic disorders depends on the nosological form and degree of a liver damage. Depending on the imbalance of the hemostasis system and accumulated clinical/laboratory data, patients with liver diseases can be subdivided into three groups as exhibiting: 1. non-cholestatic liver damage; 2. cholestatic liver damage and 3. liver damage of vascular origin.The first part of the review discusses multiple alterations in the hemostasis system in patients with noncholestatic liver diseases, which are commonly accompanied by hypocoagulation.
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Affiliation(s)
- V. I. Reshetnyak
- A. I. Evdokimov Moscow State University of medicine and dentistry, Ministry of Health of Russia
| | - I. V. Maev
- A. I. Evdokimov Moscow State University of medicine and dentistry, Ministry of Health of Russia
| | | | - S. V. Zhuravel
- N. V. Sklifosovsky Research Institute of Emergency Care, Moscow Healthcare Department
| | - V. M. Pisarev
- V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
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41
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Ramadori P, Klag T, Malek NP, Heikenwalder M. Platelets in chronic liver disease, from bench to bedside. JHEP Rep 2019; 1:448-459. [PMID: 32039397 PMCID: PMC7005648 DOI: 10.1016/j.jhepr.2019.10.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 10/04/2019] [Accepted: 10/09/2019] [Indexed: 02/07/2023] Open
Abstract
In the last decade, numerous studies revealed physiologic and pathophysiologic roles of platelets beyond haemostasis, a process to prevent and stop bleeding. These include the activation of the immune system and the promotion of inflammation, infection and cancer. Hence, the emerging view on the role of platelets has shifted - platelets are now seen as alert "sentinels" of the immune compartment, rather than passive bystanders. Herein, we review well-established and newly discovered features of platelets that define their natural role in maintaining blood haemostasis, but also their functional relationship with other cells of the immune system. We focus on recent studies underlining functional involvement of platelets in chronic liver diseases and cancer, as well as the effects of anti-platelet therapy in these contexts. Finally, we illustrate the potential of platelets as possible diagnostic and therapeutic tools in liver disease based on recently developed methodologies.
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Affiliation(s)
- Pierluigi Ramadori
- Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany
| | - Thomas Klag
- Department of Internal Medicine I, University of Tuebingen, Tuebingen, Germany
| | - Nisar Peter Malek
- Department of Internal Medicine I, University of Tuebingen, Tuebingen, Germany
- Corresponding authors. Address: Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, Tel.: 0049-6221423891, or Department of Internal Medicine I, University Hospital of Tuebingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany, Tel.: 0049-70712982721.
| | - Mathias Heikenwalder
- Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany
- Corresponding authors. Address: Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, Tel.: 0049-6221423891, or Department of Internal Medicine I, University Hospital of Tuebingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany, Tel.: 0049-70712982721.
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42
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Honma Y, Shibata M, Hayashi T, Kusanaga M, Ogino N, Minami S, Kumei S, Oe S, Miyagawa K, Senju M, Matsuoka H, Watanabe T, Hiura M, Abe S, Harada M. Effect of direct-acting antivirals on platelet-associated immunoglobulin G and thrombocytopenia in hepatitis C virus-related chronic liver disease. Liver Int 2019; 39:1641-1651. [PMID: 31009141 DOI: 10.1111/liv.14120] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 04/03/2019] [Accepted: 04/08/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) infection has been known to cause various extrahepatic autoimmune disorders. The prevalence of platelet-associated immunoglobulin G (PA-IgG) has been high in patients with HCV infection. Because thrombocytopenia in HCV-related liver diseases is a notable problem, we performed prospective study on the effect of direct-acting antivirals (DAAs) treatment on PA-IgG and platelet count. METHODS A total of 215 patients with HCV-related liver disease were enrolled in this study. The patients who discontinued DAAs or did not undergo adequate laboratory examinations and who did not achieve sustained virologic response were excluded and finally a total of 187 patients were investigated. RESULTS A total of 171 patients (91.4%) were PA-IgG positive (>46 ng/107 cells) before starting DAAs (baseline). The PA-IgG level elevation was significantly correlated with higher liver inflammation and fibrosis markers (P < 0.05) and lower platelet count (P = 0.000019). The platelet count of the patients with low PA-IgG titer tended to be higher at baseline, end of treatment (EOT), and at 12 and 24 weeks after EOT. The platelet count increased at EOT (P < 0.05) and 24 weeks after EOT (P < 0.01). The PA-IgG levels were significantly decreased at EOT, 12 and 24 weeks after EOT (P < 0.01). Multiple regression analysis found that only platelet count at baseline was closely associated with negative conversion of PA-IgG at 24 weeks after EOT (P = 0.004). CONCLUSIONS Eradication of HCV by DAAs treatment successfully decreased PA-IgG level and increased platelet count.
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Affiliation(s)
- Yuichi Honma
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Tsuguru Hayashi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masashi Kusanaga
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Noriyoshi Ogino
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Sota Minami
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shinsuke Kumei
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shinji Oe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Koichiro Miyagawa
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Michio Senju
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Hidehiko Matsuoka
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Tatsuyuki Watanabe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masaaki Hiura
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shintaro Abe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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Sha FR, Pk MU, Abuelezz NZ, Pervin R, Talukder RI, Begum M, Rahman M. Investigating the Efficiency of APRI, FIB-4, AAR and AARPRI as Noninvasive Markers for Predicting Hepatic Fibrosis in Chronic Hepatitis B Patients in Bangladesh. Open Microbiol J 2019. [DOI: 10.2174/1874285801913010034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and Aims:Accurate, affordable non-invasive markers are highly needed for efficient diagnosis and management of liver fibrosis caused by chronic hepatitis B. This is the first study to investigate the diagnostic efficiency of Aspartate Transaminase to Platelet Ratio (APRI), Fibrosis Index (FIB-4), Aspartate transaminase to Alanine Transaminase Ratio (AAR) and AAR/Platelet ratio index (AARPRI) as non-invasive markers to predict hepatic fibrosis caused by Chronic Hepatitis B (CHB) in Bangladesh.Methods:In this study, a training cohort of 1041 CHB patients were recruited, whereas 104 and 109 CHB patients of matched ages were recruited as internal and external validation cohort groups respectively. Histological and hematological data were analyzed. METAVIR scoring system was used to classify liver fibrosis stages. Area Under Receiver Operating Curve (AUROC), correlations and cutoff values for the four diagnostic markers were calculated and assessed.Results:92%, 81% and 84% of the patients had liver fibrosis in the training cohort, internal and external cohort groups respectively. Among the four noninvasive panels, APRI showed the best area under ROC; (0.767, CI: 0.780-0.914; 0.775) for the training cohort, (0.775, CI: 0.693-0.857), and (0.847, CI: 0.780-0.914) for the internal and external cohorts respectively. Cut-off value of APRI was 0.512 with sensitivity/specificity of 84%/67% in training cohort, 81% / 66% in the internal cohort, and 88% / 66% in an external cohort. The odds ratio for APRI was 32.95 (95%CI: 4.746-228.862,p<0.001).Conclusion:Among all the four tested markers, APRI is the most accurate non-invasive test to predict major liver fibrosis (F2-3) in Bangladeshi CHB patients.
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Kao W, Su C, Fang S, Tang J, Chang C, Liu J. Determination of the predictive factors for significant liver fibrosis assessed through transient elastography. ADVANCES IN DIGESTIVE MEDICINE 2019. [DOI: 10.1002/aid2.13102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Wei‐Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University Hospital Taipei Taiwan
- Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
- Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical University Taipei Taiwan
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine, School of MedicineNational Yang‐Ming University Taipei Taiwan
| | - Chien‐Wei Su
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine, School of MedicineNational Yang‐Ming University Taipei Taiwan
| | - Sheng‐Uei Fang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University Hospital Taipei Taiwan
- Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
| | - Jui‐Hsiang Tang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University Hospital Taipei Taiwan
- Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
| | - Chun‐Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University Hospital Taipei Taiwan
- Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
| | - Jean‐Dean Liu
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University Hospital Taipei Taiwan
- Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
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Yang LS, Alukaidey S, Croucher K, Dowling D. Suboptimal use of pharmacological venous thromboembolism prophylaxis in cirrhotic patients. Intern Med J 2019; 48:1056-1063. [PMID: 29468795 DOI: 10.1111/imj.13766] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/28/2018] [Accepted: 01/28/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND Cirrhosis was previously perceived as a haemorrhagic disease state due to frequent associations with coagulopathy and bleeding. However, the coagulopathy of cirrhosis is complex with defects in both procoagulant and anticoagulant factors. Derangements in common laboratory indices of coagulation do not accurately reflect bleeding risk or protection from thrombotic events. AIMS To assess the rate of pharmacological prophylaxis for venous thromboembolism (VTE) among hospital inpatients with cirrhosis and analyse factors associated with prophylaxis being inappropriately withheld. METHODS A retrospective cohort study was performed in a tertiary teaching hospital. Patients included were admitted for greater than 48 h with discharge diagnosis codes corresponding to chronic liver disease and/or cirrhosis. The use of VTE chemoprophylaxis with enoxaparin was assessed in cirrhotic patients and non-cirrhotic controls. Patient data collected included contraindications to prophylaxis, known high-risk varices, international normalised ratio (INR), creatinine, bilirubin, haemoglobin and platelet count. RESULTS Of 108 patients with cirrhosis eligible for VTE prophylaxis, 61 (56.5%) received prophylaxis compared to 104 (96.3%) non-cirrhotic patients. Platelets and INR were significantly different between those who did and did not receive VTE prophylaxis. On multivariate analysis, platelet count and INR were independent predictors for VTE not being administered. CONCLUSION The administration of chemoprophylaxis in accordance with the hospital guidelines was suboptimal in patients with cirrhosis. Platelet count and INR were independent predictors of prophylaxis use. Our results suggest persistent misperceptions that prolonged INR and thrombocytopenia predict bleeding risk in cirrhosis.
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Affiliation(s)
- Linda S Yang
- Department of Gastroenterology, University Hospital Geelong, Geelong, Victoria, Australia
| | - Sumaya Alukaidey
- Department of Gastroenterology, University Hospital Geelong, Geelong, Victoria, Australia
| | - Katherine Croucher
- Department of Gastroenterology, University Hospital Geelong, Geelong, Victoria, Australia
| | - Damian Dowling
- Department of Gastroenterology, University Hospital Geelong, Geelong, Victoria, Australia
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Zhu M, Han M, Xiao X, Lu S, Guan Z, Song Y, Liu C. Dynamic Differences Of Red Cell Distribution Width Levels Contribute To The Differential Diagnosis Of Hepatitis B Virus-related Chronic Liver Diseases: A Case-control Study. Int J Med Sci 2019; 16:720-728. [PMID: 31217740 PMCID: PMC6566733 DOI: 10.7150/ijms.31826] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 03/27/2019] [Indexed: 02/06/2023] Open
Abstract
Objective: This study aims to clarify the changes and clinical significance of red cell distribution width (RDW) during HBV-related chronic diseases, including inactive hepatitis B virus (HBV) carriers, HBV immune tolerant individuals, chronic hepatitis B (CHB) patients and HBV-related hepatocirrhosis patients. Methods: RDW was measured 288 CHB patients, 100 patients with hepatitis B e antigen(HBeAg)-negative chronic HBV infection (inactive carriers), 92 patients with HBeAg-positive chronic HBV infection (immune tolerant), and 272 patients with HBV-related hepatocirrhosis. Their RDW changes were compared with 160 healthy controls. Correlations between RDW and clinical indicators were conducted. For HBeAg+ CHB patients, RDW was measured before and after antiviral therapy. The efficiency of RDW to distinguish hepatocirrhosis from CHB and/or inactive carriers was evaluated by receiver operating characteristic (ROC) curves. Results: RDW was higher in hepatocirrhosis patients than other groups of patients and healthy controls. Besides, HBeAg+ CHB patients possessed higher RDW than HBeAg- CHB patients. For HBeAg+ patients that underwent HBeAg seroconversion after antiviral therapy, RDW was decreased. RDW was positively correlated with total bilirubin and Child-Pugh scores and negatively correlated with albumin among hepatocirrhosis patients. The areas under the curve (AUC) of ROC curves to distinguish hepatocirrhosis from CHB patients was 0.7040 for RDW-standard deviation (RDW-SD) and 0.6650 for RDW-coefficient of variation (RDW-CV), and AUC to distinguish hepatocirrhosis from inactive carriers was 0.7805 for RDW-SD and 0.7991 for RDW-CV. Conclusions: RDW is significantly increased in HBeAg+ CHB patients and patients with HBV-related hepatocirrhosis and could reflect their severity. RDW could help to distinguish hepatocirrhosis from CHB patients and inactive HBV carriers.
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Affiliation(s)
- Mengjie Zhu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Man Han
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Xiaoyu Xiao
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Songsong Lu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Zhao Guan
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Ying Song
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
| | - Chen Liu
- Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China
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Gîrleanu I, Trifan A, Stanciu C, Sfarti C. Portal vein thrombosis in cirrhotic patients - it is always the small pieces that make the big picture. World J Gastroenterol 2018; 24:4419-4427. [PMID: 30356984 PMCID: PMC6196341 DOI: 10.3748/wjg.v24.i39.4419] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 09/02/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
Portal vein thrombosis (PVT) is a frequent and serious complication in patients with liver cirrhosis (LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease (compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex end-points such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.
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Affiliation(s)
- Irina Gîrleanu
- Department of Gastroenterology, “Grigore T Popa” University of Medicine and Pharmacy, Iași 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, Iași 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T Popa” University of Medicine and Pharmacy, Iași 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, Iași 700115, Romania
| | - Carol Stanciu
- Department of Gastroenterology, “Grigore T Popa” University of Medicine and Pharmacy, Iași 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, Iași 700115, Romania
| | - Cătălin Sfarti
- Department of Gastroenterology, “Grigore T Popa” University of Medicine and Pharmacy, Iași 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, Iași 700115, Romania
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Xue J, Feng R, Fu H, Jiang Q, Jiang H, Lu J, Liu H, Wang J, Niu T, Wang X, Xie Y, Wang H, Xu L, Liu K, Huang X, Zhang X. Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism. SCIENCE CHINA. LIFE SCIENCES 2018; 61:924-933. [PMID: 29524121 DOI: 10.1007/s11427-017-9250-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Accepted: 10/26/2017] [Indexed: 12/13/2022]
Abstract
The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.
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Affiliation(s)
- Jing Xue
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Ru Feng
- Departments of Hematology, Beijing Hospital, National Center of Gerontology, Beijing, 100005, China
| | - Haixia Fu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Qian Jiang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Hao Jiang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Jing Lu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Hui Liu
- Departments of Hematology, Beijing Hospital, National Center of Gerontology, Beijing, 100005, China
| | - Jingwen Wang
- Department of Hematology, Beijing Tongren Hospital, Beijing, 100730, China
| | - Ting Niu
- Department of Hematology, Sichuan University West China Medical Center, Chengdu, 610041, China
| | - Xin Wang
- Department of Hematology, Shandong Provincial Hospital, Qingdao, 266003, China
| | - Yandi Xie
- Peking University, People's Hospital, Institute of Hepatic Diseases, Beijing, 100044, China
| | - Hao Wang
- Peking University, People's Hospital, Institute of Hepatic Diseases, Beijing, 100044, China
| | - Lanping Xu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Kaiyan Liu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China
| | - Xiaojun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China.
| | - Xiaohui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China.
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Nagareddy PR, Noothi SK, Flynn MC, Murphy AJ. It's reticulated: the liver at the heart of atherosclerosis. J Endocrinol 2018; 238:R1-R11. [PMID: 29720539 PMCID: PMC7065032 DOI: 10.1530/joe-18-0082] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 05/02/2018] [Indexed: 12/28/2022]
Abstract
Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the risk of myocardial ischemia, stroke or death due to cardiovascular disease. However, antiplatelet therapies lose their efficacy in people with diabetes mellitus, increasing the risk of future atherothrombotic events. The molecular mechanisms that promote platelet hyperactivity remain unclear but could be due to glycation-induced conformational changes of platelet membranes resulting in impaired aspirin entry or less-efficient acetylation/compensatory increase in COX-2 expression in newborn platelets. Emerging evidence from our laboratory and elsewhere suggest that enhanced platelet turnover (thrombopoiesis), particularly the production of immature reticulated platelets from the bone marrow, could contribute to atherosclerotic complications. We have identified a major role for neutrophil-derived S100A8/A9, a damage-associated molecular pattern, in driving reticulated thrombopoiesis by directly interacting with its receptors on Kupffer cells in the liver. In this review, we discuss the role of hepatic inflammation in driving reticulated platelet production and suggest potential targets to control their production, improve efficacy of current antiplatelet therapies and reduce the risk of atherothrombotic complications.
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Affiliation(s)
| | - Sunil K Noothi
- Department of Nutrition SciencesUniversity of Alabama, Birmingham, UK
| | - Michelle C Flynn
- Division of ImmunometabolismBaker Heart and Diabetes Institute, Melbourne, Australia
- Department of ImmunologyMonash University, Melbourne, Australia
| | - Andrew J Murphy
- Division of ImmunometabolismBaker Heart and Diabetes Institute, Melbourne, Australia
- Department of ImmunologyMonash University, Melbourne, Australia
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Han S, Lee S, Yang JD, Leise MD, Ahn JH, Kim S, Jung K, Gwak MS, Kim GS, Ko JS. Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation. Liver Transpl 2018; 24:44-55. [PMID: 29024412 DOI: 10.1002/lt.24961] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 09/15/2017] [Accepted: 09/25/2017] [Indexed: 12/12/2022]
Abstract
Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109 /L were matched with 97 of 119 patients who had preoperative PLT >75 × 109 /L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109 /L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] = 3.09; 95% confidence interval [CI], 1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P = 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P = 0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P = 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation. Liver Transplantation 24 44-55 2018 AASLD.
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Affiliation(s)
- Sangbin Han
- Department of Anesthesiology and Pain Medicine
| | - Sanghoon Lee
- Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
| | - Michael Douglas Leise
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
| | - Joong Hyun Ahn
- Statistics and Data Center, Samsung Medical Center, Seoul, South Korea
| | - Seonwoo Kim
- Statistics and Data Center, Samsung Medical Center, Seoul, South Korea
| | - Kangha Jung
- Department of Anesthesiology and Pain Medicine
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