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Zhang J, Yan B, Shi X. Association of iron overload with infectious complications in liver transplant recipients: a systematic review and meta-analysis. J Int Med Res 2024; 52:3000605241232920. [PMID: 38518199 PMCID: PMC10960351 DOI: 10.1177/03000605241232920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 01/29/2024] [Indexed: 03/24/2024] Open
Abstract
OBJECTIVE This study was performed to examine the possible association of iron overload with infectious complications and survival among liver transplant recipients. METHODS We conducted a systematic review and meta-analysis of studies published in the PubMed, Embase, Web of Science, and Cochrane Library databases up to September 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted to estimate the association of iron overload with infectious outcomes and overall survival after liver transplantation. RESULTS Eight studies involving 2817 recipients met the inclusion criteria. Iron overload was strongly associated with an increased risk of infection after liver transplantation (HR, 1.66; 95% CI, 1.03-2.68). An increase in the serum ferritin level was associated with an increased risk of infection after liver transplantation (HR, 1.44; 95% CI, 1.09-1.91). Iron overload was a significant predictor of worse overall survival (HR, 1.35; 95% CI, 1.11-1.64). In addition, a high serum ferritin level was significantly associated with an increased risk of death (HR, 1.34; 95% CI, 1.10-1.64). CONCLUSION Iron overload may be associated with a higher risk of infectious complications and a worse prognosis among liver transplant recipients.
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Affiliation(s)
- Jingpo Zhang
- Department of Hepatobiliary Surgery, The First Hospital of Hebei Medical University, Shijiazhuang City, P.R. China
| | - Bingzheng Yan
- Department of Hepatobiliary Surgery, The First Hospital of Hebei Medical University, Shijiazhuang City, P.R. China
| | - Xin Shi
- Department of Hepatobiliary Surgery, The First Hospital of Hebei Medical University, Shijiazhuang City, P.R. China
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2
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Liu D, Luo Y, Zheng Y, Ji R, Zhou Y. Effect of elevated serum ferritin on the risk of death in patients with decompensated cirrhosis: a meta-analysis. Eur J Gastroenterol Hepatol 2023; 35:795-802. [PMID: 37161969 DOI: 10.1097/meg.0000000000002566] [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: 05/11/2023]
Abstract
It is still debatable whether serum ferritin is a potential prognostic marker in patients with decompensated cirrhosis. In this meta-analysis, we hope to investigate the relationship between elevated serum ferritin and the risk of death in patients with decompensated cirrhosis. We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WAN FANG, and ClinicalTrials.gov without language restrictions from inception to 3 October 2022, and finally identified a total of eight eligible studies with 1829 patients. The pooled prevalence of elevated serum ferritin in decompensated cirrhosis was 40.6% [95% confidence interval (CI) 32.1-49.2%], and it was higher in males, patients with alcohol-associated liver disease, those with Child-Pugh grade C, those with hepatic encephalopathy, and nonsurvivors. Nonsurvivors had significantly higher serum ferritin levels than survivors [mean difference 247.90; 95% CI, 130.97-364.84]. With a pooled unadjusted hazard ratio of 2.38 (95% CI, 1.78-3.18), high serum ferritin was associated with an increased risk of death in patients with decompensated cirrhosis, with low heterogeneity among the included studies. In conclusion, high serum ferritin levels were associated with mortality in patients with decompensated cirrhosis. More prospective and homogeneous clinical studies are required to validate our findings.
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Affiliation(s)
- Dan Liu
- The First Clinical Medical College, Lanzhou University
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yuxin Luo
- The First Clinical Medical College, Lanzhou University
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Rui Ji
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
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Rashidi-Alavijeh J, Nuruzade N, Frey A, Huessler EM, Hörster A, Zeller AC, Schütte A, Schmidt H, Willuweit K, Lange CM. Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis. JHEP Rep 2023; 5:100688. [PMID: 36926273 PMCID: PMC10011825 DOI: 10.1016/j.jhepr.2023.100688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 12/29/2022] [Accepted: 01/12/2023] [Indexed: 01/30/2023] Open
Abstract
Background & Aims Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Methods Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. Conclusions An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Impact and implications Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. Clinical trial registration UME-ID-10042.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- AP, alkaline phosphatase
- AST, aspartate aminotransferase
- CRP, C-reactive protein
- Haemoglobin
- INR, international normalised ratio
- Iron deficiency
- Iron supplementation
- LT, liver transplantation
- Liver transplantation
- MELD, model for end-stage liver disease
- NASH, non-alcoholic steatohepatitis
- NSBBs, non-selective beta blockers
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- Rifaximin
- SSC, secondary sclerosing cholangitis
- TIPS, transjugular intrahepatic portosystemic shunt
- aPTT, activated partial thromboplastin time
- ΔHb3, difference of haemoglobin levels after 3 months
- ΔHb6, difference of haemoglobin levels after 6 months
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Affiliation(s)
- Jassin Rashidi-Alavijeh
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Nargiz Nuruzade
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Alexandra Frey
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Eva-Maria Huessler
- Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Duisburg, Germany
| | - Anne Hörster
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Amos Cornelius Zeller
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Andreas Schütte
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Hartmut Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Katharina Willuweit
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Christian Markus Lange
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
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Guo G, Sun M, Li Y, Yang W, Wang X, Yu Z, Li C, Hui Y, Fan X, Jiang K, Sun C. Serum Ferritin Has Limited Prognostic Value on Mortality Risk in Patients with Decompensated Cirrhosis: A Propensity Score Matching Analysis. Lab Med 2023; 54:47-55. [PMID: 35960775 DOI: 10.1093/labmed/lmac064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE The prognostic value of serum ferritin remains elusive in the literature. We aimed to examine the association between serum ferritin and mortality risk in cirrhosis. METHODS A total of 257 cirrhotic patients were recruited. The cut-off of serum ferritin was determined by X-tile. The Cox regression and Kaplan-Meier method were used. A 1:1 propensity score matching (PSM) was performed to diminish the impacts of selection bias and possible confounders. RESULTS The difference regarding mortality was mostly significant for serum ferritin >158 ng/mL. Before PSM, serum ferritin >158 ng/mL was an independent predictor of mortality. However, the clinical relevance of high ferritin level for prognostication was blunted after PSM (survival rate: 86.8% vs 96.3%, P = .078). Cox regression indicated that model for end-stage liver disease remains only independent risk factor of 180-day mortality after PSM. CONCLUSION Serum ferritin may not serve as an independent prognostic indicator of mortality risk in decompensated cirrhotic patients.
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Affiliation(s)
- Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Mingyu Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yifan Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaoyu Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Chaoqun Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Department of Internal Medicine, Tianjin Hexi Hospital, Tianjin, China
| | - Yangyang Hui
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaofei Fan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
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5
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Luo J, Liang X, Xin J, Li P, Li J, Jiang J, Wang Y, Lu Y, Shi D. Serum ferritin diagnosis and prediction of hepatitis B virus-related acute-on-chronic liver failure. J Med Virol 2023; 95:e28183. [PMID: 36175010 DOI: 10.1002/jmv.28183] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 09/21/2022] [Accepted: 09/26/2022] [Indexed: 01/11/2023]
Abstract
Early diagnosis and prediction of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to reduce mortality. This study aimed to assess the diagnostic and predictive value of serum ferritin (SF) in HBV-ACLF patients. Clinical data from 1905 hospitalized patients with acute deterioration of HBV-related chronic liver diseases were analyzed to explore the association between SF and ACLF. A co-expression network based on transcriptomics data for 20 HBV-ACLF patients was constructed to investigate biological processes related to ferritin. Of 1270 patients in the derivation group, 440 and 830 were diagnosed with and without ACLF, respectively, based on Chinese Group on the Study of Severe Hepatitis B-ACLF criteria. SF levels showed high diagnostic accuracy (area under the receiver operating characteristic [AUROC]: 0.820) for ACLF at admission. In patients with ACLF, SF was associated with liver and coagulation failure. In patients without ACLF, SF predicted risk for 28-day progression to ACLF (AUROC: 0.808). A validation group of 635 patients confirmed the above results. Moreover, SF was significantly associated with the immune response based on transcriptomics analysis. SF is a potential diagnostic and predictive marker for HBV-ACLF and might play a crucial role in immune disorders in HBV-ACLF.
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Affiliation(s)
- Jinjin Luo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xi Liang
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Jiaojiao Xin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Peng Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaqi Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yifan Wang
- Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Yingyan Lu
- Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Dongyan Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Curakova Ristovska E, Genadieva-Dimitrova M. Prognostic value of von-Willebrand factor in patients with liver cirrhosis and its relation to other prognostic indicators. World J Hepatol 2022; 14:812-826. [PMID: 35646274 PMCID: PMC9099105 DOI: 10.4254/wjh.v14.i4.812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/18/2021] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Von-Willebrand factor (vWF) disposes certain prognostic value in patients with liver cirrhosis, but its relation to other prognostic indicators has not been fully investigated.
AIM To analyze the relation between vWF and other prognostic indicators in cirrhotic patients and to evaluate its prognostic value for mortality.
METHODS This analytic prospective study was carried out in a tertiary center and initially enrolled 71 patients with liver cirrhosis and portal hypertension. It analyzed the relation between vWF and the stage of the disease and several inflammatory and prognostic indicators. The prospective analysis, performed on a sample of 63 patients, evaluated the association between the selected variables [vWF, Model for End-stage Liver Disease (MELD) score, C-reactive protein (CRP), ferritin, vitamin D, activated partial thromboplastin time, thrombin time, D-dimer concentration] and the survival time as well as their predictive value in terms of 3-mo, 6-mo and 1-year mortality.
RESULTS vWF was significantly higher in patients with higher Child-Turcotte-Pugh class (P = 0.0045), MELD group (P = 0.0057), ferritin group (P = 0.0278), and D-dimer concentration (P = 0.0232). vWF significantly correlated with D-dimer concentration, ferritin, CRP, International Normalized Ratio, and MELD, Child-Turcotte-Pugh, Sequential Organ Failure Assessment, and CLIF-consortium organ failure (CLIF-C OF) scores. vWF, MELD score, and CRP were significantly associated with death and were significant predictors of 3-mo, 6-mo, and 1-year mortality. Each vWF unit significantly increased the probability for 3-mo mortality by 1.005 times (P = 0.008), for 6-mo mortality by 1.006 times (P = 0.005), and for 1-year mortality by 1.007 times (P = 0.002). There was no significant difference between the diagnostic performance of vWF and MELD score and also between vWF and CRP regarding the 3-mo, 6-mo, and 1-year mortality.
CONCLUSION In patients with liver cirrhosis, vWF is significantly related to other prognostic indicators and is a significant predictor of 3-mo, 6-mo, and 1-year mortality similar to MELD score and CRP.
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Affiliation(s)
- Elena Curakova Ristovska
- Intensive Care Unit, University Clinic for Gastroenterohepatology, Skopje 1000, North Macedonia
- Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Skopje 1000, North Macedonia
| | - Magdalena Genadieva-Dimitrova
- Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Skopje 1000, North Macedonia
- Hepatology Department, University Clinic for Gastroenterohepatology, Skopje 1000, North Macedonia
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Yu J, Xu Z, Zhuo Y, Wei H, Ye Y, Xu Q, Li Y, Yu L, Feng W, Hong P, Zhang K. Development and validation of a nomogram for steroid-resistance prediction in immune thrombocytopenia patients. Hematology 2021; 26:956-963. [PMID: 34871524 DOI: 10.1080/16078454.2021.2003066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
OBJECTIVES Corticosteroid is first-line therapy in immune thrombocytopenia. However, nearly 30% of patients appear in steroid-resistance. Our research analyses the relevant indicators of patients and develops a risk prediction model to predict the poor response to steroid-therapy in ITP patients. METHODS We collected data from 111 ITP patients admitted to Xiamen University Zhongshan Hospital from 2013 to 2019 as the training cohort and 65 ITP patients during 2019-2020 as the external validation cohort. Screening significant factors(P < 0.05) in univariate analysis, and further identified to be independent variables in multivariable logistic regression analysis. Incorporated the significant risk factors in and presented them with a nomogram based on independent risk predictors. The nomogram was assessed by receiver operating characteristics curves and decision curve analysis. RESULTS We constructed a steroid-resistance prediction model based on the potential predictors including age, serum ferritin and expression of HBsAg. As a result, based on the area under the ROC curves, the training cohort (AUC: 0.718, 95% CI: 0.615-0.821) and the external validation cohort (AUC:0.799,95%CI:0.692-0.905), which displayed good discrimination. The decision curve showed that predicting the steroid-refractory risk in ITP patients using this nomogram with a range of the threshold probability between >16% and <70%. The nomogram appears good performance in predicting steroid-refractory ITP patients. CONCLUSION Prediction model shows that elder patients with a high level of ferritin and positive expression of HBsAg may appear a high possibility of steroid-resistance. For these patients, TPO-RAs can be considered to help patients to get better treatment effects and develop a better health-related quality of life.
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Affiliation(s)
- Jieni Yu
- Department of Hematology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine). Shaoxing, People's Republic of China.,Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Medical College, Xiamen University, Xiamen, People's Republic of China
| | - Zhiqiang Xu
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China
| | - Yuanyuan Zhuo
- Department of Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China
| | - Huahua Wei
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Medical College, Xiamen University, Xiamen, People's Republic of China
| | - Yinhai Ye
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Third Clinical Medical College, Fujian Medical University, Fuzhou, People's Republic of China
| | - Qinhong Xu
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Medical College, Xiamen University, Xiamen, People's Republic of China
| | - Youli Li
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Third Clinical Medical College, Fujian Medical University, Fuzhou, People's Republic of China
| | - Lihong Yu
- Department of Emergency, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.,The Third Clinical Medical College, Fujian Medical University, Fuzhou, People's Republic of China
| | - Weiying Feng
- Department of Hematology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine). Shaoxing, People's Republic of China
| | - Pan Hong
- Department of Hematology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine). Shaoxing, People's Republic of China
| | - Kejie Zhang
- Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China
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8
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Burra P, Samuel D, Sundaram V, Duvoux C, Petrowsky H, Terrault N, Jalan R. Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation. J Hepatol 2021; 75 Suppl 1:S178-S190. [PMID: 34039488 DOI: 10.1016/j.jhep.2021.01.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/04/2021] [Accepted: 01/05/2021] [Indexed: 02/07/2023]
Abstract
Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Didier Samuel
- Centre Hépato-Biliaire, Paris-Saclay University, Inserm research unit 1193, Hôpital Paul Brousse, Villejuif, France
| | - Vinay Sundaram
- Karsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Christophe Duvoux
- Department of Hepatology and Medical Liver Transplant Unit Henri Mondor Hospital-APHP, Paris Est University (UPEC), Créteil, France
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center Department of Surgery and Transplantation University Hospital Zürich, Zürich, Switzerland
| | - Norah Terrault
- Keck School of Medicine of University of Southern California, Los Angeles CA, United States
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London and European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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9
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Valantine B, Sundaray N, Mishra D, Sahu S, Narayan J, Panda BN, Singh A. Predictors of early mortality among patients with acute-on-chronic liver failure. JGH Open 2021; 5:686-694. [PMID: 34124387 PMCID: PMC8171164 DOI: 10.1002/jgh3.12557] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 04/19/2021] [Accepted: 04/29/2021] [Indexed: 11/12/2022]
Abstract
BACKGROUND AND AIM Acute-on-chronic liver failure (ACLF) is a transpiring entity, which possesses high short-term/early mortality (28 days). Several mortality predictors have been studied, but none were proved reliable. Serum ferritin, an acute phase reactant and marker of hepatic necro-inflammation, is found to predict mortality in multiple liver diseases. We aimed to evaluate the role of serum ferritin and other clinical features, biochemical parameters and conventional scoring systems in predicting early mortality among ACLF. METHODS A prospective cohort study was done from October 2017 to March 2019 at a tertiary care (non-transplant) center in eastern India. A total of consecutive 50 ACLF patients diagnosed, based on Asia Pacific Association for the Study of liver disease definition, were investigated for ferritin and other laboratory parameters on day-0, day-7, and followed up for 28 days. RESULTS Although the majority did not have organ failure (ACLF grade 0) according to European Association for Study of Liver-chronic liver failure sequential organ failure assessment criteria, early mortality was high (56%). On undergoing univariate analysis, multiple variables (ascites, HE, creatinine, total leucocyte count (TLC), bilirubin, albumin) predicted mortality. However, on multivariate analysis, only total bilirubin independently predicted. None of the scores on day-0 were predictive, while model for end-stage liver disease [area under the receiver operating characteristics (AUROC)-0.703, 95% confidence interval [CI]: 0.535-0.859] and Child-Turcotte-Pugh (AUROC-0.697, 95% CI: 0.550-0.855) on day-7 did. CONCLUSION ACLF is a dynamic process; day-7 assessment with above predictors, to be considered a milestone for prognostication and opting treatment modalities. Serum ferritin does not predict early mortality in ACLF.
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Affiliation(s)
- Bershic Valantine
- Department of General MedicineIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Nabakishore Sundaray
- Department of General MedicineIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Debakanta Mishra
- Department of GastroenterologyIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Samir Sahu
- Department of General MedicineIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Jimmy Narayan
- Department of GastroenterologyIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Baikuntha N Panda
- Department of General MedicineIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
| | - Ayaskanta Singh
- Department of GastroenterologyIMS and SUM Hospital, Siksha 'O' Anusandhan, Deemed to be UniversityBhubaneswarIndia
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10
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Llibre-Nieto G, Lira A, Vergara M, Solé C, Casas M, Puig-Diví V, Solé G, Humanes A, Grau L, Barradas JM, Miquel M, Sánchez-Delgado J. Micronutrient Deficiencies in Patients with Decompensated Liver Cirrhosis. Nutrients 2021; 13:nu13041249. [PMID: 33920134 PMCID: PMC8069759 DOI: 10.3390/nu13041249] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/07/2021] [Accepted: 04/08/2021] [Indexed: 12/11/2022] Open
Abstract
Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our main goal was to assess the prevalence of micronutrient deficiencies in patients with decompensated cirrhosis. This was a prospective single-center study including 125 consecutive patients hospitalized for acute decompensation of cirrhosis (mostly of alcoholic etiology). A blood test including trace elements and vitamins was performed on admission. The main micronutrient deficiencies observed were vitamin D (in 94.5%), vitamin A (93.5%), vitamin B6 (60.8%) and zinc (85.6%). Patients in Child-Pugh class C had lower levels of vitamin A (p < 0.0001), vitamin E (p = 0.01) and zinc (p < 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.001) than those in Child-Pugh class A and B. Patients with a higher model of end-stage liver disease (MELD) score had lower levels of vitamin A (p < 0.0001), vitamin E (p < 0.001), magnesium (p = 0.01) and zinc (p = 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.0001). Severe hepatic insufficiency correlated with lower levels of zinc, vitamin E and vitamin A, and higher levels of vitamin B12 and ferritin.
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Affiliation(s)
- Gemma Llibre-Nieto
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- Fundació Privada Hospital Assil de Granollers, 08402 Granollers, Spain
- Correspondence:
| | - Alba Lira
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
| | - Mercedes Vergara
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cristina Solé
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Meritxell Casas
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
| | - Valentí Puig-Diví
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Gastroenterology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigacio i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain
| | - Gemma Solé
- Laboratory Unit, Hospital Universitari Parc Tauli, Institut d’Investigacio i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain;
| | - Antonia Humanes
- Endocrinology and Nutrition Department, Hospital Universitari Parc Tauli, Institut d’Investigacio i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain;
| | - Laia Grau
- Statistics, Hospital Germans Trias i Pujol, Neurology Service, 08916 Badalona, Spain;
| | - Josep Maria Barradas
- Nursing Service, Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigacio i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain;
| | - Mireia Miquel
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departament de Medicina, Universitat de Vic–Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
| | - Jordi Sánchez-Delgado
- Hepatology Unit, Digestive Disease Department, Hospital Universitari Parc Tauli, Institut d’Investigació i Innovació Parc Taulí (I3PT), 08208 Sabadell, Spain; (A.L.); (M.V.); (C.S.); (M.C.); (V.P.-D.); (M.M.); (J.S.-D.)
- Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
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11
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Martín-González C, Pelazas-González R, Fernández-Rodríguez C, Alemán-Valls R, Martínez-Riera A, Ortega-Toledo P, García-Rodríguez A, Rodríguez-Gaspar M, González-Reimers E. Ferritin and liver fibrosis among patients with chronic hepatitis C virus infection. J Trace Elem Med Biol 2020; 61:126542. [PMID: 32417635 DOI: 10.1016/j.jtemb.2020.126542] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/29/2020] [Accepted: 04/27/2020] [Indexed: 12/25/2022]
Abstract
INTRODUCTION In chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described. OBJECTIVE We analyze the behavior of iron metabolism- related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients. PATIENTS AND METHODS We analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism- related variables with 34 controls. RESULTS Patients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = -0.22; p = 0.04) and TSI (ρ = -0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order). CONCLUSION Alterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection.
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Affiliation(s)
- Candelaria Martín-González
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain.
| | - Ricardo Pelazas-González
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Camino Fernández-Rodríguez
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Remedios Alemán-Valls
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Antonio Martínez-Riera
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Paula Ortega-Toledo
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Alen García-Rodríguez
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain
| | - Melchor Rodríguez-Gaspar
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain.
| | - Emilio González-Reimers
- Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain.
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12
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Paternostro R, Kapzan L, Mandorfer M, Schwarzer R, Benedikt S, Viveiros A, Bauer D, Ferlitsch M, Zoller H, Trauner M, Ferlitsch A. Anemia and iron deficiency in compensated and decompensated cirrhosis: Prevalence and impact on clinical outcomes. J Gastroenterol Hepatol 2020; 35:1619-1627. [PMID: 31972057 DOI: 10.1111/jgh.14988] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 12/19/2019] [Accepted: 01/22/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIM Iron deficiency anemia (IDA)is the leading cause of anemia worldwide. Data on prevalence and clinical impact of anemia in cirrhosis are scarce. Aim was to report on the following:(i) prevalence of anemia and IDA in cirrhosis and (ii) its possible impact on clinical outcomes. METHODS Consecutive cirrhotic patients from a prospective registry study were included. Anemia was defined as hemoglobin concentration ≤ 12 g/dL. IDA was defined as Hb ≤ 12 g/dL + transferrin-saturation < 20%. Follow up for hepatic decompensation and mortality started with study inclusion and terminated in December 2017. A retrospective validation cohort of 1244 patients was used to validate our findings. RESULTS Two hundred forty-two patients with compensated (n = 53 [21.9%]) and decompensated (n = 189 [78.1%]) cirrhosis were included. Anemia was present in 128 patients (52.9%); of those, 63 (49.2%) had IDA. Prevalence of anemia increased with Child-Pugh Score (CPS; A: 26.5%, B: 59.2%, C: 69%; P < 0.001) and with decompensated cirrhosis(62.4% vs 18.8%, P < 0.001). Within anemic patients, a higher proportion of patients in CPS A/B vs C (73% vs 35%; P = 0.025) and in compensated cirrhosis (80% vs 46.6%; P = 0.043) were found with IDA. Model for End-Stage Liver Disease (MELD) scores were significantly lower in patients with IDA (14.4 vs 17.9 non-ID-anemia; P = 0.005). Similar results were found in the validation cohort: median MELD (16[8-28]non-IDA vs 12 [7-23] IDA; P < 0.001) and within anemic patients IDA was more common in patients with MELD <15 (58%) versus >15 (24%, P < 0.001). Anemia was associated with a significant risk for hepatic decompensation and/or mortality both in the validation (aSHR: 1.65, P = 0.008) and in the derivation cohort (aSHR: 2.11, P < 0.001) and an independent risk factor for hepatic decompensation and/or mortality in compensated patients (aHR: 4.91, P = 0.004). CONCLUSION Anemia is highly prevalent in cirrhosis. In compensated cirrhosis, CPS A/B, and low MELD, IDA seems to be the most likely reason for anemia. Furthermore, anemia is associated with a significant risk for hepatic decompensation or mortality during long-term follow up.
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Affiliation(s)
- Rafael Paternostro
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Lea Kapzan
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Remy Schwarzer
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Schaefer Benedikt
- Division for Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - André Viveiros
- Division for Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - David Bauer
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Monika Ferlitsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Heinz Zoller
- Division for Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Trauner
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Vienna Hepatic Hemodynamic Lab, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine I, KH Barmherzige Brüder Vienna, Vienna, Austria
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13
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A Systematic Review for Variables to Be Collected in a Transplant Database for Improving Risk Prediction. Transplantation 2020; 103:2591-2601. [PMID: 30768569 DOI: 10.1097/tp.0000000000002652] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). METHODS We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. RESULTS Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. CONCLUSIONS Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.
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14
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Ribot-Hernández I, Martín-González C, Vera-Delgado V, González-Navarrete L, de Armas-González JF, Viña-Rodríguez J, Sánchez-Pérez MJ, Rodríguez-Gaspar M, González-Reimers E. Prognostic Value of Serum Iron, Ferritin, and Transferrin in Chronic Alcoholic Liver Disease. Biol Trace Elem Res 2020; 195:427-435. [PMID: 31486016 DOI: 10.1007/s12011-019-01887-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 08/26/2019] [Indexed: 01/01/2023]
Abstract
Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child's groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = - 0.16, p = 0.017), TIBC (ρ = - 0.20, p = 0.002), and transferrin (ρ = - 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.
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Affiliation(s)
- Ivan Ribot-Hernández
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - Candelaria Martín-González
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - Víctor Vera-Delgado
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - Lourdes González-Navarrete
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | | | - José Viña-Rodríguez
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - María José Sánchez-Pérez
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - Melchor Rodríguez-Gaspar
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain
| | - Emilio González-Reimers
- Servicio de Medicina Interna Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
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15
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Fallet E, Rayar M, Landrieux A, Camus C, Houssel-Debry P, Jezequel C, Legros L, Uguen T, Ropert-Bouchet M, Boudjema K, Guyader D, Bardou-Jacquet E. Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation. World J Gastroenterol 2020; 26:1938-1949. [PMID: 32390704 PMCID: PMC7201152 DOI: 10.3748/wjg.v26.i16.1938] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/30/2020] [Accepted: 04/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.
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Affiliation(s)
- Elodie Fallet
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
| | - Michel Rayar
- Service de Chirurgie Hepatobilaire, CHU Rennes, University Rennes, Rennes 35033, France
| | - Amandine Landrieux
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
| | - Christophe Camus
- Service de Réanimation médicale, CHU Rennes, University Rennes, Rennes 35033, France
| | - Pauline Houssel-Debry
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
- Service de Chirurgie Hepatobilaire, CHU Rennes, University Rennes, Rennes 35033, France
| | - Caroline Jezequel
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
| | - Ludivine Legros
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
| | - Thomas Uguen
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
| | | | - Karim Boudjema
- Service de Chirurgie Hepatobilaire, CHU Rennes, University Rennes, Rennes 35033, France
| | - Dominique Guyader
- Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
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16
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Meier JA, Bokemeyer A, Cordes F, Fuhrmann V, Schmidt H, Hüsing-Kabar A, Kabar I. Serum levels of ferritin and transferrin serve as prognostic factors for mortality and survival in patients with end-stage liver disease: A propensity score-matched cohort study. United European Gastroenterol J 2019; 8:332-339. [PMID: 32213016 DOI: 10.1177/2050640619891283] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Patients with end-stage liver disease are known to suffer from a significantly high risk of mortality, but accurate prediction of the course of disease is challenging. OBJECTIVE The study aim was to evaluate the independent prognostic and clinical importance of serum levels of ferritin and transferrin for 90-day survival of patients with liver disease. METHODS Patients with end-stage liver disease treated during a 2-year period were enrolled retrospectively in a single-centre study. Unmatched and propensity score matching (PSM) analyses were applied. RESULTS The study cohort comprised 286 patients with end-stage liver disease, of which 22.9% died during the observational period. High serum ferritin levels and low serum transferrin levels were associated significantly with increased 90-day mortality in the unmatched (p < 0.001) and PSM study population (p = 0.017). Serum levels of ferritin and transferrin had high prognostic capability to predict 90-day survival similar to the Model for End-stage Liver Disease. Patients with serum ferritin values >1030.5 µg/l had a 50% risk of dying within 11 days after measurement, which translated up to a 90-day mortality of 83%. CONCLUSION Serum levels of ferritin and transferrin have independent and excellent capabilities to determine prognosis in patients with end-stage liver disease. Ferritin measurements can reliably identify those with high mortality in daily practice.
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Affiliation(s)
- Jörn Arne Meier
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Arne Bokemeyer
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Friederike Cordes
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Valentin Fuhrmann
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Hartmut Schmidt
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Anna Hüsing-Kabar
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
| | - Iyad Kabar
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1 A1, Muenster, Germany
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17
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Wu SJ, Zhang ZZ, Cheng NS, Xiong XZ, Yang L. Preoperative serum ferritin is an independent prognostic factor for liver cancer after hepatectomy. Surg Oncol 2019; 29:159-167. [PMID: 31196483 DOI: 10.1016/j.suronc.2019.05.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 05/04/2019] [Accepted: 05/18/2019] [Indexed: 02/07/2023]
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18
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Czaja AJ. Review article: iron disturbances in chronic liver diseases other than haemochromatosis - pathogenic, prognostic, and therapeutic implications. Aliment Pharmacol Ther 2019; 49:681-701. [PMID: 30761559 DOI: 10.1111/apt.15173] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 01/08/2019] [Accepted: 01/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Disturbances in iron regulation have been described in diverse chronic liver diseases other than hereditary haemochromatosis, and iron toxicity may worsen liver injury and outcome. AIMS To describe manifestations and consequences of iron dysregulation in chronic liver diseases apart from hereditary haemochromatosis and to encourage investigations that clarify pathogenic mechanisms, define risk thresholds for iron toxicity, and direct management METHODS: English abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed. RESULTS Hyperferritinemia is present in 4%-65% of patients with non-alcoholic fatty liver disease, autoimmune hepatitis, chronic viral hepatitis, or alcoholic liver disease, and hepatic iron content is increased in 11%-52%. Heterozygosity for the C282Y mutation is present in 17%-48%, but this has not uniformly distinguished patients with adverse outcomes. An inappropriately low serum hepcidin level has characterised most chronic liver diseases with the exception of non-alcoholic fatty liver disease, and the finding has been associated mainly with suppression of transcriptional activity of the hepcidin gene. Iron overload has been associated with oxidative stress, advanced fibrosis and decreased survival, and promising therapies beyond phlebotomy and oral iron chelation have included hepcidin agonists. CONCLUSIONS Iron dysregulation is common in chronic liver diseases other than hereditary haemochromatosis, and has been associated with liver toxicity and poor prognosis. Further evaluation of iron overload as a co-morbid factor should identify the key pathogenic disturbances, establish the risk threshold for iron toxicity, and promote molecular interventions.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
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19
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Sungkar T, Rozi MF, Dairi LB, Zain LH. Serum Ferritin Levels: A Potential Biomarker to Represent Child-Turcotte-Pugh Score among Decompensated Liver Cirrhosis Patients. Malays J Med Sci 2019; 26:59-65. [PMID: 31447609 PMCID: PMC6687222 DOI: 10.21315/mjms2019.26.2.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 02/04/2019] [Indexed: 01/05/2023] Open
Abstract
Background Liver cirrhosis and the child-Turcotte-Pugh (CTP) score are inseparable entities in liver disease. CTP score is largely known as the mortality and prognosis predictor. Nevertheless, ferritin emerges as a simple biomarker related to prognosis. The study aimed to determine whether there was a significant correlation between serum ferritin levels and CTP score. Methods The study analysed 54 decompensated liver cirrhotic patients including 17 females and 37 males between May 2016 and May 2017 at the Haji Adam Malik General Hospital, Medan, Indonesia. Ferritin levels were, then, divided into trichotomous cut-off value (< 200 ng/mL, n = 22; 200–400 ng/mL, n = 5; and > 400 ng/mL, n = 27). Data was analysed using SPSS version 12.0 (continuous variables were assessed by the Kruskal-Wallis test and Chi-square test was used for categorical variables). In addition, Spearman correlation test was used to determine any significant correlation between ferritin levels and CTP score. Results Based on data analysis, gender and CTP score were related to higher ferritin levels (P = 0.002 and P = 0.018, respectively). Furthermore, a significant correlation between serum ferritin levels and CTP score was obtained in to moderate degree (P = 0.000; r = 0.487). Conclusions There might be a significant role of serum ferritin levels in predicting mortality and prognosis among decompensated liver cirrhosis patients but it still needs further attention.
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Affiliation(s)
- Taufik Sungkar
- Department of Internal Medicine, Gastroenterology-Hepatology Division, Universitas Sumatera Utara, Padang Bulan, Medan, Indonesia
| | | | - Leo Basa Dairi
- Department of Internal Medicine, Gastroenterology-Hepatology Division, Universitas Sumatera Utara, Padang Bulan, Medan, Indonesia
| | - Lukman Hakim Zain
- Department of Internal Medicine, Gastroenterology-Hepatology Division, Universitas Sumatera Utara, Padang Bulan, Medan, Indonesia
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20
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Serum levels of ferritin do not affect the prognosis of patients with hepatocellular carcinoma undergoing radiofrequency ablation. PLoS One 2018; 13:e0200943. [PMID: 30044835 PMCID: PMC6059486 DOI: 10.1371/journal.pone.0200943] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 07/05/2018] [Indexed: 02/07/2023] Open
Abstract
Background & aims Hepatic iron accumulation can accelerate liver injury in patients with various chronic liver diseases and lead to hepatocarcinogenesis. We elucidated the impact of serum levels of ferritin on the prognosis of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) in a large cohort. Methods We retrospectively analyzed 578 treatment-naïve HCC patients who underwent RFA. We divided our cohort into four groups by the quartile points of serum ferritin level: G1 (≤55 ng/mL, n = 148), G2 (56–130 ng/mL, n = 142), G3 (131–243 ng/mL, n = 144) and G4 (≥244 ng/mL, n = 144). We analyzed the recurrence and survival of patients using the Kaplan–Meier method. We also evaluated pathological iron deposition among patients with a solitary tumor smaller than 2 cm. Results The cumulative rates of overall recurrence and survival at 5 years were 81.6% and 66.3%, respectively. The serum levels of ferritin were correlated with pathological iron deposition. There were no significant differences in recurrence and survival rates according to serum levels of ferritin and pathological hepatic iron deposition. Conclusions Serum levels of ferritin do not affect the prognosis of HCC patients undergoing RFA.
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21
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Viveiros A, Finkenstedt A, Schaefer B, Mandorfer M, Scheiner B, Lehner K, Tobiasch M, Reiberger T, Tilg H, Edlinger M, Zoller H. Transferrin as a predictor of survival in cirrhosis. Liver Transpl 2018; 24:343-351. [PMID: 29149510 PMCID: PMC5873434 DOI: 10.1002/lt.24981] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 10/30/2017] [Accepted: 11/02/2017] [Indexed: 12/18/2022]
Abstract
Patients with cirrhosis frequently present with high serum ferritin and low transferrin concentrations, reflecting impaired liver function and inflammation. Recent studies have shown that transferrin and its saturation with iron are Model for End-Stage Liver Disease-independent predictors of mortality in patients with acute-on-chronic liver failure or decompensated cirrhosis. The aim of this study was to evaluate the prognostic utility of serum iron parameters in relation to markers of liver function and immune activation. Clinical, demographic, and biochemical data were retrospectively analyzed from a cohort of 1255 consecutive patients with cirrhosis (age ≥ 18 years) who presented from August 1, 2004 until December 31, 2014 at the University Hospital of Innsbruck. Patients with malignancies at diagnosis including hepatocellular carcinoma were excluded. Survival analysis was carried out by Cox regression by using baseline laboratory parameters, and findings were validated in an independent patient cohort. During a median follow-up of 2.4 years, 193 deaths occurred and 254 patients underwent liver transplantation. In patients with transferrin < 180 mg/dL, 3-month, 1-year, and 5-year transplant-free survival estimates were significantly lower (91.7%, 79.0%, and 30.5%) when compared with the group of patients with transferrin ≥ 180 mg/dL (98.9%, 95.5%, and 68.0%, P < 0.001). Transferrin predicted transplant-free survival independently of Model for End-Stage Liver Disease-sodium (MELD-Na) and C-reactive protein (CRP) in multivariate regression analysis including all patients. When patients with alcoholic or nonalcoholic fatty liver disease were excluded, transferrin was in addition an albumin-independent predictor of transplant-free survival. In conclusion, the association of transferrin with transplant-free survival is independent of MELD-Na score and CRP. In patients without fatty liver disease, transferrin also predicts survival independently of albumin. Liver Transplantation 24 343-351 2018 AASLD.
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Affiliation(s)
- André Viveiros
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Armin Finkenstedt
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Benedikt Schaefer
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Mattias Mandorfer
- Department of Medicine III, Division of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Department of Medicine III, Division of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Konrad Lehner
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Moritz Tobiasch
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Thomas Reiberger
- Department of Medicine III, Division of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Herbert Tilg
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
| | - Michael Edlinger
- Department of Medical Statistics, Informatics, and Health EconomicsMedical University InnsbruckInnsbruckAustria
| | - Heinz Zoller
- Department of MedicineMedical University and University Hospital of InnsbruckInnsbruckAustria
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22
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VanWagner LB, Ning H, Whitsett M, Levitsky J, Uttal S, Wilkins JT, Abecassis MM, Ladner DP, Skaro AI, Lloyd-Jones DM. A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score. Hepatology 2017; 66:1968-1979. [PMID: 28703300 PMCID: PMC5696007 DOI: 10.1002/hep.29329] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 06/08/2017] [Accepted: 06/20/2017] [Indexed: 12/12/2022]
Abstract
Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). CONCLUSION The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979).
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Affiliation(s)
- Lisa B. VanWagner
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
| | - Hongyan Ning
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
| | - Maureen Whitsett
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine
| | - Josh Levitsky
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Sarah Uttal
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
| | - John T. Wilkins
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine
| | - Michael M. Abecassis
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Anton I. Skaro
- Department of Surgery, Division of General Surgery and Multi-Organ Transplant, University of Western Ontario Schulich School of Medicine & Dentistry
| | - Donald M. Lloyd-Jones
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine
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23
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Hammad A, Kaido T, Aliyev V, Mandato C, Uemoto S. Nutritional Therapy in Liver Transplantation. Nutrients 2017; 9:E1126. [PMID: 29035319 PMCID: PMC5691742 DOI: 10.3390/nu9101126] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 10/10/2017] [Accepted: 10/12/2017] [Indexed: 12/11/2022] Open
Abstract
Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.
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Affiliation(s)
- Ahmed Hammad
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
- Department of General Surgery, Mansoura University, Mansoura 35516, Egypt.
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
| | - Vusal Aliyev
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
| | - Claudia Mandato
- L'AORN Children's Hospital Santobono and Pausilipon, Napoli 80122, Italy.
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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24
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Wood MJ, Crawford DHG, Wockner LF, Powell LW, Ramm GA. Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis. Liver Int 2017; 37:1382-1388. [PMID: 28231420 DOI: 10.1111/liv.13395] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 02/16/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Ferritin is purported to have proinflammatory and profibrogenic effects on hepatic stellate cells. Thus, rather than acting as a passive indicator of hepatic iron concentration (HIC) in haemochromatosis, ferritin may directly influence fibrosis. This study evaluated whether serum ferritin is a better predictor of hepatic fibrosis compared to variables previously associated with increased fibrosis risk in haemochromatosis. METHODS We identified 291 C282Y HFE-homozygous patients who had undergone liver biopsy for histological fibrosis staging and measurement of HIC. Ordinal logistic regression determined the best model for fibrosis stage not including serum ferritin. Then, serum ferritin was introduced into this model to assess whether the predictive power of the model was significantly increased and to evaluate the effect on other predictors of fibrosis. RESULTS Ordinal logistic regression analyses without serum ferritin demonstrated that log HIC (OR 2.89; P < .001), male gender (OR 2.93; P = .005), alcohol consumption (g/day) (OR 1.01; P = .004), steatosis (OR 2.86; P = .01), arthritis (OR 2.46; P = .01) predicted increasing fibrosis stage (n=217). Addition of serum ferritin in multivariate analysis substantially improved the predictive power of the model (χ2 = 37.15; P < .01) and was highly predictive of fibrosis stage (OR 5.44; P < .001). Inclusion of serum ferritin in this model rendered the effects of HIC, gender, alcohol and steatosis to non-significance. CONCLUSIONS In haemochromatosis, serum ferritin is a better predictor of fibrosis stage than HIC, gender, steatosis and alcohol. These data support a hypothesis that ferritin may play a role in fibrosis rather than simply acting as a passive indicator of iron storage.
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Affiliation(s)
- Marnie J Wood
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.,Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Darrell H G Crawford
- School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Greenslopes Hospital, The Gallipoli Medical Research Foundation, Brisbane, Queensland, Australia
| | - Leesa F Wockner
- Biostatistics Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Lawrie W Powell
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Centre for the Advancement of Clinical Research, Royal Brisbane and Women's Hospital and the University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
| | - Grant A Ramm
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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25
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Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis. PLoS One 2017; 12:e0179074. [PMID: 28594937 PMCID: PMC5464635 DOI: 10.1371/journal.pone.0179074] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 05/23/2017] [Indexed: 02/07/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study. Thereby, a hyperferritinemia (> 2.09 times upper limit of normal; Odds ratio (OR) = 8.82; 95% confidence interval (CI): 2.25–34.52) and lower immunoglobulins (<1.89 times upper limit of normal; OR = 6.78; CI: 1.87–24.59) at baseline were independently associated with the achievement of complete biochemical remission upon standard therapy. The predictive value increased when both variables were combined to a single treatment response score, when the cohort was randomly split into a training (area under the curve (AUC) = 0.749; CI 0.635–0.863) and internal validation cohort (AUC = 0.741; CI 0.558–0.924). Patients with a low treatment response score (<1) had significantly higher cumulative remission rates in the training (p<0.001) and the validation cohort (p = 0.024). The baseline hyperferritinemia was accompanied by a high serum iron, elevated transferrin saturations and mild hepatic iron depositions in the majority of patients. However, the abnormal iron status was quickly reversible under therapy. Mechanistically, the iron parameters were not stringently related to a hepatocellular damage. Ferritin rather seems deregulated from the master regulator hepcidin, which was down regulated, potentially mediated by the elevated hepatocyte growth factor. In conclusion, baseline levels of serum ferritin and immunoglobulins, which are part of the diagnostic work-up of AIH, can be used to predict the treatment response upon standard therapy in AIH-1, although confirmation from larger multicenter studies is pending.
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26
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Bruns T, Nuraldeen R, Mai M, Stengel S, Zimmermann HW, Yagmur E, Trautwein C, Stallmach A, Strnad P. Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis. Liver Int 2017; 37:232-241. [PMID: 27473364 DOI: 10.1111/liv.13211] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 07/23/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). METHODS Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90 days after inclusion. RESULTS Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87 mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30 days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. CONCLUSION Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30 days.
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Affiliation(s)
- Tony Bruns
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany.,The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
| | - Renwar Nuraldeen
- Department of Internal Medicine III, University Hospital Aachen, Aachen, Germany
| | - Martina Mai
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany.,The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
| | - Sven Stengel
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Henning W Zimmermann
- Department of Internal Medicine III, University Hospital Aachen, Aachen, Germany
| | - Eray Yagmur
- Laboratory Diagnostics Center, University Hospital Aachen, Aachen, Germany
| | - Christian Trautwein
- Department of Internal Medicine III, University Hospital Aachen, Aachen, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany.,The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital Aachen, Aachen, Germany.,Interdisciplinary Center for Clinical Research (IZKF), University Hospital Aachen, Aachen, Germany
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Seyedian SS, Hajiani E, Hashemi SJ, Masjedizadeh A, Shayesteh AA, Alavinejad P, Hormati A, Javaherforoushzadeh A, Khabazkhoob M. Relationship between serum ferritin level and transient elastography findings among patients with nonalcoholic fatty liver disease. J Family Med Prim Care 2017; 6:750-754. [PMID: 29564257 PMCID: PMC5848392 DOI: 10.4103/jfmpc.jfmpc_158_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is raising prevalence among children, and adolescence population in developed and developing countries as a major public health concern. The present study aims to determine the relationship between serum ferritin level and transient elastography findings in patients suffering from NAFLD. Materials and Methods: The demographic and biochemical profile of included individuals such as body mass index, age, level of serum transaminases, fasting blood sugar, lipid profile, and serum ferritin level were determined and a transient elastography was performed for all of them. Results: The mean serum ferritin level among men with mild and advanced liver stiffness was 154 ± 97 and 244 ± 214, respectively (P < 0.001), which showed a meaningful relationship. These figures among female patients with mild and advanced liver stiffness included 79 ± 91 and 161 ± 103, respectively (P = 0.003) and again revealed a significant relationship. The cutoff values of ferritin with 90% accuracy for differentiation of mild from advanced liver stiffness among male and female patients were determined as 255 ng/ml and 135 ng/ml, respectively. These cutoff values for ruling out of advanced liver stiffness with 90% accuracy among both sexes were 72.5 ng/ml and 65.5 ng/ml, respectively. Conclusion: The finding of this study revealed a significant relationship between serum ferritin level and liver stiffness among NAFLD patients, and if these results repeated in further investigations, it could be advisable to measure serum ferritin level for predicting possibility of advanced liver fibrosis.
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Affiliation(s)
- Seyed Saeed Seyedian
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Eskandar Hajiani
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Jalal Hashemi
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abdolrahim Masjedizadeh
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Akbar Shayesteh
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Pezhman Alavinejad
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ahmad Hormati
- Department of Gastroenterology, Qom University of Medical Sciences, Qom, Iran
| | - Ali Javaherforoushzadeh
- Department of Gastroenterology, Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Gastroenterology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehdi Khabazkhoob
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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28
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Oikonomou T, Goulis I, Soulaidopoulos S, Karasmani A, Doumtsis P, Tsioni K, Mandala E, Akriviadis E, Cholongitas E. High serum ferritin is associated with worse outcome of patients with decompensated cirrhosis. Ann Gastroenterol 2016; 30:217-224. [PMID: 28243043 PMCID: PMC5320035 DOI: 10.20524/aog.2016.0112] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 11/08/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Studies in patients with decompensated cirrhosis showed a correlation between serum ferritin levels and patients' prognosis. Besides, red blood cell distribution width (RDW) and mean platelet volume (MPV) have been associated with the severity of hepatic function. The aim of this study was to evaluate the prognostic impact of serum ferritin and RDW/MPV in the outcome [survival, death, or liver transplantation (LT)] of patients with stable decompensated cirrhosis. METHODS Consecutive adult patients with stable decompensated cirrhosis admitted to our department between September 2010 and February 2016 were included. Serum ferritin, RDW and MPV were recorded in every patient. They were followed up and their outcome (alive, death, or LT) was evaluated. RESULTS 192 consecutive patients with stable decompensated cirrhosis (142 men, age 54.2±12 years); at the end of follow up [12 (range: 1-64) months] 62 patients remained alive and 130 died or underwent LT. In multivariate analysis, serum ferritin (HR 1.001, 95%CI 1.00-1.002, P=0.005) and GFR (HR 0.96, 95%CI 0.92-0.99, P=0.035) were the only independent factors significantly associated with the outcome. Ferritin had low discriminative ability (AUC: 0.61) to the outcome yielding a sensitivity and specificity of 85.3% and 44.2%, respectively, at the best cut-off point (>55 ng/mL), while patients with ferritin >55 ng/mL (n=145) had a worse outcome compared to those with ferritin ≤55 ng/mL (n=47) (log rank P=0.001). RDW and MPV were not associated with the outcome. CONCLUSION High serum ferritin, but not RDW/MPV, is associated with worse outcome in patients with established decompensated cirrhosis. However, further studies are needed to elucidate better this issue.
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Affiliation(s)
- Theodora Oikonomou
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Ioannis Goulis
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Stergios Soulaidopoulos
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Areti Karasmani
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Petros Doumtsis
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Konstantina Tsioni
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Eudokia Mandala
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Evangelos Akriviadis
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
| | - Evangelos Cholongitas
- 4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki, Greece
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Sikorska K, Bernat A, Wroblewska A. Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis. Hepatobiliary Pancreat Dis Int 2016; 15:461-479. [PMID: 27733315 DOI: 10.1016/s1499-3872(16)60135-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.
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Affiliation(s)
- Katarzyna Sikorska
- Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Powstania Styczniowego 9b, 81-519 Gdynia, Poland.
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30
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Uchino K, Tateishi R, Fujiwara N, Minami T, Sato M, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Yoshida H, Moriya K, Shiina S, Omata M, Koike K. Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients. Hepatol Res 2016; 46:259-68. [PMID: 25788045 DOI: 10.1111/hepr.12517] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 03/07/2015] [Accepted: 03/13/2015] [Indexed: 02/08/2023]
Abstract
AIM To elucidate the impact of the serum ferritin level, a surrogate indicator of hepatic iron accumulation, on hepatocarcinogenesis in chronic hepatitis C patients. METHODS Serum ferritin was measured in 487 chronic hepatitis C patients without history of hepatocellular carcinoma (HCC) after excluding patients in phlebotomy, those with overt chronic gastrointestinal bleeding and those who achieved sustained virological response before enrollment. Patients were divided into four groups (G1-G4) by quartile points of serum ferritin, with sexes separated. RESULTS The serum ferritin level was positively correlated with total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase, hemoglobin and AFP, and inversely correlated with prothrombin activity in both sexes. A significant difference in HCC incidence was observed only in male patients; the incidence was higher in G1 (≤80 ng/mL, n = 54) and G4 (≥323 ng/mL, n = 54) compared with that of G2 (81-160 ng/mL, n = 54) and G3 (161-322 ng/mL, n = 52). The spline curve indicating the relationship between the hazard ratio and serum ferritin level took the form of a J-shape for male patients. In multivariate analysis, G1 and G4 showed higher incidence of HCC among men with a hazard ratio of 2.19 (95% confidence interval, 1.02-4.70; P = 0.045) compared with G2 and G3, together with older age, lower serum albumin and ALT above the normal upper limit. CONCLUSION The serum ferritin level is an independent risk factor for HCC development in male patients with chronic hepatitis C when the level is extremely high or low.
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Affiliation(s)
- Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Naoto Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yuji Kondo
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Haruhiko Yoshida
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kyoji Moriya
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Masao Omata
- Yamanashi Prefectural Hospital Organization, Yamanashi, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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31
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Wakiya T, Sanada Y, Urahashi T, Ihara Y, Yamada N, Okada N, Hirata Y, Hakamada K, Yasuda Y, Mizuta K. Impact of the serum ferritin concentration in liver transplantation. Liver Transpl 2015. [PMID: 26224663 DOI: 10.1002/lt.24222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The serum ferritin (SF) concentration is a widely available and objective laboratory parameter. SF is also widely recognized as an acute-phase reactant. The purpose of the present study was to identify the chronological changes in the recipient's SF concentration during liver transplantation (LT) and to clarify factors having an effect on the recipient's intraoperative SF level. In addition, the study retrospectively evaluated the usefulness of measuring SF during LT. Ninety-eight pediatric recipients were retrospectively analyzed. The data were analyzed and compared according to the SF level in the recipient. Patients were classified into 2 groups based on the intraoperative peak SF levels of ≤ 1000 ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased dramatically after reperfusion and fell to normal levels within the early postoperative period. The warm ischemia time (WIT) was significantly longer in the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a significant positive correlation was observed between the peak SF value and WIT (r = 0.35; P < 0.001). There were significant positive correlations between the peak SF value and the donors' preoperative laboratory data, including transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The multivariate analysis revealed that WIT and donor's SF level were a significant risk factor for high SF level in the recipient (P = 0.007 and 0.02, respectively). In conclusion, the SF measurement can suggest the degree of ischemia/reperfusion injury (IRI). A high SF level in the donor is associated with the risk of further acute reactions, such as IRI, in the recipient.
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Affiliation(s)
- Taiichi Wakiya
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan
| | - Yukihiro Sanada
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Taizen Urahashi
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Yoshiyuki Ihara
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Naoya Yamada
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Noriki Okada
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Yuta Hirata
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan
| | - Yoshikazu Yasuda
- Department of Surgery, Jichi Medical University, Shimotsuke City, Japan
| | - Koichi Mizuta
- Departments of Transplant Surgery, Jichi Medical University, Shimotsuke City, Japan
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32
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Serum Ferritin in Patients With Cirrhosis is Associated With Markers of Liver Insufficiency and Circulatory Dysfunction, but Not of Portal Hypertension. J Clin Gastroenterol 2015; 49:784-9. [PMID: 25599219 DOI: 10.1097/mcg.0000000000000283] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIMS Iron overload is an increasingly recognized phenomenon in nonhemochromatosis cirrhosis. To evaluate the relationship between iron overload and liver insufficiency and portal hypertension. PATIENTS AND METHODS Cirrhotics with hepatic hemodynamic and ferritin measurement (within 30 d) were included. Exclusion criteria were malignancy (except hepatocellular carcinoma Milan-in), severe chronic obstructive pulmonary disease, acute events in the previous 2 weeks, immunosuppression, transjugular intrahepatic portosystemic shunt or portal vein thrombosis, and end-stage renal disease. Patients were followed-up until death or liver transplant. Univariate and multivariate analysis were used. RESULTS Fifty-one patients were included (male 61%; median age 57 y; interquartile range, 47 to 66 y); Child-Pugh A 11/B 25/C 15). A positive correlation was observed between ferritin and markers of inflammation (C-reactive protein: r=0.273, P=0.06 and aspartate aminotransferase: r=0.302, P=0.035). No correlation between ferritin and hepatic venous pressure gradient was seen. Negative correlations were observed between ferritin and circulatory dysfunction (mean arterial pressure: r=-0.360, P=0.014 and serum sodium: r=-0.419, P=0.002). In contrast, associations to markers of liver failure such as international normalized ratio (r=0.333, P=0.005), bilirubin (r=0.378, P=0.007), albumin (r=-0.265, P=0.082), model for end-stage liver disease (r=0.293, P=0.041), and Child-Pugh score (r=0.392, P=0.009) were observed. No differences in survival according to ferritin was detected. CONCLUSIONS In patients with cirrhosis, serum ferritin levels are associated with markers of liver insufficiency, inflammation, and circulatory dysfunction but not portal hypertension.
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Feldman A, Aigner E, Weghuber D, Paulmichl K. The Potential Role of Iron and Copper in Pediatric Obesity and Nonalcoholic Fatty Liver Disease. BIOMED RESEARCH INTERNATIONAL 2015; 2015:287401. [PMID: 26273604 PMCID: PMC4529901 DOI: 10.1155/2015/287401] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 01/11/2015] [Indexed: 02/06/2023]
Abstract
Obesity is a rapidly growing health problem and is paralleled by a multitude of comorbidities, including nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common chronic liver disease in both adults and children. The current understanding of NAFLD is still fragmentary. While simple steatosis is characterized by the interplay between excessive free fatty acid accumulation and hepatic insulin resistance, the progression to NASH has been related to oxidative stress and a proinflammatory state with dysbalanced adipokine, cytokine levels, and endotoxin-mediated immune response. In addition, oxidative stress has been suggested to play a central role for the sequelae leading to NASH. Trace elements are critical in regulatory, immunologic, and antioxidant functions resulting in protection against inflammation and peroxidation and consequently against the known comorbidities of obesity. Disruptions of the metal detoxification processes located in the liver are plausibly related to NAFLD development via oxidative stress. Perturbations of iron and copper (Cu) homeostasis have been shown to contribute to the pathogenesis of NAFLD. This review presents current data from pediatric studies. In addition, data from adult studies are summarized where clinical relevance may be extrapolated to pediatric obesity and NAFLD.
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Affiliation(s)
- Alexandra Feldman
- First Department of Medicine, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
- Obesity Research Unit, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
| | - Elmar Aigner
- First Department of Medicine, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
- Obesity Research Unit, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
| | - Daniel Weghuber
- Obesity Research Unit, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
- Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
| | - Katharina Paulmichl
- Obesity Research Unit, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
- Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
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Serum ferritin levels predict histological severity in patients with nonalcoholic fatty liver disease in India. Indian J Gastroenterol 2015; 34:200-8. [PMID: 26108652 DOI: 10.1007/s12664-015-0572-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 05/13/2015] [Indexed: 02/04/2023]
Abstract
AIM The aims of the study were to determine the levels of serum ferritin which predict fibrosis in Indian patients with nonalcoholic fatty liver disease (NAFLD) and to establish correlation between Fibroscan values and serum ferritin levels. METHODS The clinical, biochemical, radiologic, and histological findings of consecutive adult NAFLD patients accessed at a tertiary care center over a 3-year period were analyzed. Those with concurrent liver diseases were excluded. Fifty-five of 250 NAFLD patients with fatty liver on ultrasound and raised enzymes (>40 IU/L) underwent liver biopsy. Patients were stratified into two groups based on their histological stage steatosis (with or without inflammation) but no fibrosis and nonalcoholic steatohepatitis (NASH) with fibrosis/cirrhosis. Serum ferritin levels were measured at the same time as getting liver biopsy. Fibroscan was carried out in each of these patients. These were compared with 50 age- and sex-matched controls with normal ultrasound, liver enzymes, and no history of alcohol. Student's t test was used as the test for significance. RESULTS Fifty-five NAFLD patients diagnosed on ultrasound and with raised enzymes underwent biopsy. Steatosis (with or without inflammation, but no fibrosis/ballooning) was seen in 35 patients, fibrosis/ballooning in 14 patients, and cirrhosis in 6 patients. Mean ferritin levels in groups with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) were 39.4 and 72.7 ng/mL, respectively (p < 0.001). The mean ferritin levels in NAFLD and controls were 51.2 and 35.2 ng/mL, respectively (p < 0.05). The area under the curve (AUC) of serum ferritin at value 48.0 ng/mL was 0.779. The coefficient of correlation between Fibroscan and serum ferritin levels was 0.9864 while that with alanine transaminase and aspartate aminotransferase was 0.69. Serum ferritin at the cutoff of 48 ng/mL differentiated significantly patients with fibrosis and higher Fibroscan levels. CONCLUSION Serum ferritin was low in Indian individuals, and levels even within apparently normal range indicated fibrosis and cirrhosis. A cutoff level of 48.0 IU/mL distinguished fibrosis in NAFLD. Fibroscan correlated well with serum ferritin levels.
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35
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Adams PC, Barton JC, Guo H, Alter D, Speechley M. Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study. Ann Hepatol 2015. [DOI: 10.1016/s1665-2681(19)31274-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
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36
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Aigner E, Weiss G, Datz C. Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver. World J Hepatol 2015; 7:177-188. [PMID: 25729473 PMCID: PMC4342600 DOI: 10.4254/wjh.v7.i2.177] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 12/12/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.
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Cakir M, Erduran E, Turkmen ES, Aliyazicioglu Y, Reis GP, Cobanoglu U, Demir S. Hepcidin levels in children with chronic liver disease. Saudi J Gastroenterol 2015; 21:300-5. [PMID: 26458857 PMCID: PMC4632255 DOI: 10.4103/1319-3767.166205] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIM We aimed to analyze serum hepcidin level in children with chronic liver disease (CLD) and its relationship with serum cytokines level, liver function tests, hepatic iron content, and liver fibrosis. PATIENTS AND METHODS The study included 34 children with CLD, and 15 age- and gender-matched healthy children. Serum hepcidin, ferritin, iron level, interleukin-6 (IL-6), transforming growth factor-β (TGF-β ), total oxidant status (TOS), and antioxidant status (TAS) were studied in all patients and in the control group. Liver iron content (LIC) was measured from the liver biopsy specimen. RESULTS Serum ferritin levels were higher in patients with CLD than control group (100.1 ± 98.2 ng/mL vs 50.5 ± 32.2 ng/mL, P = 0.016). No significant difference was found in hepcidin levels. Hepcidin levels in children with CLD was positively correlated with ferritin (r = 0.75, P = 0.001), pediatric end-stage liver disease (PELD) score (r = 0.56, P = 0.001), TAS (r = 0.42,P = 0.02), but negatively correlated with albumin level (r = -0.45,P = 0.008). Transferrin saturation and hepcidin:ferritin ratio were significantly low in patients with severe fibrosis compared with patients with mild/without fibrosis (15.5 ± 5.5 vs 34.3 ± 30.1, P = 0.017 and 1 ± 0.5 vs 1.9 ± 1.4,P = 0.04, respectively). CONCLUSION Serum hepcidin levels in children with CLD reflect both liver functions and TAS, and severe fibrosis is associated with low hepcidin:ferritin ratio in children with CLD.
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Affiliation(s)
- Murat Cakir
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University, Trabzon, Turkey,Address for correspondence: Dr. Murat Cakir, Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. E-mail:
| | - Erol Erduran
- Department of Pediatric Hematology, Karadeniz Technical University, Trabzon, Turkey
| | - Elif Sag Turkmen
- Department of Pediatrics, Karadeniz Technical University, Trabzon, Turkey
| | | | - Gokce Pinar Reis
- Department of Pediatric Hematology, Karadeniz Technical University, Trabzon, Turkey
| | - Umit Cobanoglu
- Department of Pathology, Karadeniz Technical University, Trabzon, Turkey
| | - Selim Demir
- Department of Biochemistry, Karadeniz Technical University, Trabzon, Turkey
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Facciorusso A, Del Prete V, Antonino M, Neve V, Crucinio N, Di Leo A, Carr BI, Barone M. Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation. J Gastroenterol Hepatol 2014; 29:1905-10. [PMID: 24731153 DOI: 10.1111/jgh.12618] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/04/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA). METHODS We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and their influence on OS and TTR was evaluated in univariate and multivariate analyses. RESULTS SF did not correlate with α-fetoprotein (rho: -0.12, P = 0.22), neutrophil/lymphocyte ratio (rho: -0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off point for SF. Median OS was 62 months (54-78) and survival rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS at multivariate analysis. Median TTR was 38 months (34-49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and age were the only predictors of TTR. CONCLUSIONS SF level, possibly reflecting the degree of hepatic inflammation and fibrosis, is a negative risk factor for survival and recurrence after percutaneous RFA in HCC patients.
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Affiliation(s)
- Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Ospedali Riuniti Foggia, Italy
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Jara M, Malinowski M, Lüttgert K, Schott E, Neuhaus P, Stockmann M. Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test. Transpl Int 2014; 28:52-8. [PMID: 25263095 DOI: 10.1111/tri.12441] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 06/02/2014] [Accepted: 08/27/2014] [Indexed: 12/11/2022]
Abstract
LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short-term survival in liver transplant candidates and compare its performance to the model for end-stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG-PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver-related death within 6 months of follow-up. Within 6 months of follow-up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99 μg/kg/h vs. 55 μg/kg/h; P = 0.024), while median ICG-PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P = 0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG-PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6 months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity.
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Affiliation(s)
- Maximilian Jara
- Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Schaefer B, Effenberger M, Zoller H. Iron metabolism in transplantation. Transpl Int 2014; 27:1109-17. [PMID: 24964028 DOI: 10.1111/tri.12374] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 06/02/2014] [Accepted: 06/17/2014] [Indexed: 01/19/2023]
Abstract
Recipient's iron status is an important determinant of clinical outcome in transplantation medicine. This review addresses iron metabolism in solid organ transplantation, where the role of iron as a mediator of ischemia-reperfusion injury, as an immune-modulatory element, and as a determinant of organ and graft function is discussed. Although iron chelators reduce ischemia-reperfusion injury in cell and animal models, these benefits have not yet been implemented into clinical practice. Iron deficiency and iron overload are associated with reduced immune activation, whose molecular mechanisms are reviewed in detail. Furthermore, iron overload and hyperferritinemia are associated with poor prognosis in end-stage organ failure in patients awaiting kidney, or liver transplantation. This negative prognostic impact of iron overload appears to persist after transplantation, which highlights the need for optimizing iron management before and after solid organ transplantation. In contrast, iron deficiency and anemia are also associated with poor prognosis in patients with end-stage heart failure. Intravenous iron supplementation should be managed carefully because parenterally induced iron overload could persist after successful transplantation. In conclusion, current evidence shows that iron overload and iron deficiency are important risk factors before and after solid organ transplantation. Iron status should therefore be actively managed in patients on the waiting list and after transplantation.
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Affiliation(s)
- Benedikt Schaefer
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
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Maiwall R, Kumar S, Chaudhary AK, Maras J, Wani Z, Kumar C, Rastogi A, Bihari C, Vashisht C, Sarin SK. Serum ferritin predicts early mortality in patients with decompensated cirrhosis. J Hepatol 2014; 61:43-50. [PMID: 24681346 DOI: 10.1016/j.jhep.2014.03.027] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 03/05/2014] [Accepted: 03/13/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Serum ferritin is a known marker of hepatic necro-inflammation and has been studied to predict 1 year mortality and post-transplant survival in decompensated cirrhotics. However, there are no studies evaluating ferritin as a predictor of early mortality. We investigated whether serum ferritin levels could predict 15 day and 30 day mortality in patients with decompensated cirrhosis. METHODS 318 patients with decompensated cirrhosis were included. RESULTS Patients of decompensated cirrhosis [257 males, mean age of 51 [±13]years, were followed for a median of 31 days. Serum ferritin levels were significantly different between survivors and non-survivors [p<0.001] and showed significant correlation with MELD score [p<0.001], CTP score [p<0.001], leucocyte counts [TLC] [p<0.001], serum sodium [p<0.001], ACLF grades [p=0.005], spontaneous bacterial peritonitis [SBP] [p=0.02], hepatic encephalopathy [HE] [p<0.001] and hepatorenal syndrome [HRS] [p=0.012]. Serum ferritin, etiology, MELD, HE, CTP score, sodium, TLC, and ACLF grades were significant predictors of mortality on univariate analysis. Ferritin [p=0.04, HR 1.66 95% CI (1.02-2.73)] was a significant predictor of early mortality on multivariate analysis along with HE [p=0.006, HR 3.47 95% CI (2.13-8.41)] (Model 1), TLC [p=0.02, HR 1.81 95% CI (1.06-3.07)] (Model 2), ACLF grades [p=0.018, HR 2.013,95% CI (1.126-3.60)], and CTP score [p<0.0001, HR 1.36 95% CI (1.17-1.59)] (Model 3). CONCLUSION Serum ferritin levels correlate with severity of hepatic decompensation and are associated with early liver related death independent of the MELD score in hospitalized patients with decompensated cirrhosis. This could also have a potential therapeutic implication.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Suman Kumar
- Department of Clinical Hematology, Command Hospital [Eastern Command], Kolkata, India
| | - A K Chaudhary
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Jaswinder Maras
- Department of Research, Institute of Liver and Biliary Sciences, Delhi, India
| | - Zeeshan Wani
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Chandan Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - A Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - C Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chitranshu Vashisht
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India.
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Al-Freah MAB, Kriese S, Foxton MR, Quaglia A, Bomford A, Heaton ND, O'Grady JG, Agarwal K, Wendon JA, Heneghan MA. The association of pretransplant ferritin level with waiting list and post-transplant survival. Does ferritin actually predict outcome? Transpl Int 2014; 26:1070-9. [PMID: 24138201 DOI: 10.1111/tri.12164] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 06/14/2013] [Accepted: 07/15/2013] [Indexed: 01/19/2023]
Abstract
Recent data suggest an association of serum ferritin (SF) with waiting list (WL) and postliver transplant (LT) outcomes. To assess the predictive capacity of SF on pre- and post-LT outcomes, and to identify whether recipient or donor liver siderosis is associated with post-LT survival; a retrospective analysis of 1079 patients assessed for first LT, 2000-2007 was performed. Iron deposition in the liver tissue was assessed using a semi-quantitative grading system. Median age was 54 (18-82) years and 67% were male. Seventeen per cent had hepatocellular carcinoma (HCC). Median Model for End-stage Liver Disease MELD score was 14 (6-40), ferritin was 174 μg/l (4-4597) with 36.5% had a SF ≥ μg/l. Age (OR = 1.028) and MELD score (OR = 1.158) were independently associated with WL mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR = 1.542) and cold ischemia time (CIT) ≥ 10 h (OR = 1.418) were independently associated with post-LT survival (P < 0.05). Explant siderosis grade <2 was seen in 376 (71.7%) patients. Patients with explant siderosis grade ≥ 2 had inferior 12-month post-LT survival (P = 0.030). Presence of graft siderosis (15.8% of patients) was not associated with survival. In conclusion, we found a limited role for SF as a prognostic indicator for pre- or post-transplant survival.
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Wu J, Chen L, Chen Y, Yang J, Wu D. Serum ferritin concentration predicts mortality in patients with hepatitis B virus-related acute on chronic liver failure. Arch Med Res 2014; 45:251-6. [PMID: 24656903 DOI: 10.1016/j.arcmed.2014.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Accepted: 03/06/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS This study was designed to investigate the association between serum ferritin concentration (SF) and hepatitis B virus infected patients with acute-on-chronic liver failure (AoCLF). In addition, we analyzed whether SF levels are associated with mortality in AoCLF patients. METHODS One hundred and seventeen patients, including 46 patients with chronic hepatitis B (CHB), 71 with AoCLF, and 55 healthy controls (HCs) were enrolled in this study. All patients were followed for 4 months. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio, and SF levels. A total of six clinical chemistry and biochemical variables (e.g., model for end-stage liver disease [MELD] score, age, levels of SF, total protein, albumin, and alanine aminotransferase) were measured and analyzed for their association with outcomes by using Cox proportional hazards and multiple regression models. RESULTS AoCLF patients had significantly higher SF levels at admission compared to HCs and CHB (all p = 0.001). Elevated SF levels were associated with increased severity of liver disease and 3-month mortality rate. Multivariate analysis demonstrated that SF levels and MELD score were independent predictors for mortality (both p <0.001). CONCLUSION The SF measured at admission may serve as an independent predictor for 3-month mortality rate in AoCLF patients.
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Affiliation(s)
- Jianping Wu
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China
| | - Linlin Chen
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, China
| | - Yuemei Chen
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China
| | - Jin Yang
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, China
| | - Dingqian Wu
- Department of Emergency, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
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Reticulocyte Count and Hemoglobin Concentration Predict Survival in Candidates for Liver Transplantation. Transplantation 2014; 97:463-9. [DOI: 10.1097/01.tp.0000437429.12356.03] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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45
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Perioperative nutritional therapy in liver transplantation. Surg Today 2014; 45:271-83. [PMID: 24473669 DOI: 10.1007/s00595-014-0842-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 12/16/2013] [Indexed: 12/21/2022]
Abstract
Protein-energy malnutrition is frequently seen in patients with end-stage liver disease who undergo liver transplantation. This causes a deterioration of the patients' clinical condition and affects their post-transplantation survival. Accurate assessment of the nutritional status and adequate intervention are prerequisites for perioperative nutritional treatment. However, the metabolic abnormalities induced by liver failure make the traditional assessment of the nutritional status difficult. The methods that were recently developed for accurately assessing the nutritional status by body bioelectrical impedance may be implemented in pre-transplant management. Because preoperative malnutrition and the loss of skeletal muscle mass, called sarcopenia, have a significant negative impact on the post-transplantation outcome, it is essential to provide adequate nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the necessary caloric intake. We herein discuss both bioelectrical impedance and the latest findings in the current perioperative nutritional interventions in liver transplant patients regarding synbiotics, micronutrients, branched-chain amino acid supplementation, the use of immune system modulating formulas, the fluid balance and the offering of nocturnal meals.
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Patil PS, Mohandas KM, Bhatia SJ, Mehta SA. Serum ferritin and the risk of hepatocellular carcinoma in chronic liver disease of viral etiology: a case-control study. Indian J Gastroenterol 2014; 33:12-8. [PMID: 24006121 DOI: 10.1007/s12664-013-0367-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2012] [Accepted: 07/28/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND The worldwide incidence rates of hepatocellular carcinoma (HCC) vary widely. Some countries like India have a low incidence despite having a large burden of chronic hepatitis B (HBV) and C virus (HCV) infection. We hypothesized that long-term iron deficiency could attenuate the hepatic inflammation and lead to a lower incidence of HCC in India than expected. METHODS We evaluated the association of serum ferritin levels and HCC in Indian patients with HBV- or HCV-related chronic liver disease (CLD) using a case-control study design. We enrolled 141 patients with HCC (cases) and 240 patients having chronic HBV or HCV infection-related CLD (controls). Study participants were grouped on the basis of ferritin values into low-normal, high-normal, and high subgroups. RESULTS Mean ferritin values were higher in cases as compared to controls (425.8 vs. 135.6 ng/mL, p = 0.000). A significant dose-response effect for serum ferritin levels and HCC was seen with an odds ratio (95 % confidence interval) of 3.0 (1.6-5.9, p = 0.001) for subjects with high-normal ferritin levels and 8.2 (4.1-16.5, p = 0.000) for subjects with high ferritin levels in a multivariate model. Other significant independent risk factors in the multivariate model included older age, male gender, alcohol and tobacco use, elevated alanine aminotransferase, higher family income, and coffee drinking. CONCLUSION We found an independent association between serum ferritin levels and HCC in patients with CLD of viral etiology. Further prospective studies are needed to confirm the hypothesis that iron deficiency protects against HCC in CLD.
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Affiliation(s)
- Prachi S Patil
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Dr Ernest Borges Road, Parel, Mumbai, 400 012, India,
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Liu Z, Ye F, Zhang H, Gao Y, Tan A, Zhang S, Xiao Q, Zhang B, Huang L, Ye B, Qin X, Wu C, Lu Z, Zhang Y, Liao M, Yang X, Mo Z. The association between the levels of serum ferritin and sex hormones in a large scale of Chinese male population. PLoS One 2013; 8:e75908. [PMID: 24146788 PMCID: PMC3795691 DOI: 10.1371/journal.pone.0075908] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Accepted: 08/19/2013] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The ferritin is an important participant of iron-storage but its regulation and related factors were not well defined. The present objective was to explore the potential association between serum ferritin levels and sex hormones. METHODS 1999 Chinese men in the Fangchenggang Area Male Health and Examination Survey (FAMHES) were recruited in this cross-sectional study. Levels of serum ferritin, total testosterone (free testosterone was calculated from the total one), estradiol and sex hormone-binding protein were detected in venous blood samples. The effects of age, BMI, smoking as well as alcohol consumption were analyzed on ferritin levels, respectively, and then the Pearson's correlation analysis was used to evaluate the association between ferritin levels and sex hormones adjusting for the above factors. RESULTS The age, BMI and alcohol consumption significantly affected serum ferritin levels, but there was no significant difference between smokers and nonsmokers. Ferritin levels were significantly and negatively associated with total testosterone (R = -0.205, P< 0.001), sex hormone-binding protein (R = -0.161, P<0.001) and free testosterone (R = -0.097, P<0.001). After age and alcohol consumption were adjusted, the above associations were still significant (R = -0.200, -0.181 and -0.083, respectively, all P<0.001). However, there was only borderline negative association between ferritin levels and estradiol (adjusted R = -0.039, P = 0.083). CONCLUSION The large scale of epidemic results showed the significantly negative associations between serum ferritin levels and sex hormones, which may provide more clues to explore the potential regulation and biological mechanism of ferritin.
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Affiliation(s)
- Zhenfang Liu
- Hematology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Fanghui Ye
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Haiying Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Yong Gao
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Aihua Tan
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Shijun Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Qiang Xiao
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Bing Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Lulu Huang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Bingbing Ye
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Xue Qin
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Chunlei Wu
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Zheng Lu
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Youjie Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Ming Liao
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaobo Yang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
- Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Zhou G, Zhang X, Ge S. Retrospective analysis of acute fatty liver of pregnancy: twenty-eight cases and discussion of anesthesia. Gynecol Obstet Invest 2013; 76:83-9. [PMID: 23796980 DOI: 10.1159/000351565] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2012] [Accepted: 04/23/2013] [Indexed: 12/15/2022]
Abstract
AIMS To summarize the clinical features, perioperative management and maternal and neonatal outcomes of patients with acute fatty liver of pregnancy (AFLP) and to discuss the management of anesthesia in these patients. METHODS This study was a retrospective review over a period of 5 years and 9 months; 28 cases from the Shanghai Public Health Clinical Center were included. Records were reviewed for symptoms, signs, laboratory findings, clinical courses, perioperative management and maternal and neonatal outcomes. RESULTS Of the AFLP cases analyzed in the present study, 75.0% occurred in primipara and 63.3% occurred with male fetuses. Prodromic symptoms included the sudden onset of fatigue, nausea, vomiting, anorexia and jaundice. Laboratory results indicated liver function abnormalities, coagulopathy, hypoglycemia, leukocytosis and negative urine bilirubin. There were 2 maternal deaths (7.1%) without fetal deaths. Cesarean sections were performed in 16 cases under neuraxial anesthesia and in 12 cases under general anesthesia with rapid-sequence induction. CONCLUSION Early diagnosis, prompt delivery and intensive supportive treatment are critical for improving the prognosis of AFLP. Anesthesia selection should be individualized and general anesthesia with rapid-sequence induction may be the best choice for patients with severe coagulopathy.
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Affiliation(s)
- GuoXia Zhou
- Department of Anesthesia, Zhongshan Hospital and Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China
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Datz C, Felder TK, Niederseer D, Aigner E. Iron homeostasis in the metabolic syndrome. Eur J Clin Invest 2013; 43:215-24. [PMID: 23289518 DOI: 10.1111/eci.12032] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Accepted: 11/21/2012] [Indexed: 02/06/2023]
Abstract
The metabolic syndrome (MetS) affects iron homeostasis in a many-faceted fashion. On the one side, hyperferritinaemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with non-alcoholic fatty liver disease (NAFLD) or the MetS. This constellation has been named the 'dysmetabolic iron overload syndrome (DIOS)'. Current evidence suggests that elevated body iron stores exert a detrimental effect on the clinical course of obesity-related conditions and that iron removal improves insulin sensitivity and delays the onset of T2DM. On the other side, iron deficiency is a frequent finding in more progressed stages of obesity. The mechanisms underlying the DIOS and obesity-related iron deficiency appear strikingly similar as elevated hepcidin concentrations, low expression of duodenal ferroportin (FPN) and impaired iron absorption are found in both conditions. This review summarizes the current knowledge about the dysregulation of iron homeostasis in the MetS and particularly in its hepatic manifestation NAFLD.
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Affiliation(s)
- Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, 5110 Oberndorf, Austria.
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Role of hyaluronic acid, its degrading enzymes, degradation products, and ferritin in the assessment of fibrosis stage in Egyptian patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2013; 25:69-76. [PMID: 23011038 DOI: 10.1097/meg.0b013e3283594924] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS Liver biopsy is considered a gold standard for fibrosis staging, but it has a high risk of morbidity. Therefore, there is an interest in developing noninvasive markers for the prediction of liver fibrosis stages. METHODS Hyaluronic acid, ferritin, N-acetyl-β-D-glucosaminidase, β-glucuronidase, glucosamine, aspartate transaminase, and alanine transaminase were assayed in 210 individuals with chronic hepatitis C infection. Statistical analysis was carried out by logistic regression and receiver-operating characteristic curves. RESULTS The best linear combination of only significant blood markers was used for the determination of the fibrosis discriminant score; score=[1.64 (numerical constant)-0.002×hyaluronic acid (pg/l)-2.68×β-glucuronidase (µmol/ml/min)-0.026×glucosamine (µg/dl)-0.001×ferritin-0.033 (ng/ml)×aspartate transaminase/alanine transaminase]. The selected fibrosis discriminant score function correctly classified 81% of patients with severe liver fibrosis at a discriminant cut-off score=0.55 (i.e. less than 0.55 indicated mild liver fibrosis and greater than 0.55 indicated severe liver fibrosis), with a sensitivity of 100% and a specificity of 73%. CONCLUSION A simple fibrosis index can be useful to select hepatitis C virus-infected patients with a very low risk of significant fibrosis in whom the protocol of liver biopsies may be avoided.
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