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Zheng L, Zhang R, Chen X, Luo Y, Du W, Zhu Y, Ruan YC, Xu J, Wang J, Qin L. Chronic kidney disease: a contraindication for using biodegradable magnesium or its alloys as potential orthopedic implants? Biomed Mater 2024; 19:045023. [PMID: 38815612 DOI: 10.1088/1748-605x/ad5241] [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: 12/28/2023] [Accepted: 05/30/2024] [Indexed: 06/01/2024]
Abstract
Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.
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Affiliation(s)
- Lizhen Zheng
- Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Special Administrative Region of China, People's Republic of China
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Ri Zhang
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Xin Chen
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Ying Luo
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Wanting Du
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Yuwei Zhu
- Department of Chemistry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Ye Chun Ruan
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Jiankun Xu
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
| | - Jiali Wang
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ling Qin
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
- Hong Kong-Shenzhen Innovation and Technology Institute (Futian), The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, People's Republic of China
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Jiang S, Wang J, Zhang Z, Zhan J, Xue R, Qiu Y, Zhu L, Zhang S, Pan Y, Yan X, Chen Y, Li J, Liu X, Zhu C, Huang R, Wu C. Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B. Infect Drug Resist 2023; 16:5065-5075. [PMID: 37576516 PMCID: PMC10416784 DOI: 10.2147/idr.s417007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 07/26/2023] [Indexed: 08/15/2023] Open
Abstract
Background Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients. Methods CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Results A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727-0.803) and 0.766 (95% CI: 0.711-0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA. Conclusion A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.
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Affiliation(s)
- Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, People’s Republic of China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, People’s Republic of China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
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Scott DA, Wang M, Grauzam S, Pippin S, Black A, Angel PM, Drake RR, Castellino S, Kono Y, Rockey DC, Mehta AS. GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. Front Immunol 2022; 13:797460. [PMID: 35197973 PMCID: PMC8858972 DOI: 10.3389/fimmu.2022.797460] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/14/2022] [Indexed: 12/13/2022] Open
Abstract
Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity).
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Affiliation(s)
| | - Mengjun Wang
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
| | - Stephane Grauzam
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
| | | | - Alyson Black
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
| | - Peggi M. Angel
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
| | - Richard R. Drake
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
| | | | - Yuko Kono
- Department of Medicine, Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, United States
| | - Don C. Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, United States
| | - Anand S. Mehta
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States
- *Correspondence: Anand S. Mehta,
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Nagamani SCS, Ali S, Izem R, Schady D, Masand P, Shneider BL, Leung DH, Burrage LC. Biomarkers for liver disease in urea cycle disorders. Mol Genet Metab 2021; 133:148-156. [PMID: 33846069 PMCID: PMC8195846 DOI: 10.1016/j.ymgme.2021.04.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/03/2021] [Accepted: 04/04/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. As therapies for hyperammonemia associated with urea cycle dysfunction have improved, chronic complications, such as liver disease, have become increasingly apparent in individuals with UCDs. Liver disease in UCDs may be associated with hepatic inflammation, hepatic fibrosis, portal hypertension, liver cancer and even liver failure. However, except for monitoring serum aminotransferases, there are no clear guidelines for screening and/or monitoring individuals with UCDs for liver disease. Thus, we systematically evaluated the potential utility of several non-invasive biomarkers for liver fibrosis in UCDs. METHODS We evaluated grey-scale ultrasonography, liver stiffness obtained from shear wave elastography (SWE), and various serum biomarkers for hepatic fibrosis and necroinflammation, in a cohort of 28 children and adults with various UCDs. RESULTS Overall, we demonstrate a high burden of liver disease in our participants with 46% of participants having abnormal grey-scale ultrasound pattern of the liver parenchyma, and 52% of individuals having increased liver stiffness. The analysis of serum biomarkers revealed that 32% of participants had elevated FibroTest™ score, a marker for hepatic fibrosis, and 25% of participants had increased ActiTest™ score, a marker for necroinflammation. Interestingly, liver stiffness did not correlate with ultrasound appearance or FibroTest™. CONCLUSION Overall, our results demonstrate the high overall burden of liver disease in UCDs and highlights the need for further studies exploring new tools for identifying and monitoring individuals with UCDs who are at risk for this complication. TRIAL REGISTRATION This study has been registered in ClinicalTrials.gov (NCT03721367).
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MESH Headings
- Adolescent
- Adult
- Argininosuccinate Lyase/blood
- Biomarkers/blood
- Child
- Child, Preschool
- Elasticity Imaging Techniques
- Female
- Genetic Diseases, Inborn/blood
- Genetic Diseases, Inborn/diagnostic imaging
- Genetic Diseases, Inborn/genetics
- Genetic Diseases, Inborn/pathology
- Humans
- Hyperammonemia/blood
- Hyperammonemia/genetics
- Hyperammonemia/metabolism
- Hyperammonemia/pathology
- Liver/diagnostic imaging
- Liver/pathology
- Liver Cirrhosis/blood
- Liver Cirrhosis/diagnostic imaging
- Liver Cirrhosis/genetics
- Liver Cirrhosis/pathology
- Liver Diseases/blood
- Liver Diseases/genetics
- Liver Diseases/metabolism
- Liver Diseases/pathology
- Male
- Metabolism, Inborn Errors/genetics
- Middle Aged
- Ultrasonography
- Urea Cycle Disorders, Inborn/blood
- Urea Cycle Disorders, Inborn/genetics
- Urea Cycle Disorders, Inborn/metabolism
- Urea Cycle Disorders, Inborn/pathology
- Young Adult
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Affiliation(s)
- Sandesh C S Nagamani
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA
| | - Saima Ali
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA
| | - Rima Izem
- Division of Biostatistics and Study Methodology, Children's National Research Institute, Silver Spring, MD, USA; Department of Pediatrics, George Washington University, Washington, DC, USA; Department of Epidemiology, George Washington University, Washington, DC, USA
| | - Deborah Schady
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
| | - Prakash Masand
- Texas Children's Hospital, Houston, TX, USA; Edward B. Singleton Department of Radiology, Texas Children's Hospital, Houston, TX 77030, USA
| | - Benjamin L Shneider
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Pediatric Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX, USA
| | - Daniel H Leung
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Pediatric Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX, USA
| | - Lindsay C Burrage
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA.
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Burrage LC, Madan S, Li X, Ali S, Mohammad M, Stroup BM, Jiang MM, Cela R, Bertin T, Jin Z, Dai J, Guffey D, Finegold M, Members of the Urea Cycle Disorders Consortium (UCDC), Nagamani S, Minard CG, Marini J, Masand P, Schady D, Shneider BL, Leung DH, Bali D, Lee B. Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency. JCI Insight 2020; 5:132342. [PMID: 31990680 PMCID: PMC7101134 DOI: 10.1172/jci.insight.132342] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/15/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUNDLiver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. However, the prevalence and underlying mechanisms are unclear.METHODSWe estimated the prevalence of chronic hepatocellular injury in UCDs using data from a multicenter, longitudinal, natural history study. We also used ultrasound with shear wave elastography and FibroTest to evaluate liver stiffness and markers of fibrosis in individuals with argininosuccinate lyase deficiency (ASLD), a disorder with high prevalence of elevated serum alanine aminotransferase (ALT). To understand the human observations, we evaluated the hepatic phenotype of the AslNeo/Neo mouse model of ASLD.RESULTSWe demonstrate a high prevalence of elevated ALT in ASLD (37%). Hyperammonemia and use of nitrogen-scavenging agents, 2 markers of disease severity, were significantly (P < 0.001 and P = 0.001, respectively) associated with elevated ALT in ASLD. In addition, ultrasound with shear wave elastography and FibroTest revealed increased echogenicity and liver stiffness, even in individuals with ASLD and normal aminotransferases. The AslNeo/Neo mice mimic the human disorder with hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen noted before death (3-5 weeks of age). This excessive hepatic glycogen is associated with impaired hepatic glycogenolysis and decreased glycogen phosphorylase and is rescued with helper-dependent adenovirus expressing Asl using a liver-specific (ApoE) promoter.CONCLUSIONOur results link urea cycle dysfunction and impaired hepatic glucose metabolism and identify a mouse model of liver disease in the setting of urea cycle dysfunction.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov (NCT03721367, NCT00237315).FUNDINGFunding was provided by NIH, Burroughs Wellcome Fund, NUCDF, Genzyme/ACMG Foundation, and CPRIT.
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Affiliation(s)
- Lindsay C. Burrage
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- Texas Children’s Hospital, Houston, Texas, USA
| | - Simran Madan
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- Interdepartmental Program in Translational Biology and Molecular Medicine and
| | - Xiaohui Li
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Saima Ali
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Mahmoud Mohammad
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Department of Food Science and Nutrition, National Research Centre, Dokki, Giza, Egypt
| | - Bridget M. Stroup
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Ming-Ming Jiang
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Racel Cela
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Terry Bertin
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Zixue Jin
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Jian Dai
- Department of Pediatrics, Duke Health, Durham, North Carolina, USA
| | - Danielle Guffey
- Dan L. Duncan Institute for Clinical and Translational Research and
| | - Milton Finegold
- Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
| | | | - Sandesh Nagamani
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- Texas Children’s Hospital, Houston, Texas, USA
| | | | - Juan Marini
- USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Prakash Masand
- Edward B. Singleton Department of Pediatric Radiology, Texas Children’s Hospital, Houston, Texas, USA
| | - Deborah Schady
- Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Benjamin L. Shneider
- Texas Children’s Hospital, Houston, Texas, USA
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas, USA
| | - Daniel H. Leung
- Texas Children’s Hospital, Houston, Texas, USA
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, Texas, USA
| | - Deeksha Bali
- Department of Pediatrics, Duke Health, Durham, North Carolina, USA
| | - Brendan Lee
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- Texas Children’s Hospital, Houston, Texas, USA
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Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B. Dig Liver Dis 2019; 51:127-134. [PMID: 30076017 DOI: 10.1016/j.dld.2018.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 05/20/2018] [Accepted: 07/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. METHODS A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. RESULTS For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. CONCLUSIONS As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.
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Zhang Z, Li J, Wang P, He T, Ouyang Y, Huang Y. Nomogram for cirrhosis in patients with chronic hepatitis B: A simple self-assessed scale for individual risk of cirrhosis. Sci Rep 2017; 7:17493. [PMID: 29235488 PMCID: PMC5727495 DOI: 10.1038/s41598-017-17685-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 11/29/2017] [Indexed: 12/26/2022] Open
Abstract
The aim of this retrospective study was to establish a simple self-assessed scale for individual risk of cirrhosis in patients with chronic hepatitis B. A total of 1808 consecutive patients were enrolled and analyzed. According to the results of multivariate logistic regression analysis, a simple nomogram was calculated for cirrhosis. The area under receiver operating characteristic curves (AUROCs) were calculated to compare the diagnostic accuracy of nomogram with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), and S index. The AUROCs of nomogram for cirrhosis were 0.807 (adjusted AUROC 0.876) in model group and 0.794 (adjusted AUROC0.866) in validation group. DeLong's test and Brier Score further demonstrated that nomogram was superior to APRI, FIB-4 and S index in both model group and validation group. The patients with nomogram <0.07 could be defined as low risk group with cirrhosis prevalence lower than 4.3% (17/397). The patients with nomogram >0.52 could be defined as high risk group with cirrhosis prevalence higher than 73.0% (119/163). In conclusion, as a self-assessed style, simple, non-invasive, economical, convenient, and repeatable scale, nomogram is suitable to serve as a massive health screening tool for cirrhosis in CHB patients and further external validation is needed.
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Affiliation(s)
- Zhiqiao Zhang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Jing Li
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Peng Wang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China.
| | - Tingshan He
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Yanling Ouyang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Yiyan Huang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
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Wang J, Xu J, Liu W, Li Y, Qin L. Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure. Sci Rep 2016; 6:26341. [PMID: 27210744 PMCID: PMC4876325 DOI: 10.1038/srep26341] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 04/27/2016] [Indexed: 11/09/2022] Open
Abstract
Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.
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Affiliation(s)
- Jiali Wang
- Musculoskeletal Research Laboratory, Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China.,Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055, P.R. China
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - Waiching Liu
- Musculoskeletal Research Laboratory, Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - Yangde Li
- Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande Dongguan 523660, P.R. China
| | - Ling Qin
- Musculoskeletal Research Laboratory, Department of Orthopaedics &Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China.,Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055, P.R. China.,Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande Dongguan 523660, P.R. China
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9
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Giannini EG, Afdhal NH, Sigal SH, Muir AJ, Reddy KR, Vijayaraghavan S, Elkashab M, Romero-Gómez M, Dusheiko GM, Iyengar M, Vasey SY, Campbell FM, Theodore D. Non-cirrhotic thrombocytopenic patients with hepatitis C virus: Characteristics and outcome of antiviral therapy. J Gastroenterol Hepatol 2015; 30:1301-8. [PMID: 25777337 DOI: 10.1111/jgh.12942] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/25/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM Thrombocytopenia is frequently observed in patients with chronic hepatitis C virus (HCV) infection and cirrhosis, although it can also be observed in patients without cirrhosis by a virus-mediated phenomenon. This study assessed the prevalence, characteristics, and outcomes of antiviral therapy in patients with chronic HCV infection and thrombocytopenia not associated with cirrhosis. METHODS The study included 1268 patients with HCV infection and thrombocytopenia enrolled in the phase 3 ENABLE studies that assessed the impact of eltrombopag on achieving a sustained virologic response to pegylated interferon and ribavirin. The study population was subdivided according to baseline FibroSURE test results into patients with non-cirrhosis (FibroSURE < 0.4) and cirrhosis-related (FibroSURE ≥ 0.75) thrombocytopenia. RESULTS Compared with patients with cirrhosis-related thrombocytopenia (n = 995; 78.5%), non-cirrhotic patients with thrombocytopenia (n = 59; 4.6%) were younger (mean age [95% confidence interval (CI)]: 43.9 [40.7-47.2] vs 52.7 [52.2-53.3] years; P < 0.0001), predominantly female (64% [51-76] vs 30% [27-33]; P < 0.0001), and less frequently had a Model for End-Stage Liver Disease score ≥ 10 (24% [14-37] vs 45% [42-49]; P = 0.0012), low albumin levels (≤ 35 g/L; 2% [0-9] vs 32% [29-35]; P < 0.0001), and prevalence of diabetes mellitus (3% [0-12] vs 21% [19-24]; P = 0.0005). The sustained virologic response rate was higher in non-cirrhotic patients with thrombocytopenia (46% [95% CI, 33-59] vs 16% [14-18]; P < 0.0001). CONCLUSIONS Patients with thrombocytopenia associated with HCV who have lower FibroSURE test results may have better preserved liver function and higher sustained virologic response rates than patients with cirrhosis.
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Affiliation(s)
| | - Nezam H Afdhal
- Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Samuel H Sigal
- Department of Medicine, New York University School of Medicine, New York, New York, USA
| | - Andrew J Muir
- Duke Clinical Research Institute, Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina, USA
| | - K Rajender Reddy
- University of Pennsylvania School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Magdy Elkashab
- Department of Hepatology, Toronto Liver Center, Toronto, Canada
| | - Manuel Romero-Gómez
- Unit for Medical and Surgical Management of Digestive Diseases and CIBERehd, Valme University Hospital, University of Seville, Sevilla, Spain
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10
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Abdollahi M, Pouri A, Ghojazadeh M, Estakhri R, Somi M. Non-invasive serum fibrosis markers: A study in chronic hepatitis. ACTA ACUST UNITED AC 2015; 5:17-23. [PMID: 25901293 PMCID: PMC4401163 DOI: 10.15171/bi.2015.05] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 12/05/2014] [Accepted: 01/04/2015] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. METHODS Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. RESULTS Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. CONCLUSION Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.
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Affiliation(s)
| | - Aliasghar Pouri
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Ghojazadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rasoul Estakhri
- Department of Pathology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammadhossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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11
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Crossan C, Tsochatzis EA, Longworth L, Gurusamy K, Davidson B, Rodríguez-Perálvarez M, Mantzoukis K, O'Brien J, Thalassinos E, Papastergiou V, Burroughs A. Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation. Health Technol Assess 2015; 19:1-vi. [PMID: 25633908 PMCID: PMC4781028 DOI: 10.3310/hta19090] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001561. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Catriona Crossan
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Louise Longworth
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | | | | | - Manuel Rodríguez-Perálvarez
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Konstantinos Mantzoukis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Julia O'Brien
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Evangelos Thalassinos
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Vassilios Papastergiou
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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12
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Poynard T, Imbert-Bismut F, Munteanu M, Ratziu V. FibroTest-FibroSURE™: towards a universal biomarker of liver fibrosis? Expert Rev Mol Diagn 2014; 5:15-21. [PMID: 15723588 DOI: 10.1586/14737159.5.1.15] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Among the noninvasive alternatives to liver biopsy, several studies have demonstrated the predictive value and superior benefit/risk ratio to biopsy of two combinations of simple serum biochemical markers in patients infected with hepatitis B and C virus. These include FibroTest (BioPredictive) for the quantitative assessment of fibrosis, and ActiTest (BioPredictive) for the quantitative assessment of necroinflammatory activity (HCV-FibroSURE, LabCorp). The possible causes of false negatives and positives are also better identified. These tests, which are now available in 12 countries, can facilitate the screening and management of the most frequent liver diseases.
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Affiliation(s)
- Thierry Poynard
- Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
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13
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Kim E, Kang Y, Hahn S, Lee MJ, Park YN, Koh H. The efficacy of aspartate aminotransferase-to-platelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice. KOREAN JOURNAL OF PEDIATRICS 2013; 56:19-25. [PMID: 23390441 PMCID: PMC3564026 DOI: 10.3345/kjp.2013.56.1.19] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 04/30/2012] [Accepted: 08/02/2012] [Indexed: 12/19/2022]
Abstract
PURPOSE Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. METHODS This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. RESULTS Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. CONCLUSION APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.
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Affiliation(s)
- Earl Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea. ; Severance Pediatric Liver Disease Group, Severance Children's Hospital, Seoul, Korea
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Wu SD, Ni YJ, Liu L, Li H, Lu LG, Wang JY. Establishment and validation of a simple noninvasive model to predict significant liver fibrosis in patients with chronic hepatitis B. Hepatol Int 2011. [DOI: 10.1007/s12072-011-9328-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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15
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Sporea I, Şirli R, Popescu A, Bota S, Badea R, Lupşor M, Focşa M, Dănilă M. Is it better to use two elastographic methods for liver fibrosis assessment? World J Gastroenterol 2011; 17:3824-3829. [PMID: 21987625 PMCID: PMC3181444 DOI: 10.3748/wjg.v17.i33.3824] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2010] [Revised: 03/25/2011] [Accepted: 04/01/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To find out if by combining 2 ultrasound based elastographic methods: acoustic radiation force impulse (ARFI) elastography and transient elastography (TE), we can improve the prediction of fibrosis in patients with chronic hepatitis C. METHODS Our study included 197 patients with chronic hepatitis C. In each patient, we performed, in the same session, liver stiffness (LS) measurements by means of TE and ARFI, respectively, and liver biopsy (LB), assessed according to the Metavir score. 10 LS measurements were performed both by TE and ARFI; median values were calculated and expressed in kilopascals (kPa) and meters/second (m/s), respectively. Only TE and ARFI measurements with IQR < 30% and SR ≥ 60% were considered reliable. RESULTS On LB 13 (6.6%) patients had F0, 32 (16.2%) had F1, 52 (26.4%) had F2, 47 (23.9%) had F3, and 53 (26.9%) had F4. A direct, strong correlation was found between TE measurements and fibrosis (r = 0.741), between ARFI and fibrosis (r = 0.730) and also between TE and ARFI (r = 0.675). For predicting significant fibrosis (F ≥ 2), for a cut-off of 6.7 kPa, TE had 77.5% sensitivity (Se) and 86.5% specificity (Sp) [area under the receiver operating characteristic curve (AUROC) 0.87] and for a cut-off of 1.2 m/s, ARFI had 76.9% Se and 86.7% Sp (AUROC 0.84). For predicting cirrhosis (F = 4), for a cut-off of 12.2 kPa, TE had 96.2% Se and 89.6% Sp (AUROC 0.97) and for a cut-off of 1.8 m/s, ARFI had 90.4% Se and 85.6% Sp (AUROC 0.91). When both elastographic methods were taken into consideration, for predicting significant fibrosis (F ≥ 2), (TE ≥ 6.7 kPa and ARFI ≥ 1.2 m/s) we obtained 60.5% Se, 93.3% Sp, 96.8% positive predictive value (PPV), 41.4% negative predictive value (NPV) and 68% accuracy, while for predicting cirrhosis (TE ≥ 12.2 kPa and ARFI ≥ 1.8 m/s) we obtained 84.9% Se, 94.4% Sp, 84.9% PPV, 94.4% NPV and 91.8% accuracy. CONCLUSION TE used in combination with ARFI is highly specific for predicting significant fibrosis; therefore when the two methods are concordant, liver biopsy can be avoided.
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Ahmad W, Ijaz B, Javed FT, Gull S, Kausar H, Sarwar MT, Asad S, Shahid I, Sumrin A, Khaliq S, Jahan S, Pervaiz A, Hassan S. A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC Gastroenterol 2011; 11:44. [PMID: 21507271 PMCID: PMC3098184 DOI: 10.1186/1471-230x-11-44] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Accepted: 04/21/2011] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers. METHODS We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)]. RESULTS Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%. CONCLUSIONS The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.
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Affiliation(s)
- Waqar Ahmad
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Bushra Ijaz
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Fouzia T Javed
- Fouzia Tahir Javed, Department of Pathology, Jinnah Hospital, Lahore-54590, Pakistan
| | - Sana Gull
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Humaira Kausar
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Muhammad T Sarwar
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Sultan Asad
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Imran Shahid
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Aleena Sumrin
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Saba Khaliq
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Shah Jahan
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Asim Pervaiz
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
| | - Sajida Hassan
- Applied and Functional Genomics Lab, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore-53700, Pakistan
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Ho AS, Cheng CC, Lee SC, Liu ML, Lee JY, Wang WM, Wang CC. Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci 2010; 17:58. [PMID: 20630109 PMCID: PMC2914022 DOI: 10.1186/1423-0127-17-58] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2009] [Accepted: 07/15/2010] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue. METHODS A total of 16 healthy volunteers and 45 patients with chronic hepatitis C virus (HCV) were enrolled (F0: n = 16, F1: n = 7, F2: n = 17, F3: n = 8 and F4: n = 13, according to the METAVIR classification). Three serum samples of each fibrotic stage were analyzed by two-dimension difference gel electrophoresis (2D-DIGE). The differential proteins were identified by the cooperation of MALDI-TOF/TOF and MASCOT; then western blotting and Bio-Plex Suspension Array were used to quantify the protein levels. RESULTS Three prominent candidate biomarkers were identified: alpha 2 macroglobulin (A2M) is up regulated; vitamin D binding protein (VDBP) and apolipoprotein AI (ApoAI) are down regulated. The serum concentration of A2M was significantly different among normal, mild (F1/F2) and advanced fibrosis (F3/F4) (p < 0.01). The protein levels of VDBP and ApoAI were significantly higher in normal/mild fibrosis, when compared to those in advanced fibrosis (both p < 0.01). CONCLUSIONS This study not only reveals three putative biomarkers of liver fibrosis (A2M, VDBP and ApoAI) but also proves the differential expressions of those markers in different stages of fibrosis. We expect that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.
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Affiliation(s)
- Ai-Sheng Ho
- Division of Gastroenterology, Buddhist Tzu Chi General Hospital, Taipei branch, Taiwan
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18
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Morais CNLD, Carvalho BDM, Melo WGD, Melo FLD, Lopes EPDA, Domingues ALC, Jucá N, Martins JRM, Diniz GTN, Montenegro SML. Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients. Mem Inst Oswaldo Cruz 2010; 105:460-6. [DOI: 10.1590/s0074-02762010000400018] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2009] [Accepted: 10/08/2009] [Indexed: 01/19/2023] Open
Affiliation(s)
| | | | | | | | | | | | - Norma Jucá
- Universidade Federal de Pernambuco, Brasil
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Wu SD, Wang JY, Li L. Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model: A comparative study. World J Gastroenterol 2010; 16:501-7. [PMID: 20101779 PMCID: PMC2811806 DOI: 10.3748/wjg.v16.i4.501] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B (CHB) patients.
METHODS: Seventy-eight CHB patients were consecutively enrolled in this study. Liver biopsy was performed and blood serum was obtained at admission. Histological diagnosis was made according to the METAVIR system. Significant fibrosis was defined as stage score ≥ 2, severe fibrosis as stage score ≥ 3. The diagnostic accuracy of 6 noninvasive liver fibrosis models, including serum aspartate aminotransferase (AST) to platelet ratio index (APRI), FIB-4, Forn’s index, Fibrometer, Hepascore, and Shanghai Liver Fibrosis Group’s index (SLFG), was investigated.
RESULTS: The APRI, FIB-4 and Forn’s index under receiver operating characteristic curve (AUROC) for significant fibrosis were 0.71, 0.75 and 0.79, respectively, with a diagnosis accuracy of 67%, 77% and 80%, respectively, and 0.80, 0.87 and 0.86, respectively, under the AUROC for severe fibrosis. The Hepascore, SLFG, and Fibrometer were 0.80, 0.83 and 0.85, respectively under the AUROC for significant fibrosis (P < 0.01). The diagnosis accuracy of Hepascore and SLFG was 86% and 88%, respectively. The Hepascore, SLFG, and Fibrometer were 0.95, 0.93, and 0.94, respectively, under the AUROC for severe fibrosis (P < 0.01).
CONCLUSION: The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.
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Smith JO, Sterling RK. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C. Aliment Pharmacol Ther 2009; 30:557-76. [PMID: 19519733 DOI: 10.1111/j.1365-2036.2009.04062.x] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus (HCV). Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. AIM To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV. METHODS A systematic review of PUBMED and EMBASE was performed through 2008 using the following search terms: HCV, liver, elastography, hepatitis, Fibroscan, SPECT, noninvasive liver fibrosis, ultrasonography, Doppler, MRI, Fibrotest, Fibrosure, Actitest, APRI, Forns and breath tests, alone or in combination. RESULTS We identified 151 studies: 87 using biochemical, 57 imaging and seven breath tests either alone or in combination. CONCLUSIONS Great strides are being made in the development of accurate non-invasive methods for determination of fibrosis. Although no single non-invasive test or model developed to date can match that information obtained from actual histology (i.e. inflammation, fibrosis, steatosis), combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis, and thereby avoid liver biopsy in a significant percentage of patients.
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Affiliation(s)
- J O Smith
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, Richmond, VA 23298-0341, USA
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Hermeziu B, Messous D, Fabre M, Munteanu M, Baussan C, Bernard O, Poynard T, Jacquemin E. Evaluation of FibroTest-ActiTest in children with chronic hepatitis C virus infection. ACTA ACUST UNITED AC 2009; 34:16-22. [PMID: 19726147 DOI: 10.1016/j.gcb.2009.06.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2008] [Revised: 04/14/2009] [Accepted: 06/03/2009] [Indexed: 12/13/2022]
Abstract
FibroTest-ActiTest (FT-AT) has been validated in adults with chronic hepatitis C virus (HCV) infection as a noninvasive alternative to liver biopsy (LB), but there are few data of its use in children. The objective of the present study was to evaluate FT-AT in children with HCV infection and to compare FT-AT analysis with liver histology. A total of 43 serum samples from 38 children with chronic HCV infection were analyzed retrospectively. Histological evaluation was performed according to the METAVIR scoring system. In 16 of the children, 21 serum samples were tested with FT-AT and compared to 21 LB (serum/LB pairs) in nontransplanted and liver-transplanted children. FT-AT was also measured in 22 infected children without LB and in 50 healthy controls. FT-AT values in controls were comparable to those of healthy adults, validating the adult FT-AT parameters in children. In most infected children (74%), the FT-AT score was <or = A1-F1. Concordance between FT-AT and METAVIR scores was found in 10 pairs and discordance in 11. FT-AT/METAVIR concordance was better in non-transplanted (8/13 pairs, 62%) than in transplanted (2/8 pairs, 25%) children. A prospective evaluation of FT-AT in non-transplanted children with chronic HCV infection would be worthwhile in future.
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Affiliation(s)
- B Hermeziu
- Pediatric Hepatology and National Reference Centre, Biliary Atresia, Bicêtre Hospital, University Paris Sud 11, Assistance publique-Hôpitaux de Paris, France
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22
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Mayo MJ, Parkes J, Adams-Huet B, Combes B, Mills AS, Markin RS, Rubin R, Wheeler D, Contos M, West AB, Saldana S, Getachew Y, Butsch R, Luketic V, Peters M, Di Bisceglie A, Bass N, Lake J, Boyer T, Martinez E, Boyer J, Garcia-Tsao G, Barnes D, Rosenberg WM. Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology 2008; 48:1549-57. [PMID: 18846542 PMCID: PMC2597274 DOI: 10.1002/hep.22517] [Citation(s) in RCA: 156] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
UNLABELLED Primary biliary cirrhosis (PBC) is sometimes diagnosed based on a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. Although a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications and sampling error and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients. Serial liver biopsy specimens and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplantation, or liver-related death. Serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and procollagen III aminopeptide were measured and entered into the previously validated enhanced liver fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, Model for End-Stage Liver Disease (MELD), and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points. Event-free survival was significantly lower in those with high baseline ELF. Each 1-point increase in ELF was associated with a threefold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years before the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score. CONCLUSION The ELF algorithm is a highly accurate noninvasive measure of PBC disease severity that provides useful long-term prognostic information.
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Affiliation(s)
- Marlyn J Mayo
- University of Texas Southwestern Medical Center, Dallas, TX 75390-9151, USA.
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Sporea I, Popescu A, Sirli R. Why, who and how should perform liver biopsy in chronic liver diseases. World J Gastroenterol 2008; 14:3396-3402. [PMID: 18528937 PMCID: PMC2716594 DOI: 10.3748/wjg.14.3396] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2007] [Revised: 04/12/2008] [Accepted: 04/19/2008] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis is a common disease in the general population. During chronic hepatitis, the prognosis and clinical management are highly dependent on the extent of liver fibrosis. The fibrosis evaluation can be performed by FibroTest (using serological markers), by Elastography or FibroScan (a noninvasive percutaneous technique using the elastic properties of the hepatic tissue) and by liver biopsy (LB), considered to be the "gold standard". Currently, there are three techniques for performing LB: percutaneous, transjugular and laparoscopic. The percutaneous LB can be performed blind, ultrasound (US) guided or US assisted. There are two main categories of specialists who perform LB: gastroenterologists (hepatologists) and radiologists, and the specialty of the individual who performs the LB determines if the LB is performed under ultrasound guidance or not. There are two types of biopsy needles used for LB: cutting needles (Tru-Cut, Vim-Silverman) and suction needles (Menghini, Klatzkin, Jamshidi). The rate of major complications after percutaneous LB ranges from 0.09% to 2.3%, but the echo-guided percutaneous liver biopsy is a safe method for the diagnosis of chronic diffuse hepatitis (cost-effective as compared to blind biopsy) and the rate of complications seems to be related to the experience of the physician and the type of the needle used (Menghini type needle seems to be safer). Maybe, in a few years we will use non-invasive markers of fibrosis, but at this time, most authorities in the field consider that the LB is useful and necessary for the evaluation of chronic hepatopathies, despite the fact that it is not a perfect test.
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MESH Headings
- Biomarkers/blood
- Biopsy, Needle/adverse effects
- Biopsy, Needle/instrumentation
- Biopsy, Needle/methods
- Chronic Disease
- Clinical Competence
- Elasticity
- Equipment Design
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/metabolism
- Hepatitis, Viral, Human/pathology
- Humans
- Laparoscopy
- Liver/chemistry
- Liver/pathology
- Liver/virology
- Liver Cirrhosis/metabolism
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Needles
- Patient Selection
- Severity of Illness Index
- Ultrasonography, Interventional
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Cacoub P, Carrat F, Bédossa P, Lambert J, Pénaranda G, Perronne C, Pol S, Halfon P. Comparison of non-invasive liver fibrosis biomarkers in HIV/HCV co-infected patients: the fibrovic study--ANRS HC02. J Hepatol 2008; 48:765-73. [PMID: 18314219 DOI: 10.1016/j.jhep.2008.01.025] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2007] [Revised: 01/07/2008] [Accepted: 01/21/2008] [Indexed: 12/28/2022]
Abstract
BACKGROUND/AIMS To compare non-invasive biological liver fibrosis scores, as alternatives to liver biopsy, in HIV/HCV co-infected patients. METHODS Two hundred and seventy-two HIV/HCV patients, nai ve for HCV treatment, underwent liver biopsy [197 (72%) men, 39.9 years, fibrosis stage (Metavir) F1 (25%), F2 (40%), F3 (25%), F4 (10%), median CD4 486/mm(3) and median HIV viral load 3.5log. Fibrotest (FT), Hepascore (HS), Fibrometer (FM), SHASTA, APRI, Forns index, and Fib-4 were tested in order to differentiate patients with mild to moderate fibrosis (F2) and those with advanced fibrosis (F3). The AUROC and the rate of well-classified patients were compared to liver biopsy. RESULTS FT, HS, and FM were able to stage liver fibrosis in all patients with AUROCs of 0.78, 0.84 and 0.89 for the diagnosis of F2, respectively. The correlation coefficient indexes were 0.37, 0.46 and 0.48, respectively. The rates of well-classified patients were 62%, 68% and 71%, respectively. Fib-4, APRI and the Forn's index were only able to stage 37-61% of patients and showed lower accuracies. Using a combination of FT, HS and FM did not significantly increase the performance of each test. CONCLUSIONS In HIV/HCV co-infected patients, Fibrometer, Hepascore and Fibrotest outperformed other non-invasive liver fibrosis biomarkers for the prediction of significant liver fibrosis.
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Affiliation(s)
- Patrice Cacoub
- Université Pierre et Marie Curie-Paris 6, CNRS, UMR 7087, Paris, France
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25
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Morais CNL, Carvalho BM, Melo WG, Lopes EPA, Domingues ALC, Jucá NT, Souza W, Abath FGC, Montenegro SML. Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection. Mem Inst Oswaldo Cruz 2008; 101 Suppl 1:353-4. [PMID: 17308796 DOI: 10.1590/s0074-02762006000900057] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2006] [Accepted: 06/26/2006] [Indexed: 01/27/2023] Open
Abstract
Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.
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Affiliation(s)
- Clarice N L Morais
- Centro de Pesquisas Aggeu Magalhães-Fiocruz, Av. Prof. Moraes Rego, 52020-020 Recife, PE, Brazil
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26
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Halfon P, Carrat F, Bédossa P, Lambert J, Pénaranda G, Perronne C, Pol S, Cacoub P. Effect of Antiviral Treatment on Serum Markers of Liver Fibrosis in HIV–Hepatitis C virus-Coinfected Patients: The Fibrovic 2 Study – ANRS HC02. Antivir Ther 2008. [DOI: 10.1177/135965350901400205] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background Non-invasive liver fibrosis scores have been proposed as alternatives to liver biopsy (LB) in hepatitis C virus (HCV)-infected patients. Here, we aimed to assess the effect of antiviral treatment on non-invasive serological markers of liver fibrosis in HIV–HCV-coinfected patients. Methods We included 114 HIV–HCV-coinfected patients with LBs performed before and 6 months after the end of treatment (week 72; W72). Fibrotest, the Forn's index, age-platelet ratio index, SHASTA, FIB-4, Hepascore and Fibrometer scores were assessed. There were 29 (25%) patients who achieved sustained virological response (SVR). Results At baseline (BL), all non-invasive fibrosis scores except the Forn's index did not show significantly lower values in SVR patients. At W72, all non-invasive scores, except Hepascore, showed a significant decrease in SVR patients ( P<0.01). There was a significant difference in fibrosis stages on LBs between BL and W72 in SVR and non-SVR patients. Conclusions In HIV–HCV-coinfected patients, HCV clearance is associated with a significant reduction in non-invasive fibrosis serological markers, which most likely reflect the histological improvement associated with SVR. If confirmed, such results will reinforce the reliability of these markers in the follow-up after HCV treatment.
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Affiliation(s)
- Philippe Halfon
- Laboratoire Alphabio, Service de Maladies Infectieuses, Hôpital Ambroise Paré, Marseille, France
| | | | - Pierre Bédossa
- Service d'Anatomopathologie, Hôpital Beaujon, Clichy, France
| | | | | | - Christian Perronne
- Service de Maladies Infectieuses, Hôpital Raymond Poincaré, Garches, France
| | - Stanislas Pol
- Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Patrice Cacoub
- Service de Médecine Interne, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
- Université Pierre et Marie Curie, Paris 6, Paris, France
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Shaheen AAM, Wan AF, Myers RP. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. Am J Gastroenterol 2007; 102:2589-600. [PMID: 17850410 DOI: 10.1111/j.1572-0241.2007.01466.x] [Citation(s) in RCA: 256] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis. METHODS Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy.
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Affiliation(s)
- Abdel Aziz M Shaheen
- Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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28
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Rosenthal-Allieri MA, Tran A, Halfon P, Imbert-Bismut F, Munteanu M, Messous D, Peritore ML, Poynard T, Bernard A. Optimal correlation between different instruments for Fibrotest-Actitest protein measurement in patients with chronic hepatitis C. ACTA ACUST UNITED AC 2007; 31:815-21. [DOI: 10.1016/s0399-8320(07)73971-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 2007; 46:32-6. [PMID: 17567829 DOI: 10.1002/hep.21669] [Citation(s) in RCA: 1592] [Impact Index Per Article: 88.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
UNLABELLED To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (kappa = 0.561, P < 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. CONCLUSION For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.
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30
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Christensen PB, Krarup HB, Møller A, Laursen AL, Kjaer MS, Orholm M, Lindberg J, Groenbaek K, Kromann-Andersen H, Weis N. Liver biopsy performance and histological findings among patients with chronic viral hepatitis: a Danish database study. ACTA ACUST UNITED AC 2007; 39:245-9. [PMID: 17366055 DOI: 10.1080/00365540600978864] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis (> or =F2) and 13.9% had cirrhosis (F4). The frequency of cirrhosis varied from 8.3 to 18.6% among centres, and was independently associated with age, male gender, elevated alanine-aminotransferase (ALT) and non-Danish origin. Among 141 patients with hepatitis C and known duration of infection, cirrhosis had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis.
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31
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Esmat G, Metwally M, Zalata KR, Gadalla S, Abdel-Hamid M, Abouzied A, Shaheen AA, El-Raziky M, Khatab H, El-Kafrawy S, Mikhail N, Magder LS, Afdhal NH, Strickland GT. Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C. J Hepatol 2007; 46:620-7. [PMID: 17316875 DOI: 10.1016/j.jhep.2006.12.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2006] [Revised: 12/05/2006] [Accepted: 12/13/2006] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS We evaluated whether surrogate serum biomarkers for liver injury are comparable to liver biopsy in Egyptian patients with hepatitis C virus (HCV) infection. SUBJECTS Two hundred and twenty Egyptian patients, 91% infected with genotype-4 HCV, undergoing liver biopsy during evaluation for interferon/ribavirin therapy. METHODS Liver biopsy scored by the Ishak method was compared to biochemical tests, platelet count and two fibrosis biomarkers: hyaluronic acid (HA) and YKL-40. Univariate and logistic regression analyses determined independent predictors of fibrotic, inflammatory, and fatty changes. Biomarkers were evaluated for ability to differentiate between severe fibrosis/cirrhosis and no/mild fibrosis. RESULTS Although increasing age, HA, YKL-40, AST, reduced platelet count, and AST and HA/platelet count ratios were associated with fibrosis by univariate analysis, the other variables were not significant after controlling for HA (p=0.0001) and age (p=0.004). Although age and some biomarkers were associated with inflammation, none remained significant after controlling for fibrosis. YKL-40 (p=0.04) and aspartate aminotransferase (p=0.05) remained associated with steatosis after controlling for fibrosis. CONCLUSIONS In Egyptians with chronic HCV, young patients with low levels of HA are at very low risk of fibrosis. This can limit the number of liver biopsies to those whose clinical findings conflict with the biomarker results.
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Affiliation(s)
- Gamal Esmat
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
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Verveer C, de Knegt RJ. Non-invasive measurement of liver fibrosis: application of the FibroScan in hepatology. Scand J Gastroenterol 2007:85-8. [PMID: 16782627 DOI: 10.1080/00365520600664359] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
The liver biopsy is still regarded as the gold standard for the assessment of liver disease. However, there is a growing demand for non-invasive assessment of liver fibrosis, which is the most important prognostic factor in chronic liver disease, in particular in viral hepatitis. Transient elastography is a novel, non-invasive and rapid bedside method for assessing liver fibrosis by measuring liver stiffness. Some recent extensive studies, mainly from France, have demonstrated that measurement with the FibroScan is a good alternative for the liver biopsy. The amount of fibrosis can be quantified very easily and reliably. In this review, we describe the technique and discuss the available studies in order to establish applicability and to provide points for discussion.
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Affiliation(s)
- Claudia Verveer
- Department Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
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Mooney P, Hayes P, Smith K. The putative use of alpha-1-acid glycoprotein as a non-invasive marker of fibrosis. Biomed Chromatogr 2007; 20:1351-8. [PMID: 17004233 DOI: 10.1002/bmc.704] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The acute phase response to injury or infection results in alterations in the expression of the plasma proteins produced by the liver. Many of these biomolecules are glycosylated with oligosaccharide chains covalently attached to the polypeptide backbone and the extent and composition of this glycosylation can be altered in a disease-dependent manner. Of particular interest is the observation that the acute phase glycoprotein, alpha-1-acid glycoprotein (AGP) has altered glycosylation in several physiological and pathological conditions. It is posited that changes induced in liver diseases may reflect disease severity and may therefore act as a non-invasive marker of fibrosis. This study has investigated the glycosylation of AGP in the plasma of people with varying degrees of cirrhosis and fibrosis. Hyperfucosylation was observed in all disease samples in comparison to normal plasma and was significantly increased in cirrhosis. Both sialic acid and N-acetylgalactosamine (GalNAc) were negatively associated with fibrosis. Two samples were found to express GalNAc, which as a constituent of the glycosylation of serum proteins is rare. In conclusion, fucose, sialic acid and other aspects of the glycosylation of AGP are influenced by the degree of fibrosis and as such may prove a valuable prognostic indicator of the development of cirrhosis.
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Affiliation(s)
- Paul Mooney
- Department of Bioscience, University of Strathclyde, Royal College Building, 204 George Street, Glasgow G1 1XW, UK
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34
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Nahon P, Thabut G, Ziol M, Htar MTT, Cesaro F, Barget N, Grando-Lemaire V, Ganne-Carrie N, Trinchet JC, Beaugrand M. Liver stiffness measurement versus clinicians' prediction or both for the assessment of liver fibrosis in patients with chronic hepatitis C. Am J Gastroenterol 2006; 101:2744-51. [PMID: 17227522 DOI: 10.1111/j.1572-0241.2006.00816.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The goal of this study was to estimate the additional value of liver stiffness measurement (LSM) with physicians' assessment of fibrosis based on epidemiological, clinical, and biological parameters. METHODS One hundred forty-two unselected patients with chronic hepatitis C were included. Liver biopsy and LSM were performed simultaneously. First, four physicians (two junior residents with limited experience in hepatology and two senior hepatologists) independently predicted the stage of fibrosis according to the METAVIR classification, using clinical, epidemiological, and biological data. For the second step, they were informed of LSM values and could modify their first evaluation if necessary. Finally, the two successive evaluations were compared with the histological fibrosis score. RESULTS Providing LSM values improved agreement between physicians and resulted in a better correlation between clinical impression and histological liver fibrosis. The diagnostic performances were only significantly improved with transient elastography for the diagnosis of cirrhosis where assessment improved in three of the four physicians (AUROC [area under receiver operating characteristic curve]: 0.76 vs 0.87, 0.80 vs 0.87, and 0.83 vs 0.89, all p < 0.05). Moreover, these performances were nearly similar for junior and senior physicians when LSM was provided with the AUROC ranging from 0.69 to 0.72 for significant fibrosis and 0.87 to 0.90 for cirrhosis. CONCLUSIONS Providing LSM values to physicians results in a better estimation of liver fibrosis and a more accurate diagnosis of cirrhosis. Moreover, it allows physicians with limited experience to predict liver fibrosis as well as experienced hepatologists.
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Affiliation(s)
- Pierre Nahon
- Service d'Hépato-gastroentérologie, Hôpital Jean Verdier, AP-HP, Bondy, France
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Trocme C, Leroy V, Sturm N, Hilleret MN, Bottari S, Morel F, Zarski JP. Longitudinal evaluation of a fibrosis index combining MMP-1 and PIIINP compared with MMP-9, TIMP-1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon-alpha and ribavirin. J Viral Hepat 2006; 13:643-51. [PMID: 16970595 DOI: 10.1111/j.1365-2893.2006.00730.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients.
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Affiliation(s)
- C Trocme
- Laboratoire d'Enzymologie, DBPC, GREPI EA 2938, France
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Sène D, Limal N, Messous D, Ghillani-Dalbin P, Charlotte F, Thiollière JM, Piette JC, Imbert-Bismut F, Halfon P, Poynard T, Cacoub P. Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis. Clin Biochem 2006; 39:715-21. [PMID: 16765932 DOI: 10.1016/j.clinbiochem.2006.04.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2005] [Revised: 03/28/2006] [Accepted: 04/04/2006] [Indexed: 01/06/2023]
Abstract
OBJECTIVE AND METHODS We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. RESULTS Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P <or= 0.05). CONCLUSION The FT-AT is a reliable non-invasive biochemical alternative to LB in HCV-infected patients with systemic vasculitis and is more reliable than other non-invasive biological indexes.
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Affiliation(s)
- Damien Sène
- Department of Internal Medicine, La Pitié-Salpêtrière Hospital, France
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Crockett SD, Kaltenbach T, Keeffe EB. Do we still need a liver biopsy? Are the serum fibrosis tests ready for prime time? Clin Liver Dis 2006; 10:513-34, viii. [PMID: 17162226 DOI: 10.1016/j.cld.2006.08.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver biopsy has been in use for more than a century for diagnosis and staging of acute and chronic liver diseases. Several serum markers and panels offer the opportunity to assess the extent of liver disease noninvasively and spare some patients the risks associated with percutaneous liver biopsy, but only a few of the noninvasive serum markers allow the determination of different stages of fibrosis on a continuum similar to that achieved with liver biopsy. This article reviews the results of recent published and preliminary studies on serum markers, focusing on their comparison with liver biopsy and their clinical utility.
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Affiliation(s)
- Seth D Crockett
- Department of Medicine, Stanford University Medical Center, 750 Welch Road, Stanford, CA 94034, USA
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Gutierrez-Reyes G, Lopez-Ortal P, Sixtos S, Cruz S, Ramirez-Iglesias MT, Gutierrez-Ruiz MC, Sanchez-Avila F, Roldan E, Vargas-Vorackova F, Kershenobich D. Effect of pentoxifylline on levels of pro-inflammatory cytokines during chronic hepatitis C. Scand J Immunol 2006; 63:461-467. [PMID: 16764700 DOI: 10.1111/j.1365-3083.2006.001761.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The cellular and humoral natural immune response induced by hepatitis C virus (HCV) is commonly unable to eradicate the virus. HCV is a highly mutable, hepatotropic RNA virus that causes acute and chronic hepatitis, an infection that involves the production of various cytokines. The aim of the study is to analyse the expression of pro-inflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma and the chemokine CXCL8 (IL-8) in liver tissue and their expression and secretion in PBMC of patients with chronic hepatitis C (CHC), in response to pentoxyfilline (PTX). We studied six CHC patients, naive to treatment. Patients received PTX 400 mg twice a day/8 weeks. Pentoxyfilline resulted in decreased expression of mRNA of liver IL-1beta, TNF-alpha and IFN-gamma: 144.2 versus 83.5 molecules of IL-1beta (P < 0.05), TNF-alpha 194.3 versus 17.6 molecules (P = 0.03) and IFN-gamma 26.1 versus 0.5 molecules (P = 0.04). Following PTX, PBMC exhibited a decrease in IFN-gamma mRNA 12.2 versus 1.5 molecules (P = 0.028) and CXCL8 4.2 versus 2.5 molecules (P = 0.027). In PBMC, only the secretion of TNF-alpha was decreased 1109 versus 933.5 pg/ml, P = 0.046. Production of cytokines both locally (within the liver) and systemically (PBMC) may serve as biomarkers of the infection with hepatitis C. PTX inhibits the expression of several pro-inflammatory cytokines in the liver. These results indicate that it is worth exploring PTX in hepatitis in future clinical trials in nonresponders to antiviral treatment.
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Affiliation(s)
- G Gutierrez-Reyes
- Facultad de Medicina, UNAM, Hospital General de México, Mexico City, Mexico
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Thabut D, Le Calvez S, Thibault V, Massard J, Munteanu M, Di Martino V, Ratziu V, Poynard T. Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease? Am J Gastroenterol 2006; 101:1260-1267. [PMID: 16771947 DOI: 10.1111/j.1572-0241.2006.00556.x] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few data are available on chronic hepatitis C (CHC) in elderly patients. The aim of this study was to compare the features and severity of CHC and the efficacy/safety of antiviral therapy in patients<65, between 65 and 80, and >80 yr old, and to determine the usefulness of biochemical markers (Fibrotest-Fibrosure/ActiTest [FT-AT]) in aged patients. METHODS This was a retrospective study with two groups of patients: Group 1: prospective cohort including all hepatitis C virus patients from our institution (N=4,182); Group 2: all consecutive patients who had FT-AT performed in France between 2002 and 2004 (N=33,738). RESULTS A total of 6,865 patients>or=65 yr old was included (Group 1=881, Group 2=5,984). Group 1: patients>or=65 had a longer duration of and a higher age at infection, more genotype 1, and a history of transfusion (p<0.001). Among the 2,169 patients who underwent liver biopsy, bridging fibrosis (F2,F3,F4) was more frequent in patients>or=65 yr old, regardless of the duration of infection. In multivariate analysis, ages at biopsy and at infection were associated with F2,F3,F4. Discovery of CHC by a complication was more frequent in patients>or=65 yr (p<0.001). One hundred seventy patients>or=65 yr received antiviral therapy. A sustained virologic response was obtained in 45% of patients>or=65 yr treated with pegylated interferon/ribavirin. Group 2: At FT, 58% of patients>80 yr, 37% of patients between 65 and 80 yr, and 14% of patients<65 yr (p<0.001) had cirrhosis. Patients>80 yr (43%) with cirrhosis had nonelevated alanine amino transferase (ALT), compared with 31% of patients<65 yr (p<0.001). CONCLUSION In patients>or=65 yr, CHC is more severe and presents with lower ALT than in younger patients. Treatment is effective. Biochemical markers seem particularly useful as a noninvasive alternative to liver biopsy in this population.
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Affiliation(s)
- Dominique Thabut
- Services d'Hépato-Gastroentérologie, Group Hospitalier Pitié-Salpêtrièe, Paris, France
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Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, Tahiri M, Munteanu M, Thabut D, Cadranel JF, Le Bail B, de Ledinghen V, Poynard T. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006; 6:6. [PMID: 16503961 PMCID: PMC1386692 DOI: 10.1186/1471-230x-6-6] [Citation(s) in RCA: 326] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2005] [Accepted: 02/14/2006] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions. The aim of this study was to determine the diagnostic utility of non-invasive markers of fibrosis, validated in chronic viral hepatitis and alcoholic liver disease (FibroTest, FT), in patients with NAFLD. METHODS 170 patients with suspected NAFLD were prospectively included in a reference center (Group 1), 97 in a multicenter study (Group 2) and 954 blood donors as controls. Fibrosis was assessed on a 5 stage histological scale validated by Kleiner et al from F0 = none, F1 = perisinusoidal or periportal, F2 = perisinusoidal and portal/periportal, F3 = bridging and F4 = cirrhosis. Histology and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) were assessed. RESULTS In both groups FT has elevated and not different AUROCs for the diagnosis of advanced fibrosis (F2F3F4): 0.86 (95%CI 0.77-0.91) versus 0.75 (95%CI 0.61-0.83; P = 0.10), and for F3F4: 0.92 (95%CI 0.83-0.96) versus 0.81 (95%CI 0.64-0.91; P = 0.12) in Group 1 and Group 2 respectively. When the 2 groups were pooled together a FT cutoff of 0.30 had a 90% NPV for advanced fibrosis (Se 77%); a FT cutoff of 0.70 had a 73% PPV for advanced fibrosis (Sp 98%). CONCLUSION In patients with NAFLD, FibroTest, a simple and non-invasive quantitative estimate of liver fibrosis reliably predicts advanced fibrosis.
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Affiliation(s)
- Vlad Ratziu
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Members of the LIDO and of the CYTOL Study Groups are listed at the end of the manuscript
| | - Julien Massard
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | | | - Djamila Messous
- Biochemistry, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | | | - Luninita Bonyhay
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Mohamed Tahiri
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | | | - Dominique Thabut
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | | | | | | | - Thierry Poynard
- Hepato-Gastroenterology, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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Zeng MD, Lu LG, Mao YM, Qiu DK, Li JQ, Wan MB, Chen CW, Wang JY, Cai X, Gao CF, Zhou XQ. Prediction of significant fibrosis in HBeAg-positive patients with chronic hepatitis B by a noninvasive model. Hepatology 2005; 42:1437-45. [PMID: 16317674 DOI: 10.1002/hep.20960] [Citation(s) in RCA: 132] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2-4 vs. stages 0-1). Consecutive treatment-naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified alpha2-macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg-positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB.
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Affiliation(s)
- Min-De Zeng
- Department of Gastroenterology, Renji Hospital, Shanghai Second Medical University, China
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42
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Poynard T, Zoulim F, Ratziu V, Degos F, Imbert-Bismut F, Deny P, Landais P, El Hasnaoui A, Slama A, Blin P, Thibault V, Parvaz P, Munteanu M, Trepo C. Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection. Am J Gastroenterol 2005; 100:1970-80. [PMID: 16128941 DOI: 10.1111/j.1572-0241.2005.41957.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression. METHODS Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis. RESULTS Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001). CONCLUSIONS In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.
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Affiliation(s)
- Thierry Poynard
- Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France
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Lok ASF, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM, Lee WM, Morgan TR, Dienstag JL, Morishima C. Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort. Hepatology 2005; 42:282-92. [PMID: 15986415 DOI: 10.1002/hep.20772] [Citation(s) in RCA: 245] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Knowledge of the presence of cirrhosis is important for the management of patients with chronic hepatitis C (CHC). Most models for predicting cirrhosis were derived from small numbers of patients and included subjective variables or laboratory tests that are not readily available. The aim of this study was to develop a predictive model of cirrhosis in patients with CHC based on standard laboratory tests. Data from 1,141 CHC patients including 429 with cirrhosis were analyzed. All biopsies were read by a panel of pathologists (blinded to clinical features), and fibrosis stage was determined by consensus. The cohort was divided into a training set (n = 783) and a validation set (n = 358). Variables that were significantly different between patients with and without cirrhosis in univariate analysis were entered into logistic regression models, and the performance of each model was compared. The area under the receiver-operating characteristic curve of the final model comprising platelet count, AST/ALT ratio, and INR in the training and validation sets was 0.78 and 0.81, respectively. A cutoff of less than 0.2 to exclude cirrhosis would misclassify only 7.8% of patients with cirrhosis, while a cutoff of greater than 0.5 to confirm cirrhosis would misclassify 14.8% of patients without cirrhosis. The model performed equally well in fragmented and nonfragmented biopsies and in biopsies of varying lengths. Use of this model might obviate the requirement for a liver biopsy in 50% of patients with CHC. In conclusion, a model based on standard laboratory test results can be used to predict histological cirrhosis with a high degree of accuracy in 50% of patients with CHC.
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Affiliation(s)
- Anna S F Lok
- Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI 48210, USA.
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Islam S, Antonsson L, Westin J, Lagging M. Cirrhosis in hepatitis C virus-infected patients can be excluded using an index of standard biochemical serum markers. Scand J Gastroenterol 2005; 40:867-72. [PMID: 16109665 DOI: 10.1080/00365520510015674] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Assessment of liver histology is pivotal in prognostication and decision-making regarding therapeutic intervention in patients with chronic hepatitis C virus (HCV). Being an invasive procedure, the liver biopsy is associated with complications, and a non-invasive alternative would be preferable. MATERIAL AND METHODS Sera samples from 179 patients with chronic HCV infection collected at the time of liver biopsy were analyzed using routinely available biochemical markers of liver disease, and liver histology was evaluated using the Ishak protocol. The relationship between the serum biochemical markers and cirrhosis (Ishak stage > or = 5) as well as bridging fibrosis (Ishak stage > or = 3) was examined. RESULTS A strong association was found in the multivariate logistic regression analysis between fibrosis stage and aspartate aminotransferase (AST), platelet count and prothrombin-INR (international normalized ratio). An index (the Göteborg University Cirrhosis Index (GUCI)) was calculated using these variables: normalized ASTxprothrombin-INRx100/platelet count (x 10(9)/l). Using a cut-off value of 1.0, the sensitivity was 80% and the specificity 78% for diagnosis of cirrhosis, and the negative predictive values (NPV) and positive predictive values (PPV) were 97% and 31%, respectively. The GUCI score proved slightly superior for sensitivity, specificity, NPV, PPV, and the area under the receiver operating characteristic (ROC) curve for prediction of cirrhosis and bridging fibrosis compared with the AST to platelet ratio index (APRI), which has been reported as a predictor of significant fibrosis and cirrhosis. CONCLUSION An index using routinely available biochemical markers can with a high degree of accuracy discriminate patients with from those without hepatitis C-related cirrhosis.
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Affiliation(s)
- Sara Islam
- Department of Infectious Diseases, Göteborg University, Sweden
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45
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Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Lédinghen V. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005; 128:343-50. [PMID: 15685546 DOI: 10.1053/j.gastro.2004.11.018] [Citation(s) in RCA: 1840] [Impact Index Per Article: 92.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Transient elastography (FibroScan; Echosens, Paris, France) is a novel, noninvasive, and rapid bedside method to assess liver fibrosis by measuring liver stiffness. We prospectively assessed the performance of FibroScan in patients with chronic hepatitis C, in comparison with and combined with currently available biochemical markers (Fibrotest; Biopredictive; and the aspartate transaminase to platelets ratio index [APRI]); a liver biopsy examination performed the same day served as the reference. METHODS We studied 183 consecutive patients with chronic hepatitis C (METAVIR fibrosis stage F1, n = 47; F2, n = 53; F3, n = 37; F4, n = 46). RESULTS FibroScan values ranged from 2.4 to 75.4 kilopascals (median, 7.4 kilopascals). Cut-off values were 7.1 kPa for F > or = 2, 9.5 kPa for F > or = 3, and 12.5 kPa for F = 4. The areas under the receiver operating characteristic (ROC) curve of FibroScan, FibroTest, and APRI values were of the same order (.83, .85, and .78, respectively, for F > or = 2; .90, .90, and .84, respectively, for F > or = 3; and .95, .87, and .83, respectively, for F = 4). The best performance was obtained by combining the FibroScan and FibroTest, with areas under the ROC curve of .88 for F > or = 2, .95 for F > or = 3, and .95 for F = 4. When the FibroScan and FibroTest results agreed, liver biopsy examination confirmed them in 84% of cases for F > or = 2, in 95% for F > or = 3, and in 94% for F = 4. CONCLUSIONS FibroScan is a simple and effective method for assessing liver fibrosis, with similar performance to FibroTest and APRI. The combined use of FibroScan and FibroTest to evaluate liver fibrosis could avoid a biopsy procedure in most patients with chronic hepatitis C.
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Affiliation(s)
- Laurent Castéra
- Service d'Hépato-gastroentérologie, Hôpital Haut Lévêque, C. H. U. Bordeaux, Pessac, France.
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Shin JL, Teitel J, Swain MG, Bain VG, Adams PC, Croitoru K, Peltekian K, Schweiger F, Simons ME, Heathcote EJ. A Canadian multicenter retrospective study evaluating transjugular liver biopsy in patients with congenital bleeding disorders and hepatitis C: is it safe and useful? Am J Hematol 2005; 78:85-93. [PMID: 15682411 DOI: 10.1002/ajh.20263] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Prior to the introduction of virally inactivated clotting factor concentrates, the majority of individuals with congenital bleeding disorders became infected with the hepatitis C virus. Although liver biopsy is valuable in prognosis and guiding antiviral therapy, there is a reluctance to perform biopsies in this population because of the risk of hemorrhage. The purpose of this study was to evaluate the safety of transjugular liver biopsy, and the usefulness of evaluating liver histology in this patient population. Liver histopathology was assessed by the METAVIR index and compared with corrected sinusoidal pressures, platelet counts, and abdominal ultrasonography. Liver biopsy was performed at seven Canadian centers in 65 patients with hemophilia or von Willebrand's disease. Biopsies were done on an outpatient basis, followed by a 4-hr observation period in hospital. Normal hemostasis was maintained during the peribiopsy period, with follow-up doses of factor concentrate self administered by the patient at home. One patient (1.4%) had significant bleeding leading to readmission and red cell transfusion. Liver histology showed 14 patients (22%) had cirrhosis. Ten patients had elevated corrected sinusoidal pressures; 7 of these (70%) had cirrhosis on biopsy, and the other 3 (30%) likely had cirrhosis although histology showed stage 3 fibrosis. This series represents the largest reported experience of transjugular biopsy in individuals with congenital bleeding disorders. We conclude that this procedure can be safely performed on an outpatient basis. The diagnosis of cirrhosis and/or portal hypertension was made in a substantial proportion of individuals (26%), all of whom had asymptomatic liver disease.
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Affiliation(s)
- Jennifer L Shin
- Department of Medicine at University Health Network, University of Toronto, Toronto, Ontario, Canada
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Naveau S, Raynard B, Ratziu V, Abella A, Imbert-Bismut F, Messous D, Beuzen F, Capron F, Thabut D, Munteanu M, Chaput JC, Poynard T. Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease. Clin Gastroenterol Hepatol 2005; 3:167-74. [PMID: 15704051 DOI: 10.1016/s1542-3565(04)00625-1] [Citation(s) in RCA: 102] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. METHODS A total of 221 consecutive patients with an alcohol intake of >50 g/day (median, 100 g/day) and available liver biopsy examination and FibroTest FibroSure (FT) results were included prospectively. Fibrosis was assessed blindly on a 5-stage histologic scale similar to that of the METAVIR scoring system. Hyaluronic acid was measured and used as a standard serum marker of fibrosis. RESULTS Advanced fibrosis (F2-F4) was present at biopsy examination in 63% of patients. The mean FT value (SE) was F0 = .29 (.05); F1 = .29 (.03), F2 = .40 (.03), F3 = .53 (.04); and F4 = .88 (.02) (P < .05 between all groups, except between F0 and F1). As opposed to FT, there was no significant difference for hyaluronic acid between F2 and F1 and between F2 and F0. For F2-F4 vs. F0-F1, the FT area under the ROC curves (AUROC) = .84 (.03) and .79 (.03) for hyaluronic acid. For the diagnosis of F4, the AUROC was very high, .95 for FT and .93 for hyaluronic acid. The discordances of the 2 stages were attributed to biopsy failures in 26 cases and to FT failures in 13 cases. CONCLUSIONS In heavy drinkers, FT is a simple and noninvasive quantitative estimate of liver fibrosis. The use of FT may decrease the need for liver biopsy examination.
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Affiliation(s)
- Sylvie Naveau
- Department of Hepato-Gastroenterology, Hôpital Antoine Béclère, Clamart, France
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Poynard T. [The Fibrotest is an ethical choice because it is a cost-effective and anti-inflationistic test. Response to Jean Louis Payen and Jean Marie Combis]. ACTA ACUST UNITED AC 2004; 28:929-31. [PMID: 15523238 DOI: 10.1016/s0399-8320(04)95166-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Thierry Poynard
- Service d'Hépato-Gastroentérologie, Groupe Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651 Paris Cedex 13
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Tanamly MD, Tadros F, Labeeb S, Makld H, Shehata M, Mikhail N, Abdel-Hamid M, Shehata M, Abu-Baki L, Medhat A, Magder LS, Afdhal NH, Strickland GT. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004; 36:752-9. [PMID: 15571006 DOI: 10.1016/j.dld.2004.06.015] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done. SUBJECTS One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements. METHODS Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.
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Affiliation(s)
- M D Tanamly
- International Health Division, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 660 West Redwood St. Suite 100, Baltimore, MD 21201, USA
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Selimoglu MA, Yagcl RV, Yüce G. Low plasma apolipoprotein A-I level is not a reliable marker of fibrosis in children with chronic hepatitis B. World J Gastroenterol 2004; 10:2864-6. [PMID: 15334687 PMCID: PMC4572119 DOI: 10.3748/wjg.v10.i19.2864] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To evaluate the clinical value of plasma apolipoprotein A-I (Apo A-I) as a marker of fibrosis in children with chronic hepatitis B (CHB).
METHODS: Liver biopsy specimens from 49 children with CHB were evaluated by using Knodell index. Plasma Apo A-I level was measured after 12-h fasting. Student’s t test, Spearman’s correlation test and receptor-operating characteristic (ROC) curve were used for statistical evaluation.
RESULTS: Mean Apo A-I level of the patients was not different from that of controls (P > 0.05). Six (8.7%) children had fibrosis score of more than 2 (severe fibrosis). No difference in the level of mean plasma Apo A-I was found among children with and without severe fibrosis (P > 0.05). No correlation between Apo A-I level and fibrosis scores was found (P > 0.05). The area under the ROC curve was 0.407 ± 0.146 (P > 0.05).
CONCLUSION: Severe fibrosis is not common in children with CHB and plasma Apo A-I level is not a reliable indicator of fibrosis.
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Affiliation(s)
- Mukadder-Ayse Selimoglu
- Ataturk Universitesi, Tlp Fakultesi, Cocuk Sagllgl ve Hastallklarl AD, Erzurum 25240, Turkey.
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