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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Chimoriya R, Ho V, Wang ZV, Chang R, Boumelhem BB, Simmons D, Kormas N, Gorrell MD, Piya MK. Application and Diagnostic Performance of Two-Dimensional Shear Wave Elastography and Liver Fibrosis Scores in Adults with Class 3 Obesity. Nutrients 2023; 16:74. [PMID: 38201904 PMCID: PMC10780854 DOI: 10.3390/nu16010074] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
There are no ideal non-invasive tests for assessing the severity of liver fibrosis in people with metabolic dysfunction-associated steatotic liver disease (MASLD) and class 3 obesity, where body habitus often makes imaging technically challenging. This study aimed to assess the applicability and diagnostic performance of two-dimensional shear wave elastography (2D-SWE), alongside several serum-based liver fibrosis scoring methods, in individuals with class 3 obesity. A cross-sectional study was conducted in patients aged ≥18 years and with a body mass index (BMI) ≥ 40 kg/m2 who were participants in a publicly funded multidisciplinary weight management program in South Western Sydney. The 2D-SWE was performed using the ElastQ Imaging (EQI) procedure with the Phillips EPIQ Elite series ultrasound. An EQI Median value of ≥6.43 kPa was taken as a cutoff score for significant fibrosis, and the scan was considered valid when the liver EQI IQR/Med value was <30%. The Fibrosis-4 (FIB-4) index, AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and circulating fibroblast activation protein index (FAP index) were calculated from fasting blood samples. The participants (n = 116; 67.2% female) were aged 47.2 ± 12.9 years, with BMI 54.5 ± 11.0 kg/m2. EQI Median values were obtained for 97.4% (113/116) of the 2D-SWE scans, and 91.4% (106/116) of the scans were considered valid. The EQI Median values exhibited a moderately positive correlation with the FIB-4 index (r = 0.438; p < 0.001) and a weakly positive correlation with the APRI (r = 0.388; p < 0.001), NFS (r = 0.210; p = 0.036) and FAP index (r = 0.226; p = 0.020). All liver fibrosis scores were positively correlated with one another. Among those referred for a liver biopsy based on the 2D-SWE and serum scores, half (11/22) underwent liver biopsy, and their 2D-SWE scores exhibited 72.7% accuracy (sensitivity: 71.4%; specificity: 75%) in detecting significant fibrosis. Our results show that 2D-SWE is a feasible, non-invasive test to assess liver fibrosis among people with class 3 obesity. Further research is needed to assess how 2D-SWE can be used alongside existing serum-based risk scores to reliably detect significant fibrosis, which would potentially reduce the need for invasive liver biopsy.
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Affiliation(s)
- Ritesh Chimoriya
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (R.C.); (V.H.); (D.S.)
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (R.C.); (V.H.); (D.S.)
- Camden and Campbelltown Hospitals, Campbelltown, NSW 2560, Australia; (R.C.); (N.K.)
| | - Ziqi Vincent Wang
- Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; (Z.V.W.); (B.B.B.); (M.D.G.)
| | - Ruby Chang
- Camden and Campbelltown Hospitals, Campbelltown, NSW 2560, Australia; (R.C.); (N.K.)
| | - Badwi B. Boumelhem
- Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; (Z.V.W.); (B.B.B.); (M.D.G.)
| | - David Simmons
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (R.C.); (V.H.); (D.S.)
- Camden and Campbelltown Hospitals, Campbelltown, NSW 2560, Australia; (R.C.); (N.K.)
| | - Nic Kormas
- Camden and Campbelltown Hospitals, Campbelltown, NSW 2560, Australia; (R.C.); (N.K.)
| | - Mark D. Gorrell
- Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; (Z.V.W.); (B.B.B.); (M.D.G.)
| | - Milan K. Piya
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (R.C.); (V.H.); (D.S.)
- Camden and Campbelltown Hospitals, Campbelltown, NSW 2560, Australia; (R.C.); (N.K.)
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Buckholz AP, Brown RS. Noninvasive Fibrosis Testing in Chronic Liver Disease Including Caveats. Clin Liver Dis 2023; 27:117-131. [PMID: 36400461 DOI: 10.1016/j.cld.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Assessment of liver fibrosis is important as the range of liver disease management has expanded, rendering biopsy both imperfect and impractical in many situations. Noninvasive tests of fibrosis leverage laboratory, imaging and elastography techniques to estimate disease extent, often with the goal of identifying advanced fibrosis. This review attempts to summarize their utility across a broad range of possible clinical scenarios while considering the central tenets of health care quality: access, quality, and cost. For each test, it also discusses the caveats whereby each test may have reduced effectiveness and how to consider each in a typical clinical setting.
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Affiliation(s)
- Adam P Buckholz
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA.
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Wang Z, Zhou Y, Yu P, Liu Y, Mei M, Bian Z, Shao W, Lv J, Li X, Lu W, Xu L. Retrospective Evaluation of Non-Invasive Assessment Based on Routine Laboratory Markers for Assessing Advanced Liver Fibrosis in Chronic Hepatitis B Patients. Int J Gen Med 2022; 15:5159-5171. [PMID: 35642202 PMCID: PMC9148603 DOI: 10.2147/ijgm.s364216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/03/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND At present, there is a lack of cheap, effective and convenient detection methods for hepatitis B-related liver fibrosis, especially in the developing area. AIM To evaluate the non-invasive methods for the significant and advanced fibrosis stage in chronic hepatitis B virus (HBV) patients in basic hospitals and to assess their diagnostic utility. METHODS The study included 436 consecutive naive HBV individuals who had their livers biopsied. They were examined in one week using aspartate aminotransferase-to-aspartate aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), Forns, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), S-index and transient elastography (TE). Scheuer scoring system was used to determine the histologic fibrosis grades (S0-S4). The diagnostic effectiveness was assessed using AUROCs and the DeLong test, both of which were based on statistical comparisons. RESULTS For both substantial (≧S2) and advanced (≧S3) fibrosis phases, TE had good diagnostic performance in determining the hepatic fibrosis. Similar diagnostic performance was shown with Forns and S-index when it came to detecting fibrosis stages lower than S3. One model's diagnostic value was not significantly improved by combining serum models. Correlation coefficients between clinical features and fibrosis phases were greatest for Forns (r = 0.397), S-index (r = 0.382) and TE (r = 0.535) when compared to other variables. CONCLUSION This investigation showed that Forns and S-index may be helpful strategies for detecting advanced fibrosis in HBV patients admitted to community hospitals.
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Affiliation(s)
- Zeyu Wang
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China
| | - Yonghe Zhou
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
| | - Pengzhi Yu
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
| | - Yonggang Liu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Pathology Department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Mei Mei
- Department of Gastroenterology, Tianjin Haihe Hospital, Tianjin, 300350, People’s Republic of China
| | - Zhuo Bian
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Wei Shao
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Jinxia Lv
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Xin Li
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Wei Lu
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Liang Xu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
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Alswat K, Al-Sohaibani F, Khathlan A, Bashmail A, Alanazi M, Kurdi A, Almakadma AH, Al-Hamoudi W. Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals. Ann Saudi Med 2022; 42:89-95. [PMID: 35380056 PMCID: PMC8981998 DOI: 10.5144/0256-4947.2022.89] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited. OBJECTIVES We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders. DESIGN Retrospective cohort study. SETTING Tertiary care centers. PATIENTS AND METHODS This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up. MAIN OUTCOME MEASURES Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up. SAMPLE SIZE AND CHARACTERISTICS 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females. RESULTS Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%). CONCLUSIONS Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality. LIMITATIONS Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen. CONFLICT OF INTEREST None.
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Affiliation(s)
- Khalid Alswat
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Fahad Al-Sohaibani
- From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Khathlan
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia.,From the Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ahmad Bashmail
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Mohammed Alanazi
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
| | - Amr Kurdi
- From the Department of Medicine, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
| | | | - Waleed Al-Hamoudi
- From the Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Saudi Arabia
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Huang C, Seah JJ, Tan CK, Kam JW, Tan J, Teo EK, Kwek A, Wong YJ, Tan M, Ang TL, Kumar R. Modified AST to platelet ratio index improves APRI and better predicts advanced fibrosis and liver cirrhosis in patients with non-alcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 2021; 45:101528. [PMID: 33268036 DOI: 10.1016/j.clinre.2020.08.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 08/13/2020] [Accepted: 08/24/2020] [Indexed: 02/08/2023]
Abstract
AIMS Advanced fibrosis (AF) and liver cirrhosis (LC) are important milestones in non-alcoholic fatty liver disease (NAFLD). FIB-4, NFS and BARD are validated scores with good accuracy in detecting AF and LC. APRI does not have similar predictive accuracy. While a modification (m-APRI) improves its use in viral hepatitis, this has yet to be evaluated in NAFLD. This study compares diagnostic performance of aforementioned scores in predicting AF and LC in NAFLD. METHODS Consecutive NAFLD patients undergoing Transient Elastography (TE) using Echosens® Fibroscan® for fibrosis staging were included. Cut-off liver stiffness measurements for AF and LC were 7.9 kPa and 11.5 kPa respectively. Anthropometric and laboratory tests done within 3 months were used. Diagnostic performances of scores were analyzed by standard statistical tests. RESULTS 161 patients qualified for the study. Mean age was 60.2 ± 14 years, BMI 26.8 ± 4.6 kg/m2. M-probe was used in 113, XL in 48. Optimal cut-offs of m-APRI for AF and LC were 5.84 and 9 respectively. Area under receiver operator characteristic curves (AUROC) for prediction of AF at optimal cut-off points were m-APRI 0.84, APRI 0.80, FIB-4: 0.77, NFS 0.77 and BARD 0.65. For prediction of LC, AUROC were m-APRI: 0.83, APRI: 0.76, FIB-4: 0.81, NFS: 0.77 and BARD: 0.66. m-APRI was significantly superior to all scores compared in detecting AF (p < 0.05 for all) and superior to APRI (p = 0.008) and BARD (p = 0.007) in predicting LC. There was no significant difference between m-APRI and FIB-4 or NFS in prediction of LC. CONCLUSIONS For prediction of AF in NAFLD, m-APRI outperforms BARD, APRI, NFS and FIB-4, while for the prediction of cirrhosis, m-APRI is superior to APRI and BARD but comparable to NFS and FIB-4.
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Affiliation(s)
- Cheryl Huang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; NUS Yong Loo Lin School of Medicine, Singapore
| | - Jun Jie Seah
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; NUS Yong Loo Lin School of Medicine, Singapore
| | - Chin Kimg Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Jia Wen Kam
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; Clinical Trials and Research Unit, Changi General Hospital, Singapore
| | - Jessica Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Andrew Kwek
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Malcolm Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore.
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Younossi ZM, Stepanova M, Anstee QM, Lawitz EJ, Wai-Sun Wong V, Romero-Gomez M, Kersey K, Li G, Subramanian GM, Myers RP, Djedjos CS, Okanoue T, Trauner M, Goodman Z, Harrison SA. Reduced Patient-Reported Outcome Scores Associate With Level of Fibrosis in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2019; 17:2552-2560.e10. [PMID: 30779990 DOI: 10.1016/j.cgh.2019.02.024] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 02/12/2019] [Accepted: 02/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis. METHODS We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI:SHP) before treatment initiation. RESULTS Compared with patients with F3 fibrosis, higher proportions of patients with F4 fibrosis were female, were white, had more hematologic and gastrointestinal comorbidities, and had type 2 diabetes (P ≤ .01). Mean physical health-related PRO scores were significantly lower than those of the general population: patients with F4 fibrosis had score reductions of 4.4% to 12.9% in 6/8 SF-36 domains and patients with F3 fibrosis had score reductions of 3.9% to 11.7% in 4/8 domains (P < .01). Compared to patients with F3 fibrosis, those with F4 fibrosis had lower scores in all but 1 domains of CLDQ-NASH, Role Physical, Bodily Pain, and Social Functioning domains of the SF-36, and EQ-5D (P ≤ 01). In multivariate regression analysis, factors independently associated with lower PRO scores included having cirrhosis, female sex, higher body mass index, history of smoking, and diabetes or other comorbidities (P < .01). CONCLUSIONS PROs are significantly lower in patients with NASH with advanced fibrosis who participated in the STELLAR clinical trials. Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia.
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease (COR-LD), Washington, District of Columbia
| | - Quentin M Anstee
- Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle-upon-Tyne, and Newcastle NIHR Biomedical Research Centre, Newcastle-upon-Tyne, United Kingdom
| | - Eric J Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | | | | | - Georgia Li
- Gilead Sciences, Inc, Foster City, California
| | | | | | | | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Zachary Goodman
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia
| | - Stephen A Harrison
- Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
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Stasi C, Tsochatzis EA, Hall A, Rosenberg W, Milani S, Dhillon AP, Pinzani M. Comparison and correlation of fibrosis stage assessment by collagen proportionate area (CPA) and the ELF panel in patients with chronic liver disease. Dig Liver Dis 2019; 51:1001-1007. [PMID: 30606698 DOI: 10.1016/j.dld.2018.12.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 11/29/2018] [Accepted: 12/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fibrosis progression is the common consequence of most chronic liver diseases. AIMS To evaluate the performance of Collagen Proportionate Area (CPA) and ELF using Ishak's score in patients with chronic liver diseases. METHODS Retrospective analysis of medical data from patients on whom a liver biopsy was performed as part of the diagnostic assessment. CPA was calculated by using digital image analysis and then compared with Ishak and ELF scores. RESULTS 143 patients (84 men (59%); mean age 48.8 ± 12.8 years) were evaluated. Patients were mainly affected by viral hepatitis (92 HCV and 8 HBV). CPA and ELF values increased with worsening Ishak stage (P < 0.001) and their median values were significantly different among Ishak stages (P < 0.001). There was a significant correlation between CPA and ELF (r = 0.5). In AUROC analysis, CPA and ELF had similar diagnostic accuracy in identifying cirrhosis, but CPA had higher diagnostic accuracy than ELF in identifying significant or absent fibrosis. High ELF scores were observed in non-cirrhotic patients who suffered non-liver related deaths. CONCLUSIONS This study demonstrated that CPA and ELF values successfully identified patients with advanced fibrosis or cirrhosis, thus confirming the role of ELF as a clinical method for non-invasive assessment of fibrosis stage in chronic hepatitis.
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Affiliation(s)
- Cristina Stasi
- Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy.
| | - Emmanuel A Tsochatzis
- Regenerative Medicine and Fibrosis Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus London, United Kingdom; Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
| | - Andrew Hall
- Department of Cellular Pathology, UCL Medical School, Royal Free Campus, United Kingdom
| | - William Rosenberg
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
| | - Stefano Milani
- Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Careggi University Hospital, Florence, Italy
| | - Amar Paul Dhillon
- Department of Cellular Pathology, UCL Medical School, Royal Free Campus, United Kingdom
| | - Massimo Pinzani
- Regenerative Medicine and Fibrosis Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus London, United Kingdom; Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
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9
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Culafic M, Vezmar Kovacevic S, Dopsaj V, Stulic M, Vlaisavljevic Z, Miljkovic B, Culafic D. A Simple Index for Nonalcoholic Steatohepatitis-HUFA-Based on Routinely Performed Blood Tests. ACTA ACUST UNITED AC 2019; 55:medicina55060243. [PMID: 31163711 PMCID: PMC6631799 DOI: 10.3390/medicina55060243] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 05/28/2019] [Accepted: 05/30/2019] [Indexed: 02/06/2023]
Abstract
Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease—whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I—simple steatosis (SS) and group II—biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included—82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.
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Affiliation(s)
- Milica Culafic
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
- Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
| | - Sandra Vezmar Kovacevic
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
| | - Violeta Dopsaj
- Department of Medical Biochemistry, Clinical Centre of Serbia, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
| | - Milos Stulic
- Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
| | - Zeljko Vlaisavljevic
- Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
| | - Branislava Miljkovic
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
| | - Djordje Culafic
- Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
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10
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Kumar R, Teo EK, How CH, Wong TY, Ang TL. A practical clinical approach to liver fibrosis. Singapore Med J 2019; 59:628-633. [PMID: 30631885 DOI: 10.11622/smedj.2018145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
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Affiliation(s)
- Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Choon How How
- Care and Health Integration, Changi General Hospital, Singapore.,Family Medicine Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore
| | - Teck Yee Wong
- Department of Continuing and Community Care, Tan Tock Seng Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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11
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Knop V, Hofmann WP, Buggisch P, Klinker H, Mauss S, Günther R, Hinrichsen H, Hüppe D, Pfeiffer-Vornkahl H, Simon KG, Berg T, Manns MP, Friedrich-Rust M. Estimation of liver fibrosis by noncommercial serum markers in comparison with transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral treatment. J Viral Hepat 2019; 26:224-230. [PMID: 30315694 DOI: 10.1111/jvh.13021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 09/13/2018] [Accepted: 09/14/2018] [Indexed: 12/13/2022]
Abstract
Treatment decisions are based on extent of fibrosis in patients with chronic hepatitis C (HCV) infection. Noninvasive diagnostic tools may help to avoid liver biopsy. We investigated the diagnostic accuracy of noncommercial serum scores in comparison with transient elastography (TE). Data analysis was undertaken based on 2458 patients enrolled in the German Hepatitis C Registry, in a prospective, observational study. Aspartate aminotransferase-to-platelet ratio index (APRI), FORNS index and FIB-4 score were calculated and the diagnostic accuracy was compared to TE. As estimated by TE, 955 (38.9%) patients had absence of significant fibrosis (SF), 736 (29.9%) patients had SF, and 767 (31.2%) patients were shown to have cirrhosis. Patients with absence of SF had a sustained virological response (SVR) rate of 97.9%, whereas SVR was attained in 96.2% and 92.2% in those with SF and cirrhosis, respectively (P < 0.0001). The area under the receiver operator characteristic curve (AUROC), sensitivity and specificity in discriminating of SF were 0.789, 0.596 and 0.939 by APRI; 0.838, 0.852 and 0.748 by FORNS index; and 0.828, 0.658 and 0.946 by FIB-4 score. AUROCs for the prediction of cirrhosis, sensitivity and specificity were 0.881, 0.851 and 0.854 by APRI; 0.846, 0.948 and 0.628 by FORNS index; and 0.907, 0.907 and 0.848 by FIB-4 score. In conclusion, in the present multicentre real-world cohort, SF and cirrhosis were predicted with high accuracy with noncommercial serum markers using TE as reference. Further prospective long-term follow-up is necessary to compare biomarkers with TE concerning liver-related outcome and overall mortality.
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Affiliation(s)
- Viola Knop
- Department of Internal Medicine 1, Goethe University Hospital, Frankfurt, Germany
| | | | - Peter Buggisch
- ifi-institute for interdisciplinary medicine, Hamburg, Germany
| | | | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | | | | | | | | | | | - Thomas Berg
- University Hospital Leipzig, Leipzig, Germany
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- Leberstiftungs-GmbH Deutschland, Hannover, Germany
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12
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Different kinetics of liver stiffness using shear wave elastography in patients with chronic hepatitis C infection treated with interferon-free regimens. Eur J Gastroenterol Hepatol 2019; 31:67-74. [PMID: 30239347 DOI: 10.1097/meg.0000000000001259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) lead to a high rate of sustained virologic response (SVR) in chronic hepatitis C infection. The aim was to evaluate liver stiffness kinetics, using acoustic radiation force impulse (ARFI) imaging elastography, during and after DAAs in patients who had reached SVR. PATIENTS AND METHODS A total of 275 consecutive chronic hepatitis C virus-infected patients were included in this longitudinal prospective single-centre study. All patients received DAAs for 8 to 24 weeks, and liver stiffness measurements (LSMs) by ARFI at baseline, at week 4, week 12, week 24, and 24 weeks (SVR24) and 48 weeks (FU48) after the end of treatment were recorded. Transient elastography was performed at baseline and at SVR24. RESULTS A decrease in LSM was detected at SVR24 by ARFI and transient elastography (P<0.001 and <0.001, respectively). A continuous gradual decrease in ARFI was observed in patients with cirrhosis versus a nonsignificant change in patients without cirrhosis until FU48 (P<0.001 vs. 0.877, respectively). At SVR24, higher baseline ARFI values (P=0.038) were associated with a decrease in LSM in patients with cirrhosis versus normal international normalization ratio (P=0.003), lower bilirubin (P=0.003), and higher albumin (P=0.007) in patients without cirrhosis. The incidence of liver stiffness decrease from baseline was higher in patients with cirrhosis than in those without cirrhosis (P<0.001), whereas the incidence of liver stiffness progression was more pronounced in advanced than in compensated cirrhosis (P<0.001). CONCLUSION After DAAs in patients with SVR, liver stiffness improves in patients with cirrhosis, whereas non-cirrhotic patients show no true change in liver stiffness. Liver stiffness worsens in patients with advanced liver disease.
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13
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Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Goodman ZD, Chalasani NP, Kowdley KV, George J, Lindor K. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 2018. [PMID: 29222917 DOI: 10.1002/hep.29721 10.1002/hep.29721] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).
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Affiliation(s)
- Zobair M Younossi
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Rohit Loomba
- NAFLD Research Center, University of California at San Diego, La Jolla, CA
| | - Quentin M Anstee
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Mary E Rinella
- University of Torino, Department of Medical Sciences, Torino, Italy
| | | | - Giulio Marchesini
- Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO
| | | | | | - Francesco Negro
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
| | - Stephen H Caldwell
- Institute of Cardiometabolim and Nutrition (ICAN) and Hospital Pitié Salpêtrière, de L'Hopital, Paris, France
| | - Vlad Ratziu
- Massachusetts General Hospital, Cambridge, MA
| | - Kathleen E Corey
- Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, New York, NY
| | - Scott L Friedman
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | - Stephen A Harrison
- Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA
| | - Arun J Sanyal
- Department of Pediatrics, Columbia College of Physicians and Surgeons, New York, NY
| | - Joel E Lavine
- Hôpital Claude Huriez Rue Michel Polonowski, Lille, France
| | | | - Michael R Charlton
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Zachary D Goodman
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Naga P Chalasani
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | | | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, Australia
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14
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Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Goodman ZD, Chalasani NP, Kowdley KV, George J, Lindor K. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 2018; 68:349-360. [PMID: 29222917 PMCID: PMC6511364 DOI: 10.1002/hep.29721] [Citation(s) in RCA: 297] [Impact Index Per Article: 42.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 11/16/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).
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Affiliation(s)
- Zobair M. Younossi
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Rohit Loomba
- NAFLD Research Center, University of California at San Diego, La Jolla, CA
| | | | - Mary E. Rinella
- University of Torino, Department of Medical Sciences, Torino, Italy
| | | | - Giulio Marchesini
- Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO
| | | | | | - Francesco Negro
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
| | - Stephen H. Caldwell
- Institute of Cardiometabolim and Nutrition (ICAN) and Hospital Pitié Salpêtrière, de L’Hopital, Paris, France
| | - Vlad Ratziu
- Massachusetts General Hospital, Cambridge, MA
| | - Kathleen E. Corey
- Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, New York, NY
| | - Scott L. Friedman
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | - Stephen A. Harrison
- Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA
| | - Arun J. Sanyal
- Department of Pediatrics, Columbia College of Physicians and Surgeons, New York, NY
| | - Joel E. Lavine
- Hôpital Claude Huriez Rue Michel Polonowski, Lille, France
| | | | - Michael R. Charlton
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Zachary D. Goodman
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Naga P. Chalasani
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | | | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, Australia
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15
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Lee J, Kim MY, Kang SH, Kim J, Uh Y, Yoon KJ, Kim HS. The gamma-glutamyl transferase to platelet ratio and the FIB-4 score are noninvasive markers to determine the severity of liver fibrosis in chronic hepatitis B infection. Br J Biomed Sci 2018; 75:128-132. [DOI: 10.1080/09674845.2018.1459147] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- J Lee
- Department of Laboratory Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - MY Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - SH Kang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - J Kim
- Department of Laboratory Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - Y Uh
- Department of Laboratory Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - KJ Yoon
- Department of Laboratory Medicine, Yonsei University Wonju College of Medicine , Wonju, Korea
| | - HS Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine , Seoul, Korea
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16
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Qi X, An M, Wu T, Jiang D, Peng M, Wang W, Wang J, Zhang C, CHESS Study Group OBOT. Transient Elastography for Significant Liver Fibrosis and Cirrhosis in Chronic Hepatitis B: A Meta-Analysis. Can J Gastroenterol Hepatol 2018; 2018:3406789. [PMID: 29977884 PMCID: PMC5994263 DOI: 10.1155/2018/3406789] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 02/25/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The hepatitis B virus infection is a global health issue and the stage of liver fibrosis affects the prognosis in patients with chronic hepatitis B (CHB). We performed the meta-analysis describing diagnostic accuracy of transient elastography (TE) for predicting CHB-related fibrosis. METHODS We performed an adequate literature search to identify studies that assessed the diagnostic accuracy of TE in CHB patients using biopsy as reference standard. Hierarchical summary receiver-operating curves model and the bivariate mixed-effects binary regression model were applied to generate summary receiver-operating characteristic curves and pooled estimates of sensitivity and specificity. RESULTS The area under the summary receiver-operating curve for significant fibrosis and cirrhosis was 0.86 (95% confidence interval (CI): 0.83-0.89) and 0.92 (95% CI: 0.90-0.94), respectively. The sensitivity, specificity, and diagnostic odds ratio of TE for significant fibrosis were 0.78 (95% CI: 0.73-0.81, p < 0.01; I2 = 85.59%), 0.81 (95% CI: 0.77-0.84, p < 0.01; I2 = 88.20%), and 14.44 (95% CI: 10.80-19.31, p < 0.01; I2 = 100%) and for cirrhosis were 0.84 (95% CI: 0.80-0.88, p < 0.01; I2 = 76.67%), 0.87 (95% CI: 0.84-0.90, p < 0.01; I2 = 90.89%), and 36.63 (95% CI: 25.38-52.87, p < 0.01; I2 = 100%), respectively. The optimal cut-off values of TE were 7.25 kPa for diagnosing significant fibrosis and 12.4 kPa for diagnosing cirrhosis, respectively. CONCLUSION TE is of great value in the detection of patients with CHB-related cirrhosis but has a suboptimal accuracy in the detection of significant fibrosis.
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Affiliation(s)
- Xiaolong Qi
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
- CHESS, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Min An
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Tongwei Wu
- CHESS, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Deke Jiang
- CHESS, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Mengyun Peng
- Department of Hepatobiliary Disease, The Affiliated (T.C.M) Hospital of Southwest Medical University, Luzhou, China
| | - Weidong Wang
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Foshan, China
| | - Jing Wang
- Department of Hepatobiliary Disease, The Affiliated (T.C.M) Hospital of Southwest Medical University, Luzhou, China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - on behalf of the CHESS Study Group
- CHESS, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
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17
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Omran D, Zayed RA, Nabeel MM, Mobarak L, Zakaria Z, Farid A, Hassany M, Saif S, Mostafa M, Saad OK, Yosry A. Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis C Egyptian Patients. Viral Immunol 2018; 31:315-320. [PMID: 29630460 DOI: 10.1089/vim.2017.0134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.
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Affiliation(s)
- Dalia Omran
- 1 Department of Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Rania A Zayed
- 2 Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Mohammed M Nabeel
- 1 Department of Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Lamiaa Mobarak
- 3 Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute , Cairo, Egypt
| | - Zeinab Zakaria
- 1 Department of Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
| | - Azza Farid
- 3 Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute , Cairo, Egypt
| | - Mohamed Hassany
- 3 Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute , Cairo, Egypt
| | - Sameh Saif
- 3 Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute , Cairo, Egypt
| | - Muhammad Mostafa
- 4 Endemic Medicine Department, Ahmed Maher Hospital , Cairo, Egypt
| | | | - Ayman Yosry
- 1 Department of Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt
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18
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SHFI: A Novel Noninvasive Predictive Model for Significant Fibrosis in Patients With Chronic Hepatitis B. HEPATITIS MONTHLY 2018. [DOI: 10.5812/hepatmon.63310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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19
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Rogler G. Challenges of Translation of Anti-Fibrotic Therapies into Clinical Practice in IBD. FIBROSTENOTIC INFLAMMATORY BOWEL DISEASE 2018:295-305. [DOI: 10.1007/978-3-319-90578-5_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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20
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21
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Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Goodman ZD, Chalasani NP, Kowdley KV, George J, Lindor K. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. HEPATOLOGY (BALTIMORE, MD.) 2017. [PMID: 29222917 DOI: 10.1002/hep.29721+10.1002/hep.29721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).
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Affiliation(s)
- Zobair M Younossi
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Rohit Loomba
- NAFLD Research Center, University of California at San Diego, La Jolla, CA
| | - Quentin M Anstee
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Mary E Rinella
- University of Torino, Department of Medical Sciences, Torino, Italy
| | | | - Giulio Marchesini
- Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO
| | | | | | - Francesco Negro
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA
| | - Stephen H Caldwell
- Institute of Cardiometabolim and Nutrition (ICAN) and Hospital Pitié Salpêtrière, de L'Hopital, Paris, France
| | - Vlad Ratziu
- Massachusetts General Hospital, Cambridge, MA
| | - Kathleen E Corey
- Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, New York, NY
| | - Scott L Friedman
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | - Stephen A Harrison
- Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA
| | - Arun J Sanyal
- Department of Pediatrics, Columbia College of Physicians and Surgeons, New York, NY
| | - Joel E Lavine
- Hôpital Claude Huriez Rue Michel Polonowski, Lille, France
| | | | - Michael R Charlton
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Zachary D Goodman
- Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA
| | - Naga P Chalasani
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | | | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, Australia
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22
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Mancini M, Salomone Megna A, Ragucci M, De Luca M, Marino Marsilia G, Nardone G, Coccoli P, Prinster A, Mannelli L, Vergara E, Monti S, Liuzzi R, Incoronato M. Reproducibility of shear wave elastography (SWE) in patients with chronic liver disease. PLoS One 2017; 12:e0185391. [PMID: 29023554 PMCID: PMC5638246 DOI: 10.1371/journal.pone.0185391] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 09/12/2017] [Indexed: 02/06/2023] Open
Abstract
The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14-16.7 kPa and were 4.49 kPa and 2.92-7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87-0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.
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Affiliation(s)
- Marcello Mancini
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | | | - Monica Ragucci
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | | | | | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University, Naples, Italy
| | - Pietro Coccoli
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University, Naples, Italy
| | - Anna Prinster
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | - Lorenzo Mannelli
- Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, United States of America
| | - Emilia Vergara
- Istituto di Ricovero e Cura a Carattere Scientifico SDN (IRCCS SDN), Naples, Italy
- Dipartimento Assistenziale Integrato di Diagnostica morfologica e funzionale, Radioterapia, Medicina Legale, A.O.U. Federico II, Naples, Italy
| | - Serena Monti
- Istituto di Ricovero e Cura a Carattere Scientifico SDN (IRCCS SDN), Naples, Italy
| | - Raffaele Liuzzi
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
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23
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Wang PW, Hung YC, Wu TH, Chen MH, Yeh CT, Pan TL. Proteome-based identification of apolipoprotein A-IV as an early diagnostic biomarker in liver fibrosis. Oncotarget 2017; 8:88951-88964. [PMID: 29179490 PMCID: PMC5687660 DOI: 10.18632/oncotarget.21627] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 08/28/2017] [Indexed: 12/31/2022] Open
Abstract
Hepatic fibrosis may ultimately result in organ failure and death, a reality compounded by the fact that most drugs for liver fibrosis appear to be effective only if given as a prophylactic or early treatment. In a dimethylnitrosamine-induced liver fibrotic model, aspartate aminotransferase/alanine aminotransferase levels could not precisely distinguish the differences between the initial stage of liver fibrosis and normal control, whereas histological examination indicated that dimethylnitrosamine treatment for two weeks has resulted in hepatic fibrogenesis. Comprehensive proteomics identified 12 proteins mainly associated with the interleukin 6-stimulated inflammatory pathway. Coordinately, cytokine profiles showed that dimethylnitrosamine administration would stimulate various signaling pathways leading to liver fibrosis. Of note, apolipoprotein A4 in serum samples obtained from patients in the early stage of liver fibrosis were significantly increased compared to the healthy controls (p<0.001) while the area under curve was 0.966. Moreover, increased apolipoprotein A4 significantly enhanced transforming growth factor beta 1-induced alpha smooth muscle actin expression. In this regard, overexpression of apolipoprotein A4 in early stage of liver fibrosis might magnify and imply the progression of hepatic fibrosis. These findings suggest that apolipoprotein A4 upregulation may correlate with hepatic fibrosis staging and that apolipoprotein A4 together with current biomarker can increase the sensitivity and specificity for the early detection of liver fibrosis in a high-throughput manner.
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Affiliation(s)
- Pei-Wen Wang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Yu-Ching Hung
- Department of Chinese Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tung-Ho Wu
- Division of Cardiovascular Surgery, Veterans General Hospital, Kaohsiung, Taiwan
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tai-Long Pan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan
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24
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Lei B, Liu Y, Dong C, Chen X, Zhang X, Diao X, Yang G, Liu J, Yao S, Li H, Yuan J, Li S, Le X, Lin Y, Zeng W. Assessment of liver fibrosis in chronic hepatitis B via multimodal data. Neurocomputing 2017. [DOI: 10.1016/j.neucom.2016.09.128] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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25
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Shiha G, Seif S, Eldesoky A, Elbasiony M, Soliman R, Metwally A, Zalata K, Mikhail N. A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C. Hepatol Int 2017; 11:286-291. [DOI: doi 10.1007/s12072-017-9796-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/31/2023]
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26
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Shiha G, Seif S, Eldesoky A, Elbasiony M, Soliman R, Metwally A, Zalata K, Mikhail N. A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C. Hepatol Int 2017; 11:286-291. [PMID: 28425016 DOI: 10.1007/s12072-017-9796-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 03/30/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION A simple non-invasive score (Fibrofast, FIB-5) was developed using five routine laboratory tests (ALT, AST, alkaline phosphatase, albumin and platelets count) for the detection of significant hepatic fibrosis in patients with chronic hepatitis C. The FIB-4 index is a non-invasive test for the assessment of liver fibrosis, and a score of ≤1.45 enables the correct identification of patients who have non-significant (F0-1) from significant fibrosis (F2-4), and could avoid liver biopsy. The aim of this study was to compare the performance characteristics of FIB-5 and FIB-4 to differentiate between non-significant and significant fibrosis. METHOD A cross-sectional study included 604 chronic HCV patients. All liver biopsies were scored using the METAVIR system. Both FIB-5 and FIB-4 scores were measured and the performance characteristics were calculated using the ROC curve. RESULTS The performance characteristics of FIB-5 at ≥7.5 and FIB-4 at ≤1.45 for the differentiation between non-significant fibrosis and significant fibrosis were: specificity 94.4%, PPV 85.7%, and specificity 54.9%, PPV 55.7% respectively. CONCLUSION FIB-5 score at the new cutoff is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis.
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Affiliation(s)
- G Shiha
- Gastrohepatology Unit, Internal Medicine Department, Faculty of Medicine, Specialized Medical Hospital, Mansoura University, Mansoura, Egypt.
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.
| | - S Seif
- Gastrohepatology Unit, Internal Medicine Department, Faculty of Medicine, Specialized Medical Hospital, Mansoura University, Mansoura, Egypt
| | - A Eldesoky
- Gastrohepatology Unit, Internal Medicine Department, Faculty of Medicine, Specialized Medical Hospital, Mansoura University, Mansoura, Egypt
| | - M Elbasiony
- Gastrohepatology Unit, Internal Medicine Department, Faculty of Medicine, Specialized Medical Hospital, Mansoura University, Mansoura, Egypt
| | - R Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
| | - A Metwally
- Community Medicine Department, National Research Center, Cairo, Egypt
| | - K Zalata
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - N Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
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27
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Hussein J, El-Banna M, Mahmoud KF, Morsy S, Abdel Latif Y, Medhat D, Refaat E, Farrag AR, El-Daly SM. The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis. Biomed Pharmacother 2017; 90:880-887. [PMID: 28437891 DOI: 10.1016/j.biopha.2017.04.020] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Revised: 03/29/2017] [Accepted: 04/10/2017] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. METHODS To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. RESULTS Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. CONCLUSION Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect carvacrol structure and increase its efficiency and stability. Moreover, nano-encapsulation of carvacrol is more efficient than nano-emulsion.
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Affiliation(s)
- Jihan Hussein
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | - Mona El-Banna
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | - Khaled F Mahmoud
- Technology Dept., National Research Centre (NRC), Dokki, Giza, Egypt
| | - Safaa Morsy
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | - Yasmin Abdel Latif
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | - Dalia Medhat
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | - Eman Refaat
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1)
| | | | - Sherien M El-Daly
- Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, Giza, Egypt(1).
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28
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Chen X, Wen H, Zhang X, Dong C, Lin H, Guo Y, Shan L, Yao S, Yang M, Le X, Liu Y. Development of a Simple Noninvasive Model to Predict Significant Fibrosis in Patients with Chronic Hepatitis B: Combination of Ultrasound Elastography, Serum Biomarkers, and Individual Characteristics. Clin Transl Gastroenterol 2017; 8:e84. [PMID: 28383564 PMCID: PMC5415893 DOI: 10.1038/ctg.2017.11] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 02/24/2017] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES The accurate assessment of liver fibrosis is clinically important in patients with chronic hepatitis B (CHB). Blood tests and elastography are now widely used for the noninvasive diagnosis of liver fibrosis in CHB patients. The aim of this study was to develop a new and more accurate predictive model, which combines elastography data, serum biomarkers, and individual characteristics, to discriminate between CHB patients with and without significant liver fibrosis. METHODS Two noninvasive methods, specifically, an ultrasound elastography technique termed acoustic radiation force impulse imaging (ARFI) and a blood test, were used to assess a cohort of 345 patients (estimation group, 218 patients; validation group, 127 patients) with CHB. Multivariate logistic regression analysis revealed that ARFI, the aspartate aminotransferase (AST) to platelet ratio, and age were significantly associated with fibrosis. Based on these results, we constructed and validated a model for the diagnosis of significant hepatic fibrosis. RESULTS The area under the receiver operating characteristic (ROC) curve was 0.921 for the estimation group and 0.929 for the validation group, significantly higher than those for ARFI (0.887, 0.893) and for the AST-to-platelet ratio index (APRI; 0.811, 0.859). Using an optimal cutoff of 3.05 in the validation group, all the indices of the proposed model, including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio, were better than those for ARFI or APRI. CONCLUSIONS We developed a simple noninvasive model that used ultrasound elastography, routine serum biomarkers, and individual characteristics to accurately differentiate significant fibrosis in patients with CHB. Compared with elastography or the biomarker index alone, this model was significantly more accurate and robust.
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Affiliation(s)
- Xin Chen
- School of Biomedical Engineering, Shenzhen University, Shenzhen, China
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Huiying Wen
- School of Biomedical Engineering, Shenzhen University, Shenzhen, China
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Xinyu Zhang
- School of Biomedical Engineering, Shenzhen University, Shenzhen, China
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Changfeng Dong
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
| | - Haoming Lin
- School of Biomedical Engineering, Shenzhen University, Shenzhen, China
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Yanrong Guo
- School of Biomedical Engineering, Shenzhen University, Shenzhen, China
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Lingbo Shan
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
| | - Simin Yao
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
| | - Min Yang
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
| | - Xiaohua Le
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
| | - Yingxia Liu
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
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29
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Zachou K, Gabeta S, Shums Z, Gatselis NK, Koukoulis GK, Norman GL, Dalekos GN. COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis. Eur J Intern Med 2017; 38:83-88. [PMID: 28100410 DOI: 10.1016/j.ejim.2017.01.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 12/22/2016] [Accepted: 01/09/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Recently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, we assessed whether serum COMP levels can be used as a non-invasive fibrosis marker in patients with chronic viral hepatitis (CVH) and compared this marker with standard methods for disease stage assessment [histology, transient elastography (TE), APRI, FIB-4]. METHODS Sera from 116 CVH patients, 66 HBV [24 female; median age 53(22-76)] and 50 HCV [21 female; median age 48.5(25-69)] were investigated by COMP-ELISA. APRI and FIB-4 score was calculated in all along with TE. Liver biopsy was performed in 61. Patients were divided into two groups (F1/F2 and F3/F4) according to Metavir score. RESULTS 55/116 (47%) CVH patients were classified in F3/F4-group according to TE [14.3(9.3-75)kPa]. APRI score was >1.5 in 21/116 and FIB-4>3.25 in 20/116. Liver histology revealed 24/61 (39%) patients with significant fibrosis (stage 3-4), while 12/61 (19.7%) had cirrhosis. COMP levels correlated with TE measurements (r=0.5; p<0.001) and APRI score (r=0.23; p<0.02). The diagnostic accuracy of COMP in detecting cirrhosis was as good as TE, APRI and FIB-4 index (AUC 0.884) with sensitivity and specificity of 83.3% and 83.7% (cut-off 11.5U/L). CONCLUSIONS COMP serum levels performed as well as TE, APRI and FIB4 score in detecting cirrhosis in CVH patients, suggesting COMP as a sensitive non-invasive, easy to perform biomarker of liver fibrosis. Further studies are needed in order to validate our findings in CVH patients.
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Affiliation(s)
- Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, Thessaly University, Larissa, Greece
| | - Stella Gabeta
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, Thessaly University, Larissa, Greece
| | - Zakera Shums
- Inova Diagnostics, Inc., San Diego, CA, United States
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, Thessaly University, Larissa, Greece
| | - George K Koukoulis
- Department of Pathology, School of Medicine, University of Thessaly, Larissa, Greece
| | - Gary L Norman
- Inova Diagnostics, Inc., San Diego, CA, United States
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, Thessaly University, Larissa, Greece.
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30
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Pieri L, Paoli C, Arena U, Marra F, Mori F, Zucchini M, Colagrande S, Castellani A, Masciulli A, Rosti V, De Stefano V, Betti S, Finazzi G, Ferrari ML, Rumi E, Ruggeri M, Nichele I, Guglielmelli P, Fjerza R, Mannarelli C, Fanelli T, Merli L, Corbizi Fattori G, Massa M, Cimino G, Rambaldi A, Barosi G, Cazzola M, Barbui T, Vannucchi AM. Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms. Am J Hematol 2017; 92:187-195. [PMID: 27880982 DOI: 10.1002/ajh.24614] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 11/19/2016] [Accepted: 11/21/2016] [Indexed: 12/19/2022]
Abstract
Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.
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Affiliation(s)
- Lisa Pieri
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Chiara Paoli
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Umberto Arena
- Internal Medicine and Hepatology; Azienda Ospedaliera-Universitaria Careggi; Florence Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Fabio Mori
- Department of Cardiology; Azienda Ospedaliera-Universitaria Careggi; Florence Italy
| | - Mery Zucchini
- Department of Cardiology; Azienda Ospedaliera-Universitaria Careggi; Florence Italy
| | - Stefano Colagrande
- Department of Experimental and Clinical Biomedical Sciences; University of Florence - Azienda Ospedaliera-Universitaria Careggi; Florence Italy
| | - Alessandro Castellani
- Department of Experimental and Clinical Biomedical Sciences; University of Florence - Azienda Ospedaliera-Universitaria Careggi; Florence Italy
| | - Arianna Masciulli
- Department of Hematology; Hospital Papa Giovanni XXIII; Bergamo Italy
| | - Vittorio Rosti
- IRCCS Policlinico San Matteo Foundation; Center for the Study of Myelofibrosis, Biotechnology Research Area; Pavia Italy
| | | | - Silvia Betti
- Institute of Hematology, Catholic University; Rome Italy
| | - Guido Finazzi
- Department of Hematology; Hospital Papa Giovanni XXIII; Bergamo Italy
| | | | - Elisa Rumi
- Department of Hematology Oncology; IRCCS Policlinico San Matteo Foundation; Pavia Italy
| | - Marco Ruggeri
- Department of Hematology; San Bortolo Hospital; Vicenza Italy
| | - Ilaria Nichele
- Department of Hematology; San Bortolo Hospital; Vicenza Italy
| | - Paola Guglielmelli
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Rajmonda Fjerza
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Carmela Mannarelli
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Tiziana Fanelli
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
- University of Siena; Siena Italy
| | - Lucia Merli
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
| | - Giuditta Corbizi Fattori
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
- University of Siena; Siena Italy
| | - Margherita Massa
- IRCCS Policlinico San Matteo Foundation; Biotechnology Research Area; Pavia Italy
| | - Giuseppe Cimino
- Department of Cellular Biotechnology and Hematology; University “La Sapienza”; Rome Italy
| | | | - Giovanni Barosi
- IRCCS Policlinico San Matteo Foundation; Center for the Study of Myelofibrosis, Biotechnology Research Area; Pavia Italy
| | - Mario Cazzola
- Department of Hematology Oncology; IRCCS Policlinico San Matteo Foundation; Pavia Italy
| | - Tiziano Barbui
- Hospital Papa Giovanni XXIII and Research Foundation; Bergamo Italy
| | - Alessandro M. Vannucchi
- CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi; Florence Italy
- DenoThe Excellence Center; Florence Italy
- Department of Experimental and Clinical Medicine; University of Florence; Florence Italy
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Shiha G, Ibrahim A, Helmy A, Sarin SK, Omata M, Kumar A, Bernstien D, Maruyama H, Saraswat V, Chawla Y, Hamid S, Abbas Z, Bedossa P, Sakhuja P, Elmahatab M, Lim SG, Lesmana L, Sollano J, Jia JD, Abbas B, Omar A, Sharma B, Payawal D, Abdallah A, Serwah A, Hamed A, Elsayed A, AbdelMaqsod A, Hassanein T, Ihab A, GHaziuan H, Zein N, Kumar M. Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update. Hepatol Int 2017; 11:1-30. [PMID: 27714681 DOI: 10.1007/s12072-016-9760-3] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/13/2016] [Indexed: 12/14/2022]
Abstract
Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.
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Affiliation(s)
- Gamal Shiha
- Internal Medicine Department, El-Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
- Egyptian Liver Research Institute And Hospital (ELRIAH), Mansoura, Egypt.
| | - Alaa Ibrahim
- Department of Internal medicine, University of Benha, Benha, Egypt
| | - Ahmed Helmy
- Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, University of Tokyo, Tokyo, Japan
| | - Ashish Kumar
- Department of Gastroenterology & Hepatology, Ganga Ram Institute for Postgraduate Medical Education & Research of Sir Ganga Ram Hospital, New Delhi, India
| | - David Bernstien
- Division of Hepatology, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, New York, USA
| | - Hitushi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Chiba Prefecture, Japan
| | - Vivek Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Yogesh Chawla
- Post Graduate Institute of Medial Education & Research, Chandigarh, India
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University & Hospital, Stadium Road, Karachi, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Pierre Bedossa
- Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France
| | - Puja Sakhuja
- Govind Ballabh Pant Hospital, Maulana Azad Medical College, New Delhi, India
| | - Mamun Elmahatab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Seng Gee Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Jose Sollano
- University of Santo Tomas, España Blvd, Manila, Philippines
| | - Ji-Dong Jia
- Liver Research Centre at the Beijing Friendship Hospital, Capital University in Beijing, Beijing, China
| | - Bahaa Abbas
- Department of Internal Medicine, Military Medical Academy, Cairo, Egypt
| | - Ashraf Omar
- Tropical Medicine Department, Cairo Medical School, Cairo, Egypt
| | - Barjesh Sharma
- Department of Gastroenterology, GB Pant Hospital, New Delhi, India
| | - Diana Payawal
- Section of Gastroenterology, Cardinal Santos Medical Center, San Juan City, Metro Manila, Philippines
| | - Ahmed Abdallah
- Pediatric Hospital, Mansoura University, Mansoura, Egypt
| | | | - Abdelkhalek Hamed
- Hepatology and Diabetes Unit, Military Medical Academy, Cairo, Egypt
| | - Aly Elsayed
- Hepatology & GIT Department, AHF Center Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Amany AbdelMaqsod
- Internal Medicine Department, Faculty of Medicine Cairo University, Liver Transplant Unit Manial Hospital and Liver ICU French Hospital, Cairo University, Cairo, Egypt
| | | | - Ahmed Ihab
- Molecular Pathology Unit & Research Group, German University in Cairo, Cairo, Egypt
| | - Hamsik GHaziuan
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Nizar Zein
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, USA
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
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Model-dependent and model-independent approaches for evaluating hepatic fibrosis in rat liver using shearwave dispersion ultrasound vibrometry. Med Eng Phys 2017; 39:66-72. [DOI: 10.1016/j.medengphy.2016.10.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 10/18/2016] [Accepted: 10/23/2016] [Indexed: 12/15/2022]
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Khattab M, Sakr MA, Fattah MA, Mousa Y, Soliman E, Breedy A, Fathi M, Gaber S, Altaweil A, Osman A, Hassouna A, Motawea I. Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients. World J Hepatol 2016; 8:1392-1401. [PMID: 27917265 PMCID: PMC5114475 DOI: 10.4254/wjh.v8.i32.1392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 09/09/2016] [Accepted: 10/05/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). RESULTS Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. CONCLUSION Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.
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Affiliation(s)
- Mahmoud Khattab
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Mohamed Amin Sakr
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Mohamed Abdel Fattah
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Youssef Mousa
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Elwy Soliman
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Ashraf Breedy
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Mona Fathi
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Salwa Gaber
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Ahmed Altaweil
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Ashraf Osman
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Ahmed Hassouna
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
| | - Ibrahim Motawea
- Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
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Anastasiou OE, Büchter M, Baba HA, Korth J, Canbay A, Gerken G, Kahraman A. Performance and Utility of Transient Elastography and Non-Invasive Markers of Liver Fiibrosis in Patients with Autoimmune Hepatitis: A Single Centre Experience. HEPATITIS MONTHLY 2016; 16:e40737. [PMID: 28070199 PMCID: PMC5203728 DOI: 10.5812/hepatmon.40737] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 09/05/2016] [Accepted: 09/30/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Autoimmune hepatitis (AIH) is a relatively rare cause of hepatic dysfunction, which can lead to acute liver failure (ALV) and cirrhosis if not treated. The performance of transient elastography (TE) compared to liver biopsy has been evaluated in many liver diseases. The aim of the present study was to evaluate the performance of TE and other non-invasive markers for liver fiibrosis in patients with biopsy-proven AIH. METHODS Fifty-three patients who were treated at the department of gastroenterology and hepatology of the University Clinic Essen from 2008 to 2013 included in this retrospective study. Laboratory parameters were used to calculate non-invasive markers for liver fiibrosis. Every patient underwent a liver biopsy within 6 months of the liver stiffness measurement. RESULTS Transient elastography score, non-alcoholic fatty liver disease (NAFLD) fiibrosis score, Fiibrosis 4 score (FIB-4), and FibroQ were associated with the stage of fiibrosis, whereas other non-invasive markers of liver fiibrosis (aspartate transaminase (AST) to alanine transaminase (ALT) ratio, and AST to platelet ratio index (APRI)) did not demonstrate a significant correlation. NAFLD fiibrosis score and FibroQ performed slightly better in ROC curve analysis than TE in differentiating mild to moderate from severe fiibrosis (AUC 0.895 and 0.773 vs. 0.739; P < 0.001 and = 0.01, respectively), while TE performed slightly better, but still not adequate, in differentiating mild from all other stages of fiibrosis compared to NAFLD fiibrosis score and FibroQ (AUC 0.779 vs. 0.752 and 0.684; P = 0.051 and 0.009). CONCLUSIONS Transient elastography, NAFLD fiibrosis score, and FibroQ are valuable non-invasive markers for the evaluation of liver fiibrosis in autoimmune hepatitis but they cannot replace liver biopsy, especially in differentiating mild from more advanced stages of fiibrosis.
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Affiliation(s)
- Olympia E Anastasiou
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany
- Corresponding Author: Olympia E. Anastasiou, Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany. Tel: +49-20172383797, Fax: +49-2017235655, E-mail:
| | - Matthias Büchter
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany
| | - Hideo A Baba
- Department of Pathology, University Hospital, University Duisburg Essen, Germany
| | - Johannes Korth
- Department of Nephrology, University Hospital, University Duisburg Essen, Germany
| | - Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany
| | - Alisan Kahraman
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg Essen, Germany
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Liberal R, Grant CR. Cirrhosis and autoimmune liver disease: Current understanding. World J Hepatol 2016; 8:1157-1168. [PMID: 27729952 PMCID: PMC5055585 DOI: 10.4254/wjh.v8.i28.1157] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 05/14/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.
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Bai Y, Chen X, Dong C, Liu Y, Zhang Z. A comparison of multimodal biomarkers for chronic hepatitis B assessment using recursive feature elimination. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2016; 2016:2448-2451. [PMID: 28268819 DOI: 10.1109/embc.2016.7591225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
An effective assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is highly desired because it is important not only for clinical courses prediction, but also for the determination of antiviral therapy schemes. In recent years, various approaches for liver biopsies analysis have been highlighted, such as elastography techniques and serum markers, due to their properties of non-invasiveness. The aim of this study is to determine the best biomarkers or their combination by comparing multimodal biomarkers (ultrasound elastography parameters, biochemical hematologic parameters, and clinical parameters) for fibrosis assessment in chronic hepatitis B using a support vector machine combined with recursive feature elimination (RFE-SVM) approach. Results revealed that biomarkers from ultrasound elastography techniques achieved better prediction performance than others in the assessment of significant fibrosis (≥ F2) and cirrhosis (F4), and the best prediction performance were (1) ≥ F2: AUC = 0.902, ACC = 86.697%; (2) F4: AUC = 0.976, ACC = 90.364%. The findings are useful in guiding biomarkers selection and features optimization and in simplifying the prediction system for evaluation of liver fibrosis stage.
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Mendes LC, Ferreira PA, Miotto N, Zanaga L, Gonçales E, Lazarini MS, Gonçales FL, Stucchi RSB, Vigani AG. Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C. ACTA ACUST UNITED AC 2016; 49:e5432. [PMID: 27533769 PMCID: PMC4988482 DOI: 10.1590/1414-431x20165432] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 05/12/2016] [Indexed: 12/17/2022]
Abstract
Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.
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Affiliation(s)
- L C Mendes
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - P A Ferreira
- Departamento de Doenças Infecciosas, Universidade Federal de São Paulo, São Paulo, SP, Brasil
| | - N Miotto
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - L Zanaga
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - E Gonçales
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - M S Lazarini
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - F L Gonçales
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - R S B Stucchi
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - A G Vigani
- Departamento de Doenças Infecciosas, Universidade Estadual de Campinas, Campinas, SP, Brasil
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Bracht T, Mölleken C, Ahrens M, Poschmann G, Schlosser A, Eisenacher M, Stühler K, Meyer HE, Schmiegel WH, Holmskov U, Sorensen GL, Sitek B. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients. J Transl Med 2016; 14:201. [PMID: 27378383 PMCID: PMC4932744 DOI: 10.1186/s12967-016-0952-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 06/21/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). METHODS MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. RESULTS MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). CONCLUSIONS We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.
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Affiliation(s)
- Thilo Bracht
- />Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany
| | - Christian Mölleken
- />Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Germany
| | - Maike Ahrens
- />Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany
| | - Gereon Poschmann
- />Molecular Proteomics Laboratory (MPL), Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-Universität, Düsseldorf, Germany
| | - Anders Schlosser
- />Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Martin Eisenacher
- />Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany
| | - Kai Stühler
- />Molecular Proteomics Laboratory (MPL), Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-Universität, Düsseldorf, Germany
| | - Helmut E. Meyer
- />Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany
| | - Wolff H. Schmiegel
- />Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Germany
| | - Uffe Holmskov
- />Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Grith L. Sorensen
- />Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Barbara Sitek
- />Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany
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Hirose K, Kanefuji T, Suda T, Sugitani S, Nagasaki K, Kubota T, Igarashi M, Terai S. Formulation for Effective Screening and Management of Nonalcoholic Steatohepatitis: Noninvasive NAFLD Management Strategy. Gastroenterol Res Pract 2016; 2016:6343656. [PMID: 27382367 PMCID: PMC4921726 DOI: 10.1155/2016/6343656] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 04/30/2016] [Accepted: 05/11/2016] [Indexed: 02/07/2023] Open
Abstract
To establish a versatile means for screening and management of nonalcoholic steatohepatitis (NASH), shear wave velocity was measured in 20 normal controls and 138 consecutive nonalcoholic fatty liver disease (NAFLD) cases. Referencing biochemical properties in 679 healthy volunteers, a formula to distinguish NASH suspects was established and validated in another cohort of 138 histologically proven NAFLD cases. NASH and simple steatosis (SS) suspects were selected based on a plot of shear wave velocity against age. A formula consisting of five factors (γ-glutamyl transpeptidase, alkaline phosphatase, platelet counts, body mass index, and presence/absence of type 2 diabetes mellitus) distinguished NASH suspects from SS suspects with area under the receiver operating characteristic curve values of 86% and 84% in the development and validation cohorts. Among 25 NAFLD cases in which shear wave velocity was repeatedly measured, 8 and 9 cases revealed an increase or decrease, respectively, of shear wave velocity in the entire liver, and the corresponding change in shear wave velocity was primarily observed in the right lobe or the left lateral segment, respectively. These results suggest that the new formula and sequential shear wave velocity measurements at each segment enable high throughput screening of NASH suspects and noninvasive assessment of pathophysiological alleviation/aggravation in cases of NASH.
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Affiliation(s)
- Kanae Hirose
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Tsutomu Kanefuji
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University, Minami-Uonuma 949-7302, Japan
| | - Takeshi Suda
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University, Minami-Uonuma 949-7302, Japan
| | - Souichi Sugitani
- Division of Gastroenterology and Hepatology, Tachikawa Medical Center, Nagaoka 940-8621, Japan
| | - Keisuke Nagasaki
- Division of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Tomoyuki Kubota
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Second Hospital, Niigata 950-1104, Japan
| | - Masato Igarashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
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Li D, He L, Guo H, Chen H, Shan H. Targeting activated hepatic stellate cells (aHSCs) for liver fibrosis imaging. EJNMMI Res 2015; 5:71. [PMID: 26650603 PMCID: PMC4674461 DOI: 10.1186/s13550-015-0151-x] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 11/27/2015] [Indexed: 12/12/2022] Open
Abstract
Following injurious stimuli, quiescent hepatic stellate cells (qHSCs) transdifferentiate into activated HSCs (aHSCs). aHSCs play pivotal roles in the onset and progression of liver fibrosis. Therefore, molecular imaging of aHSCs in liver fibrosis will facilitate early diagnosis, prognosis prediction, and instruction and evaluation of aHSC-targeted treatment. To date, several receptors, such as integrin αvβ3, mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR), collagen type VI receptor (CVIR), platelet-derived growth factor receptor-β (PDGFR-β), vimentin, and desmin, have been identified as biomarkers of aHSCs. Corresponding ligands to these receptors have also been developed. This review will discuss strategies for developing aHSC-targeted imaging in liver fibrosis.
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Affiliation(s)
- Dan Li
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.,Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, 510630, China
| | - Li He
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Huizhuang Guo
- Department of Radiology, Guangzhou Panyu Central Hospital, Guangzhou, 511400, China
| | - Hanwei Chen
- Department of Radiology, Guangzhou Panyu Central Hospital, Guangzhou, 511400, China.
| | - Hong Shan
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. .,Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, 510630, China. .,Interventional Radiology Institute of Sun Yat-sen University, Guangzhou, 510630, China.
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Salkic NN, Cickusic E, Jovanovic P, Denjagic MB, Iljazovic-Topcic S, Bevanda M, Ahmetagic S. Online combination algorithm for non-invasive assessment of chronic hepatitis B related liver fibrosis and cirrhosis in resource-limited settings. Eur J Intern Med 2015; 26:628-634. [PMID: 26194460 DOI: 10.1016/j.ejim.2015.07.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Revised: 06/20/2015] [Accepted: 07/06/2015] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The use of commercially available noninvasive markers for chronic hepatitis B (CHB) related fibrosis is not widely available in developing countries so clinicians in those countries frequently use free alternatives. We aimed to create an optimized algorithm for selection of patients with the highest probability for presence/absence of significant liver fibrosis and cirrhosis based on the use of multiple free scores. METHODS We evaluated six free noninvasive markers for CHB related fibrosis against liver biopsy and selected the best thresholds for prediction/exclusion of significant fibrosis and cirrhosis in CHB patients. Algorithm based on four scores and their corresponding thresholds was created. RESULTS The calculator based on developed algorithm can be found at http://www.chb-lfc.com. We evaluated 211 patients in main group and 65 patients in external validation group. We selected four scores for creation of combination algorithm. The algorithm was able to classify 123/211 (58.3%) patients with a 93.5% accuracy of correct classification for prediction of presence/absence of significant fibrosis in main group. In validation group, the algorithm was able to classify 48/65 (73.8%) of patients with 93.8% (45/48) overall accuracy. When used to predict presence/absence of cirrhosis, the algorithm was able to correctly classify 181/211 (85.8%) and 59/65 (90.8%) of patients in main and validation group, respectively, with an overall accuracy of 97.8% and 98.3%, respectively. CONCLUSION Developed algorithm based on routine laboratory tests is a usable, applicable and accurate tool for diagnosis of CHB related fibrosis and cirrhosis, suitable for resource-limited settings where more expensive modalities are unavailable.
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Affiliation(s)
- Nermin N Salkic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina.
| | - Elmir Cickusic
- Department of Pathology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Predrag Jovanovic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Mirela Basic Denjagic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Samra Iljazovic-Topcic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Milenko Bevanda
- Department of Gastroenterology, University Clinical Hospital Mostar, Mostar, Bosnia and Herzegovina
| | - Sead Ahmetagic
- Department of Infectious Diseases, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
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Liu Y, Dong CF, Yang G, Liu J, Yao S, Li HY, Yuan J, Li S, Le X, Lin Y, Zeng W, Lin H, Zhang X, Chen X. Optimal linear combination of ARFI, transient elastography and APRI for the assessment of fibrosis in chronic hepatitis B. Liver Int 2015; 35:816-25. [PMID: 24751289 DOI: 10.1111/liv.12564] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 04/12/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Accurate assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is necessary not only to predict the long-term clinical course but also to determine an appropriate antiviral therapy scheme. Several noninvasive approaches - serum markers and elastography - have been proposed as alternatives for the histopathological analysis of liver biopsies. The aim of this study was to evaluate two ultrasound elastography methods (ARFI and TE) and one biochemical test (APRI), as well as their optimal linear combination, in the assessment of liver fibrosis in CHB. METHODS Ninety five patients with CHB and 16 volunteers underwent ARFI, TE and APRI; and liver fibrosis was staged in the patients by a liver biopsy. An optimal linear combination of the three methods was developed, and its diagnostic performance was evaluated by a 10-fold cross-validation. RESULTS The accuracy of the linear combination was 83.86% and 91.88% for significant fibrosis (≥F2) and cirrhosis (F4), respectively, higher than those obtained for ARFI (83.50%, 88.76%), TE (75.27%, 87.61%) and APRI (73.29% and 81.67%). The combination also increased the sensitivity and the negative predictive values for the diagnosis of significant fibrosis and cirrhosis. CONCLUSIONS The optimal linear combination algorithm is effective for noninvasive staging of liver fibrosis in CHB. However, linear combination has its own limitations; nonlinear methods may eventually reveal even clearer diagnostic results.
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Affiliation(s)
- Yingxia Liu
- Shenzhen Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, China
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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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Rogler G. New therapeutic avenues for treatment of fibrosis: can we learn from other diseases? Dig Dis 2014; 32 Suppl 1:39-49. [PMID: 25531352 DOI: 10.1159/000367825] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Crohn's disease (CD) is characterized by the frequent occurrence of complications, such as fibrotic strictures and subsequently the need for CD-related surgery. Chronic or recurrent inflammation is generally regarded to be a necessary precondition for the initiation of intestinal fibrosis. In this view, fibrosis is a pathologically augmented healing response to inflammation-induced mucosal tissue destruction and injury. At present, there are no approved or effective medical therapies aimed specifically at fibrosis or stricture in IBD. Indirect benefits may occur from anti-inflammatory therapies, although there is no consensus on this. Therapy for fibrosis is complicated by the fact that a wound-healing response is essential in CD and ulcerative colitis. Several pharmaceutical companies are now working on the therapy of fibrosis in other diseases. Strategies interfering with TGF-β expression and activation are promising. Pirfenidone has been studied in several clinical trials. Further therapeutic options are second-generation and wide-spectrum tyrosine kinase inhibitors. These inhibit growth factor receptor signaling, thus reducing fibrosis in animal models and some patients with tumor-associated fibrosis. At present, the development of antifibrotic therapies takes place in other diseases such as lung and liver fibrosis. This is partially due to a lack of experimental models for gut fibrosis and the fact that reliable readouts (MRI, serum markers) in patients are lacking. It will be important to test the above-mentioned newly available treatment strategies in IBD to profit from progress in other fibrotic diseases.
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Affiliation(s)
- Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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Stefanescu H, Procopet B. Noninvasive assessment of portal hypertension in cirrhosis: liver stiffness and beyond. World J Gastroenterol 2014; 20:16811-16819. [PMID: 25492995 PMCID: PMC4258551 DOI: 10.3748/wjg.v20.i45.16811] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 07/10/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
Liver stiffness measurement (LSM) is a good, but still limited tool to noninvasively assess complications and prognosis in patients with advanced liver disease. This review aims to consider the role of LSM for the diagnosis of portal hypertension-related complications and for assessment of prognosis in cirrhotic patients, and to highlight the drawbacks as well as some alternatives for improving the performance. Hence, this field is far from being closed, and deserves more attention. There is still a place for more carefully designed studies to find new, innovative and reliable approaches.
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Qiao Y, Chen J, Li X, Wei H, Xiao F, Chang L, Zhang R, Hao X, Wei H. Serum gp73 is also a biomarker for diagnosing cirrhosis in population with chronic HBV infection. Clin Biochem 2014; 47:216-22. [PMID: 25168922 DOI: 10.1016/j.clinbiochem.2014.08.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 08/07/2014] [Accepted: 08/09/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To clarify the role of Golgi membrane glycoprotein 73 (gp73) in evaluating the progression of chronic hepatitis B virus (HBV) infection. DESIGN AND METHODS Participants included 958 controls, 421 chronic hepatitis B, 944 hepatic cirrhosis, and 127 hepatocellular carcinoma (HCC) patients. All the patients, with the exception of the controls, were diagnosed HBsAg positive. Serum biomarkers, including gp73, alpha-fetoprotein (AFP), alpha-l-fucosidase, and Lens culinaris agglutinin-reactive fraction of AFP, were determined. RESULTS The patients with Hepatic cirrhosis gp73 levels over 150 ng/mL had an odds ratio of 3.21 (95% CI: 2.07-5.00). In hepatic cirrhosis patients, serum gp73 correlated with the Child-Pugh score. gp73 is a marker for diagnosing cirrhosis in the hepatitis populations. When the cut-off was set at 75.5 ng/mL, the sensitivity, specificity, and AUC were 75.6% (95% CI: 71.30%-79.62%), 60.3% (95% CI: 56.95%-63.63%) and 0.72 (95% CI: 0.69-0.75), respectively. CONCLUSION The variation trend of gp73 in chronic liver disease may indicate that monitoring of serum gp73 is helpful to diagnose cirrhosis in population with chronic HBV infection.
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Affiliation(s)
- Yong Qiao
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jinglong Chen
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xin Li
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Honglian Wei
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Fan Xiao
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lusi Chang
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Renwen Zhang
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China; Health Science Center, Peking University, Beijing 100083, China
| | - Xiaohua Hao
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Hongshan Wei
- Institute of Infectious Disease, Ditan Hospital, Capital Medical University, Beijing 100015, China.
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Noninvasive Biomarkers of Liver Fibrosis: Clinical Applications and Future Directions. CURRENT PATHOBIOLOGY REPORTS 2014; 2:245-256. [PMID: 25396099 DOI: 10.1007/s40139-014-0061-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic liver disease is a significant cause of morbidity and mortality worldwide. Current strategies for assessing prognosis and treatment rely on accurate assessment of disease stage. Liver biopsy is the gold standard for assessing fibrosis stage but has many limitations. Noninvasive biomarkers of liver fibrosis have been extensively designed, studied, and validated in a variety of liver diseases. With the advent of direct acting antivirals and the rise in obesity-related liver disease, there is a growing need to establish these noninvasive methods in the clinic. In addition, it has become increasingly clear over the last few years that noninvasive biomarkers can also be used to monitor response to antifibrotic therapies and predict liver outcomes, including hepatocellular carcinoma development. This review highlights the most well-established noninvasive biomarkers to-date, with a particular emphasis on serum and imaging-based methodologies.
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Enomoto M, Morikawa H, Tamori A, Kawada N. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. World J Gastroenterol 2014; 20:12031-12038. [PMID: 25232240 PMCID: PMC4161791 DOI: 10.3748/wjg.v20.i34.12031] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/09/2014] [Accepted: 04/15/2014] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.
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Sebastiani G, Gkouvatsos K, Pantopoulos K. Chronic hepatitis C and liver fibrosis. World J Gastroenterol 2014; 20:11033-11053. [PMID: 25170193 PMCID: PMC4145747 DOI: 10.3748/wjg.v20.i32.11033] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 04/14/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.
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Kessoku T, Ogawa Y, Yoneda M, Imajo K, Sumida Y, Eguchi Y, Fujii H, Hyogo H, Ono M, Suzuki Y, Kawaguchi T, Chayama K, Tanaka S, Fujimoto K, Anzai K, Saibara T, Sata M, Itoh Y, Nakajima A, (JSG-NAFLD) TOJSGONAFLD. Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20:10108-10114. [PMID: 25110437 PMCID: PMC4123339 DOI: 10.3748/wjg.v20.i29.10108] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Revised: 01/09/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease (NAFLD) patients.
METHODS: A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing. Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h. Laboratory evaluation was performed in all patients. Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD.
RESULTS: The optimal cutoff value of platelet count, serum albumin, and aminotransferase/alanine aminotransferase ratio (AAR) was set at < 15.3 104/μL, < 4.0 g/dL, and > 0.9, respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AAR = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AAR) score. The diagnosis of PLALA ≥ 2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients.
CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.
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