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Li Z, Sun X, Zhao Z, Yang Q, Ren Y, Teng X, Tai DCS, Wanless IR, Schattenberg JM, Liu C. A machine learning based algorithm accurately stages liver disease by quantification of arteries. Sci Rep 2025; 15:3143. [PMID: 39856155 PMCID: PMC11759706 DOI: 10.1038/s41598-025-87427-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025] Open
Abstract
A major histologic feature of cirrhosis is the loss of liver architecture with collapse of tissue and vascular changes per unit. We developed qVessel to quantify the arterial density (AD) in liver biopsies with chronic disease of varied etiology and stage. 46 needle liver biopsy samples with chronic hepatitis B (CHB), 48 with primary biliary cholangitis (PBC) and 43 with metabolic dysfunction-associated steatotic liver disease (MASLD) were collected at the Shuguang Hospital. The METAVIR system was used to assess stage. The second harmonic generation (SHG)/two-photon images were generated from unstained slides. Collagen proportionate area (CPA) using SHG. AD was counted using qVessel (previously trained on manually labeled vessels by stained slides (CD34/a-SMA/CK19) and developed by a decision tree algorithm). As liver fibrosis progressed from F1 to F4, we observed that both AD and CPA gradually increases among the three etiologies (P < 0.05). However, at each stage of liver fibrosis, there was no significant difference in AD or CPA between CHB and PBC compared to MASLD (P > 0.05). AD and CPA performed similar diagnostic efficacy in liver cirrhosis (P > 0.05). Using the qVessel algorithm, we discovered a significant correlation between AD, CPA and METAVIR stages in all three etiologies. This suggests that AD could underpin a novel staging system.
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Affiliation(s)
- Zhengxin Li
- Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
| | - Xin Sun
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China
| | - Zhimin Zhao
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
| | - Qiang Yang
- Hangzhou Choutu Tech. Co., Ltd., Hangzhou, China
| | - Yayun Ren
- Hangzhou Choutu Tech. Co., Ltd., Hangzhou, China
| | - Xiao Teng
- Histoindex Pte. Ltd, Singapore, Singapore
| | | | - Ian R Wanless
- Department of Pathology, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Canada
| | - Jörn M Schattenberg
- Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany
- Saarland University, Saarbrücken, Germany
| | - Chenghai Liu
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China.
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China.
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Oluwagbenga OO, Lukman Olaitan A, Ihiovi UB, Gideon OO, Maryjoy II, Elijah AO, Samson JO, Adenike OO. Non-invasive assessment of hepatic fibrosis among patients with chronic hepatitis B virus infection in three tertiary hospitals in Nigeria. SAGE Open Med 2024; 12:20503121241264313. [PMID: 39119474 PMCID: PMC11307341 DOI: 10.1177/20503121241264313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 06/03/2024] [Indexed: 08/10/2024] Open
Abstract
Objective This study aimed to assess hepatic fibrosis, using noninvasive tests, among patients with chronic hepatitis B virus infection in Nigeria. Methods The study was a retrospective cross-sectional, hospital-based, multicentered study. The data of adult Nigerians who were aged 18 years and above who had been diagnosed with chronic hepatitis B infection and were not on treatment were extracted from three tertiary health institutions across Nigeria. Sociodemographic and relevant clinical data were obtained from the case notes of the patients. Fibrosis-4 and aspartate aminotransferase platelet ratio index scores were calculated to determine the presence and severity of liver fibrosis in the patients. The data obtained were analyzed using Statistical Package for the Social Sciences (version 25.0). A p-value of less than 0.05 was considered as statistically significant. Results The data of a total of 234 patients were extracted for this study from across 3 tertiary hospitals in Nigeria. There were 132 (56.4%) males and 102 (43.6%) females in a ratio of 1.29:1 with a mean age of 37.92 ± 12.34 years. The fibrosis-4 score of the patients showed that 62.8% had "Normal/Mild Fibrosis," 25.6% had "Moderate Fibrosis," and 11.5% had "Severe Fibrosis/Cirrhosis." The aspartate aminotransferase platelet ratio index score of the patients showed that 64.1% had "No Fibrosis," 20.9% had "Mild Fibrosis," 6.4% had "Moderate Fibrosis," and 8.5% had "Severe Fibrosis/Cirrhosis." The median fibrosis-4 score of the patients was 1.18 (0.77-1.74), while the median aspartate aminotransferase platelet ratio index score was 0.40 (0.26-0.69). Liver ultrasonography detected cirrhosis in 8.5% of the patients. All the patients were not yet on treatment for hepatitis B infection. Conclusion The prevalence of hepatic fibrosis is high among patients with chronic hepatitis B virus infection in Nigeria and a large number of these patients were not yet on therapy. Noninvasive assessment of hepatic fibrosis should be considered as a critical part of the work-up of patients with chronic hepatitis B infection.
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Affiliation(s)
- Oguntoye Oluwatosin Oluwagbenga
- Department of Medicine, Afe Babalola University Ado-Ekiti, Ado-Ekiti, Ekiti State, Nigeria
- Department of Medicine, Federal Teaching Hospital Ido-Ekiti, Ido-Ekiti, Ekiti State, Nigeria
- Enlightenment Initiative on Viral Hepatitis, Ede, Osun State, Nigeria
| | - Abdulkareem Lukman Olaitan
- Enlightenment Initiative on Viral Hepatitis, Ede, Osun State, Nigeria
- Department of Internal Medicine, University of Abuja Teaching Hospital Gwagwalada, Abuja, Federal Capital Territory, Nigeria
| | - Umoru Benedict Ihiovi
- Department of Internal Medicine, Federal Teaching Hospital Lokoja, Lokoja, Kogi State, Nigeria
| | - Osasona Oluwadamilola Gideon
- Enlightenment Initiative on Viral Hepatitis, Ede, Osun State, Nigeria
- Department of Medical Laboratory Sciences, Faculty of Basic Sciences, Redeemers University Ede, Ede, Osun State, Nigeria
- Department of Medical Services, Hospitals Management Board, Ado-Ekiti, Ekiti State, Nigeria
| | - Ifeorah Ijeoma Maryjoy
- Enlightenment Initiative on Viral Hepatitis, Ede, Osun State, Nigeria
- Center for Translation and Implementation Research, College of Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, University of Nigeria Enugu Campus, Enugu, Enugu State, Nigeria
| | - Ariyo Olumuyiwa Elijah
- Department of Medicine, Afe Babalola University Ado-Ekiti, Ado-Ekiti, Ekiti State, Nigeria
- Department of Medicine, Federal Teaching Hospital Ido-Ekiti, Ido-Ekiti, Ekiti State, Nigeria
- Enlightenment Initiative on Viral Hepatitis, Ede, Osun State, Nigeria
| | - Jegede Oluwatosin Samson
- Division of Global Public Health, Herbert Wertheim School of Public Health, University of California San Diego, La Jolla, CA, USA
| | - Oguntoye Oluwafunmilayo Adenike
- Department of Medicine, Afe Babalola University Ado-Ekiti, Ado-Ekiti, Ekiti State, Nigeria
- Department of Medicine, Federal Teaching Hospital Ido-Ekiti, Ido-Ekiti, Ekiti State, Nigeria
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Cheng R, Tan N, Luo H, Kang Q, Xu X. Noninvasive Methods for Detecting Advanced Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis B: A Single-Center Retrospective Study. Infect Drug Resist 2023; 16:6323-6331. [PMID: 37786453 PMCID: PMC10541529 DOI: 10.2147/idr.s426374] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 09/14/2023] [Indexed: 10/04/2023] Open
Abstract
Background and Aims The performance of noninvasive assessments to rule-in or rule-out fibrosis may improve when combined. We aimed to evaluate the efficiencies of sequential algorithms based on the aspartate aminotransferase-to-platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and transient elastography (TE) for the assessment of advanced fibrosis (AF) and cirrhosis. Methods This study enrolled 179 CHB subjects who underwent liver biopsy (LB) before antiviral treatment. Results AF and cirrhosis were identified in 71 (39.7%) and 28 (15.7%) patients, respectively. Compared with TE alone, sequential FIB-4-TE and APRI-TE algorithms saved a slightly higher number of liver biopsies for the identification of advanced fibrosis (69.3% or 68.2% vs 63.7%, P=0.263 or P=0.372, respectively). For the identification of cirrhosis, sequential FIB-4-TE and APRI-TE algorithms saved a significantly higher number of liver biopsies than TE alone (83.2% or 88.3% vs 69.8%, P=0.003 or P=0.000, respectively). No significant difference was found between the sequential algorithms and TE alone in the diagnostic accuracy for the detection of AF and cirrhosis. Conclusion The sequential algorithms could significantly reduce the need for liver biopsy with high accuracy for diagnosis of AF and cirrhosis in CHB patients, which would be optimal especially in resource-limited areas.
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Affiliation(s)
- Ran Cheng
- Department of Infectious Diseases, Peking University Third Hospital, Beijing, People’s Republic of China
| | - Ning Tan
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China
| | - Hao Luo
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China
| | - Qian Kang
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China
| | - Xiaoyuan Xu
- Department of Gastroenterology, Peking University First Hospital, Beijing, People’s Republic of China
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Liang XE, Hu XM, Wang HY, Dai L, Lin XY, Chen JJ, Chen YP, Wen B, Jiang RL. Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection. Hepatol Int 2022; 16:649-657. [PMID: 35412215 DOI: 10.1007/s12072-022-10327-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 03/03/2022] [Indexed: 11/26/2022]
Abstract
AIMS To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.
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Affiliation(s)
- Xie-Er Liang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China
| | - Xiao-Min Hu
- Hepatology Unit, Shenzhen Hospital, Southern Medical University, No. 1333 Xinhu Road, Shenzhen, 518110, Guangdong, China
| | - Hai-Yu Wang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China
| | - Lin Dai
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China
| | - Xiao-Yu Lin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China
| | - Jin-Jun Chen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China
| | - Yong-Peng Chen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China.
- Hepatology Unit, Shenzhen Hospital, Southern Medical University, No. 1333 Xinhu Road, Shenzhen, 518110, Guangdong, China.
| | - Biao Wen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China.
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Road, Chengdu, 610000, Sichuan, China.
| | - Rong-Long Jiang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou North Avenue, Guangzhou, 510515, Guangdong, China.
- Hepatology Unit, Shenzhen Hospital, Southern Medical University, No. 1333 Xinhu Road, Shenzhen, 518110, Guangdong, China.
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Kayadibi H, Yilmaz B, Ozgur Yeniova A, Koseoglu H, Simsek Z. Development and evaluation of a novel noninvasive index for predicting significant fibrosis, advanced fibrosis, and cirrhosis in patients with chronic hepatitis B infection. Eur J Gastroenterol Hepatol 2021; 33:e121-e130. [PMID: 33177385 DOI: 10.1097/meg.0000000000001973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Development of noninvasive liver fibrosis indexes has been research of interest due to the limitations of liver biopsy. Therefore, we aimed to develop and evaluate the diagnostic accuracy of a novel noninvasive index for predicting significant fibrosis, advanced fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) infection based on age and routine clinical laboratory tests. METHODS A total of 396 treatment naïve liver biopsy performed patients were divided into training (n = 262) and validation cohorts (n = 134). Histological staging was assessed by Ishak fibrosis scoring system. RESULTS In training cohort, we developed a novel fibrosis index, GAPI, using γ-glutamyl transpeptidase (GGT), age, platelet, and international normalized ratio (INR) results. The diagnostic accuracies of alanine aminotransferase ratio, age platelet index, aspartate aminotransferase to platelet ratio index, GGT to platelet ratio index, AST to lymphocyte ratio index, fibrosis index based on the four factors, Fibro Q, Goteborg University Cirrhosis Index, King's score, Pohl score, Wang I, fibrosis index, fibrosis cirrhosis index, cirrhosis discriminant score, Lok score, Doha score, Mehdi's model, GqHBsAg, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, RDW to lymphocyte ratio, RDW to platelet ratio, GGT/INR, GGT/albumin, white blood cell/platelet distribution width (PDW), mean platelet volume/PDW and platelet/PDW indexes were compared to GAPI index. For the prediction of significant fibrosis, advanced fibrosis and cirrhosis, the area under the receiver operating characteristic curves (AUROCs) of GAPI index were 0.776, 0.868, and 0.885 in training cohort, and 0.731, 0.883, and 0.919 in validation cohort, respectively. The AUROCs of the GAPI index were higher than those of the evaluated 27 noninvasive indexes to predict significant fibrosis, advanced fibrosis, and cirrhosis. CONCLUSION In resource limited settings, GAPI is a promising noninvasive liver fibrosis index for predicting significant fibrosis, advanced fibrosis and cirrhosis, and for decreasing the need for liver biopsy in patients with CHB infection using cutoff points of 2.00 and 3.50.
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Affiliation(s)
| | - Baris Yilmaz
- Department of Gastroenterology, Hitit University School of Medicine, Corum
| | - Abdullah Ozgur Yeniova
- Department of Gastroenterology, Tokat Gaziosmanpasa University School of Medicine, Tokat
| | - Huseyin Koseoglu
- Department of Gastroenterology, Hitit University School of Medicine, Corum
| | - Zahide Simsek
- Clinic of Gastroenterology, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara
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A Combination Model of Radiomics Features and Clinical Biomarkers as a Nomogram to Differentiate Nonadvanced From Advanced Liver Fibrosis: A Retrospective Study. Acad Radiol 2021; 28 Suppl 1:S45-S54. [PMID: 34023199 DOI: 10.1016/j.acra.2020.08.029] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/20/2020] [Accepted: 08/20/2020] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To develop and validate a combination model of radiomics features and clinical biomarkers to differentiate nonadvanced from advanced liver fibrosis. MATERIALS AND METHODS One hundred and eight consecutive patients with pathologically diagnosed liver fibrosis were randomly placed in a training or a test cohort at a ratio of 2:1. For each patient, 1674 radiomics features extracted from portal venous phase CT images were reduced by using minimum redundancy and maximum relevant. The optimal features identified were incorporated into the radiomics model. Eight clinical markers were evaluated. Integrated with clinical independent risk factors, a combination model was built. A nomogram was also established from the model. The performance of the models was assessed. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomogram. RESULTS The radiomics model established using five features achieved a promising level of discrimination between nonadvanced and advanced liver fibrosis. The combination model incorporated the radiomics signature with two clinical biomarkers and showed good calibration and discrimination. The training and testing cohort results of the radiomics model were area under curve values 0.864 and 0.772, accuracy 77.8% and 77.8%, sensitivity 86.7% and 73.1%, and specificity 71.4% and 90.0%, respectively. For the combination model, the training and testing cohort results were area under curve values 0.915 and 0.897, accuracy 83.3% and 86.1%, sensitivity 86% and 80.6%, and specificity 82.6% and 92.3%, respectively. The decision curve indicated the nomogram has potential in clinical application. CONCLUSION This combination model provides a promising approach for differentiating non-advanced from advanced liver fibrosis.
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Dong B, Lyu G, Chen Y, Lin G, Wang H, Qin R, Gu J. Comparison of two-dimensional shear wave elastography, magnetic resonance elastography, and three serum markers for diagnosing fibrosis in patients with chronic hepatitis B: a meta-analysis. Expert Rev Gastroenterol Hepatol 2021; 15:1077-1089. [PMID: 33487039 DOI: 10.1080/17474124.2021.1880894] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Two-dimensional shear wave elastography (2D-SWE), magnetic resonance elastography (MRE), aspartate transaminase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and King's score have been proposed for diagnosing fibrosis. METHODS Literature databases were searched until October 1st, 2020. The summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities were used to assess the performance of these noninvasive methods for staging fibrosis. RESULTS Our final data contained 72 studies. The prevalence of significant fibrosis, advanced fibrosis, and cirrhosis was 58.3%, 36.2%, and 20.5%, respectively, in chronic hepatitis B (CHB). For 2D-SWE and MRE, the summary AUROCs were 0.89 and 0.97, 0.95 and 0.97, and 0.94 and 0.97 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. The summary AUROCs using APRI and FIB-4 for detecting significant fibrosis, advanced fibrosis, and cirrhosis were 0.76 and 0.75, 0.74 and 0.77, and 0.77 and 0.82, respectively. The summary AUROCs of King's score for detecting significant fibrosis and cirrhosis were 0.77 and 0.83, respectively. CONCLUSION MRE and 2D-SWE may show the best diagnostic accuracy for predicting fibrosis in CHB. Among the three serum markers, King's score may be more useful for diagnosing fibrosis.
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Affiliation(s)
- Bingtian Dong
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Guorong Lyu
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.,Department of Clinical Medicine, Quanzhou Medical College, Quanzhou, Fujian Province, China
| | - Yuping Chen
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Guofu Lin
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Respirology Medicine Centre of Fujian Province, Quanzhou, Fujian Province, China
| | - Huaming Wang
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Ran Qin
- Department of Ultrasound, The Chenggong Hospital, Xiamen University, Xiamen, Fujian Province, China
| | - Jionghui Gu
- Department of Ultrasound, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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The Cook Score: A Novel Assessment for the Prediction of Liver-Associated Clinical Events in a Diverse Population. J Gastrointest Cancer 2021; 53:387-393. [PMID: 33683645 DOI: 10.1007/s12029-021-00620-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Transient elastography (TE) provides accurate quantification of liver fibrosis. Its usefulness could be significantly amplified in terms of predicting liver-associated clinical events (LACE). Our aim was to create a model that accurately predicts LACE by combining the information provided by TE with other variables in patients with chronic liver disease (CLD). METHODS We retrospectively reviewed the electronic medical records of patients who underwent liver elastography, at John H. Stroger Hospital in Cook County, Chicago, IL. The incidences of LACE were documented including decompensation of CLD, new hepatocellular carcinoma, and liver-associated mortality. Significant predicting factors were identified through a forward stepwise Cox regression model. We used the beta-coefficients of these risk factors to construct the Cook Score for prediction of LACE. Receiver-operating characteristic (ROC) curves were plotted for Cook Score to evaluate its efficiency in prediction, in comparison with MELD-Na Score and FIB-4 Score. RESULTS A total of 3097 patients underwent liver elastography at our institution. Eighty-eight LACE were identified. Age (hazard ratio (HR) 1.04, p = 0.002), aspartate aminotransferase to alanine aminotransferase ratio (HR 2.61, p < 0.001), platelet count (HR 0.98, p < 0.001), international normalized ration (INR) (HR 17.80, p < 0.001), and liver stiffness measurement (HR1.04, p < 0.001) were identified as significant predictors. The Cook Score was constructed with two optimal cut-off points to stratify patients into low-, intermediate-, and high-risk groups for LACE. The Cook Score proved superior than MELD-Na Score and FIB4 Score in predicting LACE with an area under curve of 0.828. CONCLUSION This novel score based on a large robust sample would provide accurate prediction of prognosis in patients with chronic liver disease and guide individualized surveillance strategy once validated with future studies.
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Chen YP, Huang LW, Lin XY, Hu XM, Liang XE, Jiang RL. Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis. J Viral Hepat 2020; 27:826-836. [PMID: 32187804 DOI: 10.1111/jvh.13293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 02/11/2020] [Accepted: 02/20/2020] [Indexed: 12/13/2022]
Abstract
The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was ∝ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.
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Affiliation(s)
- Yong-Peng Chen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China.,Department of Internal Medicine, Nanfang Hospital Taihe Branch, Guangzhou, China
| | - Li-Wen Huang
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Shunde, China
| | - Xiao-Yu Lin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao-Min Hu
- Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xie-Er Liang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong-Long Jiang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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Fu X, Lou H, Chen F, Gao X, Lin Z. Hepatitis B core antibody and liver stiffness measurements predict HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with minimally elevated alanine aminotransferase (ALT) levels. Clin Exp Med 2020; 20:241-248. [PMID: 32052245 DOI: 10.1007/s10238-019-00603-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 12/26/2019] [Indexed: 12/23/2022]
Abstract
Alanine aminotransferase (ALT) levels between 1 and 2 times the upper limit of normal (ULN) are common in patients with chronic hepatitis B (CHB) infection. There are few clinical studies focused on this group of patients because of the poorer treatment outcomes compared to those with more than 2 × ULN ALT level. However, treatments are necessary to reduce liver damage for patients with minimally elevated ALT levels. And biomarkers are needed in predicting the treatment response. In this study, a total of 106 patients with CHB were enrolled and treated with entecavir, telbivudine or tenofovir disoproxil fumarate. Liver stiffness was measured by transient elastography, and quantitative levels of hepatitis B core antibody (HBcAb) were detected by ELISA. At week 96, 31 (29.25%) patients achieved hepatitis B e antigen (HBeAg) seroconversion. Notably, baseline HBcAb levels and liver stiffness measurements (LSM) were higher in patients who achieved HBeAg seroconversion. The multivariate analysis showed that the baseline HBcAb levels and LSM were independent predictors for HBeAg seroconversion. The area under receiver operating characteristic curve of baseline HBcAb, LSM and the combination of them for HBeAg seroconversion was 0.714, 0.720 and 0.717, respectively. In addition, we discovered that the patients with baseline HBcAb levels ≥ 4.15 log10 IU/mL and LSM ≥ 9.85 kPa had higher rates of HBeAg seroconversion. Therefore, the measurement of HBcAb and liver stiffness might be good approaches for the optimization of antiviral therapy for HBeAg-positive CHB patients with minimally elevated ALT levels.
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Affiliation(s)
- Xihua Fu
- Department of Infectious Diseases and Hepatology Unit, Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Haibo Lou
- Department of Infectious Diseases and Hepatology Unit, Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Fang Chen
- Department of Infectious Diseases and Hepatology Unit, Panyu Central Hospital, Guangzhou, Guangdong, China
| | - Xueping Gao
- Department of Hepatology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China.
| | - Zhanzhou Lin
- Department of Hepatology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China.
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11
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Yue W, Li Y, Geng J, Wang P, Zhang L. Aspartate aminotransferase to platelet ratio can reduce the need for transient elastography in Chinese patients with chronic hepatitis B. Medicine (Baltimore) 2019; 98:e18038. [PMID: 31804310 PMCID: PMC6919398 DOI: 10.1097/md.0000000000018038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED In the absence of liver biopsy and transient elastography (TE), aspartate aminotransferase to platelet ratio (APRI), fibrosis-4 score (FIB-4), and gammaglutamyl transpeptidase to platelet ratio (GPR) are simple and inexpensive methods for the detection of liver fibrosis. AIMS We compared the performance of APRI, FIB-4, and GPR scores against TE in predicting the presence of liver fibrosis and cirrhosis, determined the optimal cut-off values for fibrosis and cirrhosis prediction, and reviewed the need for further TE assessment in resource-limited areas in China. METHODS TE and basic laboratory tests were performed in 2014 consecutive patients with chronic hepatitis B (CHB), and then compared to APRI, FIB-4, and GPR. RESULTS For the detection of significant fibrosis, the areas under the receiver operating characteristic (AUROC) curves for APRI, FIB-4, and GPR were 0.83, 0.75, and 0.77, respectively. For the detection of cirrhosis, the AUROC curves for APRI, FIB-4, and GPR were 0.90, 0.84, and 0.84, respectively. The cutoff of APRI was 0.35, with 78% sensitivity and 63% negative predictive value (NPV), to exclude significant fibrosis (F ≥ 2). At an APRI of 0.6, results showed a 94% specificity, 100% positive predictive value (PPV) and 7.9 positive likelihood ratio (PLR) in detecting significant fibrosis. Thus, patients with an APRI of <0.35 or >0.6 demonstrated correct prediction of liver fibrosis. These results translated to 1250 out of the 2014 patients avoiding the need for TE with a diagnostic accuracy of >80%. CONCLUSIONS The APRI score accurately assessed fibrosis and reduced the need for TE in almost two-thirds of Chinese patients with CHB.
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Affiliation(s)
- Wei Yue
- Department of Infectious Disease, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Yan Li
- Department of VIP Internal Medicine, The First People's Hospital of Yunnan Province
| | - Jiawei Geng
- Department of Infectious Disease, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Ping Wang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology
| | - Li Zhang
- Faculty of Environmental Science and Engineering, Kunming University of Science and Technology
- Department of VIP Internal Medicine, The First People's Hospital of Yunnan Province
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12
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Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B. Dig Liver Dis 2019; 51:127-134. [PMID: 30076017 DOI: 10.1016/j.dld.2018.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 05/20/2018] [Accepted: 07/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. METHODS A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. RESULTS For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. CONCLUSIONS As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.
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Chen YP, Hu XM, Liang XE, Huang LW, Zhu YF, Hou JL. Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection. J Gastroenterol Hepatol 2018; 33:256-263. [PMID: 28452125 DOI: 10.1111/jgh.13811] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/11/2017] [Accepted: 04/19/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.
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Affiliation(s)
- Yong-Peng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Xiao-Min Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xie-Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Li-Wen Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - You-Fu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jin-Lin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
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Liang XE, Chen YP. Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B. J Clin Transl Hepatol 2017; 5:368-375. [PMID: 29226103 PMCID: PMC5719194 DOI: 10.14218/jcth.2017.00006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 05/28/2017] [Accepted: 06/26/2017] [Indexed: 12/14/2022] Open
Abstract
Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B.
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Affiliation(s)
- Xie-Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yong-Peng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence to: Yong-Peng Chen, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Tel: +86-20-62787432, Fax: +86-20-62786530, E-mail:
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Zhang Z, Li J, Wang P, He T, Ouyang Y, Huang Y. Nomogram for cirrhosis in patients with chronic hepatitis B: A simple self-assessed scale for individual risk of cirrhosis. Sci Rep 2017; 7:17493. [PMID: 29235488 PMCID: PMC5727495 DOI: 10.1038/s41598-017-17685-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 11/29/2017] [Indexed: 12/26/2022] Open
Abstract
The aim of this retrospective study was to establish a simple self-assessed scale for individual risk of cirrhosis in patients with chronic hepatitis B. A total of 1808 consecutive patients were enrolled and analyzed. According to the results of multivariate logistic regression analysis, a simple nomogram was calculated for cirrhosis. The area under receiver operating characteristic curves (AUROCs) were calculated to compare the diagnostic accuracy of nomogram with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), and S index. The AUROCs of nomogram for cirrhosis were 0.807 (adjusted AUROC 0.876) in model group and 0.794 (adjusted AUROC0.866) in validation group. DeLong's test and Brier Score further demonstrated that nomogram was superior to APRI, FIB-4 and S index in both model group and validation group. The patients with nomogram <0.07 could be defined as low risk group with cirrhosis prevalence lower than 4.3% (17/397). The patients with nomogram >0.52 could be defined as high risk group with cirrhosis prevalence higher than 73.0% (119/163). In conclusion, as a self-assessed style, simple, non-invasive, economical, convenient, and repeatable scale, nomogram is suitable to serve as a massive health screening tool for cirrhosis in CHB patients and further external validation is needed.
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Affiliation(s)
- Zhiqiao Zhang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Jing Li
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Peng Wang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China.
| | - Tingshan He
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Yanling Ouyang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Yiyan Huang
- Department of Infectious Diseases, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
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16
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Liang XE, Zhong C, Huang L, Yang S, Zhu Y, Chen Y, Hou J. Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers. J Gastroenterol Hepatol 2017; 32:459-465. [PMID: 27346683 DOI: 10.1111/jgh.13475] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers. METHODS A total of 236 compensated CHB patients with alanine transferase lower than five times upper limit of normal, liver biopsies, transient elastography, and routine blood tests were included. Performance of stepwise combination of transient elastography and routine biomarkers was analyzed. RESULTS The area under the receiver operating characteristics curve for detecting cirrhosis was 0.876 for transient elastography, 0.794 for fibrosis index based on the four factors (FIB-4), 0.765 for age-platelet index (API), 0.715 for aspartate aminotransferase-platelet ratio index (APRI), and 0.661 for alanine-aspartate aminotransferase ratio, respectively. The numbers for significant fibrosis were 0.844, 0.662, 0.595, 0.695, and 0.510 in the same order. The proportion of patients determined as cirrhosis or non-cirrhosis was 66.5% by transient elastography, 41.1% by FIB-4, 14.4% by API, and 24.2% by APRI, respectively; the numbers for significant fibrosis were 55.5% by transient elastography, 11.9% by APRI, and none by the other serum markers. Stepwise combination of transient elastography and FIB-4/APRI increased positive predictive value of confirming cirrhosis diagnosis from 0.677 to 0.808 and 0.724, respectively; and the proportion of patients being determined in the state of cirrhosis and obviating liver biopsy was up to 76%. CONCLUSION By transient elastography-based stepwise combination with readily available serum markers, performance of detecting compensated CHB cirrhosis could be significantly improved in terms of diagnosis accuracy and proportion of obviating liver biopsy.
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Affiliation(s)
- Xie Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chunxiu Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liwen Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuling Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Youfu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Liang XE, Dai L, Yang SL, Zhong CX, Peng J, Zhu YF, Chen YP, Hou JL. Combining routine markers improves the accuracy of transient elastography for hepatitis B cirrhosis detection. Dig Liver Dis 2016; 48:512-518. [PMID: 26965782 DOI: 10.1016/j.dld.2016.02.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 02/08/2016] [Accepted: 02/10/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Vibration Controlled Transient Elastography (VCTE) is a non-invasive test for liver fibrosis and cirrhosis but may be inaccurate in some patients, especially in those with chronic hepatitis B. This study aims at improving the accuracy of VCTE in cirrhosis detection by combining ultrasound and routine blood parameters. METHODS Hepatitis B patients with liver biopsies samples ≥20mm underwent VCTE, ultrasound and blood tests, and were divided into training set (n=170) and validation set (n=75). RESULTS An algorithm consisting of VCTE, international normalization ratio (INR), ultrasonic hepatic vessel and platelet count (CIR-4) and a VCTE-based cirrhosis six-index score (CIR-6) comprised VCTE, INR, platelet, albumin, ultrasonic hepatic vessel and liver parenchyma were derived. In training set, area under receiver operating characteristics curve of CIR-6 and CIR-4 to detect cirrhosis was 0.946 and 0.945, respectively, which was superior to that of VCTE 0.907. CIR-4 could save more liver biopsies. In validation set, CIR-6 detected cirrhosis with accuracy similar to that in training set. However, the sensitivity of CIR-4 and VCTE in validation set lowered to 0.538 and 0.846, respectively. CONCLUSIONS Combining routine markers improve the accuracy of VCTE for cirrhosis detection in hepatitis B patients. CIR-6 may be more valuable.
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Affiliation(s)
- Xie Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lin Dai
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shu Ling Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chun Xiu Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - You Fu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yong Peng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Jin Lin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Peng J, Cai S, Yu T, Chen Y, Zhu Y, Sun J. Aspartate aminotransferase to platelet ratio index – a reliable predictor of therapeutic efficacy and improvement of Ishak score in chronic hepatitis B patients treated with nucleoside analogues. Scandinavian Journal of Clinical and Laboratory Investigation 2016; 76:133-42. [DOI: 10.3109/00365513.2015.1125013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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19
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1918] [Impact Index Per Article: 213.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Huang YH, Chen YX, Zhang LJ, Chen ZX, Wang XZ. Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells. Int J Mol Med 2014; 34:677-86. [PMID: 24993843 PMCID: PMC4121348 DOI: 10.3892/ijmm.2014.1831] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 06/17/2014] [Indexed: 12/19/2022] Open
Abstract
Liver fibrosis is the common pathological outcome for the majority of chronic liver diseases. Interleukin-10 (IL-10) is a cytokine that downregulates proinflammatory responses and has a modulatory effect on liver fibrogenesis. However, little is known regarding the effect of rat interleukin-10 (rIL-10) gene by hydrodynamics-based transfection (HBT) on liver fibrosis in rats. The aim of this study was to investigate the effect of the rIL-10 gene by HBT on the progression of liver fibrosis induced by porcine serum (PS) in rats and explore its possible mechanism. Plasmid-expressing rIL-10 was transferred into rats by HBT and immunohistochemistry and RT-PCR were used to detect the major organ expressing rIL-10. Liver fibrosis was induced in rats by intraperitoneal administration of PS for 8 weeks. Plasmid pcDNA3-rIL-10 solution was administered weekly by HBT starting at the 5th week. Liver function and hepatic histology were examined. The possible molecular mechanisms of rIL-10 gene therapy were assessed in liver tissue and hepatic stellate cells (HSCs) co-cultured with BRL cells (a hepatocyte line) in vitro. The results showed rIL-10 expression occurred mainly in the liver following rIL-10 gene transfer by HBT. Maintaining a stable expression of rIL-10 in serum was assessed by repeated administration. The rIL-10 gene treatment attenuated liver inflammation and fibrosis in PS-induced fibrotic rats, reduced the deposition of collagen and the expression of α-smooth muscle actin (α-SMA) in fibrotic rats. The in vitro experiment showed that the expression of a-SMA and procollagen type I in HSCs co-cultured with the BRL-transfected rIL-10 gene were significantly decreased. These findings indicate that rIL-10 gene therapy by HBT attenuates PS-induced liver fibrosis in rats and that its mechanism is associated with rIL-10 inhibiting the activation of HSCs and promoting the degeneration of collagen.
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Affiliation(s)
- Yue-Hong Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Yun-Xin Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Li-Juan Zhang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Zhi-Xin Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xiao-Zhong Wang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
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