|
1
|
Buzas R, Ciubotaru P, Faur AC, Preda M, Ardelean M, Georgescu D, Dumitrescu P, Lighezan DF, Popa MD. Correlation of the FIB-4 Liver Biomarker Score with the Severity of Heart Failure. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1943. [PMID: 39768827 PMCID: PMC11679668 DOI: 10.3390/medicina60121943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 11/19/2024] [Accepted: 11/23/2024] [Indexed: 01/11/2025]
Abstract
Background and Objectives: Heart failure is associated with high morbidity and mortality and linked with several pre-existing health conditions and risk factors. Early detection and prompt management in heart failure improves patient outcomes. Liver involvement is associated with heart failure disease progression, and hence liver biomarkers and liver fibrosis may have a prognostic impact. Several blood test based markers and scoring systems estimate liver fibrosis and hence can be useful prognostic tools. Materials and Methods: We retrospectively analyzed a series of 303 patients with decompensated heart failure in a city in western Romania over a period of 6 months. Several biochemical parameters were measured, the FIB-4 score was estimated and echocardiography was performed. Results for targeted variables are presented using descriptive statistics. Patients were analyzed based on their LVEF categories. Statistical analysis was based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables. Pairwise comparisons were performed based on Bonferroni adjusted significance tests. The correlations between FIB-4 score, LVEF and NT-pro BNP in patients with and without diabetes and hypertension were explored using Spearman's correlation coefficient. Result: Age, gender, NYHA class, death, history of (h/o) type 2 diabetes mellitus (T2DM), h/o coronary artery disease (CAD), h/o arrhythmias, sodium, potassium, creatinine, eGFR, uric acid, NT-pro BNP, left atrial volume, LDL, HDL, and TG were analyzed by LVEF categories using ANOVA one-way tests, Chi-square tests, and Bonferroni correction comparisons. We found a strong statistically significant correlation between each of NT-pro BNP, left atrial volume, LDL, and HDL with the LVEF categories. Discussion: Early detection of cardiac dysfunction leads to better management in patients with cardiovascular risk factors including diabetes and hypertension. High LDL and low HDL levels contribute to a reduction in left ventricular (LV) function. Available literature suggests the FIB-4 score as superior to other non-invasive markers of fibrosis. It utilizes the patient's age, platelet count, AST, and ALT, which can be available retrospectively, making it an easy and inexpensive tool. FIB-4 score has a few limitations. Conclusions: Our study has shown a statistically significant positive correlation between severity categories of LVEF and FIB-4 score for heart failure patients with and without diabetes, and for heart failure patients with or without hypertension. We propose the implementation of FIB-4 score as a prognostic tool for heart failure.
Collapse
Affiliation(s)
- Roxana Buzas
- 1st Medical Semiology, Internal Medicine, Department V, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania (P.C.); (D.G.)
- Center for Advanced Research in Cardiovascular Pathology and in Hemostaseology, 300041 Timisoara, Romania
| | - Paul Ciubotaru
- 1st Medical Semiology, Internal Medicine, Department V, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania (P.C.); (D.G.)
- Center for Advanced Research in Cardiovascular Pathology and in Hemostaseology, 300041 Timisoara, Romania
| | - Alexandra Corina Faur
- Department of Anatomy and Embryology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania
| | - Marius Preda
- Second Discipline of Surgical Semiology, Department IX—Surgery—1, “Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Second Clinic of General Surgery and Surgical Oncology, Emergency Clinical Municipal Hospital, 300079 Timisoara, Romania
- Breast Surgery Research Center, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Melania Ardelean
- 1st Medical Semiology, Internal Medicine, Department V, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania (P.C.); (D.G.)
- Center for Advanced Research in Cardiovascular Pathology and in Hemostaseology, 300041 Timisoara, Romania
| | - Doina Georgescu
- 1st Medical Semiology, Internal Medicine, Department V, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania (P.C.); (D.G.)
- Center for Advanced Research in Cardiovascular Pathology and in Hemostaseology, 300041 Timisoara, Romania
| | - Patrick Dumitrescu
- General Medicine, “Victor Babeș” University of Medicine and Pharmacy from Timișoara, Eftimie Murgu Sq. No. 2, 300041 Timișoara, Romania;
| | - Daniel Florin Lighezan
- 1st Medical Semiology, Internal Medicine, Department V, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania (P.C.); (D.G.)
- Center for Advanced Research in Cardiovascular Pathology and in Hemostaseology, 300041 Timisoara, Romania
| | - Mihaela-Diana Popa
- Department of Microbiology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| |
Collapse
|
|
2
|
Talebzadeh A, Ghaffari H, Ghaffari K, Yazdanpanah S, Yousefi Goltappeh B, Eslami M, Ghasemi A. The effect of vitamin D deficiency on platelet parameters in patients with COVID-19. Front Cell Infect Microbiol 2024; 14:1360075. [PMID: 38524183 PMCID: PMC10957640 DOI: 10.3389/fcimb.2024.1360075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/26/2024] [Indexed: 03/26/2024] Open
Abstract
Introduction Since there is very little information about the relationship between platelet parameters and vitamin D concentration in patients with COVID-19, the aim of this study is to investigate the relationship between serum vitamin D level and platelet parameters in patients with COVID-19 and to compare these parameters in patients with COVID-19 without vitamin D deficiency and, subsequently, the prognostic value of these parameters in cases of vitamin D deficiency. Methods Seven hundred and forty-three patients diagnosed with COVID-19 were enrolled in this study. Patients were divided into two groups: those with and without vitamin D deficiency. The associations between platelet indices and vitamin D levels were analyzed by Pearson's correlation analysis and a one-way ANOVA test. Results Platelet count and mean platelet volume (MPV) were significantly higher in the patients with vitamin D deficiency than in the patients without vitamin D deficiency. There was a significant negative correlation between platelet count and MPV with vitamin D levels in patients with vitamin D deficiency (r = -0.835, P = 0.001 & r = -0.324, P = 0.042, respectively). Vitamin D levels in COVID-19 patients can determine the platelet count and MPV of the patients. Discussion The aforementioned results imply that maintaining an elevated concentration of vitamin D in COVID-19 patients is important because it is associated with a decrease in MPV, which in turn reduces susceptibility to diseases such as coronary artery disease.
Collapse
Affiliation(s)
- Amirhossein Talebzadeh
- Department of Biochemistry and Hematology, Semnan University of Medical Sciences, Semnan, Iran
| | - Hadi Ghaffari
- Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran
| | - Kazem Ghaffari
- Department of Base and Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran
| | - Sorur Yazdanpanah
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Majid Eslami
- Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Ghasemi
- Department of Biochemistry and Hematology, Semnan University of Medical Sciences, Semnan, Iran
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| |
Collapse
|
|
3
|
Bolat S, Büyüktuna SA, İpekten F, Doğan K, Zararsız G, Doğan HO. Analysis of liver fibrosis equations as a potential role of predictive models in Crimean-Congo hemorrhagic fever. Acta Trop 2024; 251:107121. [PMID: 38218391 DOI: 10.1016/j.actatropica.2024.107121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/27/2023] [Accepted: 01/10/2024] [Indexed: 01/15/2024]
Abstract
Crimean-Congo Hemorrhagic Fever (CCHF) is a formidable global health concern, characterized by its rapid onset and high fatality rate. Distinguishing between patients at different stages remains challenging because of overlapping clinical features. This study aimed to evaluate the diagnostic efficacy of 14 hepatic fibrosis indices for distinguishing fatal cases and intensive care unit requirement (ICU) in CCHF. This study enrolled 194 patients with confirmed CCHF. Laboratory measurements were performed using auto analyzers. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas. Time-dependent receiver operating characteristic (tdROC) curve analyses were employed to evaluate the predictive effects of hepatic fibrosis indices on both intensive care unit requirement and overall survival among patients. Regarding the tdROC analyses results, the highest area under the curve statistics were obtained for the baseline S-INDEX, KING, and GPRI scores (0.920, 0.913, and 0.909 respectively) in the estimation of ten-day survival, and the baseline KING, Goteborg University cirrhosis index (GUCI), and gamma-glutamyl transferase to platelet ratio index (GPRI) scores (0.783, 0.773, and 0.769 respectively) in the estimation of intensive care requirements for up to ten days. S-index and KING index emerged as early predictors of ten-day survival, while KING, GUCI, and GPRI indices demonstrated predictive capabilities for ICU admission on the first day. The identified indices have the potential to assist healthcare providers in making timely and informed decisions regarding patient management and treatment strategies. Further research and validation are warranted to solidify the role of these hepatic fibrosis indices in the clinical setting and enhance their broader applicability in the management of CCHF.
Collapse
Affiliation(s)
- Serkan Bolat
- Department of Medical Biochemistry, School of Medicine, Sivas Cumhuriyet University, Sivas 58140, Turkey.
| | - Seyit Ali Büyüktuna
- Department of Infectious Diseases, School of Medicine, Sivas Cumhuriyet University, Sivas 58140, Turkey
| | - Funda İpekten
- Department of Biostatistics, School of Medicine, Erciyes University, Kayseri 38280, Turkey
| | - Kübra Doğan
- Department of Biochemistry, Sivas Numune Hospital, Sivas 58140, Turkey
| | - Gökmen Zararsız
- Department of Biostatistics, School of Medicine, Erciyes University, Kayseri 38280, Turkey
| | - Halef Okan Doğan
- Department of Medical Biochemistry, School of Medicine, Sivas Cumhuriyet University, Sivas 58140, Turkey
| |
Collapse
|
|
4
|
Escouto GS, Port GZ, Tovo CV, Fernandes SA, Peres A, Dorneles GP, Houde VP, Varin TV, Pilon G, Marette A, Buss C. Probiotic Supplementation, Hepatic Fibrosis, and the Microbiota Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial. J Nutr 2023; 153:1984-1993. [PMID: 37225124 DOI: 10.1016/j.tjnut.2023.05.019] [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: 10/26/2022] [Revised: 04/28/2023] [Accepted: 05/19/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment. OBJECTIVES To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients. METHODS In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE. RESULTS The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment. CONCLUSIONS Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047.
Collapse
Affiliation(s)
- Giselle S Escouto
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriela Z Port
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Cristiane V Tovo
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Sabrina A Fernandes
- Graduate Study Program (GSP) in Medicine: Hepatology (GSP-Hepatology), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Alessandra Peres
- Basic Health Sciences Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gilson P Dorneles
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Vanessa P Houde
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Thibault V Varin
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Geneviève Pilon
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - André Marette
- Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada
| | - Caroline Buss
- Graduate Study Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Nutrition Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
| |
Collapse
|
|
5
|
Evlice M, Bedir Ö, Coşkun M, Paçacı E, Cerşit S, Öcal L, Gürsoy MO, Şen Ö, Kurt İH. The relationship between echocardiographic parameters and albumin bilirubin (ALBI) score in patients with isolated secundum type atrial septal defect. Echocardiography 2023; 40:350-358. [PMID: 36973228 DOI: 10.1111/echo.15556] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/08/2023] [Accepted: 02/24/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND It has been shown that the increase in volume and pressure in the right heart chambers increases liver stiffness. The Albumin-Bilirubin (ALBI) score is a useful and easy-to-use score for objectively assessing liver function. There is no information in the literature about changes in ALBI score in patients with atrial septal defect (ASD). The aim of our study is to investigate the changes in ALBI score and its clinical impact in patients with ASD. METHODS Of the 206 analyzed patients, 77 were excluded. The remaining 129 patients with secundum type ASD with left to right shunt were divided into three groups; Group I (16 patients with Qp/Qs < 1.5 and defect diameter < 10 mm), Group II (52 patients with Qp/Qs > 1.5 and defect diameter 10-20 mm) and Group III (61 patients with Qp/Qs > 1.5 and defect diameter > 20 mm). The ALBI score was calculated based on serum albumin and total bilirubin levels using the following formula: ALBI = (log10 bilirubin [umol/L] * .66) + (albumin [g/L] * -.085). RESULTS ALBI scores as well as total bilirubin levels, transaminases, and functional-structural heart abnormalities (increase in RA and RV dimensions, sPAP, ASD size and decrease in LVEF and TAPSE) showed a significant increasing trend from Group I to Group III (p < .001 for all comparisons). The mean ALBI scores for Group I, Group II, and Group III were -3.71 ± .37, -3.51 ± .25, and -3.27 ± .34, respectively. In multivariate linear regression analysis, ASD size, sPAP, RV-RA diameter were found to be significantly associated with increased ALBI score. CONCLUSION The ALBI score offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in patients with ASD. ASD size, sPAP, RV and RA diameters were significantly associated with ALBI score.
Collapse
Affiliation(s)
- Mert Evlice
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| | - Ömer Bedir
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| | - Mükremin Coşkun
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| | - Emre Paçacı
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| | - Sinan Cerşit
- Department of Cardiology, Health Sciences University -Kartal Koşuyolu Training and Research Hospital, İstanbul, Turkey
| | - Lütfi Öcal
- Department of Cardiology, Health Sciences University -Kartal Koşuyolu Training and Research Hospital, İstanbul, Turkey
| | | | - Ömer Şen
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| | - İbrahim Halil Kurt
- Department of Cardiology, Health Sciences University -Adana City Training and Research Hospital, Adana, Turkey
| |
Collapse
|
|
6
|
Tu Z, Wang Y, Wang Y, Huang J, Han Y, Ji Q, Cao X, Wen X, Wang Y, Jin Q. TR score: A noninvasive model to predict histological stages in patients with primary biliary cholangitis. Front Immunol 2023; 14:1152294. [PMID: 37006277 PMCID: PMC10060872 DOI: 10.3389/fimmu.2023.1152294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
IntroductionThe aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate.MethodsA total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model.ResultsThis study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer’s stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000).ConclusionTR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC.
Collapse
Affiliation(s)
- Zhixin Tu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yao Wang
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, China
| | - Yan Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jianjie Huang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yujin Han
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Qijia Ji
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaoxuan Cao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaoyu Wen
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yang Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Qinglong Jin
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
- *Correspondence: Qinglong Jin,
| |
Collapse
|
|
7
|
Gluvic Z, Tomasevic R, Bojovic K, Obradovic M, Isenovic ER. Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines. EMERGENCY AND CRITICAL CARE MEDICINE 2021; 2:12-22. [DOI: 10.1097/ec9.0000000000000016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD's possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients.
Collapse
Affiliation(s)
- Zoran Gluvic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ksenija Bojovic
- Clinical Centre of Serbia, Clinic of Infectious and Tropical Diseases, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
|
8
|
Roe JD, Garcia LA, Klimentidis YC, Coletta DK. Association of PNPLA3 I148M with Liver Disease Biomarkers in Latinos. Hum Hered 2021; 86:21-27. [PMID: 34749354 DOI: 10.1159/000520734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/03/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help to estimate liver damage, including AST-to-ALT ratio, AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. The aims of the present study were to (1) perform an association analysis of the patatin-like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) variant with ALT, AST, and various liver fibrosis indices, and (2) determine whether there are gender-related differences in these associations. METHODS We obtained demographic, anthropometric, and metabolic phenotypes from Latino adult participants (n = 503, 64% female, 36.4 ± 0.5 years) from the Arizona Insulin Resistance (AIR) registry. SNP genotyping of I148M was performed using the TaqMan allelic discrimination assay. We used linear regression for the association analyses of the genotypes with ALT, AST, and the various liver fibrosis indices. We included genotype, age, body mass index, and alcohol status in the linear regression model. RESULTS The variant I148M was in Hardy-Weinberg equilibrium, with genotype distribution: non-risk CC 118, heterozygous CG 246, and risk GG 139. The G allele was significantly associated with increased ALT and AST levels (p = 7.8 × 10-7 and p = 9.7 × 10-6, respectively). Moreover, we showed that the G allele was significantly associated with higher APRI (p = 3.7 × 10-7) and FIB-4 score (p = 4.1 × 10-3). When we analyzed the data by gender, we observed similar significant trends for ALT, AST, and APRI (all, p < 0.01). In females, the G allele was significantly associated with increased FIB-4 score (p = 6.9 × 10-3), which was not observed in the males (p > 0.05). There was no association of the I148M variant with AST/ALT ratio nor NAFLD risk score, whether analyzed in all adults or by gender. DISCUSSION/CONCLUSION Our findings provide additional evidence of an association of PNPLA3 I148M with several liver disease biomarkers in male and female Latinos residing in the Southwest of the United States.
Collapse
Affiliation(s)
- Jonathan D Roe
- Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona, USA
| | - Luis A Garcia
- Department of Medicine, Division of Endocrinology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Center for Disparities in Diabetes Obesity, and Metabolism, University of Arizona, Tucson, Arizona, USA
| | - Yann C Klimentidis
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, USA
| | - Dawn K Coletta
- Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Department of Medicine, Division of Endocrinology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Center for Disparities in Diabetes Obesity, and Metabolism, University of Arizona, Tucson, Arizona, USA
| |
Collapse
|
|
9
|
Sato S, Tsuzura H, Kita Y, Ikeda Y, Kabemura D, Sato S, Amano N, Yatagai N, Murata A, Shimada Y, Genda T. Post‐treatment serum Wisteria floribunda agglutinin‐positive mac‐2‐binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication. JGH Open 2021; 5:1203-1209. [PMID: 34622009 PMCID: PMC8485411 DOI: 10.1002/jgh3.12655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 08/18/2021] [Accepted: 09/03/2021] [Indexed: 11/29/2022]
Abstract
Aims Recent advances of direct‐acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin‐positive mac‐2‐binding protein (WFA+‐M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+‐M2BP level and HCC development after the achievement of an SVR is unclear. Methods and Results We examined the association between WFA+‐M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]‐based therapy, n = 228; IFN‐free therapy, n = 294). Multivariate analysis revealed that a high WFA+‐M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215, P = 0.020), low platelet counts (HR = 0.876, P = 0.037), and old age (HR = 1.073, P = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA+‐M2BP level at SVR24 of ≥1.62 cut‐off index (COI) was the cut‐off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501–45.092, P < 0.001). The 3‐ and 5‐year cumulative incidences of HCC were 1% and 1.6% in patients with low WFA+‐M2BP at SVR24 (<1.62 COI), and 4.7% and 12.5% in patients with high WFA+‐M2BP (≥1.62 COI) were, respectively (P < 0.001). Conclusions The assessment of liver fibrosis using the WFA+‐M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN‐free therapy era.
Collapse
Affiliation(s)
- Shunsuke Sato
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Hironori Tsuzura
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Yuji Kita
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Yuji Ikeda
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Daishi Kabemura
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Sho Sato
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Nozomi Amano
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Noboru Yatagai
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Ayato Murata
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Yuji Shimada
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology Juntendo University Shizuoka Hospital Shizuoka Japan
| |
Collapse
|
|
10
|
Yamashita Y, Joshita S, Sugiura A, Yamazaki T, Kobayashi H, Wakabayashi SI, Yamada Y, Shibata S, Kunimoto H, Iwadare T, Matsumura M, Miyabayashi C, Okumura T, Ozawa S, Nozawa Y, Kobayashi N, Komatsu M, Fujimori N, Saito H, Umemura T. aMAP score prediction of hepatocellular carcinoma occurrence and incidence-free rate after a sustained virologic response in chronic hepatitis C. Hepatol Res 2021; 51:933-942. [PMID: 34216422 DOI: 10.1111/hepr.13689] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/14/2021] [Accepted: 06/25/2021] [Indexed: 02/08/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low-, medium-, and high-risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC-free following an SVR. CONCLUSION The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR.
Collapse
Affiliation(s)
- Yuki Yamashita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satoru Joshita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Ayumi Sugiura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Tomoo Yamazaki
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroyuki Kobayashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shun-Ichi Wakabayashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yosuke Yamada
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Soichiro Shibata
- Department of Gastroenterology, Japanese Red Cross Society Nagano Hospital, Nagano, Japan
| | - Hideo Kunimoto
- Department of Gastroenterology, Nagano Municipal Hospital, Nagano, Japan
| | - Takanobu Iwadare
- Department of Gastroenterology, Nagano Municipal Hospital, Nagano, Japan
| | - Makiko Matsumura
- Department of Gastroenterology, Nagano Chuo Hospital, Nagano, Japan
| | | | - Taiki Okumura
- Department of Gastroenterology, NHO Matsumoto Medical Center, Matsumoto, Japan
| | - Sachie Ozawa
- Department of Internal Medicine, Nagano Prefectural Kiso Hospital, Kiso, Japan
| | - Yuichi Nozawa
- Department of Gastroenterology, Ina Central Hospital, Ina, Japan
| | | | - Michiharu Komatsu
- Department of Gastroenterology, Japanese Red Cross Society Suwa Hospital, Suwa, Japan
| | - Naoyuki Fujimori
- Department of Gastroenterology, NHO Shinshu Ueda Medical Center, Ueda, Japan
| | - Hiromi Saito
- Department of Gastroenterology, Aizawa Hospital, Matsumoto, Japan
| | - Takeji Umemura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan.,Department of Life Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan
| |
Collapse
|
|
11
|
Oliveira A, Fernandes SA, Carteri RB, Tovo CV. EVALUATION OF REST ENERGY EXPENDITURE IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:157-163. [PMID: 34190778 DOI: 10.1590/s0004-2803.202100000-27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/17/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is currently considered a global public health problem, with changes in lifestyle being the effective way to treat the disease. To date, there is no recommended standard of assessment to determine the resting energy expenditure (REE) of patients with NAFLD, so that dietary therapy can be properly guided. OBJECTIVE To evaluate the REE of patients with NAFLD through indirect calorimetry and compare with different predictive formulas of REE and with REE by electrical bioimpedance analysis (BIA). Assess body composition through BIA, with NAFLD staging and the presence of comorbidities. METHODS They were evaluated in patients with NAFLD over 18 years of age treated at the Gastroenterology outpatient clinic of a tertiary level hospital in southern Brazil. NAFLD staging was performed using liver biopsy or a non-invasive method. Weight, height and body mass index (BMI) were determined in all patients. The short version of the International Physical Activity Questionnaire was used to assess physical activity. Comorbidities as arterial hypertension, diabetes mellitus and dyslipidemia were evaluated. To estimate energy expenditure at rest, Harris-Benedict, Jeor Mifflin-St, World Health Organization and Schofield formulas were used. BIA was used to assess resting metabolic rate (RMR) and body mass, and to measure RMR, indirect calorimetry was also used. Associations between categorical variables were tested with Pearson's χ2 test and between groups with McNemar's test. The level of significance assumed was 5%. The degree of agreement between the REE measurement methods was assessed using the Blan-Altman test. RESULTS A total of 67 patients were evaluated, 70.5% male, with a mean age of 59 years and a mean BMI of 33.08 kg/m2 ±5.13. The average RMR per CI was 1,753 kcal ±614.58. When comparing the RMR estimate by different formulas with indirect calorimetry, only the Jeor Mifflin-St formula showed a statistically significant difference (P=0.0001), with a difference of +318.49 kcal. BIA and Harris Benedict's formula presented values closer to CI, 1,658 and 1,845 kcal respectively. CONCLUSION We suggest that the Jeor Mifflin-St formula should not be used to estimate the RMR in patients with NAFLD. In the absence of indirect calorimetry, some alternatives can be used safely in this population, such as BIA and the predictive formulas of Harris Benedict, Schofield and the World Health Organization.
Collapse
Affiliation(s)
- Andressa Oliveira
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Sabrina Alves Fernandes
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Randhall Bruce Carteri
- Universidade Federal do Rio Grande do Sul (UFRGS), Bioquímica, Porto Alegre, RS, Brasil.,Centro Universitário Metodista - IPA, Curso de Nutrição, Porto Alegre, RS, Brasil
| | - Cristiane Valle Tovo
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil.,UFCSPA, Departamento de Medicina Interna: Gastroenterologia, Porto Alegre, RS, Brasil
| |
Collapse
|
|
12
|
Bert F, Stahmeyer JT, Parpalea AL, Rossol S. Non-Invasive Reliable Methods to Objectify the Positive Influence of Hepatitis C Virus Treatment on Liver Stiffness. Gastroenterology Res 2021; 14:31-40. [PMID: 33737997 PMCID: PMC7935613 DOI: 10.14740/gr1347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 01/22/2021] [Indexed: 11/11/2022] Open
Abstract
Background Chronic active hepatitis C virus (HCV) infection is a major public health problem and causes liver fibrosis (LF) up to liver cirrhosis (LC). LF can be estimated by non-invasive, easy handling methods. With implementation of new HCV therapies, elimination rates of HCV are near 100%, resulting in less clinical complications and costs. The aim of our study was to evaluate the positive influence of HCV treatment on liver stiffness by non-invasive assessments of LF. Methods Sixty-two patients with HCV were treated with antiviral drug regimes. Serological fibrosis scores and ultrasound elastography (acoustic radiation force impulse and shear wave elasticity imaging (ARFI-SWEI)) were used for LF assessment on day 0 and 6 months after therapy. Results Antiviral treatment was successful in all cases. ARFI-SWEI measurements showed an improvement of all LF stages. Results of serological markers and scores were heterogeneous. Significant positive effects of treatment were seen for aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores, only. Further Pearson's coefficient showed moderate till very high correlations for ARFI-SWEI and FIB-4/APRI scores. Conclusion Today HCV therapy is able to cure HCV. Positive influences are improvement of LF stages. ARFI-SWEI, APRI and FIB-4 score are useful, easy handling tools to verify positive influence of HCV treatment on LF alone or in combination.
Collapse
Affiliation(s)
- Florian Bert
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/Main, Germany
| | - Jona Theodor Stahmeyer
- Institute for Epidemiology, Social Medicine and Health Systems Research, Medical School, Hannover, Germany
| | | | - Siegbert Rossol
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/Main, Germany
| |
Collapse
|
|
13
|
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.
Collapse
|
|
14
|
Tovo CV, Villela-Nogueira CA, Leite NC, Panke CL, Port GZ, Fernandes S, Buss C, Coral GP, Cardoso AC, Cravo CM, Calçado FL, Rezende GFM, Ferreira FC, Araujo-Neto JM, Perez RDM, Moraes-Coelho HS, de Mattos AA. Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 2020; 18:445-449. [PMID: 31031166 DOI: 10.1016/j.aohep.2018.09.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/17/2018] [Accepted: 09/28/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.
Collapse
Affiliation(s)
- Cristiane V Tovo
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
| | | | - Nathalie C Leite
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Carine L Panke
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Gabriela Z Port
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Sabrina Fernandes
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Caroline Buss
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Gabriela P Coral
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Ana C Cardoso
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Claudia M Cravo
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Fernanda L Calçado
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Guilherme F M Rezende
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Frederico C Ferreira
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - João M Araujo-Neto
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Renata de M Perez
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Henrique S Moraes-Coelho
- Department of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Angelo A de Mattos
- Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| |
Collapse
|
|
15
|
Zhang TT, Ye SS, Liang J, Bai L. Prognostic value of non-invasive fibrosis indices post-curative resection in hepatitis-B-associated hepatocellular carcinoma patients. Exp Biol Med (Maywood) 2020; 245:703-710. [PMID: 32223331 DOI: 10.1177/1535370220914252] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPACT STATEMENT Non-invasive fibrosis indices, according to regular laboratory and clinical data, could be useful in assessing liver fibrosis in chronic hepatitis patients. However, the role of these biomarkers remains unclear in predicting the outcome of HBV-associated HCC in patients. This study was carried out retrospectively and included a relatively large sample size (n = 405) with a heterogeneous population of HBV infected patients and longer duration of prospective follow-up. Our study suggested that APRI and Fibro-α Scores are inversely correlated with overall survival in HBV-associated HCC patients. Meanwhile, GUCI, King Score, and APRI were highly correlated with cirrhosis status. Also, in subgroups of cirrhosis or non-cirrhosis, Fibro-α Scores could differentiate patients with good prognosis from those with poor outcome. This result would aid clinicians in acquiring preventive and therapeutic methods in patients with high risk.
Collapse
Affiliation(s)
- Ting-Ting Zhang
- Department of Oncology, Peking University International Hospital, Beijing 102206, China
| | - Si-Si Ye
- Department of Oncology, Chinese PLA General Hospital, Beijing 100853, China
| | - Jun Liang
- Department of Oncology, Beijing Cancer Hospital, Beijing 101142, China
| | - Li Bai
- Department of Oncology, Chinese PLA General Hospital, Beijing 100853, China
| |
Collapse
|
|
16
|
Hu CL, Du QC, Wang ZX, Pang MQ, Wang YY, Li YY, Zhou Y, Wang HJ, Fan HN. Relationship between platelet-based models and the prognosis of patients with malignant hepatic tumors. Oncol Lett 2020; 19:2384-2396. [PMID: 32194738 PMCID: PMC7039130 DOI: 10.3892/ol.2020.11317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors.
Collapse
Affiliation(s)
- Chen-Liang Hu
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Qian-Cheng Du
- Department of General Surgery, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, P.R. China
| | - Zhi-Xin Wang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Ming-Quan Pang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Yan-Yan Wang
- Department of Hematology, Affiliated Fuyang Hospital of Anhui Medical University, Fuyang, Anhui 236000, P.R. China
| | - Ying-Yu Li
- Department of Medical Record Room, The Affiliated Hospital of Qinghai University, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Ying Zhou
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Hai-Jiu Wang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| | - Hai-Ning Fan
- Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, Qinghai 81000, P.R. China
| |
Collapse
|
|
17
|
Zhou YL, Guo JL, Tang RJ, Ma HJ, Chen YJ, Lin SM. High dietary lipid level alters the growth, hepatic metabolism enzyme, and anti-oxidative capacity in juvenile largemouth bass Micropterus salmoides. FISH PHYSIOLOGY AND BIOCHEMISTRY 2020; 46:125-134. [PMID: 31522360 DOI: 10.1007/s10695-019-00705-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 09/04/2019] [Indexed: 06/10/2023]
Abstract
The present study was conducted to investigate the effects of high dietary lipid levels on growth, metabolism, antioxidant capacity, and immune responses of largemouth bass. Fish (initial body weight 13.38 ± 0.11 g) were fed three isonitrogenous semi-purified diets containing 5%, 10%, and 20% lipid, respectively. The results indicated that fish fed 10% lipid diet showed significantly better final body weight, specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) compared with that fed 5% lipid diet. Meanwhile, fish fed 20% lipid diet had a significantly higher viscera ratio (VR), hepatosomatic index (HSI), intraperitoneal fat ratio (IPF), and liver lipid content than those fed the other diets. Higher alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) contents, and LDL-C/HDL-C value in plasma were recorded in fish fed 20% lipid diet, while higher insulin contents were obtained in fish fed 5% lipid diet. In addition, the highest carnitine palmitoyltransferase I (CPT1), AMP-activated protein kinase (AMPK), fructose-1,6-bisphosphatase (FBPase), and phosphoenolpyruvate carboxykinase (PEPCK) activities in the liver were also observed in fish fed 20% lipid diet. However, fish fed 20% lipid diet had a significantly lower superoxide dismutase (SOD) and catalase (CAT) activities and higher MDA contents in liver than those fed the other diets. The higher nitric oxide (NO) contents and inducible nitric oxide synthase (iNOS) activity in liver were recorded in fish fed 10% lipid diet. Moreover, the alkaline phosphatase (ALP), inducible nitric oxide synthase (iNOS) and lysozyme activities, and nitric oxide (NO) contents in plasma were higher in fish fed the 10% diets than the other groups. In conclusion, high dietary lipid levels could suppress growth performance and liver anti-oxidative capacity, and reduce immune responses of largemouth bass.
Collapse
Affiliation(s)
- Yue-Lang Zhou
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Animal Science and Technology, Southwest University, Chongqing, 400715, People's Republic of China
| | - Jia-Ling Guo
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Animal Science and Technology, Southwest University, Chongqing, 400715, People's Republic of China
| | - Ren-Jun Tang
- Liangping District Agriculture Commission, Chongqing, 400020, People's Republic of China
| | - Hui-Jia Ma
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Animal Science and Technology, Southwest University, Chongqing, 400715, People's Republic of China
| | - Yong-Jun Chen
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Animal Science and Technology, Southwest University, Chongqing, 400715, People's Republic of China
| | - Shi-Mei Lin
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Animal Science and Technology, Southwest University, Chongqing, 400715, People's Republic of China.
| |
Collapse
|
|
18
|
Shao LN, Zhang ST, Wang N, Yu WJ, Chen M, Xiao N, Duan Y, Pan LZ, Song WQ, Xia YX, Zhang L, Qi N, Liu M, Zhou SH. Platelet indices significantly correlate with liver fibrosis in HCV-infected patients. PLoS One 2020; 15:e0227544. [PMID: 31917827 PMCID: PMC6952095 DOI: 10.1371/journal.pone.0227544] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 11/22/2019] [Indexed: 12/14/2022] Open
Abstract
AIM A total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices. METHODS The determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan). RESULTS The analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group. CONCLUSIONS Our results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression.
Collapse
Affiliation(s)
- Lin-Nan Shao
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Shu-Ting Zhang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ni Wang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Wei-Jian Yu
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Mei Chen
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Nan Xiao
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ying Duan
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ling-Zi Pan
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Wen-Qian Song
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Yue-Xin Xia
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Li Zhang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ning Qi
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ming Liu
- Department of Cell Biology, Dalian Medical University, Dalian, Liaoning, China
| | - Shi-Hang Zhou
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| |
Collapse
|
|
19
|
The assessment of liver fibrosis in children with obesity on two methods: transient and two dimensional shear wave elastography. Sci Rep 2019; 9:19800. [PMID: 31875010 PMCID: PMC6930277 DOI: 10.1038/s41598-019-56358-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022] Open
Abstract
The aim of this study was to assess the liver stiffness values in children with obesity versus healthy children on 2D-SWE and TE taking into account different laboratory parameters. We performed a case-control study on 287 children aged between 3 to 18 years, admitted in a Romanian Pediatric Tertiary Hospital, which we divided according to the body mass index (BMI) into two groups: the study group-77 children with obesity, and control group-210 children with normal weight. All children underwent anamnesis, clinical exam, laboratory parameters, ultrasound exam, and elastography. Children with obesity presented higher values of platelets, AST, ALT, and AAR as compared to control group (p = 0.0005/p = 0.0065/p < 0.0001/p < 0.0001). We found no significant differences for APRI between the two groups (p = 0.9827), although the values were higher in children with obesity. Significantly higher values of liver stiffness in children with obesity on both 2D-SWE and TE (p = 0.0314/p < 0.0001) were obtained. Similarly, the velocity values measured by 2D-SWE were also significantly higher in the study group (p < 0.0001). Our findings revealed significantly higher levels of platelets, transaminases, AAR, and liver stiffness values on both TE and 2D-SWE in children with obesity. 2D-SWE and TE might represent useful non-invasive methods for predicting liver impairment associated to pediatric obesity.
Collapse
|
|
20
|
Sayyar M, Saidi M, Zapatka S, Deng Y, Ciarleglio M, Garcia-Tsao G. Platelet count increases after viral elimination in chronic HCV, independent of the presence or absence of cirrhosis. Liver Int 2019; 39:2061-2065. [PMID: 31365178 PMCID: PMC11340272 DOI: 10.1111/liv.14203] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 07/02/2019] [Accepted: 07/28/2019] [Indexed: 12/29/2022]
Abstract
Platelet (PLT) count is included in non-invasive scores assessing liver fibrosis in patients with chronic liver disease. Improvement in fibrosis scores after antiviral treatment for hepatitis C virus (HCV) has been interpreted as indicative of an improvement in fibrosis. HCV itself can lower PLT and, therefore, an increase in PLT would be expected after viral elimination irrespective of pretreatment fibrosis stage. The aim of this study was to investigate this hypothesis by assessing changes in PLT after viral elimination in patients with chronic HCV stratified by the absence or presence of cirrhosis. METHODS Retrospective analysis of patients with chronic HCV infection treated with direct-acting antivirals (DAAs) who achieved viral elimination and in whom PLT were obtained prior to treatment, at first negative HCV-RNA, at treatment completion and at 6 months, and 1 year after treatment completion. Comparisons were made between patients with and without cirrhosis. RESULTS A total of 420 patients with chronic HCV were treated, of which 208 were excluded, leaving 212 patients eligible for analysis (142 without cirrhosis, 70 with cirrhosis). Overall, a significant increase in PLT was observed up to 1 year after antiviral treatment completion (P < .001). Changes in PLT between patients with and without cirrhosis were not significantly different at any of the time points. CONCLUSION Platelet count increased significantly in patients with HCV who achieved viral elimination irrespective of the absence or presence of cirrhosis. This suggests that changes in PLT post-viral elimination should not be interpreted as being reflective of changes in liver fibrosis or portal hypertension.
Collapse
Affiliation(s)
- Mubarak Sayyar
- Section of Digestive Diseases, VA-Connecticut Healthcare System, West Haven, CT, USA
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Marie Saidi
- Section of Digestive Diseases, VA-Connecticut Healthcare System, West Haven, CT, USA
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Susan Zapatka
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Yanhong Deng
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Maria Ciarleglio
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, VA-Connecticut Healthcare System, West Haven, CT, USA
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
21
|
Du QC, Hu CL, Wang YY, Zhou Y. Comparison of the prognostic value of platelet-based prognostic models in patients with malignant hepatic tumors after TACE therapy. Acta Cir Bras 2019; 34:e201900710. [PMID: 31531530 PMCID: PMC6756010 DOI: 10.1590/s0102-865020190070000010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
PURPOSE To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. METHODS In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. RESULTS Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. CONCLUSION This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.
Collapse
Affiliation(s)
- Qian Cheng Du
- Master, Department of General Surgery, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China. Intellectual, scientific, conception and design of the study; acquisition, analysis and interpretation of data; technical procedures; statistical analysis; manuscript preparation, final approval
| | - Chen Liang Hu
- Master, Department of Hepatopancreatobiliary Surgery, the Affiliated Hospital of Qinghai University, Xining, China. Intellectual, scientific, conception and design of the study; acquisition, analysis and interpretation of data; technical procedures; statistical analysis; manuscript preparation, final approval
| | - Yan Yan Wang
- Master, Department of Hematology, Affiliated Fuyang Hospital of Anhui Medical University, Fuyang, China. Intellectual, scientific, conception and design of the study; acquisition, analysis and interpretation of data; technical procedures; statistical analysis; manuscript preparation, final approval
| | - Ying Zhou
- Full Professor, Department of Hepatopancreatobiliary Surgery, the Affiliated Hospital of Qinghai University and Qinghai Province Key Laboratory of Hydatid Disease Research, Qinghai University, Xining, China. Acquisition, analysis and interpretation of data; technical procedures; critical revision; manuscript preparation, final approval
| |
Collapse
|
|
22
|
Brock WJ, Beaudoin JJ, Slizgi JR, Su M, Jia W, Roth SE, Brouwer KLR. Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease. Int J Toxicol 2019; 37:144-154. [PMID: 29587557 DOI: 10.1177/1091581818760746] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Polycystic kidney disease is characterized by the progressive development of kidney cysts and declining renal function with frequent development of cysts in other organs including the liver. The polycystic kidney (PCK) rat is a rodent model of polycystic liver disease that has been used to study hepatorenal disease progression and evaluate pharmacotherapeutic interventions. Biomarkers that describe the cyst progression, liver impairment, and/or hepatic cyst burden could provide clinical utility for this disease. In the present study, hepatic cyst volume was measured by magnetic resonance imaging in PCK rats at 12, 16, and 20 weeks. After 20 weeks, Sprague Dawley (n = 4) and PCK (n = 4) rats were sacrificed and 42 bile acids were analyzed in the liver, bile, serum, and urine by liquid chromatography coupled to tandem mass spectrometry. Bile acid profiling revealed significant increases in total bile acids (molar sum of all measured bile acids) in the liver (13-fold), serum (6-fold), and urine (3-fold) in PCK rats, including those speciated bile acids usually associated with hepatotoxicity. Total serum bile acids correlated with markers of liver impairment (liver weight, total liver bile acids, total hepatotoxic liver bile acids, and cyst volume [ r > 0.75; P < 0.05]). Based on these data, serum bile acids may be useful biomarkers of liver impairment in polycystic hepatorenal disease.
Collapse
Affiliation(s)
- William J Brock
- 1 Brock Scientific Consulting, LLC, Montgomery Village, MD, USA
| | - James J Beaudoin
- 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jason R Slizgi
- 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Mingming Su
- 3 Metabolomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, USA
| | - Wei Jia
- 3 Metabolomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, USA
| | | | - Kim L R Brouwer
- 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| |
Collapse
|
|
23
|
Sha FR, Pk MU, Abuelezz NZ, Pervin R, Talukder RI, Begum M, Rahman M. Investigating the Efficiency of APRI, FIB-4, AAR and AARPRI as Noninvasive Markers for Predicting Hepatic Fibrosis in Chronic Hepatitis B Patients in Bangladesh. Open Microbiol J 2019. [DOI: 10.2174/1874285801913010034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and Aims:Accurate, affordable non-invasive markers are highly needed for efficient diagnosis and management of liver fibrosis caused by chronic hepatitis B. This is the first study to investigate the diagnostic efficiency of Aspartate Transaminase to Platelet Ratio (APRI), Fibrosis Index (FIB-4), Aspartate transaminase to Alanine Transaminase Ratio (AAR) and AAR/Platelet ratio index (AARPRI) as non-invasive markers to predict hepatic fibrosis caused by Chronic Hepatitis B (CHB) in Bangladesh.Methods:In this study, a training cohort of 1041 CHB patients were recruited, whereas 104 and 109 CHB patients of matched ages were recruited as internal and external validation cohort groups respectively. Histological and hematological data were analyzed. METAVIR scoring system was used to classify liver fibrosis stages. Area Under Receiver Operating Curve (AUROC), correlations and cutoff values for the four diagnostic markers were calculated and assessed.Results:92%, 81% and 84% of the patients had liver fibrosis in the training cohort, internal and external cohort groups respectively. Among the four noninvasive panels, APRI showed the best area under ROC; (0.767, CI: 0.780-0.914; 0.775) for the training cohort, (0.775, CI: 0.693-0.857), and (0.847, CI: 0.780-0.914) for the internal and external cohorts respectively. Cut-off value of APRI was 0.512 with sensitivity/specificity of 84%/67% in training cohort, 81% / 66% in the internal cohort, and 88% / 66% in an external cohort. The odds ratio for APRI was 32.95 (95%CI: 4.746-228.862,p<0.001).Conclusion:Among all the four tested markers, APRI is the most accurate non-invasive test to predict major liver fibrosis (F2-3) in Bangladeshi CHB patients.
Collapse
|
|
24
|
Wu Z, Dong X, Wang G, Zhao H. Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal. J Viral Hepat 2019; 26:287-296. [PMID: 30380162 DOI: 10.1111/jvh.13030] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/01/2018] [Accepted: 10/04/2018] [Indexed: 12/12/2022]
Abstract
Liver biopsy is the reference method for antiviral therapy decision-making in chronic hepatitis B (CHB) when alanine aminotransferase (ALT) is less than two times of upper limit of normal (<2ULN). Our aim was to explore noninvasive markers for antiviral therapy decision in CHB with ALT <2ULN. A total of 452 treatment-naïve CHB patients with ALT < 2ULN who had undergone liver biopsy were analysed in this prospective multi-centre study. If liver biopsy showed moderate or severe inflammation (histology activity index ≥ 5) or significant fibrosis (Ishak fibrosis score ≥ 3), antiviral treatment was recommended. We analysed data using univariate and multivariate analyses and receiver operating characteristic curves (ROC). Two hundred and sixty-nine (59.5%) of 452 cases with ALT < 2ULN had moderate, severe or significant inflammation. Aspartate aminotransferase (AST) (P = 0.03), anti-hepatitis B virus core antibody (anti-HBc) (P = 0.003) and liver stiffness measurement (LSM) (P = 0.000) were independent variables for antiviral therapy decision-making, with area under the ROC curve (AUROC) of 0.718, 0.703 and 0.819, respectively. Our novel AAF index, which combined AST, anti-HBc and LSM, showed better performance with AUROC of 0.876, 0.877 and 0.876 in estimation, validation and total set. Finally, 247 (54.6%) of 452 patients could avoid liver biopsy based on AAF index. Furthermore, performances of 23 noninvasive models were unsatisfactory for antiviral therapy decision with AUROC < 0.800, which were inferior to AAF index. In conclusion, AST, anti-HBc and LSM were related to antiviral therapy decision-making among CHB patients with ALT < 2ULN. Thus, the novel AAF index was a more reliable noninvasive model for antiviral therapy decision-making.
Collapse
Affiliation(s)
- Zhao Wu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Xiaoqin Dong
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China.,Peking University International Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China
| | | |
Collapse
|
|
25
|
Dong XQ, Wu Z, Zhao H, Wang GQ. Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients. J Viral Hepat 2019; 26:297-307. [PMID: 30380170 DOI: 10.1111/jvh.13031] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/07/2018] [Accepted: 10/09/2018] [Indexed: 12/15/2022]
Abstract
The limitations of liver biopsy have led to the development of indirect noninvasive models for liver fibrosis assessment. We aimed to evaluate and compare the performance of 30 noninvasive models to predict fibrosis stage in treatment-naïve and treated chronic hepatitis B (CHB) patients. A total of 576 Chinese treatment-naïve CHB patients and 236 treated CHB patients who had undergone percutaneous liver biopsy were included in the analysis. Histological grading and staging was assessed by the Ishak scoring system. The diagnostic accuracies of 30 noninvasive models were assessed by area under the receiver operating characteristic curves (AUROCs). In treatment-naïve CHB patients, the AUROCs of the 30 noninvasive models for discriminating significant fibrosis (SF) were less than 0.800, and only the AUROC of the PP score for diagnosing advanced fibrosis (AF) was more than 0.800, while the AUROCs of FIB-4, FibroQ, HB-F, Lok index, PHP score and PP score for predicting cirrhosis were greater than 0.800. In treated CHB patients, only the AUROCs of APRI, GUCI, King's score and Wang I for identifying cirrhosis were more than 0.800. The Spearman correlation analysis identified that only the changes in FCI and Virahep-C model values were weakly correlated with changes in Ishak fibrosis scores before and after treatment (r = 0.206, p = 0.008; r = 0.187, p = 0.016, respectively). In conclusion, in Chinese CHB patients, the 30 existing noninvasive models were not suitable for assessing each stage of fibrosis except cirrhosis before and after antiviral therapy, especially in gauging progression and regression of liver fibrosis following therapy.
Collapse
Affiliation(s)
- Xiao-Qin Dong
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Zhao Wu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China
| | - Gui-Qiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | | |
Collapse
|
|
26
|
Lv L, Li Y, Fan X, Xie Z, Liang H, Shen T. HCV coinfection aggravated the decrease of platelet counts, but not mean platelet volume in chronic HIV-infected patients. Sci Rep 2018; 8:17497. [PMID: 30504858 PMCID: PMC6269489 DOI: 10.1038/s41598-018-35705-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 11/09/2018] [Indexed: 01/06/2023] Open
Abstract
Either HIV or HCV monoinfection could result in an abnormal status of platelets. As two key indicators reflecting activation and function of platelets, the changes of platelet counts and mean platelet volume (MPV) in HIV/HCV-coinfected patients have not been clearly identified. In the present study, a total of 318 former plasma donors were investigated in 2006, and 66% (201 individuals) of primary recruiters were followed up in 2014. By horizontal comparison in 2006, the decrease of platelet counts in HIV/HCV coinfection was greater than that in HIV or HCV monoinfection. MPV scores were lower in HIV monoinfection compared with healthy controls, while no difference was found in HIV/HCV coinfection. Platelet counts were shown to be negatively correlated with MPV scores in total recruited population (r = 0.432, P < 0.001). Interestingly, by comparison of data from two time points of 2006 and 2014, significant decrease of platelets (P = 0.004) and increase of MPV (P = 0.004) were found only in HCV monoinfected patients, which may associate with slow progression of hepatic fibrosis induced by chronic HCV infection. Nonetheless, no significant changes of platelet counts and MPV were found from 2006 to 2014 in coinfected patients. In conclusion, HCV coinfection aggravated the decrease of platelet counts, but not MPV score in chronic HIV infection. MPV showed poor applicability in reflecting the status of platelets in HIV/HCV-coinfected patients.
Collapse
Affiliation(s)
- Linting Lv
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Yuantao Li
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Xueying Fan
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Zhe Xie
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Hua Liang
- State Key laboratory of Infectious Disease Prevention and Control (SKLID), National Center for AIDS/STD Control and Prevention, China CDC, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, 102206, China.
| | - Tao Shen
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
| |
Collapse
|
|
27
|
Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma. Sci Rep 2018; 8:15074. [PMID: 30305679 PMCID: PMC6180073 DOI: 10.1038/s41598-018-33536-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 09/26/2018] [Indexed: 02/08/2023] Open
Abstract
The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok’s index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok’s index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.
Collapse
|
|
28
|
Sirinawasatien A, Techasirioangkun T, Thongsri S. Prevalence and Determinants of Significant Liver Fibrosis by Vibration-Controlled Transient Elastography in Thai Chronic Hepatitis B Patients. Int J Hepatol 2018; 2018:4310102. [PMID: 30386662 PMCID: PMC6189681 DOI: 10.1155/2018/4310102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Accepted: 09/16/2018] [Indexed: 11/17/2022] Open
Abstract
AIMS To describe the prevalence of significant liver fibrosis by ultrasound-based vibration-controlled transient elastography (VCTE; FibroScan®) and to identify the determinants of significant liver fibrosis in Thai chronic hepatitis B patients. METHODS A cross-sectional study of consecutive chronic hepatitis B patients performed VCTE and followed up at Rajavithi Hospital, Bangkok, Thailand, was conducted between 1 January, 2013, and 31 December, 2016. Liver fibrosis was defined as minimal (METAVIR F0-1) by VCTE < 7.2 kPa and significant (METAVIR F2-4) by VCTE ≥ 7.2 kPa. VCTE assessments and medical records were retrospectively reviewed. The prevalence and determinants of significant liver fibrosis were analyzed. RESULTS A total of 206 eligible patients were included; 120 patients (58.3%) were female. The mean age was 50 years (SD 12.4 years), and 32.5% had a body mass index ≥ 25. The prevalences of minimal (F 0-1) and significant fibrosis (F2-4) were 74.3% and 25.7%, respectively. The prevalence of hepatitis B e antigen negative (HBeAg -ve) was 83%. The median serum hepatitis B virus viral load was 4,340 IU/mL (range 20-271,883,036). Significant determinants of significant fibrosis (F2-4) were male gender (aOR 3.24 [95%CI: 1.36-7.72]) and high aspartate transaminase (AST) level (aOR 5.71 [95%CI: 2.03-16.04]). CONCLUSION Around one-quarter of the Thai patients with chronic viral hepatitis B had significant liver disease defined by VCTE, requiring further evaluation for specific treatment for hepatitis B virus. Determinants of significant liver fibrosis were male gender and high AST level.
Collapse
Affiliation(s)
- Apichet Sirinawasatien
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Thanaya Techasirioangkun
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Siriporn Thongsri
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| |
Collapse
|
|
29
|
Dong M, Wu J, Yu X, Li J, Yang S, Qi X, Mao R, Zhang Y, Yu J, Zhu H, Yang F, Qin Y, Zhang J. Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients. Liver Int 2018; 38:1562-1570. [PMID: 29314613 DOI: 10.1111/liv.13688] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 12/25/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS To avoid liver biopsy, many noninvasive models comprised of serum markers for liver fibrosis assessment have been developed. Given that most of them were developed in hepatitis C cohorts and few of them have been validated in Chinese hepatitis B patients, we aim to conduct this validation and compare their diagnostic accuracies in such a population. METHODS A total of 937 HBV-infected patients who underwent liver biopsy were included in this single-centre retrospective study. The diagnostic accuracies of the 17 noninvasive models were assessed by areas under the receiver-operating characteristic curves (AUROCs), using histologically evaluated fibrotic stages of the biopsy specimens as standards. To compare efficiencies of the models, a grading system based on AUROC levels was developed. RESULTS For discriminating significant fibrosis in all patients, the best three noninvasive models were King's score (AUROC = 0.756), Virahep-C model (AUROC = 0.756) and GPR (AUROC = 0.744); and for diagnosing cirrhosis, Lok index (AUROC = 0.832), FI (AUROC = 0.820) and FIB-4 (AUROC = 0.818) got the first three places. AUROCs in HBeAg-positive group were generally higher than those in HBeAg-negative group. In addition, based on the grading system, Virahep-C and GPR outstood others in evaluating liver fibrosis in all patients. CONCLUSIONS In Chinese HBV-infected patients, Virahep-C models and GPR had high accuracies in diagnosing liver fibrosis and cirrhosis, while the most discussed models like APRI and FIB-4 did not outstand. Assessment should take into account the HBeAg sero-status, since these noninvasive models were more appropriate for HBeAg-positive patients than HBeAg-negative ones.
Collapse
Affiliation(s)
- Minhui Dong
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jingwen Wu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xueping Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jing Li
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Sisi Yang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Richeng Mao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yongmei Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Haoxiang Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Feifei Yang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yanli Qin
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
30
|
Sofosbuvir Based Regimens in the Treatment of Chronic Hepatitis C with Compensated Liver Cirrhosis in Community Care Setting. Int J Hepatol 2018; 2018:4136253. [PMID: 30155312 PMCID: PMC6093047 DOI: 10.1155/2018/4136253] [Citation(s) in RCA: 6] [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: 04/09/2018] [Accepted: 07/19/2018] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) drugs have been highly effective in the treatment of chronic hepatitis C (CHC) infection. We aim to evaluate the treatment response of Sofosbuvir based DAA in CHC patients with compensated liver cirrhosis as limited data exists in the real-world community setting. METHODS All the CHC patients with compensated liver cirrhosis treated with Sofosbuvir based DAAs between January 2014 and December 2017 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks posttreatment (SVR12), and adverse reactions were assessed. RESULTS One hundred and twelve patients with CHC infection and concurrent compensated cirrhosis were included in the study. Black patients represented the majority of the study population (64%). Eighty-seven patients were treated with Ledipasvir/Sofosbuvir (LDV/SOF) ±Ribavirin and 25 patients were treated with Sofosbuvir/Velpatasvir (SOF/VEL). Overall, SVR 12 after treatment was achieved in 90% in patients who received one of the two DAA regimens (89.7% in LDV/SOF group and 92% in SOF/VEL group). SVR 12 did not vary based on age, sex, body mass index, baseline HCV viral load, HCV/HIV coinfection, type of genotype, and prior treatment status. Apart from a low platelet count, there were no other factors associated with a statistical difference in SVR 12(p=0.002) between the two regimens. Fatigue (35%) was the most common adverse effect and no patients discontinued treatment due to adverse effects. CONCLUSION In the community care setting, Sofosbuvir based DAAs are safe, effective with high overall SVR, and well tolerated in patients with CHC patients with compensated liver cirrhosis.
Collapse
|
|
31
|
Huang CF, Yeh ML, Huang CI, Lin ZY, Chen SC, Dai CY, Huang JF, Chuang WL, Yu ML. Interference of hepatitis B virus dual infection in platelet count recovery in chronic hepatitis C patients with curative antiviral therapy. J Gastroenterol Hepatol 2018; 33:1108-1114. [PMID: 29023927 DOI: 10.1111/jgh.14017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/25/2017] [Accepted: 09/30/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIM Hepatitis C virus infection is associated with thrombocytopenia. Thrombocytopenia recovers after viral eradication. The current study explored the rate and factors associated with platelet (PLT) recovery, which may represent the degree of liver fibrosis regression. METHODS A total of 466 patients who achieved a sustained virological response were enrolled to compare the PLT change after a mean follow-up period of 85.5 months (range 12-163 months). RESULTS Platelet counts increased significantly after achieving sustained virological response (from 166 ± 55 × 103 to 201 ± 61 × 103 u/L, P < 0.001). The median PLT count increment was 5.03 × 103 u/L per year. Logistic regression analysis revealed that factors associated with slow PLT count recovery were high pretreatment PLT counts (odds ratio [OR]/ 95% confidence intervals [CI]: 0.992/0.989-0.996, P < 0.001) and hepatitis B virus (HBV) co-infection (OR/CI: 0.416/0.220-0.785, P = 0.007). High PLT counts were the only factor associated with slow PLT recovery in patients with mild liver disease (F0-2) (OR/CI: 0.992/0.987-0.996, P < 0.001). On the other hand, HBV co-infection was the only factor associated with slow PLT recovery in patients with advanced fibrosis (OR/CI: 0.207/0.054-0.789, P = 0.02). Linear regression analysis of factors correlated to the delta PLT count change per year in patients with F0-2 included pretreatment white blood cell (β: -0.001; CI: -0.002-0.000; P = 0.01) and pretreatment PLT counts (β: -0.037; CI: -0.061 to -0.013; P = 0.003). HBsAg seropositivity was the only factor correlated to the delta PLT count change per year (β: -10.193; CI: -16.752-3.635; P = 0.003) among patients with F3-4. CONCLUSIONS Platelet counts recovered after hepatitis C virus eradication. HBV dual infection disrupted PLT count recovery, especially in CHC patients with advanced liver disease.
Collapse
Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.,Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
32
|
Mendes LC, Stucchi RS, Vigani AG. Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies. Hepat Med 2018; 10:13-22. [PMID: 29662329 PMCID: PMC5892613 DOI: 10.2147/hmer.s125234] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.
Collapse
Affiliation(s)
- Leandro César Mendes
- Department of Infectious Diseases, State University of Campinas, Campinas, SP, Brazil
| | - Raquel Sb Stucchi
- Department of Infectious Diseases, State University of Campinas, Campinas, SP, Brazil
| | - Aline G Vigani
- Department of Infectious Diseases, State University of Campinas, Campinas, SP, Brazil
| |
Collapse
|
|
33
|
Diagnostic Accuracy of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis 4 Scores in Predicting Advanced Liver Fibrosis in Patients with End-stage Renal Disease and Chronic Viral Hepatitis: Experience from Pakistan. J Transl Int Med 2018; 6:38-42. [PMID: 29607303 DOI: 10.2478/jtim-2018-0008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
Collapse
|
|
34
|
Liao R, Fu YP, Wang T, Deng ZG, Li DW, Fan J, Zhou J, Feng GS, Qiu SJ, Du CY. Metavir and FIB-4 scores are associated with patient prognosis after curative hepatectomy in hepatitis B virus-related hepatocellular carcinoma: a retrospective cohort study at two centers in China. Oncotarget 2018; 8:1774-1787. [PMID: 27662665 PMCID: PMC5352096 DOI: 10.18632/oncotarget.12152] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 09/14/2016] [Indexed: 12/17/2022] Open
Abstract
Although Metavir and Fibrosis-4 (FIB-4) scores are typically used to assess the severity of liver fibrosis, the relationship between these scores and patient outcome in hepatocellular carcinoma (HCC) is unclear. The aim of this study was to evaluate the prognostic value of the severity of hepatic fibrosis in HBV-related HCC patients after curative resection. We examined the prognostic roles of the Metavir and preoperative FIB-4 scores in 432 HBV-HCC patients who underwent curative resection at two different medical centers located in western (Chongqing) and eastern (Shanghai) China. In the testing set (n = 108), the Metavir, FIB-4, and combined Metavir/FIB-4 scores were predictive of overall survival (OS) and recurrence-free survival (RFS). Additionally, they were associated with several clinicopathologic variables. In the validation set (n = 324), the Metavir, FIB-4, and combined Metavir/FIB-4 scores were associated with poor prognosis in HCC patients after curative resection. Importantly, in the negative alpha-fetoprotein subgroup (≤ 20 ng/mL), the FIB-4 index (I vs. II) could discriminate between patient outcomes (high or low OS and RFS). Thus Metavir, preoperative FIB-4, and combined Metavir/FIB-4 scores are prognostic markers in HBV-HCC patients after curative hepatectomy.
Collapse
Affiliation(s)
- Rui Liao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yi-Peng Fu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ting Wang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhi-Gang Deng
- Department of General Surgery, Mianyang Central Hospital, Mianyang, China
| | - De-Wei Li
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Gen-Sheng Feng
- Department of Pathology and Division of Biological Sciences, University of California San Diego, La Jolla, California, USA
| | - Shuang-Jian Qiu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng-You Du
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
35
|
Yu LL, Yu HH, Liang XF, Li N, Wang X, Li FH, Wu XF, Zheng YH, Xue M, Liang XF. Dietary butylated hydroxytoluene improves lipid metabolism, antioxidant and anti-apoptotic response of largemouth bass (Micropterus salmoides). FISH & SHELLFISH IMMUNOLOGY 2018; 72:220-229. [PMID: 29108969 DOI: 10.1016/j.fsi.2017.10.054] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 10/18/2017] [Accepted: 10/28/2017] [Indexed: 06/07/2023]
Abstract
A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides). Four experimental diets were prepared with BHT supplement levels of 0 (B0), 150 (B150), 300 (B300) and 1500 (B1500) mg/kg, in which B150 was at the maximum recommended level established by European Union Regulation, and the B300 and B1500 levels were 2 and 10-fold of B150, respectively. Each diet was fed to 6 replicates with 30 largemouth bass (initial body weight, IBW = 6.20 ± 0.01 g) in each tank. The BHT inclusion level did not affect the specific growth rate, but fish in the B150 group showed the lowest feed conversion rate (P < 0.05). BHT inclusion significantly decreased the levels of plasma TC, TG, LDL, ALT and AKP, and increased the (HDL-C)/TC ratio (P < 0.05). Plasma MDA was significantly decreased in the B150 group and GSH-Px was extremely enhanced in each BHT inclusion group (P < 0.05). Hepatic T-AOC was significantly enhanced and O2- was significantly decreased in each BHT inclusion group compared to the B0 group (P < 0.05), as well as hepatic MDA was significantly decreased in B1500 group (P < 0.05). Dietary BHT inclusion down-regulated the hepatic mRNA levels of inflammation, apoptosis and fibrosis related genes, including TNFα, TGF-β1, α-SMA, IL8, IL11β and caspase-9. Moreover, BHT could improve hepatic lipid metabolism via up-regulating the mRNA levels of APOA1, CYP7A1, CYP8B1, and down-regulating the mRNA levels of PPAR-γ and APOB. Histological examination of the liver morphology with H&E and Sirius Red staining showed that BHT inclusion decreased necrotic degenerative changes and collagen deposition in largemouth bass. An immunofluorescence examination revealed significantly decreased cleaved caspase-3 signals in the BHT groups. In conclusion, the results demonstrated that ROS induces hepatic cell apoptosis and fibrosis via the intrinsic pathway of apoptosis by activating caspase-9 in the mitochondria and then initiates apoptosis by activating caspase-3. Consuming 2.32-23.80 mg/kg·bw/d (150-1500 mg/kg in diet) of BHT effectively improved the plasma and hepatic lipid metabolism, antioxidant response as well as reduced ROS production, protecting hepatic cells from injury. It is implied that even a 10-fold increase of the maximum level of BHT (150 mg/kg) is safe for the largemouth bass.
Collapse
Affiliation(s)
- L L Yu
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - H H Yu
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China; Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - X F Liang
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - N Li
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - X Wang
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - F H Li
- Beijing General Station of Animal Husbandry Senior Veterinary, 100107, China
| | - X F Wu
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Y H Zheng
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - M Xue
- National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China; Key Laboratory of Feed Biotechnology of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, 430070, China.
| | - X F Liang
- Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, 430070, China; College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China
| |
Collapse
|
|
36
|
Ahn HS, Han SH, Kim YH, Park BJ, Kim DH, Lee JB, Park SY, Song CS, Lee SW, Choi C, Myoung J, Choi IS. Adverse fetal outcomes in pregnant rabbits experimentally infected with rabbit hepatitis E virus. Virology 2017; 512:187-193. [PMID: 28982029 DOI: 10.1016/j.virol.2017.09.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/29/2017] [Accepted: 09/22/2017] [Indexed: 01/16/2023]
Abstract
Hepatitis E virus (HEV) causes severe hepatitis in pregnant women, with associated poor fetal outcomes. To study HEV viral pathogenesis, pregnant rabbits were infected with low- and high-dose rabbit HEV at 2 weeks gestation. HEV was identified in the serum, feces, and liver tissue of infected rabbits, and dose-dependent fetal mortality rates ranging from 67% to 80% were observed. The aspartate transaminase (AST)/alanine transaminase ratio was significantly higher (P < 0.01) in high-dose infected rabbits than low-dose infected and negative control rabbits 14 days post infection (dpi). Tumor necrosis factor-α (TNF-α) was significantly higher in low-dose (P < 0.01) and high-dose infected rabbits (P < 0.001) than in negative controls 7 dpi. High-dose HEV-infected rabbits produced significantly more interferon-γ (IFN-γ; P < 0.05) than negative control rabbits at 7 and 14 dpi. High levels of AST, TNF-α, and IFN-γ may substantially influence adverse fetal outcomes in pregnant rabbits infected with high-dose HEV.
Collapse
Affiliation(s)
- Hee-Seop Ahn
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sang-Hoon Han
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Yong-Hyun Kim
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Byung-Joo Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Dong-Hwi Kim
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Joong-Bok Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Seung-Yong Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Chang-Seon Song
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sang-Won Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Changsun Choi
- Department of Food and Nutrition, School of Food Science and Technology, Chung-Ang University, Ansung 17546, Republic of Korea
| | - Jinjong Myoung
- Korea Zoonosis Research Institute, Chonbuk National University, Jeonju 54896, Republic of Korea
| | - In-Soo Choi
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
| |
Collapse
|
|
37
|
Hai H, Tamori A, Thuy LTT, Yoshida K, Hagihara A, Kawamura E, Uchida-Kobayashi S, Morikawa H, Enomoto M, Murakami Y, Kawada N. Polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with chronic hepatitis C-related hepatocellular carcinoma. Sci Rep 2017; 7:11912. [PMID: 28928439 PMCID: PMC5605683 DOI: 10.1038/s41598-017-10363-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 08/09/2017] [Indexed: 12/21/2022] Open
Abstract
Recently, the MICA rs2596542 and DEPDC5 rs1012068 variants in Japanese individuals as well as the HCP5 rs2244546 and PNPLA3 rs738409 variants in European individuals have been found associated with hepatocellular carcinoma (HCC). The present study determined which single nucleotide polymorphism (SNP) is the most predictive for developing hepatitis C virus (HCV)-related HCC in a Japanese cohort. Of the 4 SNPs analysed, only the MICA genotypes were significantly associated with development of HCC (p = 0.0185). The major (MA), hetero (HE), and minor (MI) genotypes occurred in 40%, 41%, and 19% of HCC patients and in 43%, 47%, and 10% of non-HCC patients, respectively. Interestingly, the MICA genotype was significantly correlated with MICA mRNA and soluble protein levels. In patients older than 70 years, the MI genotype was significantly associated with HCC development. In addition, the MI genotype was related to HCC development when the platelet count range was 10-15 × 104/μL, corresponding with the fibrosis stage; but not when the range was less than 10, indicating advanced fibrosis; or greater than 15 × 104/μL, as mild fibrosis. Thus, polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with HCC development in Japanese patients with chronic HCV infection.
Collapse
Affiliation(s)
- Hoang Hai
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
| | - Le Thi Thanh Thuy
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kanako Yoshida
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Etsushi Kawamura
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Hiroyasu Morikawa
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yoshiki Murakami
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| |
Collapse
|
|
38
|
Zhu MY, Zou X, Li Q, Yu DM, Yang ZT, Huang D, Chen J, Gong QM, Zhang DH, Zhang Y, Chen L, Chen PZ, Zhang XX. A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection. J Viral Hepat 2017; 24:589-598. [PMID: 28130852 DOI: 10.1111/jvh.12682] [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] [Received: 07/19/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023]
Abstract
Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV-infected and treatment-naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty-nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma-glutamyltransferase-to-platelet ratio (GPR), red cell volume distribution width-to-platelet ratio (RPR), FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB-4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR-HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR-HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment-naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.
Collapse
Affiliation(s)
- M-Y Zhu
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - X Zou
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Q Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - D-M Yu
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Z-T Yang
- Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - D Huang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - J Chen
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Q-M Gong
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - D-H Zhang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Y Zhang
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.,Collaborative Innovation Center of Systems Biomedicine, Shanghai, China
| | - L Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - P-Z Chen
- Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - X-X Zhang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
39
|
Wang HW, Peng CY, Lai HC, Su WP, Lin CH, Chuang PH, Chen SH, Chen CH, Hsu WF, Huang GT. New noninvasive index for predicting liver fibrosis in Asian patients with chronic viral hepatitis. Sci Rep 2017; 7:3259. [PMID: 28607450 PMCID: PMC5468237 DOI: 10.1038/s41598-017-03589-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 05/02/2017] [Indexed: 01/03/2023] Open
Abstract
We developed an optimal noninvasive index comprising routine laboratory parameters for predicting cirrhosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. This study included 992 CHB patients and 1,284 CHC patients who received liver biopsy. We developed the new index, named modified Fibrosis-4 (mFIB-4) according to four independent variables of the model: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The formula of the mFIB-4 index is 10 × Age(years) × AST(U/L)/Platelet count(109/L) × AST(U/L). For predicting cirrhosis, the bootstrap areas under the receiver operating characteristic curve for platelet count, AST/ALT ratio (AAR), AAR/platelet ratio index (AARPRI), AST/platelet ratio index (APRI), FIB-4, Pohl score, age-platelet (AP) index, Lok index, fibrosis quotient (FibroQ), and mFIB-4 were 0.7680, 0.7400, 0.8070, 0.6090, 0.7690, 0.6990, 0.7850, 0.7960, 0.8110, and 0.8070 in CHB patients, and 0.8170, 0.7210, 0.8400, 0.7310, 0.8310, 0.6730, 0.8220, 0.8440, 0.8570, and 0.8480 in CHC patients, respectively. FibroQ and mFIB-4 exhibited the highest diagnostic performance levels for liver cirrhosis in CHB and CHC despite the inclusion of the international normalised ratio in the formulation of FibroQ. Thus, mFIB-4 is a simple, inexpensive, and readily available method for assessing the liver fibrosis stage of Asian patients with CHB or CHC.
Collapse
Affiliation(s)
- Hung-Wei Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
- School of Medicine, China Medical University, Taichung, Taiwan.
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hsin Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ching-Hsiang Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wei-Fan Hsu
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Guan-Tarn Huang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| |
Collapse
|
|
40
|
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]
|
|
41
|
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] [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.
Collapse
|
|
42
|
Abstract
Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.
Collapse
|
|
43
|
Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein. Int J Mol Sci 2016; 17:ijms17122143. [PMID: 27999409 PMCID: PMC5187943 DOI: 10.3390/ijms17122143] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 11/30/2016] [Accepted: 12/14/2016] [Indexed: 01/06/2023] Open
Abstract
We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA+-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA+-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA+-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA+-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA+-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA+-M2BP level is a useful predictor for HCC development after achieving SVR.
Collapse
|
|
44
|
Clinical Advancements in the Targeted Therapies against Liver Fibrosis. Mediators Inflamm 2016; 2016:7629724. [PMID: 27999454 PMCID: PMC5143744 DOI: 10.1155/2016/7629724] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 10/11/2016] [Accepted: 10/19/2016] [Indexed: 12/11/2022] Open
Abstract
Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.
Collapse
|
|
45
|
Fuster D, Sanvisens A, Bolao F, Rivas I, Tor J, Muga R. Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections. World J Hepatol 2016; 8:1295-1308. [PMID: 27872681 PMCID: PMC5099582 DOI: 10.4254/wjh.v8.i31.1295] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 08/04/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023] Open
Abstract
Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.
Collapse
|
|
46
|
Kliemann DA, Wolff FH, Tovo CV, Alencastro PR, Ikeda MLR, Brandão ABM, Barcellos N, Fuchs SC. Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients. Ann Hepatol 2016; 15:27-32. [PMID: 26626637 DOI: 10.5604/16652681.1184197] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND RATIONALE The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.
Collapse
Affiliation(s)
- Dimas A Kliemann
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Fernando H Wolff
- Postgraduate Program Studies in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Cristiane V Tovo
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | | | - Maria L R Ikeda
- Therapeutic Attention Service, Sanatorio Partenon Hospital, Brazil
| | - Ajácio B M Brandão
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Nêmora Barcellos
- Therapeutic Attention Service, Sanatorio Partenon Hospital, Brazil
| | - Sandra C Fuchs
- Postgraduate Program Studies in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| |
Collapse
|
|
47
|
Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C? J Clin Gastroenterol 2016; 50:518-23. [PMID: 26974762 DOI: 10.1097/mcg.0000000000000489] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. MATERIALS AND METHODS From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. RESULTS The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10(9)/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. CONCLUSIONS King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.
Collapse
|
|
48
|
Chin JL, Pavlides M, Moolla A, Ryan JD. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy? Front Pharmacol 2016; 7:159. [PMID: 27378924 PMCID: PMC4913110 DOI: 10.3389/fphar.2016.00159] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 05/31/2016] [Indexed: 12/13/2022] Open
Abstract
Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.
Collapse
Affiliation(s)
- Jun L Chin
- School of Medicine and Medical Science, University College Dublin Dublin, Ireland
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford Oxford, UK
| | - Ahmad Moolla
- Radcliffe Department of Medicine, University of Oxford Oxford, UK
| | - John D Ryan
- Translational Gastroenterology Unit, University of Oxford Oxford, UK
| |
Collapse
|
|
49
|
van der Meer AJ, Maan R, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Manns MP, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HLA. Improvement of platelets after SVR among patients with chronic HCV infection and advanced hepatic fibrosis. J Gastroenterol Hepatol 2016; 31:1168-76. [PMID: 26647353 DOI: 10.1111/jgh.13252] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 11/05/2015] [Accepted: 11/25/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Patients with chronic hepatitis C virus (HCV) infection may develop cirrhosis with portal hypertension, reflected by decreased platelet count and splenomegaly. This retrospective cohort study aimed to assess changes in platelet counts after antiviral therapy among chronic HCV-infected patients with advanced fibrosis. METHODS Platelet counts and spleen sizes were recorded in an international cohort of patients with Ishak 4-6 fibrosis who started antiviral therapy between 1990 and 2003. Last measured platelet counts and spleen sizes were compared with their pre-treatment values (within 6 months prior to the start of therapy). All registered platelet count measurements from 24-week following cessation of antiviral therapy were included in repeated measurement analyses. RESULTS This study included 464 patients; 353 (76%) had cirrhosis and 187 (40%) attained sustained virological response (SVR). Among patients with SVR, median platelet count, increased by 35 × 10(9) /L (IQR 7-62, P < 0.001). In comparison, patients without SVR showed a median decline of 17 × 10(9) /L (IQR -5-47, P < 0.001). In a subgroup of 209 patients, median decrease in spleen size was 1.0 cm (IQR 0.3-2.0) for patients with SVR, while median spleen size increased with 0.6 cm (IQR -0.1-2.0, P < 0.001) among those without SVR. The changes in spleen size and platelet count were significantly correlated (R = -0.41, P < 0.001). CONCLUSIONS Among chronic HCV-infected patients with advanced hepatic fibrosis, the platelet counts improved following SVR and the change in platelets correlated with the change in spleen size following antiviral therapy. These results suggest that HCV eradication leads to reduced portal pressure.
Collapse
Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bart J Veldt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jordan J Feld
- The Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Jean-François Dufour
- Hepatology, Department of Clinical research, University of Bern, Bern, Switzerland
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Arkansas, USA
| | - Michael P Manns
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - W Peter Hofmann
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Harry LA Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.,The Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| |
Collapse
|
|
50
|
Andrés-Otero MJ, De-Blas-Giral I, Puente-Lanzarote JJ, Serrano-Aulló T, Morandeira MJ, Lorente S, Lou-Bonafonte JM. Multiple approaches to assess fourteen non-invasive serum indexes for the diagnosis of liver fibrosis in chronic hepatitis C patients. Clin Biochem 2016; 49:560-5. [PMID: 26968102 DOI: 10.1016/j.clinbiochem.2015.12.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 12/15/2015] [Accepted: 12/19/2015] [Indexed: 12/28/2022]
Abstract
BACKGROUND The aim of this study was to compare fourteen non-invasive indexes/scores: AAR, APRI, Fibroindex, MODEL3, Forns index, FIB4, GUCI, FI, FCI, Pohl score, AP index, CDS, HGM-1 and HGM-2, in order to diagnose the hepatic fibrosis stage in a survey of patients with chronic hepatitis C. METHODS 84 patients with chronic hepatitis C were studied. Liver fibrosis was staged according to the Scheuer scoring system. The diagnostic accuracy of these indexes/scores was evaluated by AUROC, contingency tables and logistic regression analysis. RESULTS The best AUROCs (>0.9) to discriminate cirrhosis (F=4), were observed for CDS, FI, AAR, MODEL3, FIB4, HGM-2 and FCI. To discriminate at least advance fibrosis (F≥3), the best AUROCs (>0.89) were for CDS, FI, FIB4, HGM2-2, MODEL3 and FCI. To discriminate at least significant fibrosis (F≥2), the best AUROCs (>0.8) were for FIB4, GUCI, APRI, FI, Forns index, HGM-2 and FCI. Contingency tables and logistic regression analysis supported the results obtained by AUROC. CONCLUSIONS This study compares the diagnostic performance of fourteen indexes for the diagnosis of liver fibrosis stage in the same group of CHC patients. These results allow the selection of the best indexes for further studies in larger populations, in order to build diagnostic algorithms as an alternative to liver biopsy for fibrosis staging in patients with chronic HCV infection. These algorithms would allow to take therapeutical decisions and the continuous follow-up of hepatic fibrosis in these patients.
Collapse
Affiliation(s)
| | - Ignacio De-Blas-Giral
- Dpto. Patología Animal, Universidad de Zaragoza, Zaragoza, Spain; Instituto Agroalimentario de Aragón, Zaragoza, Spain
| | - Juan José Puente-Lanzarote
- Servicio de Bioquímica Clínica, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - Trinidad Serrano-Aulló
- Servicio de Digestivo, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - María José Morandeira
- Servicio Anatomía patológica, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - Sara Lorente
- Servicio de Digestivo, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - José Manuel Lou-Bonafonte
- Dpto. Farmacología y Fisiología, Universidad de Zaragoza, Zaragoza, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain; Instituto Agroalimentario de Aragón, Zaragoza, Spain.
| |
Collapse
|