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Huang P, Huang Y, Dong T, Wang H, Wang M, Li X, Dong W, Yang Y, He W, Yang W. Mechanistic Insights Into GDFMD-Mediated Inhibition of Liver Fibrosis via miRNA-29b-3p Upregulation in Wilson's Disease. Mediators Inflamm 2025; 2025:2776808. [PMID: 40322065 PMCID: PMC12049248 DOI: 10.1155/mi/2776808] [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: 12/07/2024] [Accepted: 03/19/2025] [Indexed: 05/08/2025] Open
Abstract
Background: Wilson's disease (WD) is an abnormal copper metabolism disease. GanDouFuMu decoction (GDFMD) is a traditional Chinese medicine, whicn has shown good therapeutic effects in clinical treatment of WD liver fibrosis;but its regulatory mechanism is still unclear. Methods: The serum of WD patients before and after GDFMD treatment were collected, the four items of liver fibrosis were detected by ELISA. The hepatic stellate cell (HSC) activities were assesed via CCK8 assay. The mRNA levels were evaluated by qPCR. The protein levels were checked by western blot. The autophygosomes were observed by transmission electron microscope (TEM). The transdifferentiation ability of HSCs into myofibroblasts was evaluated with anti-α-SMA antibody by immunofluorescence (IF). In copper-laden rats with WD, the autophagy levels, and fibrosis level were observed by IF. Results: The four items of liver fibrosis levels were decreased. GDFMD could increase the HSCs cell activity. GDFMD could increase miRNA-29b-3p levels, which was decreased by TGF-β1. miRNA-29b-3p inhibitors could reversed the suppression response of GDFMD on the the protein expression of ULK1, beclin1, LC3, α-SMA, and Col1. GDFMD blocked the transdifferentiation of HSCs into myofibroblasts, inhibited liver fibrosis. Conclusion: GDFMD blocked the transdifferentiation of HSCs into myofibroblasts by upregulating miRNA-29b-3p, and then inhibited liver fibrosis in WD.
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Affiliation(s)
- Peng Huang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Yuzhe Huang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Ting Dong
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Han Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Meixia Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Xiang Li
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Wei Dong
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Yulong Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Wei He
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
| | - Wenming Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Anhui University of Chinese Medicine Key Laboratory of Xin'an Medicine of the Ministry of Education, Hefei, Anhui, China
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Pozowski P, Bilski M, Bedrylo M, Sitny P, Zaleska-Dorobisz U. Modern ultrasound techniques for diagnosing liver steatosis and fibrosis: A systematic review with a focus on biopsy comparison. World J Hepatol 2025; 17:100033. [PMID: 40027573 PMCID: PMC11866135 DOI: 10.4254/wjh.v17.i2.100033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/04/2024] [Accepted: 01/24/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND This review evaluated the diagnostic effectiveness of various ultrasound (US) methods compared to liver biopsy. AIM To determine the diagnostic accuracy of US techniques in assessing liver fibrosis and steatosis in adults, using the area under the receiver operating characteristic curve (AUROC) as the standard measure. METHODS The review included original retrospective or prospective studies published in the last three years in peer-reviewed medical journals, that reported AUROC values. Studies were identified through PubMed searches on January 3 and April 30, 2024. Quality was assessed using the QUADAS-2 tool. Results were tabulated according to the diagnostic method and the type of liver pathology. RESULTS The review included 52 studies. For liver fibrosis detection, 2D-shear wave elastography (SWE) AUROCs ranged from 0.54 to 0.994, showing better accuracy for advanced stages. Modifications, including 2D-SWE with propagation map guidance and supersonic imagine achieved AUROCs of 0.84 to nearly 1.0. point SWE and classical SWE had AUROCs of 0.741-0.99, and 0.507-0.995, respectively. Transient elastography (TE), visual TE, vibration-controlled TE (VCTE), and FibroTouch reported AUROCs close to 1.0. For steatosis, VCTE with controlled attenuation parameter showed AUROCs up to 0.89 (for ≥ S1), acoustic radiation force impulse ranged from 0.762 to 0.784, US attenuation parameter from 0.88 to 0.93, and normalized local variance measurement from 0.583 to 0.875. Most studies had a low risk of bias across all or most domains, but evidence was limited by variability in study quality and small sample sizes. Innovative SWE variants were evaluated in a single study. CONCLUSION Modern US techniques can serve as effective noninvasive diagnostic tools for liver fibrosis and steatosis, with the potential to reduce the reliance on biopsies.
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Affiliation(s)
- Patryk Pozowski
- Department of General and Pediatric Radiology, Wroclaw Medical University, Wrocław 50-367, Lower Silesia, Poland.
| | - Mateusz Bilski
- Department of General and Pediatric Radiology, Wroclaw Medical University, Wrocław 50-367, Lower Silesia, Poland
| | - Maciej Bedrylo
- Department of General and Pediatric Radiology, Wroclaw Medical University, Wrocław 50-367, Lower Silesia, Poland
| | - Paweł Sitny
- Department of General and Pediatric Radiology, Wroclaw Medical University, Wrocław 50-367, Lower Silesia, Poland
| | - Urszula Zaleska-Dorobisz
- Department of General and Pediatric Radiology, Wroclaw Medical University, Wrocław 50-367, Lower Silesia, Poland
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Youssef EM, Wu GY. Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance. J Clin Transl Hepatol 2024; 12:428-435. [PMID: 38638374 PMCID: PMC11022067 DOI: 10.14218/jcth.2023.00446] [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: 12/13/2023] [Revised: 02/09/2024] [Accepted: 02/18/2024] [Indexed: 04/20/2024] Open
Abstract
Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.
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Affiliation(s)
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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Berenguer M, Vergara M, Almohalla C, Hernandez A, Blanco S, Testillano M, Girona E, Casado M, García M, Catalina MV, Muñoz C, Gutierrez ML, Molina E, Romero M, Otero A, Hernáez-Alsina T, Bernal-Monterde V, Lorente S, Masnou H, Bonet L, Soto S, Gisbert C, Valer MP, Gomez J, Pacheco G, Morillas J, Gonzalez M, Dominguez N, Lazaro M, Pascual S, Castelló I, Gonzalez R. Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:577-584. [PMID: 36372257 DOI: 10.1016/j.gastrohep.2022.10.018] [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: 06/17/2022] [Revised: 10/15/2022] [Accepted: 10/24/2022] [Indexed: 11/13/2022]
Abstract
There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.
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Affiliation(s)
- Marina Berenguer
- Hepatology - Liver Transplantation Unit, IIS La Fe and CIBER-EHD, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Department of Medicine, Universitat de València, Valencia, Spain.
| | - Mercedes Vergara
- Parc Tauli Sabadell Hospital Universitari, Institut d'Investigació i Innovació Parc Tauli I3PT, Univ Autonoma de Barcelona, Sabadell, Barcelona, Spain; Dept Medicina, Universitat Autonoma de Barcelona and CIBERhed, Insituto Carlos III, Madrid, Spain
| | - Carolina Almohalla
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Alicia Hernandez
- Servicio de Aparato Digestivo, Hospital universitario de Ciudad Real, Ciudad real, Spain
| | - Sonia Blanco
- Servicio de Aparato Digestivo, Hospital Universitario Basurto, Euskadi, Spain
| | - Milagros Testillano
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital Universitario Cruces, Bizkaia, Spain
| | - Eva Girona
- Servicio de Aparato Digestivo, Hospital de Elx, Alicante, Spain
| | - Marta Casado
- Servicio de Aparato Digestivo, Hospital Universitario Torrecárdenas, Almería, Spain
| | - Miren García
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de La Victoria, Málaga, Spain
| | - Maria-Vega Catalina
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital General Universitario Gregorio Marañon. Madrid, Spain
| | - Carolina Muñoz
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital 12 de Octubre, Madrid, Spain
| | - Maria Luisa Gutierrez
- Servicio de Aparato Digestivo, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - Esther Molina
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Miriam Romero
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital La Paz, Madrid, Spain
| | - Alejandra Otero
- Servicio de Aparato Digestivo, Hospital Universitario de A Coruña, Coruña, Spain
| | | | - Vanessa Bernal-Monterde
- Servicio de Aparato Digestivo, Hospital Miguel Servet, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - Sara Lorente
- Unidad de Hepatología y Trasplante Hepático, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Helena Masnou
- Servei Aparell Digestiu, Unitat de Hepatologia, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Lucia Bonet
- Servicio Aparato Digestivo, Hospital Universitari Son Espases, Spain
| | - Susana Soto
- Servicio de Aparato Digestivo, Hospital del Tajo, Aranjuez, Spain
| | - Concha Gisbert
- Servicio de Medicina Interna, Hospital de Dénia - Marina Salud, Denia, Spain
| | - María-Paz Valer
- Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Judith Gomez
- Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Burgos, Spain
| | - Gemma Pacheco
- Servicio de Aparato Digestivo, Hospital Universitario La Ribera, Spain
| | - Julia Morillas
- Servicio de Aparato Digestivo, Hospital Virgen de la Luz, Cuenca, Spain
| | - Martha Gonzalez
- Servicio de Aparato Digestivo, Hospital El Bierzo, Ponferrada, León, Spain
| | - Nuria Dominguez
- Servicio de Aparato Digestivo, Hospital University Infanta Cristina, Parla, Spain
| | - Maria Lazaro
- Servicio de Aparato Digestivo, Hospital General San Jorge, Huesca, Spain
| | - Sonia Pascual
- Servicio de Aparato Digestivo, Unidad Hepática, Hospital General Universitario de Alicante, Alicante, Spain; CiberEHD, Madrid, Spain
| | | | - Rocio Gonzalez
- Servicio de Aparato Digestivo, Hospital Regional Universitario de Málaga, Málaga, Spain
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Natarajan A, Daniel AR, Mangal RK, Stead TS, Ganti L. Geographic Liver. Cureus 2023; 15:e45563. [PMID: 37868471 PMCID: PMC10585187 DOI: 10.7759/cureus.45563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
The authors present the case of a man with a relatively benign clinical presentation who had a computed tomography scan that revealed a "geographic liver" pattern. The radiologic appearance of hepatic steatosis, its significance, and its association with metabolic syndrome highlight the importance of this radiologic finding.
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Affiliation(s)
- Ariya Natarajan
- Biomedical Sciences, University of Central Florida, Orlando, USA
| | | | - Rohan K Mangal
- Medicine, University of Miami Miller School of Medicine, Miami, USA
| | - Thor S Stead
- Medicine, The Warren Alpert Medical School of Brown University, Providence, USA
| | - Latha Ganti
- Medical Sciences, The Warren Alpert Medical School of Brown University, Providence, USA
- Emergency Medicine & Neurology, University of Central Florida College of Medicine, Orlando, USA
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Nehring P, Szeligowska J, Przybyłkowski A. Elastography of the Liver in Wilson's Disease. Diagnostics (Basel) 2023; 13:diagnostics13111898. [PMID: 37296749 DOI: 10.3390/diagnostics13111898] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/22/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Staging of liver fibrosis is of special significance in Wilson's disease as it determines the patient's prognosis and treatment. Histopathological examination is a standard method for fibrosis assessment; however, non-invasive methods like transient elastography and share wave elastography are believed to be reliable and repetitive and are expected to replace liver biopsy in Wilson's disease. This article presents a short description of available elastography techniques and the results of the most recent studies on elastography of the liver in patients with Wilson's disease.
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Affiliation(s)
- Piotr Nehring
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
| | - Jowita Szeligowska
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
| | - Adam Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
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Wang J, Wang J, Wang H, Li B, Wang Y, Sun L, Wu X. Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease. BMC Med Imaging 2023; 23:24. [PMID: 36739392 PMCID: PMC9898910 DOI: 10.1186/s12880-023-00979-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/30/2023] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.
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Affiliation(s)
- Jiajia Wang
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Jinping Wang
- Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031, Anhui, China.
| | - Han Wang
- grid.412679.f0000 0004 1771 3402Department of Encephalopathy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Boqi Li
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Yixing Wang
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Lanting Sun
- grid.412679.f0000 0004 1771 3402Department of Encephalopathy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Xiaoqian Wu
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
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8
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Application of alkaline phosphatase‑to‑platelet ratio as a novel noninvasive index predicts liver fibrosis in patients with chronic hepatitis B. Exp Ther Med 2022; 24:619. [PMID: 36160889 PMCID: PMC9468833 DOI: 10.3892/etm.2022.11556] [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: 04/08/2022] [Accepted: 07/13/2022] [Indexed: 11/23/2022] Open
Abstract
Assessment of the extent of liver fibrosis is a crucial requirement for the design of antiviral treatments for patients with chronic hepatitis B (CHB). Several non-invasive predictive indices have been developed as potential alternatives to liver biopsy for fibrosis assessment. The present study aimed to establish a novel non-invasive method for predicting liver fibrosis in patients with CHB. A total of 382 patients with CHB who underwent liver biopsy and pathological examination at The Second Hospital of Anhui Medical University (Hefei, China) were enrolled into the present study. Liver fibrosis was assessed according to the meta-analysis of histological data in viral hepatitis scoring system. Logistic regression analyses were performed to explore possibly significant characteristics associated with liver fibrosis. In addition, potential correlations between the alkaline phosphatase (AKP)-to-platelet count (PLT) ratio (APPR) and the aspartate transaminase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and γ-glutamyl transpeptidase-to-platelet ratio (GPR) were assessed using Spearman's correlation analysis. Subsequently, the performance of APPR was compared with APRI, FIB-4 and GPR using receiver operating characteristic (ROC) analysis. Logistic regression analysis identified AKP and PLT to be significant independent predictors of fibrosis. Therefore, an index was then constructed for predicting the degree of fibrosis, which was expressed using the formula APPR=AKP (IU/ml)/PLT (1x109/l). APPR was found to be positively associated with the fibrotic stage of the liver in addition to being positively correlated with APRI, FIB-4 and GPR. The area under the ROC curve (AUROC) values of APPR were also significantly higher compared with those of APRI and FIB-4 in predicting significant fibrosis but were equal to those of GPR. However, for advanced fibrosis and cirrhosis, the AUROC value of APPR was shown to be higher compared with that of APRI, FIB-4 and GPR. In conclusion, these observations suggest that APPR is a viable marker that can be used to assess liver fibrosis in patients with CHB.
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9
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Schroeder SM, Matsukuma KE, Medici V. Wilson disease and the differential diagnosis of its hepatic manifestations: a narrative review of clinical, laboratory, and liver histological features. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1394. [PMID: 34733946 PMCID: PMC8506558 DOI: 10.21037/atm-21-2264] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 07/25/2021] [Indexed: 01/05/2023]
Abstract
Objective The goal of the present work is to provide an overview of the differential diagnosis of Wilson disease. Background Wilson disease is a rare condition due to copper accumulation primarily in the liver and brain. Although there is no definitive cure, current anti-copper treatments are associated with better outcomes if initiated early and if the diagnosis is made promptly. However, diagnostic delays are frequent and often Wilson disease represents a diagnostic challenge. The diagnosis ultimately relies on a combination of clinical, laboratory and genetic findings, and it is crucial that clinicians list Wilson disease in their differential diagnosis, especially in patients presenting with a hepatocellular pattern of liver injury. Some biochemical and liver histological features of Wilson disease overlap with those of more common conditions including nonalcoholic fatty liver disease, alcohol-associated liver disease, and autoimmune hepatitis. In particular, hepatic steatosis, hepatocyte glycogenated nuclei, ballooning degeneration, and Mallory-Denk bodies are often identified in Wilson disease as well as more common liver diseases. In addition, the natural history of liver damage in Wilson disease and the risk of developing liver cancer are largely understudied. Methods We conducted an enlarged review of published papers on Wilson disease focusing on its diagnosis and distinctive clinical and liver pathology features in relation to common non-cholestatic liver diseases with the final goal in aiding clinicians in the diagnostic process of this rare but treatable condition. Conclusions Aside from markedly altered copper metabolism, Wilson disease has essentially no pathognomonic features that can distinguish it from more common liver diseases. Clinicians should be aware of this challenge and consider Wilson disease in patients presenting with a hepatocellular pattern of liver injury.
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Affiliation(s)
- Shannon M Schroeder
- Department of Internal Medicine, University of California Davis, Sacramento, CA, USA
| | - Karen E Matsukuma
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA
| | - Valentina Medici
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
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10
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Sánchez-Monteagudo A, Ripollés E, Berenguer M, Espinós C. Wilson's Disease: Facing the Challenge of Diagnosing a Rare Disease. Biomedicines 2021; 9:1100. [PMID: 34572285 PMCID: PMC8471362 DOI: 10.3390/biomedicines9091100] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/20/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD's phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.
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Affiliation(s)
- Ana Sánchez-Monteagudo
- Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain; (A.S.-M.); (E.R.)
- Joint Unit on Rare Diseases CIPF-IIS La Fe, 46012 Valencia, Spain;
| | - Edna Ripollés
- Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain; (A.S.-M.); (E.R.)
- Joint Unit on Rare Diseases CIPF-IIS La Fe, 46012 Valencia, Spain;
| | - Marina Berenguer
- Joint Unit on Rare Diseases CIPF-IIS La Fe, 46012 Valencia, Spain;
- Hepatology-Liver Transplantation Unit, Digestive Medicine Service, IIS La Fe and CIBER-EHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
- Department of Medicine, Universitat de València, 46010 Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Carmen Espinós
- Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain; (A.S.-M.); (E.R.)
- Joint Unit on Rare Diseases CIPF-IIS La Fe, 46012 Valencia, Spain;
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Li Y, Ma J, Li B, Zhu X, Wang J. Cirrhosis of Wilson's disease: High and low cutoff using acoustic radiation force impulse (ARFI) -Comparison and combination with serum fibrosis index. Clin Hemorheol Microcirc 2021; 79:575-585. [PMID: 34334385 DOI: 10.3233/ch-211219] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Acoustic Radiation Force Impulse (ARFI), Fibrosis-4(FIB-4) and Aspartate transaminase to platelet ratio index (APRI) are valuable non-invasive methods to evaluate fibrosis in hepatitis virus. Yet, they are rarely used in Wilson's disease. OBJECTIVE Evaluate the diagnostic efficacy of ARFI, FIB-4, APRI, combined detection in cirrhosis with WD, and speculate the optimal high, low cutoff. METHODS This retrospective study was authorized by hospital ethics Committee (number:2021MCZQ02). 102 patients with WD completed ARFI and laboratory examination on the same day. The intraclass correlation coeffcient (ICC) of ARFI among three sonographers was 0.896 (95%CI:0.859-0.925, p = 0.000). The stage of liver involvement was classified into 5 categories according to clinical manifestations, laboratory examination, and liver morphologic characteristics: I, normal; II, biochemical abnormal only; III, abnormal liver morphologic features without sighs of cirrhosis; IV, clinical and imaging sighs of compensateded cirrhosis (Child-Pugh A); V, decompensated cirrhosis (Child-Pugh B and C). This stage system served as the reference standard. The diagnostic efficacy was analyzed by Logistic regression, ROC curve. The optimal low cut-off with high sensitivity (SE) and low negative likelihood ratio (NLR) and high cut-off with high specificity (SP) and positive likelihood ratio (PLR) were derived. RESULTS The diagnostic value of ARFI (0.85, 95%CI:0.77-0.92, p = 0.000) in distiguishing cirrhosis with WD was higher than FIB-4 (0.59, 95%CI: 0.47-0.70, p = 0.127), APRI (0.70, 95%CI: 0.59-0.81, p = 0.000). The low, high cut-off of ARFI for excluding, diagnosing cirrhosis with WD was 1.47 m/s(SE: 98%, NLR:0.09), 2.11 m/s(SP:98%, PLR:27.4), 37 (36%) patients could be spared a liver biopsy. When ARFI was 1.47∼2.11 m/s, liver biopsy was recommended. After combined with ARFI, the AUROC of FIB-4, APRI were increased respectively (p < 0.001), there were not different between ARFI and combined detection(p > 0.05). CONCLUSION ARFI could replace some unnecessary liver biopsy according to high diagnostic efficacy for identifying cirrhosis of WD. The combined detection can also be used as an important model to predict cirrhosis in WD.
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Affiliation(s)
- Yan Li
- Department of Intervention, The First Affiliated Hospital of Soochow University, Jiangsu, China
| | - Jianbing Ma
- Department of Radiology, the First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Zhejiang, China
| | - Baoqi Li
- Department of Ultrasound, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Anhui, China
| | - Xiaoli Zhu
- Department of Intervention, The First Affiliated Hospital of Soochow University, Jiangsu, China
| | - Jingping Wang
- Department of Ultrasound, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Anhui, China
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