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Liguori A, Zoncapè M, Casazza G, Easterbrook P, Tsochatzis EA. Staging liver fibrosis and cirrhosis using non-invasive tests in people with chronic hepatitis B to inform WHO 2024 guidelines: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2025; 10:332-349. [PMID: 39983746 DOI: 10.1016/s2468-1253(24)00437-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 12/14/2024] [Accepted: 12/18/2024] [Indexed: 02/23/2025]
Abstract
BACKGROUND Non-invasive tests (aspartate aminotransferase-to-platelet ratio index [APRI] and transient elastography [FibroScan]) were recommended in the 2015 WHO guidelines to guide treatment decisions in people with chronic hepatitis B. We updated the systematic review and meta-analysis that informed the 2015 guidelines to inform new cutoffs for non-invasive tests for the diagnosis of significant fibrosis and cirrhosis for the 2024 WHO guidelines for chronic hepatitis B. METHODS We searched PubMed (MEDLINE), Embase, and Science Citation Index Expanded (Web of Science) for studies published in any language between Jan 1, 2014, and Feb 15, 2023. We included all studies that reported cross-sectional data on the staging of fibrosis or cirrhosis with APRI, Fibrosis-4 (FIB-4), and FibroScan compared with liver biopsy as the reference standard in people with chronic hepatitis B. We excluded studies in which the maximum interval between liver biopsy and non-invasive fibrosis test was more than 6 months; that reported on fewer than ten patients with advanced fibrosis or cirrhosis; that were done exclusively in children; and did not report diagnostic accuracy across our prespecified ranges of test cutoffs. The results of this updated search were collated with the meta-analysis that informed the 2015 guidelines. Outcomes of interest were the sensitivity and specificity of non-invasive tests using defined index test cutoffs for detecting significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) based on the METAVIR staging system. We performed meta-analyses using a bivariate random-effects model. FINDINGS Of 19 933 records identified by our search strategy, 195 were eligible for our systematic review and combined with the 69 studies from the previous meta-analysis to total 264. Two studies were at low risk of bias, 31 studies had unclear risk of bias, and 231 studies had a high risk of bias. Of these 264, 211 studies with 61 665 patients were used in the meta-analysis. For the diagnosis of significant fibrosis (≥F2), sensitivity and specificity were 72·9% (95% CI 70·2-75·5) and 64·7% (95% CI 61·0-68·2) for the APRI low cutoff (>0·3 to 0·7), 30·5% (23·7-38·3) and 92·3% (89·3-94·6) for the APRI high cutoff (>1·3 to 1·7), and 75·1% (72·2-77·7) and 79·3% (76·2-82·2) for FibroScan (>6·0 to 8·0 kPa), respectively. For the diagnosis of cirrhosis (F4), sensitivity and specificity were 59·4% (53·2-65·2) and 73·9% (70·1-77·4) for the APRI low cutoff (>0·8 to 1·2), 30·2% (24·2-36·9) and 88·2% (85·4-90·6) for the APRI high cutoff (>1·8 to 2·2), and 82·6% (77·8-86·5) and 89·0% (86·3-91·2) for FibroScan (>11·0 to 14·0 kPa), respectively. Using a hypothetical population of 1000 unselected patients with chronic hepatitis B with a 25% prevalence of significant fibrosis (≥F2), the APRI low cutoff for significant fibrosis (≥F2) would result in 262 (26·2%) false positives but only 68 (6·8%) false negatives. The FibroScan cutoff would result in 158 (15·8%) false positives and 63 (6·3%) false negatives. In a population with a 5% prevalence of cirrhosis (F4), the APRI low cutoff for cirrhosis (F4) would result in 247 (24·7%) false positives and 21 (2·1%) false negatives and the FibroScan cutoff would result in 105 (10·5%) false positives and nine (0·9%) false negatives. INTERPRETATION These findings have informed new thresholds of APRI and FibroScan for diagnosis of significant fibrosis and cirrhosis in the 2024 WHO guidelines on chronic hepatitis B, with an APRI score greater than 0·5 or a FibroScan value greater than 7·0 kPa considered to identify most adults with significant fibrosis (≥F2) and an APRI score greater than 1·0 or a FibroScan value greater than 12·5 kPa to identify most adults with cirrhosis (F4). These patients are a priority for antiviral treatment. FUNDING WHO.
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Affiliation(s)
- Antonio Liguori
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK; Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Mirko Zoncapè
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK; Liver Unit, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Philippa Easterbrook
- Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK.
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Pecoraro V, Nascimbeni F, Cuccorese M, Gabrielli F, Fasano T, Trenti T. Diagnostic Accuracy of Golgi Protein 73 (GP73) for Liver Fibrosis Staging in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Scoping Review and Cohort Study. Diagnostics (Basel) 2025; 15:544. [PMID: 40075792 PMCID: PMC11898419 DOI: 10.3390/diagnostics15050544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: Golgi protein 73 (GP73) is a transmembrane protein expressed by epithelial cells of the bile duct in the normal liver. High serum levels of GP73 have been detected in patients with acute or chronic liver diseases, MASLD, and its measurement has been suggested as a potential biomarker for liver fibrosis staging. We evaluated the utility of GP73 in the diagnosis of MASLD, MASH, and for liver fibrosis staging. Methods: We performed a literature scoping review to map the current evidence about the accuracy of GP73 in patients with MASLD. We searched in Medline and EMBASE for English studies reporting an AUC value of GP73 in diagnosing MASLD and MASH and evaluating GP73 for fibrosis staging. A narrative synthesis of the evidence was conducted. Moreover, we performed an observational study including 84 patients with MASLD, of which 60 were biopsy-confirmed MASH, and different liver fibrosis stages, and 15 healthy controls. Serum GP73 levels were determined using a chemiluminescent assay and reported as mean and standard deviation (SD). Sensitivity (SE), specificity (SP), the area under the receiver operating characteristic (AUROC) curve, and the optimal cut-off value were calculated. Data were considered statistically significant when p < 0.05. Results: Available studies evaluating GP73 in MASLD reported the ability to discriminate MASH from simple steatosis and distinguish patients at different fibrotic stages, but the evidence is still scarce. Our experimental study showed that the serum levels of GP73 were 30 ± 12 ng/mL in MASLD and 32 ± 12 ng/mL in MASH patients and were statistically higher than those of the control group (19 ± 30 ng/mL), increasing from liver fibrosis stage F0 to F4. GP73 levels were significantly higher in patients with significant and advanced fibrosis than controls and no significant fibrosis (p > 0.05). ROC analysis demonstrated that serum GP73 had a good diagnostic potential for MASLD (AUROC 0.85; SE 90%; SP 73%), MASH (AUROC 0.75; SE 82%; SP64%), and significant fibrosis (AUROC 0.7; SE 56%; SP 79%) and was better than other biomarkers for chronic liver diseases. Conclusions: Serum GP73 could support clinicians in the evaluation of patients with MASH and significant fibrosis.
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Affiliation(s)
- Valentina Pecoraro
- Complex Structure of Laboratory Medicine, Department of Laboratory Medicine and Pathological Anatomy, AUSL Modena, 41121 Modena, Italy
| | | | - Michela Cuccorese
- Complex Structure of Laboratory Medicine, Department of Laboratory Medicine and Pathological Anatomy, AUSL Modena, 41121 Modena, Italy
| | | | - Tommaso Fasano
- Complex Structure of Laboratory Medicine, Department of Laboratory Medicine and Pathological Anatomy, AUSL Modena, 41121 Modena, Italy
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Patel K, Asrani SK, Fiel MI, Levine D, Leung DH, Duarte-Rojo A, Dranoff JA, Nayfeh T, Hasan B, Taddei TH, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Alzuabi M, Ding J, Sofiyeva N, Murad MH, Alsawas M, Rockey DC, Sterling RK. Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:358-379. [PMID: 38489517 DOI: 10.1097/hep.0000000000000842] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 02/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.
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Affiliation(s)
- Keyur Patel
- Department of Medcine, Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Sumeet K Asrani
- Department of Medicine, Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA
| | - Maria Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jonathan A Dranoff
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tamar H Taddei
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Muayad Alzuabi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Jingyi Ding
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Nigar Sofiyeva
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mohammad H Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Don C Rockey
- Department of Medicine, Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Richard K Sterling
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
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Kim BK. [Serological Markers to Assess Liver Fibrosis and Their Roles]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:195-200. [PMID: 39582306 DOI: 10.4166/kjg.2024.123] [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: 10/19/2024] [Accepted: 10/24/2024] [Indexed: 11/26/2024]
Abstract
Chronic liver disease is a significant public health issue worldwide, with the degree of liver fibrosis and its progression significantly influencing the treatment and prognosis. A liver biopsy is the standard diagnostic method, but it is invasive and presents various issues. Therefore, numerous non-invasive diagnostic methods have been developed. Serum markers are categorized into indirect markers, which reflect liver damage, inflammation, or functional changes, and direct markers, which measure the components released into the bloodstream during fibrosis. In addition, various kinds of formulas that combined direct/indirect markers and demographic variables were developed and validated with encouraging outcomes. Nevertheless, despite their convenience, serum indicators require cautious interpretation because they are affected by a number of factors. More research will be needed to determine if the clinical course of chronic liver disease under a disease-specific treatment could be monitored appropriately using serological markers.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
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Jun YJ, Lee M, Chun HS, Kim TH. [Non-Invasive Test for Assessment of Liver Fibrosis in Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:206-214. [PMID: 39582308 DOI: 10.4166/kjg.2024.106] [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: 09/25/2024] [Accepted: 10/05/2024] [Indexed: 11/26/2024]
Abstract
Chronic hepatitis B (CHB) is a high-risk condition that requires continuous monitoring and appropriate management during the natural course of the disease. In particular, the assessment of liver fibrosis is crucial for determining the optimal timing of antiviral therapy, evaluating the treatment response, and predicting the occurrence and prognosis of hepatocellular carcinoma (HCC) in the management of CHB. Although a liver biopsy is the gold standard for diagnosing liver inflammation, steatosis, and fibrosis, there has been a growing trend in the use of non-invasive tests, such as serum biomarkers, transient elastography, and shear wave elastography in CHB patients. This review provides a summary of the key research findings on the use of serum biomarkers and transient elastography in assessing liver fibrosis, monitoring the disease progression, and predicting the prognosis of CHB patients, with an emphasis on their clinical applicability.
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Affiliation(s)
- Ye Ji Jun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU, on behalf of The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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López Tórrez SM, Ayala CO, Ruggiro PB, Costa CAD, Wagner MB, Padoin AV, Mattiello R. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants. Front Nutr 2024; 11:1284509. [PMID: 38419854 PMCID: PMC10899345 DOI: 10.3389/fnut.2024.1284509] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established. Objective The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD. Methods Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Results In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87. Conclusion The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].
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Affiliation(s)
- Sergio M. López Tórrez
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Camila O. Ayala
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Paula Bayer Ruggiro
- School of Medicine, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Caroline Abud Drumond Costa
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Mario B. Wagner
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Alexandre Vontobel Padoin
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rita Mattiello
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- School of Medicine, Postgraduate Program in Epidemiology, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Wan L, Hu C, Wang F, Xu K, Li F, He B, Wu Z, Luo L, Wen Z. Evaluation of the efficacy of Biejia decoction pill combined with entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis by VCTE. Sci Rep 2023; 13:19616. [PMID: 37949927 PMCID: PMC10638370 DOI: 10.1038/s41598-023-46459-4] [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: 08/29/2023] [Accepted: 11/01/2023] [Indexed: 11/12/2023] Open
Abstract
The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P < 0.0001); The LSM of the observation group after treatment was significantly lower than that of the control group, and the difference was also statistically significant (P = 0.0005 < 0.05). In the subgroup of liver fibrosis, the number of patients with moderate and severe liver fibrosis who completely reversed liver fibrosis after treatment in the treatment group was far more than that in the control group, and the difference between the two groups was statistically significant (χ2 = 4.82 P = 0.028 < 0.05) 。 When the treatment course was more than 9 months, the negative conversion rate of patients in the observation group reached 87.4%, which was higher than that in the control group (70.8%), and the difference was statistically significant (P = 0.002 < 0.05); After 12 months of treatment, the negative conversion rate of patients in the observation group was as high as 95%, which was significantly higher than 76.67% in the control group (P < 0.001). The degree of liver fibrosis was significantly improved when Biejia Decoction Pill was combined with ETV in patients with liver fibrosis/cirrhosis due to hepatitis B. The virological response rate to HBV-DNA increased with the prolongation of treatment, and the Biejia Decoction Pill assists with entecavir in antiviral therapy.
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Affiliation(s)
- Lijun Wan
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Chungen Hu
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Fenfen Wang
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Kedong Xu
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Fan Li
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Bo He
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Zhengqiang Wu
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Linfei Luo
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China
| | - Zhili Wen
- Department of Gastroenterology Department, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, China.
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9
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Nyarko ENY, Obirikorang C, Owiredu WKBA, Adu EA, Acheampong E. Assessment of the performance of haematological and non-invasive fibrotic indices for the monitoring of chronic HBV infection: a pilot study in a Ghanaian population. BMC Res Notes 2023; 16:312. [PMID: 37925465 PMCID: PMC10625242 DOI: 10.1186/s13104-023-06581-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 10/18/2023] [Indexed: 11/06/2023] Open
Abstract
OBJECTIVE Haematological and liver fibrotic markers could be appreciably utilized for effective monitoring of Chronic Hepatitis B viral (HBV) infection, thereby increasing patient's treatment outcome. The objective of this study was to assess the applicability of complete blood count (CBC) and non-invasive liver-fibrotic indices as markers of prognostic outcome and monitoring in HBV infections. RESULTS Significant differences in levels of white cell and differentials counts, red blood cell count, hemoglobin indices, and platelet indices were observed between HBV-infected patients (cases) and uninfected persons (controls). Levels of haemoglobin (Hb), total white blood cells (tWBC), neutrophils, monocytes, platelets, and Platelet Distribution width (PDW) were significantly lower (p < 0.05) in the cases compared to the controls. Total and indirect bilirubin; De-Ritis ratio, Aspartate transaminase to platelet ratio index (APRI) and RDW-to-platelet ratio (RPR) were elevated in cases compared with controls (p-value < 0.05). In a multivariate adjusted model to test the significance of markers, Hemoglobin Index (beta coefficient = - 0.876, p-value < 0.001), NLR (beta coefficient = - 0.839, p-value < 0.001), MPV_10000 (beta coefficient = - 0.333, p-value < 0.001) and Albumin (beta coefficient = - 0.059, p-value = 0.014), were associated with HBV infection status. Receiver operative characteristics curve analysis showed Hemoglobin Index (AUC = 0.744) and MPV_10000 (AUC = 0.730) as better prognostic markers for HBV-infection.
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Affiliation(s)
- Eric N Y Nyarko
- Department of Chemical Pathology, University of Ghana Medical School, University of Ghana, Accra, Ghana.
| | - Christian Obirikorang
- Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- Global Health and Infectious Diseases Group, Kumasi Centre for Collaborative Research, Kumasi, Ghana
| | - W K B A Owiredu
- Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Evans Asamoah Adu
- Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- Global Health and Infectious Diseases Group, Kumasi Centre for Collaborative Research, Kumasi, Ghana
| | - Emmanuel Acheampong
- Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
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10
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Mangia A, Piazzolla AV, Squillante MM, Cocomazzi G, Valori VM, Copetti M, Parente P, Attino V, Guido M. Nonalcoholic Steatohepatitis: A 9-Year Follow Up Cohort Study. J Clin Med 2022; 11:5969. [PMID: 36233834 PMCID: PMC9573625 DOI: 10.3390/jcm11195969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/26/2022] [Accepted: 10/07/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) may progress to severe liver fibrosis and cirrhosis. A limited number of studies with a long follow up assessed fibrosis progression and related predictors in untreated patients with a histological diagnosis of NAFLD. This study aims to investigate rate and predictors of NAFLD progression. METHODS For 9 (2-16.7) years, we followed up a cohort of patients histologically diagnosed. Disease progression was defined by a composite endpoint as evidence of cirrhosis in patients without cirrhosis at baseline, evidence of de novo occurrence of cirrhosis complications, histologically established worsening of stage 1 of fibrosis or increase of 20% in liver stiffness by transient elastography in patients rejecting a second liver biopsy. RESULTS A total of 91 patients were enrolled. Of them, 31 had NAFL and 60 NASH. A second liver biopsy was performed in 22 NASH patients and in 4 NAFL. Disease progression was observed in 38.5% NASH and in 12.0% NAFL (p = 0.034). Patients with portal inflammation had a higher risk of progression (66.7% vs 26%, p = 0.021). High triglycerides levels, advanced fibrosis at baseline and the duration of follow-up predict disease progression (p = 0.021; OR = 6.93, 95% CI 1.33-36.08, p = 0.43; OR 8.37; 95% CI 1.07-65.58 and p = 0.034; OR = 0.88; 95% CI 0.78-0.99, respectively). CONCLUSIONS Our results reinforce the evidence that, in the absence of pharmacologic treatment, NASH progresses in about 40% of patients. Liver biopsy is the only mean to discriminate NAFL from NASH. The prognostic role of portal inflammation needs to be explored in larger series.
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Affiliation(s)
- Alessandra Mangia
- Liver Unit, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | | | | | - Giovanna Cocomazzi
- Liver Unit, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Vanna Maria Valori
- Oncology Division, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Ostatistics Department, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Paola Parente
- Pathology Division, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Vito Attino
- Pathology Division, IRCCS Fondazione “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Maria Guido
- Department of Pathology, Azienda ULSS2, 31100 Treviso, Italy
- Department of Medicine, University of Padua, 35131 Padua, Italy
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11
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Kristensen H, Kimer N, Møller S. Indications and methods for measuring portal hypertension in cirrhosis. Scand J Gastroenterol 2022; 57:1149-1157. [PMID: 35514215 DOI: 10.1080/00365521.2022.2065889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Over the last decade our understanding of the pathophysiology of portal hypertension has increased. Novel diagnostic technologies have facilitated and improved the diagnosis and treatment of hepatic fibrosis and cirrhosis. With this review we aim to provide an overview of contemporary diagnostic principles of portal hypertension and indications for measuring portal pressure in cirrhosis.Methods: By review of current literature, we assessed new and old principles of measuring portal hypertension and the diagnostic values of the methods.Results: Invasive measurement of the portal pressure is still the gold standard to quantitate portal hypertension and to assess response to vasoactive treatment. The size of the portal pressure is important to assess since it contains information on the course of the disease and risk of developing hepatic decompensation, hepatocellular carcinoma, and mortality. Reliable non-invasive Elastography techniques are emerging that adequately assess portal pressure, but the available methods are not yet sufficiently accurate.Conclusion: Although elastography techniques provide valuable information and are good monitoring tools, liver vein catheterization remains valuable in diagnosing and monitoring portal hypertension, especially in combination with a trans-jugular liver biopsy.
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Affiliation(s)
- Helle Kristensen
- Gastro Unit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center of Functional Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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12
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Liver Disease Assessment in Children with Fontan and Glenn Surgeries for Univentricular Hearts—The Role of Elastography and Biochemical Fibrosis Markers. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12157481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Children born with single-ventricle hearts require surgery in order to survive. Liver fibrosis is a known complication of Fontan surgery for univentricular hearts. Methods: In this study on 13 post-Fontan and 21 post-Glenn patients, we used elastography (shearwave and transient elastography) as well as serum biochemical fibrosis markers to evaluate the degree of liver fibrosis in comparison to 32 controls. Results: The mean Emedian and Vmedian values determined by shear wave elastography in the Fontan Group were significantly higher than the controls (4.85 kPa vs. 3.91 kPa and 1.25 m/s vs. 1.12 m/s, respectively). Fontan patients had significantly increased Fibrotest, Actitest, AST-to-Platelet Ratio index, ALT and GammaGT levels compared to controls. For post-Glenn patients, the mean Emedian and Vmedian values were similar to healthy controls, whereas the Fibrotest, Actitest and AST-to-Platelet Ratio index were significantly increased. Using transient elastography, we found significantly higher values for Emedian and Vmedian in Fontan patients compared to Glenn patients. Conclusions: Elastography and biochemical fibrosis markers are valuable non-invasive tools for screening and monitoring liver fibrosis in patients with Fontan and Glenn interventions.
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13
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Zhang X, Huang P, Wang X, Zhou K, Chen F, Zhou C, Yu L, Lu Q, Zhou J, Hu J, Wang Z. Development and validation of a non-invasive model for diagnosing HBV-related liver cirrhosis. Clin Chim Acta 2021; 523:525-531. [PMID: 34748781 DOI: 10.1016/j.cca.2021.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 11/02/2021] [Accepted: 11/02/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver cirrhosis is closely related to the abnormal liver function and occurrence of liver cancer. Accurate non-invasive assessment of liver cirrhosis is of great significance for preventing disease progression and treatment decision-making. We aim to develop and validate a non-invasive diagnostic model for liver cirrhosis in patients with chronic hepatitis B (CHB). METHODS From July 2015 to April 2017, seven-hundred fifty-four patients with primary HBV-related liver cancer who underwent hepatectomy were reprospectively recruited. All patients were examined with 2D-SWE and serologic testing preoperatively, which were utilized for measurement of liver stiffness and serum fibrosis models. The stage of liver fibrosis was evaluated using a resected liver specimen. Least absolute shrinkage and selection operator (Lasso) regression was used for feature selection and binary logistic regression analysis was chosen to build a diagnostic model, which was presented as a nomogram and evaluated for calibration, discrimination and clinical usefulness. The performance of noninvasive model was then prospectively validated in an independent cohort (361 patients) by the ROC curve analysis. RESULTS The diagnostic model, which consists of 5 selected clinical characteristics (PIII-NP, IV-C, Hyaluronan, Platelet and Liver stiffness), showed the strongest correlation with liver fibrosis stage (ρ = 0.702, P < 0.05). Compared with APRI, FIB-4, King's Score, and Forns Index, the model presented the optimal discrimination and the best predictive performance with the highest AUC in the training cohort (0.866, 95%CI 0.840-0.892, P < 0.05) and validation cohorts (0.852, 95%CI 0.813-0.890, P < 0.05). Decision curve analysis demonstrated that nomogram based on the model was extremely useful for diagnosing cirrhosis in patients with chronic hepatitis B. CONCLUSION This study proposes a non-invasive diagnostic model that incorporates the clinical predictors which can be conveniently used in the individualized diagnosis of HBV-related liver cirrhosis.
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Affiliation(s)
- Xiangyu Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Peiran Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Xinyu Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Kaiqian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Feiyu Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Cheng Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Lei Yu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China
| | - Jie Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China.
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai 200032, China.
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14
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Karkampouna S, van der Helm D, Scarpa M, van Hoek B, Verspaget HW, Goumans MJ, Coenraad MJ, Kruithof BP, Kruithof-de Julio M. Oncofetal Protein CRIPTO Is Involved in Wound Healing and Fibrogenesis in the Regenerating Liver and Is Associated with the Initial Stages of Cardiac Fibrosis. Cells 2021; 10:3325. [PMID: 34943832 PMCID: PMC8699799 DOI: 10.3390/cells10123325] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/18/2021] [Accepted: 11/22/2021] [Indexed: 12/20/2022] Open
Abstract
Oncofetal protein, CRIPTO, is silenced during homeostatic postnatal life and often re-expressed in different neoplastic processes, such as hepatocellular carcinoma. Given the reactivation of CRIPTO in pathological conditions reported in various adult tissues, the aim of this study was to explore whether CRIPTO is expressed during liver fibrogenesis and whether this is related to the disease severity and pathogenesis of fibrogenesis. Furthermore, we aimed to identify the impact of CRIPTO expression on fibrogenesis in organs with high versus low regenerative capacity, represented by murine liver fibrogenesis and adult murine heart fibrogenesis. Circulating CRIPTO levels were measured in plasma samples of patients with cirrhosis registered at the waitlist for liver transplantation (LT) and 1 year after LT. The expression of CRIPTO and fibrotic markers (αSMA, collagen type I) was determined in human liver tissues of patients with cirrhosis (on a basis of viral hepatitis or alcoholic disease), in cardiac tissue samples of patients with end-stage heart failure, and in mice with experimental liver and heart fibrosis using immuno-histochemical stainings and qPCR. Mouse models with experimental chronic liver fibrosis, induced with multiple shots of carbon tetrachloride (CCl4) and acute liver fibrosis (one shot of CCl4), were evaluated for CRIPTO expression and fibrotic markers. CRIPTO was overexpressed in vivo (Adenoviral delivery) or functionally sequestered by ALK4Fc ligand trap in the acute liver fibrosis mouse model. Murine heart tissues were evaluated for CRIPTO and fibrotic markers in three models of heart injury following myocardial infarction, pressure overload, and ex vivo induced fibrosis. Patients with end-stage liver cirrhosis showed elevated CRIPTO levels in plasma, which decreased 1 year after LT. Cripto expression was observed in fibrotic tissues of patients with end-stage liver cirrhosis and in patients with heart failure. The expression of CRIPTO in the liver was found specifically in the hepatocytes and was positively correlated with the Model for End-stage Liver Disease (MELD) score for end-stage liver disease. CRIPTO expression in the samples of cardiac fibrosis was limited and mostly observed in the interstitial cells. In the chronic and acute mouse models of liver fibrosis, CRIPTO-positive cells were observed in damaged liver areas around the central vein, which preceded the expression of αSMA-positive stellate cells, i.e., mediators of fibrosis. In the chronic mouse models, the fibrosis and CRIPTO expression were still present after 11 weeks, whereas in the acute model the liver regenerated and the fibrosis and CRIPTO expression resolved. In vivo overexpression of CRIPTO in this model led to an increase in fibrotic markers, while blockage of CRIPTO secreted function inhibited the extent of fibrotic areas and marker expression (αSMA, Collagen type I and III) and induced higher proliferation of residual healthy hepatocytes. CRIPTO expression was also upregulated in several mouse models of cardiac fibrosis. During myocardial infarction CRIPTO is upregulated initially in cardiac interstitial cells, followed by expression in αSMA-positive myofibroblasts throughout the infarct area. After the scar formation, CRIPTO expression decreased concomitantly with the αSMA expression. Temporal expression of CRIPTO in αSMA-positive myofibroblasts was also observed surrounding the coronary arteries in the pressure overload model of cardiac fibrosis. Furthermore, CRIPTO expression was upregulated in interstitial myofibroblasts in hearts cultured in an ex vivo model for cardiac fibrosis. Our results are indicative for a functional role of CRIPTO in the induction of fibrogenesis as well as a potential target in the antifibrotic treatments and stimulation of tissue regeneration.
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Affiliation(s)
- Sofia Karkampouna
- Department for Biomedical Research, Urology Research Laboratory, Bern University, 3008 Bern, Switzerland; (S.K.); (M.S.)
| | - Danny van der Helm
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (D.v.d.H.); (B.v.H.); (H.W.V.); (M.J.C.)
| | - Mario Scarpa
- Department for Biomedical Research, Urology Research Laboratory, Bern University, 3008 Bern, Switzerland; (S.K.); (M.S.)
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (D.v.d.H.); (B.v.H.); (H.W.V.); (M.J.C.)
| | - Hein W. Verspaget
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (D.v.d.H.); (B.v.H.); (H.W.V.); (M.J.C.)
| | - Marie-Jose Goumans
- Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands; (M.-J.G.); (B.P.T.K.)
| | - Minneke J. Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (D.v.d.H.); (B.v.H.); (H.W.V.); (M.J.C.)
| | - Boudewijn P.T. Kruithof
- Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands; (M.-J.G.); (B.P.T.K.)
- Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Marianna Kruithof-de Julio
- Department for Biomedical Research, Urology Research Laboratory, Bern University, 3008 Bern, Switzerland; (S.K.); (M.S.)
- Department of Urology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland
- Translational Organoid Resource Core, Department for BioMedical Research, Bern University, 3008 Bern, Switzerland
- Bern Center for Precision Medicine, Inselspital, University Hospital of Bern, 3010 Bern, Switzerland
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Wang H, Zheng P, Wang X, Sang L. Effect of Q-Box size on liver stiffness measurement by two-dimensional shear wave elastography. JOURNAL OF CLINICAL ULTRASOUND : JCU 2021; 49:978-983. [PMID: 34609006 DOI: 10.1002/jcu.23075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/16/2021] [Accepted: 09/19/2021] [Indexed: 06/13/2023]
Abstract
PURPOSE To investigate the effect of the Q-Box size on liver stiffness (LS) measurement by two-dimensional shear wave elastography (2D SWE). METHODS Ninety-eight patients with chronic liver disease were enrolled. Each patient was continuously measured five times. The Q-Box diameter was adjusted to 10, 20, and 30 mm each time. The liver stiffness values (LSVs) at different diameters were compared in the following groups: LSVs ≤6.2 kPa, 6.2 kPa < LSVs ≤11 kPa, LSVs >11 kPa. The reliability and repeatability of LS measurement at different diameters were evaluated. RESULTS The differences in LSVs at different Q-Box diameters were statistically significant only when LSV ≤6.2 kPa (p = 0.004). There were no statistically significant differences in standard deviation (SD), SD/median, coefficient of variation (CV), and interquartile range (IQR)/median at different Q-Box diameters (p > 0.05). There were statistical differences in minimum LSVs and percentage of minimum LSVs ≤0.2 kPa as well as in stability index (SI) and percentage of SI <90% at different Q-Box diameters (p < 0.05). The intraclass correlation coefficients (ICCs) were up to 0.98 at Q-Box diameters of 10, 20, and 30 mm. CONCLUSIONS Our study showed that Q-Box size may lead to significant differences in LSVs, especially when LSVs ≤6.2 kPa. The Q-Box size had a large effect on the reliability of a single LS measurement but did not affect the repeatability of multiple measurements.
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Affiliation(s)
- Huipeng Wang
- Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Pengchao Zheng
- Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xuemei Wang
- Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Liang Sang
- Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
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Predict Early Recurrence of Resectable Hepatocellular Carcinoma Using Multi-Dimensional Artificial Intelligence Analysis of Liver Fibrosis. Cancers (Basel) 2021; 13:cancers13215323. [PMID: 34771487 PMCID: PMC8582529 DOI: 10.3390/cancers13215323] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the third most commonly diagnosed cancer in the world, and surgical resection is the commonly used curative management of early-stage disease. However, the recurrence rate is high after resection, and liver fibrosis has been thought to increase the risk of recurrence. Conventional histological staging of fibrosis is highly subjective to observer variations. To overcome this limitation, we used a fully quantitative fibrosis assessment tool, qFibrosis (utilizing second harmonic generation and two-photon excitation fluorescence microscopy), with multi-dimensional artificial intelligence analysis to establish a fully-quantitative, accurate fibrotic score called a “combined index”, which can predict early recurrence of HCC after curative intent resection. Therefore, we can pay more attention on the patients with high risk of early recurrence. Abstract Background: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. Methods: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model “combined index” according to the morphological collagen features of each patient’s non-tumor hepatic tissues. Results: Our results showed that the “combined index” can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher “combined index” is also a poor prognostic factor of disease-free survival and overall survival. Conclusions: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed.
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Sorino P, Campanella A, Bonfiglio C, Mirizzi A, Franco I, Bianco A, Caruso MG, Misciagna G, Aballay LR, Buongiorno C, Liuzzi R, Cisternino AM, Notarnicola M, Chiloiro M, Fallucchi F, Pascoschi G, Osella AR. Development and validation of a neural network for NAFLD diagnosis. Sci Rep 2021; 11:20240. [PMID: 34642390 PMCID: PMC8511336 DOI: 10.1038/s41598-021-99400-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/24/2021] [Indexed: 12/18/2022] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) affects about 20–30% of the adult population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Liver ultrasound (US) is widely used as a noninvasive method to diagnose NAFLD. However, the intensive use of US is not cost-effective and increases the burden on the healthcare system. Electronic medical records facilitate large-scale epidemiological studies and, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Our goal was to develop and validate a simple Neural Network (NN)-based web app that could be used to predict NAFLD particularly its absence. The study included 2970 subjects; training and testing of the neural network using a train–test-split approach was done on 2869 of them. From another population consisting of 2301 subjects, a further 100 subjects were randomly extracted to test the web app. A search was made to find the best parameters for the NN and then this NN was exported for incorporation into a local web app. The percentage of accuracy, area under the ROC curve, confusion matrix, Positive (PPV) and Negative Predicted Value (NPV) values, precision, recall and f1-score were verified. After that, Explainability (XAI) was analyzed to understand the diagnostic reasoning of the NN. Finally, in the local web app, the specificity and sensitivity values were checked. The NN achieved a percentage of accuracy during testing of 77.0%, with an area under the ROC curve value of 0.82. Thus, in the web app the NN evidenced to achieve good results, with a specificity of 1.00 and sensitivity of 0.73. The described approach can be used to support NAFLD diagnosis, reducing healthcare costs. The NN-based web app is easy to apply and the required parameters are easily found in healthcare databases.
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Affiliation(s)
- Paolo Sorino
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Angelo Campanella
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Caterina Bonfiglio
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonella Mirizzi
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Isabella Franco
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonella Bianco
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Maria Gabriella Caruso
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Giovanni Misciagna
- Scientific and Ethical Committee, Polyclinic Hospital, University of Bari, Piazza Giulio Cesare, 11, 70124, Bari, BA, Italy
| | - Laura R Aballay
- Human Nutrition Research Center (CenINH), School of Nutrition, Faculty of Medical Sciences, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Claudia Buongiorno
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Rosalba Liuzzi
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Anna Maria Cisternino
- Clinical Nutrition Outpatient Clinic, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Maria Notarnicola
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Marisa Chiloiro
- San Giacomo Hospital, Largo S. Veneziani, 21, 70043, Monopoli, BA, Italy
| | - Francesca Fallucchi
- Department of Engineering Sciences, Guglielmo Marconi University, Via plinio 44, 00193, Rome, Italy
| | - Giovanni Pascoschi
- Department of Electrical and Information Engineering, Polytechnic of Bari, Via Re David, 200, 70125, Bari, BA, Italy
| | - Alberto Rubén Osella
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology, "S de Bellis" Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy.
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18
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Dong B, Lyu G, Chen Y, Lin G, Wang H, Qin R, Gu J. Comparison of two-dimensional shear wave elastography, magnetic resonance elastography, and three serum markers for diagnosing fibrosis in patients with chronic hepatitis B: a meta-analysis. Expert Rev Gastroenterol Hepatol 2021; 15:1077-1089. [PMID: 33487039 DOI: 10.1080/17474124.2021.1880894] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Two-dimensional shear wave elastography (2D-SWE), magnetic resonance elastography (MRE), aspartate transaminase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and King's score have been proposed for diagnosing fibrosis. METHODS Literature databases were searched until October 1st, 2020. The summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities were used to assess the performance of these noninvasive methods for staging fibrosis. RESULTS Our final data contained 72 studies. The prevalence of significant fibrosis, advanced fibrosis, and cirrhosis was 58.3%, 36.2%, and 20.5%, respectively, in chronic hepatitis B (CHB). For 2D-SWE and MRE, the summary AUROCs were 0.89 and 0.97, 0.95 and 0.97, and 0.94 and 0.97 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. The summary AUROCs using APRI and FIB-4 for detecting significant fibrosis, advanced fibrosis, and cirrhosis were 0.76 and 0.75, 0.74 and 0.77, and 0.77 and 0.82, respectively. The summary AUROCs of King's score for detecting significant fibrosis and cirrhosis were 0.77 and 0.83, respectively. CONCLUSION MRE and 2D-SWE may show the best diagnostic accuracy for predicting fibrosis in CHB. Among the three serum markers, King's score may be more useful for diagnosing fibrosis.
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Affiliation(s)
- Bingtian Dong
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Guorong Lyu
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.,Department of Clinical Medicine, Quanzhou Medical College, Quanzhou, Fujian Province, China
| | - Yuping Chen
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Guofu Lin
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Respirology Medicine Centre of Fujian Province, Quanzhou, Fujian Province, China
| | - Huaming Wang
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
| | - Ran Qin
- Department of Ultrasound, The Chenggong Hospital, Xiamen University, Xiamen, Fujian Province, China
| | - Jionghui Gu
- Department of Ultrasound, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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19
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Abdel-Hameed EA, Rouster SD, Kottilil S, Sherman KE. The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients. Clin Infect Dis 2021; 73:450-459. [PMID: 32459305 DOI: 10.1093/cid/ciaa646] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 05/22/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. METHODS The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. RESULTS The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. CONCLUSIONS ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.
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Affiliation(s)
| | - Susan D Rouster
- University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore, Maryland, USA
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20
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Vali Y, Lee J, Boursier J, Spijker R, Verheij J, Brosnan MJ, Anstee QM, Bossuyt PM, Zafarmand MH, on behalf of the LITMUS Systematic Review Team. FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:jcm10112415. [PMID: 34072480 PMCID: PMC8198930 DOI: 10.3390/jcm10112415] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 05/23/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022] Open
Abstract
(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.
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Affiliation(s)
- Yasaman Vali
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
- Correspondence: ; Tel.: +31-(0)20-5668520
| | - Jenny Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
| | - Jérôme Boursier
- Hepato-Gastroenterology Department, Angers University Hospital, 49933 Angers, France;
- HIFIH Laboratory, UPRES EA3859, Angers University, 49035 Angers, France
| | - René Spijker
- Medical Library AMC, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
| | - M. Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139, USA;
| | - Quentin M. Anstee
- The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
- Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 7RU, UK
| | - Patrick M. Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
| | - Mohammad Hadi Zafarmand
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
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21
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Ballestri S, Mantovani A, Baldelli E, Lugari S, Maurantonio M, Nascimbeni F, Marrazzo A, Romagnoli D, Targher G, Lonardo A. Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease. Diagnostics (Basel) 2021; 11:98. [PMID: 33435415 PMCID: PMC7827076 DOI: 10.3390/diagnostics11010098] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/29/2020] [Accepted: 01/06/2021] [Indexed: 02/07/2023] Open
Abstract
Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 patients with viral hepatitis (157 HCV and 16 HBV) and 107 with a non-alcoholic fatty liver disease (NAFLD) were consecutively enrolled. Various liver fibrosis biomarkers: aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (ARR), AST to Platelet Ratio Index (APRI), Fibrosis-4 (FiB-4), Forns index, NAFLD fibrosis score (NFS), BARD (body mass index (BMI), AAR, Diabetes) score, and Hepamet fibrosis score (HFS), were used to identify significant/advanced fibrosis. CVR was assessed by using the SCORE, the Progetto CUORE, or the Framingham risk scoring systems. Liver fibrosis biomarkers performed better in predicting advanced rather than significant liver fibrosis in all patients, regardless of chronic liver disease aetiology. Forns index and HFS performed best in predicting advanced fibrosis in patients with viral chronic liver disease and NAFLD. Lower cut-offs of these liver fibrosis biomarkers had high negative predictive values for advanced fibrosis overall, as well as in patients with NAFLD or viral chronic liver disease. FIB-4, Forns index, NFS, and HFS were positively correlated with SCORE and Framingham risk scores. In conclusion, liver fibrosis biomarkers accurately exclude advanced fibrosis and positively correlate with CVR scores in patients with chronic liver disease.
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Affiliation(s)
- Stefano Ballestri
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, 41026 Modena, Italy;
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (A.M.); (G.T.)
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy;
| | - Simonetta Lugari
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | - Mauro Maurantonio
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | - Fabio Nascimbeni
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | | | - Dante Romagnoli
- Gastroenterology Unit, Ospedale Policlinico di Modena, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy;
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (A.M.); (G.T.)
| | - Amedeo Lonardo
- Metabolic Syndrome Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy;
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22
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Shahin AE, Alshmmary SN, Aljabarah NS, Alshammari AM, Alshammari KM, Alabedah RS, Almudayni HK, Alquwaiay DAS, Alghaithi AM. An Overview on Non-invasive Assessment of Cirrhosis. ARCHIVES OF PHARMACY PRACTICE 2021. [DOI: 10.51847/zpadewrmgx] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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23
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Chen YP, Huang LW, Lin XY, Hu XM, Liang XE, Jiang RL. Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis. J Viral Hepat 2020; 27:826-836. [PMID: 32187804 DOI: 10.1111/jvh.13293] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 02/11/2020] [Accepted: 02/20/2020] [Indexed: 12/13/2022]
Abstract
The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was ∝ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.
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Affiliation(s)
- Yong-Peng Chen
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China.,Department of Internal Medicine, Nanfang Hospital Taihe Branch, Guangzhou, China
| | - Li-Wen Huang
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Shunde, China
| | - Xiao-Yu Lin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao-Min Hu
- Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xie-Er Liang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong-Long Jiang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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24
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Androutsakos T, Schina M, Pouliakis A, Kontos A, Sipsas N, Hatzis G. Liver Fibrosis Assessment in a Cohort of Greek HIV Mono-Infected Patients by Non-Invasive Biomarkers. Curr HIV Res 2020; 17:173-182. [PMID: 31549590 DOI: 10.2174/1570162x17666190809153245] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/26/2019] [Accepted: 08/03/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Non-alcoholic Fatty Liver Disease (NAFLD) is common in HIV-infected individuals. Liver biopsy remains the gold-standard procedure for the diagnosis of liver fibrosis, but both Transient Elastography (TE) and Non-invasive Biomarkers (NIBMs) have emerged as alternatives. OBJECTIVES Our study's aim was to validate commonly used NIBMs for the assessment of liver fibrosis in a cohort of Greek HIV-mono-infected patients. METHODS Inclusion criteria were confirmed HIV-infection and age>18 years and exclusion criteria HBV or HCV seropositivity, liver disease other than NAFLD, alcohol abuse, ascites, transaminases levels>4xULN(upper limit of normal) and Body-Mass index(BMI)>40. Liver stiffness (LS) measurement with TE and thorough laboratory work up and medical history were acquired at study entry. FIB-4, APRI, NFS, BARD, Forns and Lok scores were calculated for each patient. RESULTS A total of 157 patients were eligible for this study. Significant liver fibrosis, compatible with Metavir score of F3-F4, was found in only 11(7%) patients. These findings were in accordance with those of the NIBMs; the BARD score constituting the only exception, allocating 102(65%) patients as having significant liver fibrosis. In order to obtain a balance between sensitivity and specificity new cut-offs for each NIBM were calculated; FIB-4 score yielded the best results, since by changing the cut-off to 1.49 a sensitivity and specificity balanced for both close to 85% was achieved. CONCLUSION Our findings suggest that NIBMs can be used for the evaluation of liver fibrosis in HIV mono-infected patients. New cut-offs for NIBMs should probably be calculated, to help distinguishing patients with significant from those with mild/no fibrosis.
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Affiliation(s)
- Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Schina
- Liver unit, Euroclinic of Athens, Athens, Greece
| | - Abraham Pouliakis
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Nikolaos Sipsas
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.,Infectious Diseases Unit, Laiko General Hospital, Athens, Greece
| | - Gregorios Hatzis
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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25
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Loomba R, Adams LA. Advances in non-invasive assessment of hepatic fibrosis. Gut 2020; 69:1343-1352. [PMID: 32066623 PMCID: PMC7945956 DOI: 10.1136/gutjnl-2018-317593] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 01/27/2020] [Accepted: 01/28/2020] [Indexed: 12/14/2022]
Abstract
Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more 'complex' serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.
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Affiliation(s)
- Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, California, USA
| | - Leon A Adams
- Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
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26
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Wang H, Zheng P, Sang L, Wang X. Does Operator Experience and the Q-Box Diameter Affect the Repeatability of Liver Stiffness Measurements Obtained by 2-Dimensional Shear Wave Elastography? JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2020; 39:741-747. [PMID: 31626345 DOI: 10.1002/jum.15153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 09/19/2019] [Accepted: 09/26/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVES The purpose of this research was to evaluate whether operator experience and the quantitative analysis system (Q-Box; SuperSonic Imagine, Aix-en-Provence, France) diameter affect the repeatability of liver stiffness measurements. METHODS We enrolled 417 outpatients. All measurements were performed by 2 operators, including an expert and a novice. Each patient was continuously measured 3 times by the 2 operators. The Q-Box diameter was adjusted to 10, 20, and 30 mm each time, and the mean elasticity values were recorded. Intraobserver repeatability was evaluated by the intraclass correlation coefficient (ICC). Interobserver repeatability was evaluated by the ICC, coefficient of variation (CV), and Bland-Altman plots. RESULTS The study group included 241 male and 176 female patients. The expert operator had higher ICCs than the novice operator at each Q-Box diameter. The overall interobserver agreement was excellent, and the results showed that compared to other groups, the ICC was the lowest and the CV was the largest for the 30-mm-diameter group. The ICC and CV values were similar between the 10- and 20 mm-diameter groups. The Bland-Altman plots showed that the mean difference was -0.2 kPa for the 10-, 20-, and 30 mm-diameter groups. However, the limits of agreement were the largest in the 30-mm-diameter group and were similar between the 10- and 20-mm-diameter groups. CONCLUSIONS The repeatability of liver stiffness measurements is affected not only by experience but also by the Q-Box diameter.
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Affiliation(s)
- Huipeng Wang
- Department of Ultrasound, First Hospital of China Medical University, Shenyang, China
| | - Pengchao Zheng
- Department of Ultrasound, First Hospital of China Medical University, Shenyang, China
| | - Liang Sang
- Department of Ultrasound, First Hospital of China Medical University, Shenyang, China
| | - Xuemei Wang
- Department of Ultrasound, First Hospital of China Medical University, Shenyang, China
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Evon DM, Lin HHS, Khalili M, Fontana RJ, Yim C, Wahed AS, Fried MW, Hoofnagle JH, Hepatitis B Research Network (HBRN). Patient-reported outcomes in a large North American cohort living with chronic hepatitis B virus: a cross-sectional analysis. Aliment Pharmacol Ther 2020; 51:457-468. [PMID: 31943262 PMCID: PMC6989387 DOI: 10.1111/apt.15618] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 11/04/2019] [Accepted: 11/27/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patient-reported outcomes (PROs) such as health-related quality of life (HRQoL) and symptoms associated with chronic hepatitis B viral (HBV) infection have not been well-described in North American cohorts. AIMS To evaluate several PROs and associations with HBV disease activity markers. METHODS Cross-sectional analysis including 876 adults who completed PRO measures during the Hepatitis B Research Network Adult Cohort Study. Participants on HBV treatment were excluded. Outcomes included: HRQoL using the SF-36 mental component summary and physical component summary scores; symptom burden using a 10-item Total Symptom Checklist and fatigue using an instrument from the Patient-Reported Outcomes Measurement Information System®. Covariates included laboratory markers of disease severity, virological status, comorbidities and medications. RESULTS Median age was 42 (range: 19-79), 51% were female, 73% Asian, 19% HBeAg (+), 2% had AST-platelet ratio index (APRI) ≥1.5 and 74% without comorbidities. Mean mental component summary T-score = 52, physical component summary T-score = 54 and PROMIS Fatigue T-score = 47. On a scale from 0 (none) to 40 (extreme), the mean Symptom Checklist score = 3 and 25% reported no symptoms. The most frequent symptoms were fatigue (60%), irritability (32%) and itching (32%). Most symptoms were 'a little bit' bothersome. In multivariable regressions, APRI ≥1.50 and more comorbidities were associated with worse patient-reported outcomes; virological markers were not. Adding the Total Symptom Checklist score to original regression models increased explanation of variation in the mental component summary score from 4% to 44% and the Physical Component Summary Score from 17% to 34%. CONCLUSIONS Untreated North American HBV patients with mild liver disease report favourable health-related quality of life and minimal symptoms. HBV does not impact health-related quality of life unless advanced liver disease or comorbidities are present. High symptom burden explains substantial variation in health-related quality of life. (CT.gov identifier: NCT01263587).
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Affiliation(s)
- Donna M. Evon
- Department of Medicine, University of North Carolina at Chapel Hill
| | - Hsing-Hua S. Lin
- Departments of Epidemiology and Biostatistics, University of Pittsburgh
| | - Mandana Khalili
- Department of Medicine, University of California at San Francisco
| | | | - Colina Yim
- Toronto Centre for Liver Disease, University of Toronto
| | - Abdus S. Wahed
- Departments of Epidemiology and Biostatistics, University of Pittsburgh
| | - Michael W. Fried
- Department of Medicine, University of North Carolina at Chapel Hill
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Fujita K, Nomura T, Morishita A, Oura K, Yoneyama H, Kobara H, Tsutsui K, Himoto T, Masaki T. Albumin-Bilirubin Score Differentiates Liver Fibrosis Stage and Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Virus Infection: A Retrospective Cohort Study. Am J Trop Med Hyg 2020; 101:220-225. [PMID: 31115300 PMCID: PMC6609180 DOI: 10.4269/ajtmh.19-0129] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The albumin-bilirubin (ALBI) score was originally established to stratify prognosis in patients with cirrhosis. The diagnostic accuracy of ALBI score in liver fibrosis staging in patients with chronic hepatitis B remains to be investigated. The present retrospective study, therefore, aimed to evaluate the ability of this score to stage liver fibrosis in these patients. Briefly, consecutive patients with hepatitis B virus (HBV) infection who underwent liver biopsy examinations in Kagawa University Hospital were enrolled. Liver fibrosis stage was assessed using a modified Meta-Analysis of Histological Data in Viral Hepatitis score. Albumin-bilirubin scores were calculated according to the following equation: (log10 total bilirubin [T-Bil] × 0.66) + (albumin [Alb] × -0.085). A total of 91 patients were enrolled in this study. Albumin-bilirubin score was able to differentiate stage 4 from stage 3 fibrosis (P < 0.05). When an ALBI score of -2.190 was adopted as the cutoff value for differentiating stage 4 from stages 1-3, the sensitivity, specificity, and positive likelihood ratio were 85.7%, 74.0%, and 3.300, respectively. Kaplan-Meier analysis showed that baseline ALBI scores < -2.190 correlated with better hepatocellular carcinoma (HCC)-free survival (P < 0.05). In conclusion, ALBI score can be used for liver fibrosis staging in Japanese chronic hepatitis B patients and can help distinguish cirrhotic from non-cirrhotic status. Furthermore, ALBI score was useful as a prognosis biomarker in our patients, with smaller ALBI scores predicting better HCC-free survival. Because calculating ALBI score is easy using serum T-Bil and Alb alone, ALBI score will help clinicians with decision-making in management of HBV-infected patients.
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Affiliation(s)
- Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Takako Nomura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Kunihiko Tsutsui
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
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Milas GP, Karageorgiou V, Cholongitas E. Red cell distribution width to platelet ratio for liver fibrosis: a systematic review and meta-analysis of diagnostic accuracy. Expert Rev Gastroenterol Hepatol 2019; 13:877-891. [PMID: 31389726 DOI: 10.1080/17474124.2019.1653757] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Red cell distribution width to platelet ratio (RPR) may be a useful marker for the evaluation of liver fibrosis in chronic liver disease (CLD). We sought to investigate its value in fibrosis-related outcomes in a meta-analysis of diagnostic accuracy. Areas covered: We searched MEDLINE (1966-2019), Clinicaltrials.gov (2008-2019), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2019), Google Scholar (2004-2019) and WHO (International Clinical Trials Register Platform) databases using a structured algorithm. The articles were assessed by Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). In over 1,800 patients for each outcome, pooled sensitivity and specificity for a) significant fibrosis, b) advanced fibrosis and c) cirrhosis were: a) 0.635 and 0.769 with an AUC of 0.747, b) 0.607 and 0.783 with an AUC of 0.773, c) 0.739 and 0.768 with an AUC of 0.818 respectively. Similar results were found for chronic hepatitis B in all outcomes. Subgroup analysis indicated a high specificity for advanced fibrosis detection in primary biliary cirrhosis. Sensitivity analysis did not alter the results. Expert opinion: RPR is a good predictor of fibrosis, especially as severity of chronic liver disease progresses. Future research should elucidate its value in specific etiologies of chronic liver disease.
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Affiliation(s)
- Gerasimos P Milas
- First Department of Internal Medicine, Medical School of National & Kapodistrian University, General Hospital of Athens "Laiko" , Athens , Greece
| | - Vasilios Karageorgiou
- First Department of Internal Medicine, Medical School of National & Kapodistrian University, General Hospital of Athens "Laiko" , Athens , Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National & Kapodistrian University, General Hospital of Athens "Laiko" , Athens , Greece
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Xu XY, Wang WS, Zhang QM, Li JL, Sun JB, Qin TT, Liu HB. Performance of common imaging techniques vs serum biomarkers in assessing fibrosis in patients with chronic hepatitis B: A systematic review and meta-analysis. World J Clin Cases 2019; 7:2022-2037. [PMID: 31423434 PMCID: PMC6695542 DOI: 10.12998/wjcc.v7.i15.2022] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 06/25/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Noninvasive biomarkers have been developed to predict hepatitis B virus (HBV) related fibrosis owing to the significant limitations of liver biopsy. Both serum biomarkers and imaging techniques have shown promising results and may improve the evaluation of liver fibrosis. However, most of the previous studies focused on the diagnostic effects of various imaging techniques on fibrosis in all chronic liver diseases.
AIM To compare the performance of common imaging methods and serum biomarkers for prediction of significant fibrosis caused only by HBV infection.
METHODS A systematic review was conducted on the records available in PubMed, EMBASE, and the Cochrane Library electronic databases until December 2018. We systematically assessed the effectiveness of two serum biomarkers and three imagine techniques in predicting significant fibrosis solely caused by HBV infection. The serum biomarkers included aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4). The three imaging techniques included acoustic radiation force impulse (ARFI), FibroScan, and magnetic resonance elastography (MRE). Three parameters, the area under the summary receiver operating characteristic curve (AUSROC), the summary diagnostic odds ratio, and the summary sensitivity and specificity, were used to examine the accuracy of all tests for liver fibrosis.
RESULTS Out of 2831 articles evaluated for eligibility, 204 satisfied the predetermined inclusion criteria for this current meta-analysis. Eventually, our final data contained 81 studies. The AUSROCs of serum biomarkers of APRI and FIB-4 were both 0.75. For imaging techniques (ARFI, FibroScan, and MRE), the areas were 0.89, 0.83, and 0.97, respectively. The heterogeneities of ARFI and FibroScan were statistically significant (I2 > 50%). The publication bias was not observed in any of the serum biomarkers or imaging methods.
CONCLUSION These five methods have attained an acceptable level of diagnostic accuracy. Imaging techniques, MRE in particular, demonstrate significant advantages in accurately predicting HBV-related significant fibrosis, while serum biomarkers are admissible methods.
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Affiliation(s)
- Xue-Ying Xu
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Wu-Sheng Wang
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Qi-Meng Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Jun-Ling Li
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Jin-Bin Sun
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Tian-Tian Qin
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Hong-Bo Liu
- Department of Epidemiology and Health Statistics, School of Public Health, China Medical University, Shenyang 110122, Liaoning Province, China
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Yu JB, Xiong H, Yuan XC, Zhou AY. Liver Stiffness Detected by Shear Wave Elastography Predicts Esophageal Varices in Cirrhotic Patients. Ultrasound Q 2019; 37:118-122. [PMID: 31299039 DOI: 10.1097/ruq.0000000000000466] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
ABSTRACT Ultrasound elastography has become a promising noninvasive approach for assessing liver fibrosis. The purpose of this study was to evaluate the diagnosis ability of liver stiffness detected by shear wave elastography (SWE) for predicting the presence of esophageal varices (EVs) in cirrhotic patients. Four hundred sixty-eight cirrhotic patients were enrolled consecutively. Liver stiffness and EVs were detected by SWE and endoscopy, respectively. The baseline characteristics were recorded, and areas under the receiver operating characteristic curves (AUROCs) were used to compare the diagnosis accuracy. Multivariate analysis was used to identify the risk factors for EVs in cirrhosis. The mean liver stiffness was 18.4 kPa with a range of 6.8 to 52.5 kPa. Two hundred seventy-one patients had no EVs (57.9%), 139 patients had F1 EVs (29.7%), and 58 patients had high-risk EVs (12.4%). The optimal cutoff values of SWE for predicting EVs and high-risk varices were 18.5 and 20.4 kPa, respectively. The AUROCs for predicting the incidence of EVs were 0.792 (95% confidence interval [CI], 0.884-0.842), 0.814 (95% CI, 0.658-0.875), and 0.895 (95% CI, 0.813-0.918) for platelet, platelet count-to-spleen diameter ratio, and liver stiffness, respectively. For predicting the presence of high-risk varices, liver stiffness again had the highest AUROC. Multivariate analysis identified liver stiffness and platelet count-to-spleen diameter ratio as independent predictive factors for EVs in cirrhosis. Liver stiffness measured by SWE is an effective diagnostic tool for predicting EVs with greater accuracy, and SWE value is an independent factor for predicting high-risk EVs.
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Affiliation(s)
| | | | - Xin-Chun Yuan
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Ai-Yun Zhou
- The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
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Abstract
: Elevation of liver transaminases is common in patients infected with the HIV. Although this is usually an incidental finding during regular work-up, HIV-infected patients with transaminase elevations require additional visits for laboratory studies and clinical assessments, and often undergo interruptions and changes in antiretroviral therapy (ART). Alanine aminotransferase is present primarily in the liver, thus being a surrogate marker of hepatocellular injury. Aspartate aminotransferase is present in the liver and other organs, namely cardiac and skeletal muscle, kidney and brain. Serum levels of both liver transaminases predict liver-related mortality. Moreover, serum fibrosis biomarkers based on alanine aminotransferase and aspartate aminotransferase predict all-cause mortality. In a busy clinical setting, a diagnostic approach to elevated liver transaminases could be complicated given the frequency and nonspecificity of this finding. Indeed, HIV-infected individuals present multiple risk factors for liver damage and chronic elevation of transaminases, including coinfection with hepatitis B and C viruses, alcohol abuse, hepatotoxicity due to ART, HIV itself and frequent metabolic comorbidities leading to nonalcoholic fatty liver disease. This review provides an update on epidemiology of elevated liver transaminases, summarizes the main etiologic contributors and discusses the prognostic significance and a pragmatic approach to this frequent finding in the clinical practice of HIV medicine. With the aging of the HIV-infected population following the successful implementation of ART in Western countries, liver-related conditions are now a major comorbidity in this setting. As such, clinicians should be aware of the frequency, clinical significance and diagnostic approach to elevated liver transaminases.
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Chen Y, Wang Y, Chen Y, Yu Z, Chi X, Hu KQ, Li Q, Tan L, Xiang D, Shang Q, Lei C, Chen L, Hu X, Wang J, Liu H, Lu W, Chi W, Dong Z, Wang X, Li Z, Xiao H, Chen D, Bai W, Zhang C, Xiao G, Qi X, Chen J, Zhou L, Sun H, Deng M, Qi X, Zhang Z, Qi X, Yang Y. A Novel Noninvasive Program for Staging Liver Fibrosis in Untreated Patients With Chronic Hepatitis B. Clin Transl Gastroenterol 2019; 10:1-12. [PMID: 31033506 PMCID: PMC6602766 DOI: 10.14309/ctg.0000000000000033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 02/22/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.
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Affiliation(s)
- Yan Chen
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
| | - Yongji Wang
- Department of Health Statistics, the Fourth Military Medical University, Xi'an, Shanxi Province, China
| | - Yongping Chen
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Zujiang Yu
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xiaoling Chi
- Traditional Chinese Medicine Hospital of Guangdong Province, Guangdong Province, China
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, California, USA
| | - Qin Li
- Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China
| | - Lin Tan
- Liver Disease Department, Fuyang 2nd People's Hospital, Fuyang, Anhui Province, China
| | - Dedong Xiang
- Department of Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing, China
| | - Qinghua Shang
- Therapeutic Center for Liver Disease, the 88th Hospital of PLA, Taian, Shandong Province, China
| | - Chunliang Lei
- Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China
| | - Liang Chen
- Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Xiaoyu Hu
- National Integrative Medicine Clinical Base for Infectious Diseases/Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Jing Wang
- Affiliated Traditional Chinese Medicine Hospital of Luzhou Medical University, Luzhou, Sichuan Province, China
| | - Huabao Liu
- Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China
| | - Wei Lu
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Weilai Chi
- Center for Quantitative Biology, Peking University, Beijing, China
| | - Zheng Dong
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
| | - Xiaodong Wang
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Zhiqin Li
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Huanming Xiao
- Traditional Chinese Medicine Hospital of Guangdong Province, Guangdong Province, China
| | - Da Chen
- Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, California, USA
| | - Wenlin Bai
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
| | - Changjiang Zhang
- Department of Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing, China
| | - Guangming Xiao
- Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China
| | - Xun Qi
- Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Jing Chen
- National Integrative Medicine Clinical Base for Infectious Diseases/Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Li Zhou
- Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China
| | - Huiwei Sun
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
| | - Minghua Deng
- Center for Quantitative Biology, Peking University, Beijing, China
| | - Xiaolong Qi
- CHESS, The Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zheng Zhang
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning Province, China
| | - Yongping Yang
- Center of Therapeutic Research for Liver Cancer, Beijing 302 Hospital, Beijing, China
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Lv DD, Wang ML, Chen EQ, Wu DB, Tao YC, Zhang DM, Tang H. A retrospective study of the efficacy of sofosbuvir plus NS5A inhibitors for patients with hepatitis C virus genotype-2 chronic infection. Eur J Gastroenterol Hepatol 2019; 31:382-388. [PMID: 30383554 DOI: 10.1097/meg.0000000000001299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND A combination of sofosbuvir (SOF)+NS5A inhibitor therapies is the main treatment for patients with hepatitis C virus (HCV) genotype-2 (GT-2) chronic infection, but the data are rarely reported in China. This study aimed to investigate the virological response and liver fibrosis improvement among GT-2 patients receiving SOF+NS5A inhibitors. PATIENTS AND METHODS In this retrospective study, patients who received SOF+NS5A inhibitors between March 2016 and July 2017 were recruited. The treatment duration was 12 weeks and the treatment strategies included SOF+daclatasvir, SOF/ledipasvir, and SOF/velpatasvir. The primary endpoint was a sustained virologic response (serum HCV RNA undetectable) at week 12 after the end of therapy and the secondary endpoint was the improvement in liver stiffness and scores of apartate aminotransferase to platelet ratio index and fibrosis-4. RESULTS A total of 30 GT-2 patients were enrolled, with 13 (43.3%) patients in SOF+daclatasvir, 13 (43.3%) patients in SOF/ledipasvir, and four (13.3%) patients in SOF/velpatasvir. All patients [30/30 (100%)] achieved SVR, irrespective of treatment regimens and degree of liver fibrosis. After the treatment, liver fibrosis scores of apartate aminotransferase to platelet ratio index (2.27±2.14 vs. 0.89±0.77, P=0.003) and fibrosis-4 (1.17±1.22 vs. 0.42±0.25, P=0.013) were both significantly lower than those before treatment. CONCLUSION SOF+NS5A inhibitor therapies may induce an excellent virological response and fibrosis improvement in HCV GT-2-infected patients.
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Affiliation(s)
- Duo-Duo Lv
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, People's Republic of China
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Zhang W, Zhu Y, Zhang C, Ran H. Diagnostic Accuracy of 2-Dimensional Shear Wave Elastography for the Staging of Liver Fibrosis: A Meta-analysis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:733-740. [PMID: 30171621 PMCID: PMC7379518 DOI: 10.1002/jum.14760] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 06/01/2018] [Accepted: 06/29/2018] [Indexed: 05/12/2023]
Abstract
OBJECTIVES To evaluate the overall accuracy of 2-dimensional shear wave elastography (SWE) for the staging of liver fibrosis. METHODS Literature databases and conference abstracts were searched from 2000 to September 2017. Sensitivity, specificity, and other information were extracted from the included studies. Methodological quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tools. Data were synthesized by a bivariate hierarchical model. RESULTS The summary sensitivity and specificity were 0.85 (95% confidence interval [CI], 0.80-0.89) and 0.79 (95% CI, 0.72-0.85) for fibrosis stage F≥2, 0.90 (95% CI, 0.87-0.93) and 0.85 (95% CI, 0.80-0.89) for F≥3, and 0.89 (95% CI, 0.84-0.93) and 0.92 (95% CI, 0.89-0.95) for F=4, respectively. The areas under the summary receiver operating characteristic curve for F≥2, F≥3, and F=4 was 0.81, 0.77, and 0.84. CONCLUSIONS Two-dimensional SWE is a good noninvasive method for the diagnosis of substantial liver fibrosis and cirrhosis. Further studies are needed to assess severe fibrosis and to perform head-to-head comparisons of 2-dimensional SWE and other imaging modalities for the evaluation of liver fibrosis.
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Affiliation(s)
- Wei Zhang
- Institute of Ultrasound Imaging and Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular ImagingChongqingChina
| | - Ya Zhu
- Department of Obstetrics and Gynecology, Dong Feng Affiliated HospitalHubei University of MedicineShiyanChina
| | - Cuncheng Zhang
- Institute of Ultrasound Imaging and Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular ImagingChongqingChina
| | - Haitao Ran
- Institute of Ultrasound Imaging and Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular ImagingChongqingChina
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Shata MTM, Abdel-Hameed EA, Rouster SD, Yu L, Liang M, Song E, Esser MT, Shire N, Sherman KE. HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles. Pathog Immun 2019; 4:39-65. [PMID: 30815625 PMCID: PMC6388707 DOI: 10.20411/pai.v4i1.267] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFβ1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods: Levels of soluble Fas/FasL, TGFβ1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). Results: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFβ-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1β. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. Conclusion: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.
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Affiliation(s)
| | | | - Susan D Rouster
- Internal medicine; University of Cincinnati; Cincinnati, Ohio
| | - Li Yu
- MedImmune; Gaithersburg, Maryland
| | - Meina Liang
- MedImmune; 121 Oyster Point Boulevard; South San Francisco, California
| | - Esther Song
- MedImmune; 121 Oyster Point Boulevard; South San Francisco, California
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Li C, Dhyani M, Bhan AK, Grajo JR, Pratt DS, Gee MS, Samir AE. Diagnostic Performance of Shear Wave Elastography in Patients With Autoimmune Liver Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:103-111. [PMID: 29761535 PMCID: PMC6586413 DOI: 10.1002/jum.14668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Revised: 04/02/2018] [Accepted: 04/03/2018] [Indexed: 05/04/2023]
Abstract
OBJECTIVES To assess performance of shear wave elastography for evaluation of fibrosis and the histologic stage in patients with autoimmune liver disease (ALD) and to validate previously established advanced fibrosis cutoff values in this cohort. METHODS Shear wave elastography was performed on patients with ALD with an Aixplorer ultrasound system (SuperSonic Imagine, Aix-en-Provence, France) using an SC6-1 transducer. The median estimated tissue Young modulus was calculated from sets of 8 to 10 elastograms. A blinded, subspecialty-trained pathologist reviewed biopsy specimens. The METAVIR classification was used to stage liver fibrosis and necroinflammation. Steatosis was graded from 0 to 4+. The Kendall τ-b correlation test was performed to identify the correlation between the estimated tissue Young modulus and fibrosis, steatosis, and the necroinflammatory score. The Spearman correlation test was performed to identify the correlation between the estimated tissue Young modulus and clinical data. The diagnostic performance of shear wave elastography for differentiating METAVIR stage F2 or higher from F0 and F1 fibrosis was evaluated by a receiver operating characteristic (ROC) curve analysis. RESULTS Fifty-one patients with ALD were analyzed. The estimated tissue Young modulus was positively correlated with the fibrosis stage and necroinflammation score (r = 0.386; P < .001; r = 0.338; P = .002, respectively) but not steatosis (r = -0.091; P = .527). Serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin values were positively correlated with the estimated tissue Young modulus (r = 0.501; P < .001; r = 0.44; P = .001; r = 0.291; P = .038). The serum albumin value was negatively correlated (r = -0.309; P = .033). The area under the ROC curve was 0.781 (95% confidence interval, 0.641-0.921) for distinguishing F2 or greater fibrosis from F0 and F1 fibrosis. Based on the ROC curve, an optimal cutoff value of 9.15 kPa was identified (sensitivity, 83.3%; specificity, 72.7%). CONCLUSIONS Shear wave elastography is a novel noninvasive adjunct to liver biopsy in evaluation and staging of patients with ALD, showing the potential for serial evaluations of disease progression and treatment responses.
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Affiliation(s)
- Changtian Li
- Department of Ultrasound, The Southern Building, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Manish Dhyani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Atul K Bhan
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Joseph R Grajo
- Department of Radiology, Division of Abdominal Imaging, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Daniel S Pratt
- Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Michael S Gee
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B. Dig Liver Dis 2019; 51:127-134. [PMID: 30076017 DOI: 10.1016/j.dld.2018.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 05/20/2018] [Accepted: 07/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. METHODS A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. RESULTS For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. CONCLUSIONS As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.
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Lidofsky A, Holmes JA, Feeney ER, Kruger AJ, Salloum S, Zheng H, Seguin IS, Altinbas A, Masia R, Corey KE, Gustafson JL, Schaefer EA, Hunt PW, Deeks S, Somsouk M, Chew KW, Chung RT, Alatrakchi N. Macrophage Activation Marker Soluble CD163 Is a Dynamic Marker of Liver Fibrogenesis in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection. J Infect Dis 2018; 218:1394-1403. [PMID: 29868909 PMCID: PMC6151081 DOI: 10.1093/infdis/jiy331] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 05/31/2018] [Indexed: 12/12/2022] Open
Abstract
Background Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking. Methods We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy. Results sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis. Conclusions In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.
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Affiliation(s)
- Anna Lidofsky
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jacinta A Holmes
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Eoin R Feeney
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- HIV Molecular Research Group, University College of Dublin, Ireland
| | - Annie J Kruger
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Shadi Salloum
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Hui Zheng
- Biostatistics Center, Massachusetts General Hospital, Boston
| | - Isabel S Seguin
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Akif Altinbas
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Ricard Masia
- Department of Pathology, Massachusetts General Hospital, Boston
| | - Kathleen E Corey
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jenna L Gustafson
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Esperance A Schaefer
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Peter W Hunt
- Department of Medicine, University of California, San Francisco
| | - Steven Deeks
- Department of Medicine, University of California, San Francisco
| | - Ma Somsouk
- Department of Medicine, University of California, San Francisco
| | - Kara W Chew
- Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles
| | - Raymond T Chung
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Nadia Alatrakchi
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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Shiha GE, El-Etreby S, Bahgat M, Hamed M, El Sherbini M, Ghoneem EA, Zalata K, Soliman RE, El Basiouny MA, Mikhail NN. Chronic Hepatitis C Patients with Obesity: Do we Need two Operators for Accurate Evaluation of Liver Stiffness? Ann Hepatol 2018; 17:795-801. [PMID: 30145567 DOI: 10.5604/01.3001.0012.3138] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Transient elastography is gaining popularity as a non-invasive method for predicting liver fibrosis, but inter observer agreement and factors influencing reproducibility have not been adequately assessed. MATERIAL AND METHODS This cross-sectional study was conducted at Specialized Medical Hospital and the Egyptian Liver Foundation, Mansoura, Egypt. The inclusion criteria were: age older than 18 years and chronic infection by hepatitis C. The exclusion criteria were the presence of ascites, pacemaker or pregnancy. Three hundred and fifty-six patients participated in the study. Therefore, 356 pairs of exams were done by two operators on the same day. RESULTS The overall inter observer agreement ICC was 0.921. The correlation the two operators was excellent (Spearman's value q = 0.808, p < 0.001). Inter-observer reliability values were κ = 0.557 (p < 0.001). A not negligible discordance of fibrosis staging between operators was observed (87 cases, 24.4%). Discordance of at least one stage and for two or more stages of fibrosis occurred in 60 (16.9%) and 27 cases (7.6%) respectively. Obesity (BMI ≥ 30 kg/m2) is the main factor associated with discordance (p = 0.002). CONCLUSION Although liver stiffness measurement has had an excellent correlation between the two operators, TE presented an inter-observer variability that may not be negligible.
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Affiliation(s)
- Gamal E Shiha
- Egyptian Liver Research Institute and Hospital (ELRIH), Sherbin, El Mansoura, Egypt
| | - Shahira El-Etreby
- Hepatology and Gastroenterology Unit, Internal Medicine. Department, Faculty of Medicine, Mansoura University, Egypt
| | - Mounir Bahgat
- Hepatology and Gastroenterology Unit, Internal Medicine. Department, Faculty of Medicine, Mansoura University, Egypt
| | - Magdy Hamed
- Hepatology and Gastroenterology Unit, Internal Medicine. Department, Faculty of Medicine, Mansoura University, Egypt
| | - Mohamed El Sherbini
- Hepatology and Gastroenterology Unit, Internal Medicine. Department, Faculty of Medicine, Mansoura University, Egypt
| | - Elsayed A Ghoneem
- Hepatology and Gastroenterology Unit, Internal Medicine. Department, Faculty of Medicine, Mansoura University, Egypt
| | - Khaled Zalata
- Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Reham E Soliman
- Egyptian Liver Research Institute and Hospital (ELRIH), Sherbin, El Mansoura, Egypt
| | | | - Nabiel Nh Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIH), Sherbin, El Mansoura, Egypt
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Kelly ML, Riordan SM, Bopage R, Lloyd AR, Post JJ. Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study. PLoS One 2018; 13:e0192763. [PMID: 29438397 PMCID: PMC5811020 DOI: 10.1371/journal.pone.0192763] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 01/30/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings. MATERIALS AND METHODS This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined. RESULTS The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An 'APRI' algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91-96%). Newly derived cut-offs of 'APRI' (0.49), 'FIB-4' (0.93) and 'GUCI' (0.5) algorithms each had NPVs of 99% (95%CI: 97-100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection. CONCLUSIONS Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.
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Affiliation(s)
- Melissa Louise Kelly
- Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW, Australia
- Department of Medicine, The Albion Centre, Surry Hills, NSW, Australia
- Population Heath, Justice Health & Forensic Mental Health Network, Malabar, NSW Australia
| | - Stephen M. Riordan
- Prince of Wales Clinical School, School of Medicine, UNSW, Kensington, NSW, Australia
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, Randwick, NSW, Australia
| | - Rohan Bopage
- Department of Medicine, The Albion Centre, Surry Hills, NSW, Australia
| | - Andrew R. Lloyd
- Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW, Australia
- Population Heath, Justice Health & Forensic Mental Health Network, Malabar, NSW Australia
- The Kirby Institute, Viral Immunology Systems Program, Kensington, NSW, Australia
| | - Jeffrey John Post
- Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW, Australia
- Department of Medicine, The Albion Centre, Surry Hills, NSW, Australia
- Population Heath, Justice Health & Forensic Mental Health Network, Malabar, NSW Australia
- Prince of Wales Clinical School, School of Medicine, UNSW, Kensington, NSW, Australia
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Lim S, Kim SH, Kim Y, Cho YS, Kim TY, Jeong WK, Sohn JH. Coefficient of Variance as Quality Criterion for Evaluation of Advanced Hepatic Fibrosis Using 2D Shear-Wave Elastography. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2018; 37:355-362. [PMID: 28804946 DOI: 10.1002/jum.14341] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 04/17/2017] [Accepted: 05/02/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES To compare the diagnostic performance for advanced hepatic fibrosis measured by 2D shear-wave elastography (SWE), using either the coefficient of variance (CV) or the interquartile range divided by the median value (IQR/M) as quality criteria. METHODS In this retrospective study, from January 2011 to December 2013, 96 patients, who underwent both liver stiffness measurement by 2D SWE and liver biopsy for hepatic fibrosis grading, were enrolled. The diagnostic performances of the CV and the IQR/M were analyzed using receiver operating characteristic curves with areas under the curves (AUCs) and were compared by Fisher's Z test, based on matching the cutoff points in an interactive dot diagram. All P values less than 0.05 were considered significant. RESULTS When using the cutoff value IQR/M of 0.21, the matched cutoff point of CV was 20%. When a cutoff value of CV of 20% was used, the diagnostic performance for advanced hepatic fibrosis ( ≥ F3 grade) with CV of less than 20% was better than that in the group with CV greater than or equal to 20% (AUC 0.967 versus 0.786, z statistic = 2.23, P = .025), whereas when the matched cutoff value IQR/M of 0.21 showed no difference (AUC 0.918 versus 0.927, z statistic = -0.178, P = .859). CONCLUSIONS The validity of liver stiffness measurements made by 2D SWE for assessing advanced hepatic fibrosis may be judged using CVs, and when the CV is less than 20% it can be considered "more reliable" than using IQR/M of less than 0.21.
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Affiliation(s)
- Sanghyeok Lim
- Departments of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Seung Hyun Kim
- Departments of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Radiology, Suncheon Medical Center, Suncheon-si, Korea
| | - Yongsoo Kim
- Departments of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Young Seo Cho
- Departments of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Tae Yeob Kim
- Institute of Medical Science, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joo Hyun Sohn
- Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
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Chen YP, Hu XM, Liang XE, Huang LW, Zhu YF, Hou JL. Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection. J Gastroenterol Hepatol 2018; 33:256-263. [PMID: 28452125 DOI: 10.1111/jgh.13811] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/11/2017] [Accepted: 04/19/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.
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Affiliation(s)
- Yong-Peng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Xiao-Min Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xie-Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
| | - Li-Wen Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - You-Fu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jin-Lin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Research Center for Liver Fibrosis, Guangzhou, China
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Lee JE, Shin KS, Cho JS, You SK, Min JH, Kim KH, Song IS, Cheon KS. Non-invasive Assessment of Liver Fibrosis with ElastPQ: Comparison with Transient Elastography and Serologic Fibrosis Marker Tests, and Correlation with Liver Pathology Results. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:2515-2521. [PMID: 28844464 DOI: 10.1016/j.ultrasmedbio.2017.07.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 07/02/2017] [Accepted: 07/10/2017] [Indexed: 06/07/2023]
Abstract
We investigated the feasibility of using ultrasound shear wave elastography point quantification (ElastPQ) for liver fibrosis staging and compared it with other non-invasive tools with respect to efficacy in liver stiffness measurement. A total of 106 patients who underwent liver stiffness measurements, using ElastPQ and biochemical investigations, before parenchymal liver biopsy or surgery were included. Among these, 51 also underwent transient elastography (TE). Correlations of ElastPQ, TE and aspartate aminotransferase-to-platelet ratio index (APRI) with histopathological findings (as the reference standard) were determined using Spearman's correlation coefficient. The diagnostic performance of ElastPQ, TE and APRI was evaluated using receiver operating characteristic (ROC) curve analysis. ElastPQ had good diagnostic accuracy in identifying each liver fibrosis stage, with an area under the ROC curve (AUC) of 0.810 to 0.864. Stiffness values obtained using ElastPQ, TE and APRI were significantly positively correlated (r = 0.686, r = 0.732 and r = 0.454, respectively) with histologic fibrosis staging (p < 0.001). According to the AUC for the diagnosis of significant fibrosis (≥F2) and cirrhosis (=F4), ElastPQ had better diagnostic accuracy (AUC = 0.929 and 0.834, respectively) than APRI (AUC = 0.656 and 0.618, respectively) (p < 0.05), and was similar to TE (AUC = 0.915 and 0.879, respectively). ElastPQ is a promising ultrasound-based imaging technique for evaluation of liver fibrosis, with a diagnostic accuracy comparable to that of TE.
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Affiliation(s)
- Jeong Eun Lee
- Department of Radiology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Kyung Sook Shin
- Department of Radiology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea.
| | - June-Sik Cho
- Department of Radiology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Sun Kyoung You
- Department of Radiology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Ji Hye Min
- Department of Radiology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Kyung-Hee Kim
- Department of Pathology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - In Sang Song
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Kwang Sik Cheon
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, South Korea
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45
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Staufer K, Dengler M, Huber H, Marculescu R, Stauber R, Lackner C, Dienes HP, Kivaranovic D, Schachner C, Zeitlinger M, Wulkersdorfer B, Rauch P, Prager G, Trauner M, Mikulits W. The non-invasive serum biomarker soluble Axl accurately detects advanced liver fibrosis and cirrhosis. Cell Death Dis 2017; 8:e3135. [PMID: 29072690 PMCID: PMC5680921 DOI: 10.1038/cddis.2017.554] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 07/28/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023]
Abstract
Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastography (TE; Fibroscan) for its value to detect significant (F≥2), advanced fibrosis (F≥3), and cirrhosis (F4) in different liver disease etiologies and healthy controls. To properly determine the diagnostic accuracy of sAxl, a test cohort as well as a validation cohort was employed using liver biopsy as a reference method. Most notably, sAxl was confirmed to be an accurate biomarker of liver fibrosis and cirrhosis. Its accuracy was increased, if total serum albumin was added to build a sAxl/albumin ratio. Thereby an AUC of 0.763, 0.776, 0.826, and 0.832 was achieved corresponding to histological fibrosis stages F≥2, F≥3, F4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 1.29, a sensitivity, specificity, PPV, and NPV of 78.5%, 80.1%, 44%, 94.9% for the detection of cirrhosis was achieved. In comparison, ELF test and TE showed an AUC of 0.910, and 0.934, respectively, for the detection of cirrhosis. However, performance of TE was not possible in 14.4% of patients and both, ELF™ test and TE bear the disadvantage of high costs. In conclusion, the sAxl/albumin ratio is suggested as an accurate biomarker of liver fibrosis and cirrhosis. Due to its easy applicability and low costs it is suitable as screening parameter for significant to advanced liver fibrosis and cirrhosis, especially if TE is not available or not applicable.
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Affiliation(s)
- Katharina Staufer
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mirko Dengler
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Heidemarie Huber
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Rudolf Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Carolin Lackner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Hans-Peter Dienes
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Danijel Kivaranovic
- Department of Statistics and Operations Research, University of Vienna, Vienna, Austria
| | - Christian Schachner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Zeitlinger
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | | | - Peter Rauch
- Candor Bioscience GmbH, Wangen im Allgäu, Germany
| | - Gerhard Prager
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Mikulits
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
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46
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Yin Z, Zou J, Li Q, Chen L. Diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B: a meta-analysis of diagnostic test. Oncotarget 2017; 8:22944-22953. [PMID: 28060754 PMCID: PMC5410276 DOI: 10.18632/oncotarget.14430] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 12/13/2016] [Indexed: 12/14/2022] Open
Abstract
This study is aimed at evaluating the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B through a meta-analysis of diagnostic test. We conducted a comprehensive search in the Pubmed, Embase, Web of Science, and Chinese National Knowledge Infrastructure before October 31, 2016. Stata 14.0 software was used for calculation and statistical analyses. We used the sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CIs) to evaluate the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B. Twenty-six studies were included in the final analyses, with a total of 8274 individuals. The pooled parameters are calculated from all studies: sensitivity of 0.69 (95%CI:0.63-0.75), specificity of 0.81 (95%CI: 0.73-0.87), PLR of 3.63 (95%CI:2.66-4.94), NLR of 0.38 (95%CI:0.32-0.44), DOR of 9.57 (95%CI: 6.67-13.74), and area under the curve (AUC) of 0.80 (95%CI: 0.76-0.83). We also conducted subgroup based on the range of cut-off values. Results from subgroup analysis showed that cut-off was the source of heterogeneity in the present study. The sensitivity and specificity of cut-off>2 were 0.69 and 0.95 with the AUC of 0.90 (95%CI: 0.87-0.92). The overall diagnostic value of FIB-4 is not very high for liver fibrosis in patients with hepatitis B. However, the diagnostic value is affected by the cut-off value. FIB-4 has relatively high diagnostic value for detecting liver fibrosis in patients with hepatitis B when the diagnostic threshold value is more than 2.0.
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Affiliation(s)
- Zhi Yin
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China.,Division of Recruitment and Employment, University of South China, Hengyang, Hunan Province 421001, China
| | - Jin Zou
- Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan Province 421001, China
| | - Qiongxuan Li
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China
| | - Lizhang Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China
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47
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Dhyani M, Grajo JR, Bhan AK, Corey K, Chung R, Samir AE. Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:1125-1133. [PMID: 28341490 PMCID: PMC5610928 DOI: 10.1016/j.ultrasmedbio.2017.01.022] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 01/14/2017] [Accepted: 01/26/2017] [Indexed: 05/12/2023]
Abstract
The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0-F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p < 0.001). A cut-off value of 7.29 kPa yielded sensitivity of 95.4% and specificity of 50.5% for the diagnosis of METAVIR stage ≥F2 liver fibrosis in patients with liver disease using the SuperSonic Imagine Aixplorer SWE system.
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Affiliation(s)
- Manish Dhyani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
| | - Joseph R Grajo
- Department of Radiology, Division of Abdominal Imaging, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Atul K Bhan
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kathleen Corey
- Department of Hepatology, Liver and GI Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond Chung
- Department of Hepatology, Liver and GI Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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48
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Jiang H, Song JM, Gao PF, Qin XJ, Xu SZ, Zhang JF. Metabolic characterization of the early stage of hepatic fibrosis in rat using GC-TOF/MS and multivariate data analyses. Biomed Chromatogr 2017; 31. [PMID: 27859443 DOI: 10.1002/bmc.3899] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Revised: 10/30/2016] [Accepted: 11/13/2016] [Indexed: 12/22/2022]
Affiliation(s)
- Hui Jiang
- Department of Pharmacy; The first affiliated hospital of Anhui university of Chinese medicine; Hefei China
- College of Basic Medicine; Anhui Medical University; Hefei China
| | - Jun-mei Song
- Department of Pharmacy; The first affiliated hospital of Anhui university of Chinese medicine; Hefei China
| | - Peng-fei Gao
- College of Pharmacy; Dali University; Dali China
| | - Xiu-juan Qin
- Department of Pharmacy; The first affiliated hospital of Anhui university of Chinese medicine; Hefei China
| | - Shuang-zhi Xu
- Department of Pharmacy; The first affiliated hospital of Anhui university of Chinese medicine; Hefei China
| | - Jia-fu Zhang
- Department of Pharmacy; The first affiliated hospital of Anhui university of Chinese medicine; Hefei China
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49
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Liang XE, Zhong C, Huang L, Yang S, Zhu Y, Chen Y, Hou J. Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers. J Gastroenterol Hepatol 2017; 32:459-465. [PMID: 27346683 DOI: 10.1111/jgh.13475] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers. METHODS A total of 236 compensated CHB patients with alanine transferase lower than five times upper limit of normal, liver biopsies, transient elastography, and routine blood tests were included. Performance of stepwise combination of transient elastography and routine biomarkers was analyzed. RESULTS The area under the receiver operating characteristics curve for detecting cirrhosis was 0.876 for transient elastography, 0.794 for fibrosis index based on the four factors (FIB-4), 0.765 for age-platelet index (API), 0.715 for aspartate aminotransferase-platelet ratio index (APRI), and 0.661 for alanine-aspartate aminotransferase ratio, respectively. The numbers for significant fibrosis were 0.844, 0.662, 0.595, 0.695, and 0.510 in the same order. The proportion of patients determined as cirrhosis or non-cirrhosis was 66.5% by transient elastography, 41.1% by FIB-4, 14.4% by API, and 24.2% by APRI, respectively; the numbers for significant fibrosis were 55.5% by transient elastography, 11.9% by APRI, and none by the other serum markers. Stepwise combination of transient elastography and FIB-4/APRI increased positive predictive value of confirming cirrhosis diagnosis from 0.677 to 0.808 and 0.724, respectively; and the proportion of patients being determined in the state of cirrhosis and obviating liver biopsy was up to 76%. CONCLUSION By transient elastography-based stepwise combination with readily available serum markers, performance of detecting compensated CHB cirrhosis could be significantly improved in terms of diagnosis accuracy and proportion of obviating liver biopsy.
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Affiliation(s)
- Xie Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chunxiu Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liwen Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuling Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Youfu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
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50
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Herman M, Okoji O, Castaneda D, Jirru E, Kotler D. Letter: APRI and FIB-4 do not correlate with Fibrosure in the evaluation of liver fibrosis in hepatitis C patients. Aliment Pharmacol Ther 2017; 45:190-191. [PMID: 27910146 DOI: 10.1111/apt.13836] [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: 12/08/2022]
Affiliation(s)
- M Herman
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - O Okoji
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA.,Department of Gastroenterology, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - D Castaneda
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - E Jirru
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - D Kotler
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA.,Department of Gastroenterology, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
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