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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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Pavan Sai Kumar Rao D, Patro S, Sharma V, Choudhary A, Desale S, Nath P. Diagnostic Accuracy of Red Cell Distribution Width to Platelet Ratio for the Prediction of Liver Fibrosis in Patients With Chronic Liver Disease From Eastern India. Cureus 2025; 17:e82014. [PMID: 40352011 PMCID: PMC12065511 DOI: 10.7759/cureus.82014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 04/10/2025] [Indexed: 05/14/2025] Open
Abstract
Background Early diagnosis of liver cirrhosis in patients with chronic liver disease (CLD) can help delay/prevent complications and thereby improve survival. The currently available diagnostic modalities for the non-invasive assessment of hepatic fibrosis, especially FibroScan, are costly and not widely available, whereas various non-invasive scores for the assessment of fibrosis are cumbersome. Hence, we aimed to develop an easy and simple score for predicting cirrhosis in patients from Eastern India suffering from CLD with a better diagnostic accuracy. Methodology This cross-sectional, observational study was conducted between September 2019 and September 2021 in East India. Our study participants were patients who had CLD of etiologies such as alcohol-related liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis B, chronic viral hepatitis C, primary biliary cholangitis, and autoimmune hepatitis, who had undergone FibroScan of the liver. All demographic details were noted, and the patients were subjected to physical examination, followed by hematological as well as biochemical investigations, including liver function tests. Non-invasive scores (such as aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 score (FIB-4) and red cell distribution width (RDW) to platelet ratio (RPR)) were computed, and their diagnostic accuracy for prediction of advanced fibrosis and cirrhosis were evaluated by receiver operating characteristic curve (ROC curve) analysis with comparison of area under the ROC curves. Pearson correlation and logistic regression analysis were also performed to study the association of these scores with advanced fibrosis and cirrhosis. Results The area under the ROC (AUROC) curve of the APRI score, FIB-4 score, RPR, and RPR × AST for prediction of advanced liver fibrosis was 0.817, 0.799, 0.706, and 0.811, respectively. Similarly, the AUROC of the above scores for the prediction of cirrhosis was 0.889, 0.858, 0.797, and 0.898. However, the product of RPR and AST was superior than APRI and FIB-4 for predicting cirrhosis. An RPR × AST value above the cut-off of 4.818 can help predict liver cirrhosis with 85.7% sensitivity and 85.5% specificity. Pearson correlation and logistic regression analysis also proved the association of these scores with liver fibrosis. Conclusions RPR is a simple, inexpensive, and easily available marker for predicting liver cirrhosis. Nevertheless, the variable RPR × AST can predict liver cirrhosis in patients with CLD with even greater diagnostic accuracy.
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Affiliation(s)
- D Pavan Sai Kumar Rao
- Department of Medical Gastroenterology, Gleneagles BGS Global Hospitals, Bengaluru, IND
| | - Shubhransu Patro
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Vibha Sharma
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Arushi Choudhary
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Shubham Desale
- General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Preetam Nath
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
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Zheng MH, Lonardo A. Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease. World J Gastroenterol 2025; 31:100393. [PMID: 39839903 PMCID: PMC11684166 DOI: 10.3748/wjg.v31.i3.100393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 11/12/2024] [Accepted: 12/02/2024] [Indexed: 12/20/2024] Open
Abstract
Prognostication of compensated advanced chronic liver disease (cACLD) is of paramount importance for the physician-and-patient communication and for rational clinical decisions. The paper published by Dallio et al reports on red cell distribution width (RDW)/platelet ratio (RPR) as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cACLD. Differently from other biomarkers and algorithms, RPR is inexpensive and widely available, based on parameters which are included in a complete blood count. RPR is computed on the grounds of two different items, one of which, RDW, mirrors the host's response to a variety of disease stimuli and is non-specific. The second parameter involved in RPR, platelet count, is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades. Cardiovascular disease is the primary cause of mortality among MASLD subjects, followed by extra-hepatic cancers and liver-related mortality. Therefore, MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers. Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.
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Affiliation(s)
- Ming-Hua Zheng
- Department of Hepatology, MAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Amedeo Lonardo
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena (2023), Modena 41126, 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: 0] [Impact Index Per Article: 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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Chon YE, Kim SU, Seo YS, Lee HW, Lee HA, Kim MN, Roh YH, Park JY, Kim DY, Ahn SH, Tak WY, Park SY, Kim BK. Long-term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B. J Gastroenterol Hepatol 2022; 37:200-207. [PMID: 34478195 DOI: 10.1111/jgh.15678] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. METHODS Treatment-naïve chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. RESULTS In the entire population (n = 3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P < 0.001) and FIB-4 (3.60 vs 2.80, P < 0.001) than those treated with TDF, significant fibrosis regression was identified during 6 years of AVT in both ETV (APRI, mean 1.71 → 0.48, P < 0.001; FIB-4, mean 3.60 → 2.21, P < 0.001) and TDF groups (APRI, mean 1.07 → 0.43, P < 0.001; FIB-4, mean 2.80 → 2.19, P < 0.001). In patients without cirrhosis (n = 2366), baseline APRI was significantly higher in ETV group than in TDF group (1.72 vs 0.97, P < 0.001); however, they became similar after 6 months. Similarly, baseline FIB-4 was significantly higher in ETV group than in TDF group (3.25 vs 2.35, P < 0.001), but became similar from 4 to 6 years. In patients with cirrhosis (n = 911), baseline APRI (1.70 vs 1.34, P < 0.001) and FIB-4 (4.62 vs 3.91, P = 0.005) were higher in ETV group than in TDF, however, both parameters became statistically similar from 6 months to 6 years. CONCLUSION Significant regression of APRI and FIB-4 was observed during long-term ETV and TDF treatment. Despite higher baseline fibrotic burden in ETV group, fibrotic burden between the groups eventually converged through significant fibrosis regression after 1 to 4 years of AVT.
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Affiliation(s)
- Young Eun Chon
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Mi Na Kim
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Chen M, Wu Z, Du Z, Sun S, Wu J, Luo J. Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting liver fibrosis in patients with chronic hepatitis B: A meta-analysis. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:361-372. [PMID: 34757161 DOI: 10.1016/j.gastrohep.2021.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 09/17/2021] [Accepted: 10/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study aims to systematically review the performance of red blood cell distribution width to platelet ratio (RPR) in the diagnosis of significant or advanced fibrosis, and cirrhosis associated with Hepatitis B virus (HBV). METHODS The relevant studies were comprehensively searched in English databases such as Web of Science, PubMed, EMBASE, Cochrane Library, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Data from the inception to March 2021. Accuracy of RPR in diagnosing significant or advanced fibrosis and liver cirrhosis was assessed by area under the curve (AUC), pooled sensitivity and specificity, as well as positive and negative likelihood ratios. Stata 15.0 software was applied to analyze the data. RESULTS In total, 13 literature met the requirements, including patients with significant fibrosis (n=1890), advanced fibrosis (n=645), and cirrhosis (n=499). The prevalence rates of significant fibrosis, advanced fibrosis and cirrhosis were 49.31% (range: 17.25%-84.21%), 37.07% (range: 9.60%-58.20%) and 2.18% (range: 2.78%-44.19%), respectively. The AUCs for predicting significant fibrosis, advanced fibrosis, and cirrhosis by RPR were 0.73 (95%CI: 0.69-0.76),0.80 (95%CI: 0.77-0.84) and 0.80 (95%CI: 0.76-0.83), respectively. CONCLUSION RPR is of some diagnostic value to the prediction of HBV-related significant fibrosis, advanced fibrosis and cirrhosis.This conclusion is urgently needed to be verified by further multi-center studies of large sample size and rigorous design.
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Affiliation(s)
- Mingfa Chen
- Department of Infectious Diseases, Shenzhen Luohu People's Hospital, the third Affiliated Hospital, Shenzhen University, Shenzhen, Guangdong, China
| | - Zhiguo Wu
- Department of Infectious Diseases, the second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Zhan Du
- Healthcare center, Shenzhen Luohu People's Hospital, the third Affiliated Hospital, Shenzhen University, Shenzhen, Guangdong, China
| | - Shuilin Sun
- Department of Infectious Diseases, the second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Jun Wu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jie Luo
- Department of Infectious Diseases, Shenzhen Luohu People's Hospital, the third Affiliated Hospital, Shenzhen University, Shenzhen, Guangdong, China.
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Čustović N, Rašić S. RELATIONSHIP OF SERUM ADIPONECTIN AND RESISTIN LEVELS WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B. J Med Biochem 2021; 41:176-183. [PMID: 35510200 PMCID: PMC9010048 DOI: 10.5937/jomb0-33793] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/17/2021] [Indexed: 12/04/2022] Open
Abstract
Background Recent research has closely linked adipocytokines to liver inflammation and fibrosis progression in patients with non-alcoholic liver disease. This study aimed to determine the relationship of serum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B (CHB), depending on the duration of antiviral therapy. Methods The cross-sectional study included 75 patients with CHB divided into two groups: the T1 group (undergoing antiviral therapy for up to 2 years) and the T2 group (undergoing antiviral therapy over 2 years). The control group consisted of 40 healthy people. Serum concentrations of adiponectin and resistin were estimated with the ELISA method, while the degree of liver fibrosis was determined using FIB-4 and APRI score. Results There were no statistically significant differences in the mean serum adiponectin levels in relation to the duration of antiviral therapy. Higher values of serum resistin concentration were confirmed in patients of the T1 group compared to healthy controls (p=0.001) and to the T2 group (p=0.031). The mean level of serum resistin concentration was significantly higher in the group of patients with a higher FIB-4 score (9.12±3.39 vs 5.58±3.36 ng/mL, p=0.001) and higher APRI score (17.45±3.96 ng/mL vs 4.82±1.11 ng/mL, p=0.001). A positive correlation was found between serum resistin levels and the degree of liver fibrosis (p<0.001). There was no significant difference between mean serum adiponectin levels according to the values of FIB-4 and APRI scores. Conclusions Progression of liver fibrosis estimated by FIB4 and APRI scores as well as the length of antiviral treatment had a significant effect on serum resistin values in CHB patients on antiviral therapy.
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Affiliation(s)
- Nerma Čustović
- University of Sarajevo, Clinical Center, Clinic for Gastroenterohepatology, Sarajevo, Bosnia and Herzegovina
| | - Senija Rašić
- University of Sarajevo, Faculty of Medicine, Department of Internal Medicine, Sarajevo, Bosnia and Herzegovina
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Damiris K, Tafesh ZH, Pyrsopoulos N. Efficacy and safety of anti-hepatic fibrosis drugs. World J Gastroenterol 2020; 26:6304-6321. [PMID: 33244194 PMCID: PMC7656211 DOI: 10.3748/wjg.v26.i41.6304] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/30/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease (the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.
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Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States
| | - Zaid H Tafesh
- Medicine-Gastroenterology and Hepatology, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Medicine-Gastroenterology and Hepatology, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States
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Review of Serum Biomarkers and Models Derived from Them in HBV-Related Liver Diseases. DISEASE MARKERS 2020; 2020:2471252. [PMID: 32774512 PMCID: PMC7391085 DOI: 10.1155/2020/2471252] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 07/11/2020] [Indexed: 12/13/2022]
Abstract
A series of predictive scoring systems is available for stratifying the severity of conditions and assessing the prognosis in patients with HBV-related liver diseases. We show nine of the most popular serum biomarkers and their models (i.e., serum cystatin C, homocysteine, C-reactive protein, C-reactive protein to albumin ratio, aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, gamma-glutamyl transpeptidase to platelet ratio, albumin-bilirubin score, and gamma-glutamyl transpeptidase to albumin ratio) that have gained great interest from clinicians. Compared with traditional scoring systems, these serum biomarkers and their models are easily acquired, simple, and relatively inexpensive. In the present review, we summarize the latest studies focused on these serum biomarkers and their models as diagnostic and prognostic indexes in HBV-related liver diseases.
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Mao W, Wu J. Haematologic indices in hepatitis B virus-related liver disease. Clin Chim Acta 2019; 500:135-142. [PMID: 31654630 DOI: 10.1016/j.cca.2019.10.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 10/05/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Several markers and prognostic scores have been identified for predicting the development and progression of liver disease; among them, haematological parameters (the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), red cell distribution width (RDW), RDW to platelet ratio (RPR), mean platelet volume (MPV), and mean corpuscular volume (MCV)) have recently gained significant interest. Compared with traditional prognostic factors, haematological indices are easy to obtain and relatively inexpensive. There is growing evidence that these haematological indices play a key role in HBV-related liver diseases and has been proposed as a predictive marker of adverse outcomes in these patients. This article focuses on discussing the diagnostic and prognostic value of the haematological indices in patients with HBV-related liver diseases.
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Affiliation(s)
- WeiLin Mao
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, PR China
| | - JianPing Wu
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, PR China.
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Cai Y, Liu D, Cui J, Sha Y, Zhou H, Tang N, Wang N, Huang A, Xia J. Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting staging liver fibrosis in chronic liver disease patients: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e15096. [PMID: 30946368 PMCID: PMC6455720 DOI: 10.1097/md.0000000000015096] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Red cell volume distribution width to platelet ratio (RPR), as a novel noninvasive assessment, is frequently investigated. However, the utility of RPR to evaluate the diagnostic accuracy of liver fibrosis remains controversial. We performed a meta-analysis to determine the diagnostic performance of RPR for detecting staging liver fibrosis in patients with chronic liver disease. METHODS MEDLINE, EMBASE, and Cochrane Library databases were systematically searched. Summary receiver operating characteristic curves (SROC), diagnostic odds ratios (DOR), pooled estimates of sensitivity, specificity, and likelihood ratios were used to assess the diagnostic accuracy of RPR. Meta-regression and subgroup analyses were also performed to identify factors that contributed to heterogeneity. The Quality Assessment for Studies of Diagnostic Accuracy Studies-2 tool was applied to assess the quality. RESULTS Fifteen studies with a total of 3346 patients were included in the meta-analysis. The area under the curve for SROC to summarize diagnostic accuracy of RPR for prediction of significant fibrosis, advanced fibrosis, and cirrhosis was 0.73 (standard error [SE] = 0.02), 0.83 (SE = 0.03), and 0.85 (SE = 0.04), respectively. Pooled DOR with corresponding 95% confidence interval (CI) was 4.93 (95% CI: 3.78-6.43), 10.27 (95% CI: 6.26-16.84), and 12.16 (95% CI: 5.85-25.28), respectively, using a random effects model. Meta-regression showed that length of liver biopsy specimen potentially contributed to heterogeneity. There was no significant publication bias observed across the eligible studies. CONCLUSIONS In chronic liver disease patients, RPR presented a good performance for prediction of significant fibrosis, advanced fibrosis, and cirrhosis. More future trials are required for prospective validation.
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Affiliation(s)
- Ying Cai
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- Department of Intensive Care Medicine, The Second Affiliated Hospital of Chongqing Medical University
| | - Dina Liu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Jing Cui
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Yu Sha
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Hengyu Zhou
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- College of Nursing, Chongqing Medical University, Chongqing
| | - Ni Tang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Na Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
| | - Ailong Huang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Jie Xia
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University
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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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Han Y, Zeng A, Liao H, Liu Y, Chen Y, Ding H. The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis. Int Immunopharmacol 2017; 42:168-175. [PMID: 27915131 DOI: 10.1016/j.intimp.2016.11.022] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/09/2016] [Accepted: 11/21/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND The purpose of this study was to assess the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis. Methods The electronic databases of PubMed, the Cochrane Library, Nature, CNKI and WanFang data were searched. The key words were: ("tenofovir", "entecavir") and ("Chronic Hepatitis B" or "CHB") and "Liver cirrhosis". Heterogeneity and report bias were analyzed. RESULTS There was significant difference of ALT norm level in the short-term period of 3months (RR=1.43, 95%CI: 1.06-1.94, P<0.017) and 6months (RR=0.89, 95%CI: 0.81-0.97, P<0.017), and significant difference of undetectable HBV-DNA only in 3months follow-up period (RR=1.59, 95%CI: 1.04-2.42, P<0.017) between TDF and ETV, but no significant difference in the long-term period. There is significant difference between TDF and ETV in eGFR level (RR=1.601, 95%CI: 1.035-2.478, P=0.0034) and hypophosphatemia incidence (RR=4.008, 95%CI: 1.485-10.820, P=0.006). CONCLUSION TDF has a better efficacy than ETV in 3months treatment duration, but intriguingly, TDF might not better than ETV during the 6months treatment period in the viral suppression and liver function improvement. There's no significant difference between TDF and ETV in the long-term treatment duration and in the treatment of HBV related liver cirrhosis. Both TDF and ETV could influence renal function but patients under TDF therapy may have more risk to suffer from renal damage and hypophosphatemia.
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Affiliation(s)
- Ying Han
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China
| | - Ajuan Zeng
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China
| | - Huiyu Liao
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China
| | - Yanmin Liu
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China
| | - Yuhan Chen
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China
| | - Huiguo Ding
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, China.
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