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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [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: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, 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
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, 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
| | - 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
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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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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Righetti R, Cinque F, Patel K, Sebastiani G. The role of noninvasive biomarkers for monitoring cell injury in advanced liver fibrosis. Expert Rev Gastroenterol Hepatol 2025; 19:65-80. [PMID: 39772945 DOI: 10.1080/17474124.2025.2450717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/04/2025] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis. AREAS COVERED We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms. EXPERT OPINION The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future.
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Affiliation(s)
- Riccardo Righetti
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Felice Cinque
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
- Department of Pathophysiology, Transplantation University of Milan, Milan, Italy
| | - Keyur Patel
- University Health Network Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Canada
| | - Giada Sebastiani
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada
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Huttman M, Parigi TL, Zoncapè M, Liguori A, Kalafateli M, Noel-Storr AH, Casazza G, Tsochatzis E. Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C. Cochrane Database Syst Rev 2024; 8:CD011929. [PMID: 39136280 PMCID: PMC11320661 DOI: 10.1002/14651858.cd011929.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
BACKGROUND The presence and severity of liver fibrosis are important prognostic variables when evaluating people with chronic hepatitis C (CHC). Although liver biopsy remains the reference standard, non-invasive serological markers, such as the four factors (FIB-4) score and the Forns index, can also be used to stage liver fibrosis. OBJECTIVES To determine the diagnostic accuracy of the FIB-4 score and Forns index in staging liver fibrosis in people with chronic hepatitis C (CHC) virus, using liver biopsy as the reference standard (primary objective). To compare the diagnostic accuracy of these tests for staging liver fibrosis in people with CHC and explore potential sources of heterogeneity (secondary objectives). SEARCH METHODS We used standard Cochrane search methods for diagnostic accuracy studies (search date: 13 April 2022). SELECTION CRITERIA We included diagnostic cross-sectional or case-control studies that evaluated the performance of the FIB-4 score, the Forns index, or both, against liver biopsy, in the assessment of liver fibrosis in participants with CHC. We imposed no language restrictions. We excluded studies in which: participants had causes of liver disease besides CHC; participants had successfully been treated for CHC; or the interval between the index test and liver biopsy exceeded six months. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data. We performed meta-analyses using the bivariate model and calculated summary estimates. We evaluated the performance of both tests for three target conditions: significant fibrosis or worse (METAVIR stage ≥ F2); severe fibrosis or worse (METAVIR stage ≥ F3); and cirrhosis (METAVIR stage F4). We restricted the meta-analysis to studies reporting cut-offs in a specified range (+/-0.15 for FIB-4; +/-0.3 for Forns index) around the original validated cut-offs (1.45 and 3.25 for FIB-4; 4.2 and 6.9 for Forns index). We calculated the percentage of people who would receive an indeterminate result (i.e. above the rule-out threshold but below the rule-in threshold) for each index test/cut-off/target condition combination. MAIN RESULTS We included 84 studies (with a total of 107,583 participants) from 28 countries, published between 2002 and 2021, in the qualitative synthesis. Of the 84 studies, 82 (98%) were cross-sectional diagnostic accuracy studies with cohort-based sampling, and the remaining two (2%) were case-control studies. All studies were conducted in referral centres. Our main meta-analysis included 62 studies (100,605 participants). Overall, two studies (2%) had low risk of bias, 23 studies (27%) had unclear risk of bias, and 59 studies (73%) had high risk of bias. We judged 13 studies (15%) to have applicability concerns regarding participant selection. FIB-4 score The FIB-4 score's low cut-off (1.45) is designed to rule out people with at least severe fibrosis (≥ F3). Thirty-nine study cohorts (86,907 participants) yielded a summary sensitivity of 81.1% (95% confidence interval (CI) 75.6% to 85.6%), specificity of 62.3% (95% CI 57.4% to 66.9%), and negative likelihood ratio (LR-) of 0.30 (95% CI 0.24 to 0.38). The FIB-4 score's high cut-off (3.25) is designed to rule in people with at least severe fibrosis (≥ F3). Twenty-four study cohorts (81,350 participants) yielded a summary sensitivity of 41.4% (95% CI 33.0% to 50.4%), specificity of 92.6% (95% CI 89.5% to 94.9%), and positive likelihood ratio (LR+) of 5.6 (95% CI 4.4 to 7.1). Using the FIB-4 score to assess severe fibrosis and applying both cut-offs together, 30.9% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the FIB-4 score when used for assessing significant fibrosis (≥ F2) and cirrhosis (F4) in the main review text. Forns index The Forns index's low cut-off (4.2) is designed to rule out people with at least significant fibrosis (≥ F2). Seventeen study cohorts (4354 participants) yielded a summary sensitivity of 84.7% (95% CI 77.9% to 89.7%), specificity of 47.9% (95% CI 38.6% to 57.3%), and LR- of 0.32 (95% CI 0.25 to 0.41). The Forns index's high cut-off (6.9) is designed to rule in people with at least significant fibrosis (≥ F2). Twelve study cohorts (3245 participants) yielded a summary sensitivity of 34.1% (95% CI 26.4% to 42.8%), specificity of 97.3% (95% CI 92.9% to 99.0%), and LR+ of 12.5 (95% CI 5.7 to 27.2). Using the Forns index to assess significant fibrosis and applying both cut-offs together, 44.8% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the Forns index when used for assessing severe fibrosis (≥ F3) and cirrhosis (F4) in the main text. Comparing FIB-4 to Forns index There were insufficient studies to meta-analyse the performance of the Forns index for diagnosing severe fibrosis and cirrhosis. Therefore, comparisons of the two tests' performance were not possible for these target conditions. For diagnosing significant fibrosis and worse, there were no significant differences in their performance when using the high cut-off. The Forns index performed slightly better than FIB-4 when using the low/rule-out cut-off (relative sensitivity 1.12, 95% CI 1.00 to 1.25; P = 0.0573; relative specificity 0.69, 95% CI 0.57 to 0.84; P = 0.002). AUTHORS' CONCLUSIONS Both the FIB-4 score and the Forns index may be considered for the initial assessment of people with CHC. The FIB-4 score's low cut-off (1.45) can be used to rule out people with at least severe fibrosis (≥ F3) and cirrhosis (F4). The Forns index's high cut-off (6.9) can be used to diagnose people with at least significant fibrosis (≥ F2). We judged most of the included studies to be at unclear or high risk of bias. The overall quality of the body of evidence was low or very low, and more high-quality studies are needed. Our review only captured data from referral centres. Therefore, when generalising our results to a primary care population, the probability of false positives will likely be higher and false negatives will likely be lower. More research is needed in sub-Saharan Africa, since these tests may be of value in such resource-poor settings.
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Affiliation(s)
- Marc Huttman
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Tommaso Lorenzo Parigi
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Mirko Zoncapè
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Antonio Liguori
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Maria Kalafateli
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | | | - Giovanni Casazza
- Department of Clinical Sciences and Community Health - Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
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Epstein RL, Buzzee B, White LF, Feld JJ, Castera L, Sterling RK, Linas BP, Taylor LE. Test characteristics for combining non-invasive liver fibrosis staging modalities in individuals with Hepatitis C virus. J Viral Hepat 2024; 31:277-292. [PMID: 38326950 PMCID: PMC11102317 DOI: 10.1111/jvh.13925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 12/27/2023] [Accepted: 01/17/2024] [Indexed: 02/09/2024]
Abstract
Non-invasive methods have largely replaced biopsy to identify advanced fibrosis in hepatitis C virus (HCV). Guidelines vary regarding testing strategy to balance accuracy, costs and loss to follow-up. Although individual test characteristics are well-described, data comparing the accuracy of using two tests together are limited. We calculated combined test characteristics to determine the utility of combined strategies. This study synthesizes empirical data from fibrosis staging trials and the literature to estimate test characteristics for Fibrosis-4 (FIB4), APRI or a commercial serum panel (FibroSure®), followed by transient elastography (TE) or FibroSure®. We simulated two testing strategies: (1) second test only for those with intermediate first test results (staged approach), and (2) second test for all. We summarized empiric data with multinomial distributions and used this to estimate test characteristics of each strategy on a simulated population of 10,000 individuals with 4.2% cirrhosis prevalence. Negative predictive value (NPV) for cirrhosis from a single test ranged from 98.2% (95% CB 97.6-98.8%) for FIB-4 to 99.4% (95% CB 99.0-99.8%) for TE. Using a staged approach with TE second, sensitivity for cirrhosis rose to 93.3-96.9%, NPV to 99.7-99.8%, while PPV dropped to <32%. Using TE as a second test for all minimally changed estimated test characteristics compared with the staged approach. Combining two non-invasive fibrosis tests barely improves NPV and decreases or does not change PPV compared with a single test, challenging the utility of serial testing modalities. These calculated combined test characteristics can inform best methods to identify advanced fibrosis in various populations.
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Affiliation(s)
- Rachel L. Epstein
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Pediatrics, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Benjamin Buzzee
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Laura F. White
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Laurent Castera
- Department of Hepatology, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Université Paris Cité, Clichy, France
| | - Richard K. Sterling
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Benjamin P. Linas
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Lynn E. Taylor
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
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Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL. Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus. JAMA Pediatr 2024; 178:489-496. [PMID: 38466273 PMCID: PMC10928541 DOI: 10.1001/jamapediatrics.2024.0114] [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: 09/06/2023] [Accepted: 01/10/2024] [Indexed: 03/12/2024]
Abstract
Importance Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. Objective To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. Design, Setting, and Participants The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. Interventions The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Main Outcomes and Measures Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). Results The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. Conclusions and Relevance These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.
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Affiliation(s)
- Megan Rose Curtis
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston
- Harvard Medical School, Boston, Massachusetts
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Rachel L. Epstein
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
- Department of Pediatrics, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Pamela Pei
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
| | - Benjamin P. Linas
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Andrea L. Ciaranello
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston
- Harvard Medical School, Boston, Massachusetts
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Sakhuja S, Staples HM, Minard CG, Ramm LE, Lewindon PJ, Ramm GA, Leung DH. Risk factors for more rapid progression of severe liver fibrosis in children with cystic fibrosis-related liver disease: A multi-center study validated by liver biopsy. Liver Int 2023; 43:1277-1286. [PMID: 37035868 DOI: 10.1111/liv.15572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 03/15/2023] [Accepted: 03/18/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND AND AIMS Early identification of risk factors for the development of severe fibrosis in children with cystic fibrosis-related liver disease (CFLD) is crucial as promising therapies emerge. METHODS This multi-center cohort study of children with a priori defined CFLD from 1999 to 2016, was designed to evaluate the clinical utility of CF-specific characteristics and liver biomarkers assessed years prior to liver biopsy-proven CFLD to predict risk of developing severe fibrosis (F3-4) over time. Fibrosis was staged by Metavir classification. RESULTS The overall study cohort of 42 patients (F0-2 (n = 22) and F3-4 (n = 20)) was 57% male (n = 24) with median age of 7.6 years at baseline visit versus 10.3 years at biopsy. Median FEV1 % predicted was lower in F3-4 participants at baseline versus F0-2 (59% vs. 85%; p = .002), while baseline FIB-4, APRI and GGT were higher in F3-4. Median splits for FIB-4 (≥.13), APRI (≥.36), GPR (≥.09), GGT (≥25.5), and FEV1 % (<64%) were associated with more rapid progression to F3-4 (p < .01 for all). Using a combination of change/year in FIB-4, APRI, and GPR to predict F3-4, the AUROC was .81 (95% CI, .66, .96; p < .0001). For up to 5.8 years prior, thresholds for GPR were met 6.5-fold more rapidly, and those for APRI and FIB-4 were met 2.5-fold more rapidly, in those who progressed to F3-4 than those that did not. CONCLUSIONS This study suggests mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.
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Affiliation(s)
- Shruti Sakhuja
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Division of Pediatric Gastroenterology, Hepatology, Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Heather M Staples
- Department of Pediatrics, University of South Carolina School of Medicine, Columbia, South Carolina, USA
- Division of Pediatric Pulmonology, Prisma Health Children's Hospital-Midlands, Columbia, South Carolina, USA
| | - Charles G Minard
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
| | - Louise E Ramm
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Peter J Lewindon
- Department of Gastroenterology, Queensland Children's Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Grant A Ramm
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
- Division of Pediatric Gastroenterology, Hepatology, Nutrition, Texas Children's Hospital, Houston, Texas, USA
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8
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Shikuma CM, Le T, Phuong TV, Chew GM, Nguyen VVC, Vo TL, Siriwardhana C, Chow D, Ghukasyan H, Limpruttidham N, Premeaux T, Gangcuangco LM, Paul R, Ndhlovu LC. Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam. AIDS Res Hum Retroviruses 2022; 38:441-450. [PMID: 34861767 PMCID: PMC10027344 DOI: 10.1089/aid.2021.0076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+, and TIGIT+ CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan® correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD1+, TIGIT+, and dual PD1+TIGIT+ CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.
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Affiliation(s)
- Cecilia M. Shikuma
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Thuy Le
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
- Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | - Thao Vu Phuong
- Department of Medicine, University of Saskatchewan, Saskatoon, Canada
- Saskatchewan Infectious Disease Care Network, Saskatoon, Canada
| | - Glen M. Chew
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | | | - Trieu Ly Vo
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- Department of Infectious Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Chathura Siriwardhana
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Dominic Chow
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Hayk Ghukasyan
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Nath Limpruttidham
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Thomas Premeaux
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Louie Mar Gangcuangco
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Robert Paul
- Department of Psychological Sciences, Missouri Institute of Mental Health, University of Missouri–St. Louis, St. Louis, Missouri, USA
| | - Lishomwa C. Ndhlovu
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
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9
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Yang R, Gui X, Ke H, Xiong Y, Gao S. Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection. AIDS Res Ther 2021; 18:98. [PMID: 34924016 PMCID: PMC8684625 DOI: 10.1186/s12981-021-00419-y] [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: 08/09/2021] [Accepted: 11/23/2021] [Indexed: 11/12/2022] Open
Abstract
Background Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. Methods This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. Results Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009–0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2–5 years and 5–10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). Conclusion cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection. Supplementary Information The online version contains supplementary material available at 10.1186/s12981-021-00419-y.
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10
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Kolesova O, Vanaga I, Laivacuma S, Derovs A, Kolesovs A, Radzina M, Platkajis A, Eglite J, Hagina E, Arutjunana S, Putrins DS, Storozenko J, Rozentale B, Viksna L. Intriguing findings of liver fibrosis following COVID-19. BMC Gastroenterol 2021; 21:370. [PMID: 34635073 PMCID: PMC8503733 DOI: 10.1186/s12876-021-01939-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 09/22/2021] [Indexed: 12/19/2022] Open
Abstract
Background Studies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4.
Methods The study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3–6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups.
Results Sixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT. Conclusion More than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.
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Affiliation(s)
- Oksana Kolesova
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia. .,Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia.
| | - Ieva Vanaga
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.,Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia.,Riga East Clinical University Hospital, Riga, Latvia
| | - Sniedze Laivacuma
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.,Riga East Clinical University Hospital, Riga, Latvia
| | - Aleksejs Derovs
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
| | - Aleksandrs Kolesovs
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.,Faculty of Education, Psychology, and Art, University of Latvia, Riga, Latvia
| | - Maija Radzina
- Faculty of Medicine, University of Latvia, Riga, Latvia.,Radiology Research Laboratory, Rīga Stradiņš University, Riga, Latvia.,Diagnostic Radiology Institute, Paula Stradina Clinical University Hospital, Riga, Latvia
| | - Ardis Platkajis
- Department of Radiology, Rīga Stradiņš University, Riga, Latvia
| | - Jelena Eglite
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia
| | - Elvira Hagina
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia
| | | | - Davis Simanis Putrins
- Diagnostic Radiology Institute, Paula Stradina Clinical University Hospital, Riga, Latvia
| | - Jelena Storozenko
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.,Central Laboratory Ltd., Riga, Latvia
| | - Baiba Rozentale
- Riga East Clinical University Hospital, Riga, Latvia.,Department of Public Health and Epidemiology, Rīga Stradiņš University, Riga, Latvia
| | - Ludmila Viksna
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.,Riga East Clinical University Hospital, Riga, Latvia
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11
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Bischoff J, Gu W, Schwarze-Zander C, Boesecke C, Wasmuth JC, van Bremen K, Dold L, Rockstroh JK, Trebicka J. Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART). EClinicalMedicine 2021; 40:101116. [PMID: 34522873 PMCID: PMC8427211 DOI: 10.1016/j.eclinm.2021.101116] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 08/14/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD. METHODS This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates. FINDINGS 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m2 (OR: 4·238, 95% CI: 2·078-8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362-10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370-4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315-24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12-0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101-0·945; p = 0·04). INTERPRETATION Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m2. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis. FUNDING There was no additional funding received for this project. All funders mentioned in the 'declaration of interests' section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Key Words
- APRI, AST to platelet ratio index
- ART, antiretroviral treatment
- AST, aspartate aminotransferase
- BMI, body mass index
- CAP, controlled attenuation parameter
- Cap
- DAA, direct-acting antiviral
- FAST, FibroScan-AST
- FIB4, fibrosis-4
- HCV, chronic hepatitis C
- Hiv
- INSTI, integrase strand transfer inhibitors
- NAFLD, Non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- Nafld
- PLHIV, people living with HIV
- PrEP, pre-exposure prophylaxis
- Steatosis
- TAF, tenofovir-alafenamid
- TDF, Tenofovir disoproxilfumarate
- TE, transient elastography
- cART
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Affiliation(s)
- Jenny Bischoff
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
| | - Wenyi Gu
- Department of Internal Medicine I, University Hospital Frankfurt, Germany
| | - Carolynne Schwarze-Zander
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
- German Center for Infection Research (DZIF), partner site Cologne-Bonn, Bonn, Germany
| | - Christoph Boesecke
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
- German Center for Infection Research (DZIF), partner site Cologne-Bonn, Bonn, Germany
| | - Jan-Christian Wasmuth
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
- German Center for Infection Research (DZIF), partner site Cologne-Bonn, Bonn, Germany
| | - Kathrin van Bremen
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
| | - Leona Dold
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
- German Center for Infection Research (DZIF), partner site Cologne-Bonn, Bonn, Germany
| | - Jürgen K Rockstroh
- Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, 53127 Bonn Germany,
- German Center for Infection Research (DZIF), partner site Cologne-Bonn, Bonn, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, University Hospital Frankfurt, Germany
- Corresponding author.
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12
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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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13
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Saleem N, Miller LS, Dadabhai AS, Cartwright EJ. Using vibration controlled transient elastography and FIB-4 to assess liver cirrhosis in a hepatitis C virus infected population. Medicine (Baltimore) 2021; 100:e26200. [PMID: 34115003 PMCID: PMC8202644 DOI: 10.1097/md.0000000000026200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 05/12/2021] [Indexed: 01/04/2023] Open
Abstract
We assessed the performance characteristics of the Fibrosis-4 (FIB-4) score in a veteran population with chronic hepatitis C virus (HCV) infection and used vibration controlled transient elastography (VCTE) as the gold standard.All VCTE studies were performed by a single operator on United States veterans with HCV infection presenting for care at the Atlanta VA Medical Center (AVAMC) over a 2 year period. VCTE liver stiffness measurements (LSM) were categorized as cirrhotic if LSM was >12.5 kPa and non-cirrhotic if LSM was ≤12.5 kPa. FIB-4 scores ≤3.25 were considered non-cirrhotic and scores >3.25 were considered cirrhotic. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the FIB-4 score. A second analysis was done which identified and excluded indeterminate FIB-4 scores, defined as any value between 1.45 and 3.25.When FIB-4 was used to screen for liver cirrhosis using VCTE as the gold standard, sensitivity was 42%, specificity was 88%, PPV was 62%, and NPV was 76%. When indeterminate FIB-4 scores were excluded from the analysis, sensitivity was 95%, specificity was 61%, PPV was 62%, and NPV was 94.4%. In a veteran population with chronic HCV infection, we found the sensitivity of the FIB-4 score to be unacceptably low for ruling out liver cirrhosis when using a binary cutoff at 3.25. Using a second staging method like VCTE may be an effective way to screen for liver cirrhosis in persons with chronic HCV, especially when the FIB-4 score is in the indeterminate range.
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Affiliation(s)
| | | | | | - Emily J. Cartwright
- Emory University School of Medicine, Atlanta
- Atlanta VA Medical Center, Decatur, GA
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14
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Itakura J, Kurosaki M, Setoyama H, Simakami T, Oza N, Korenaga M, Tanaka M, Torimura T, Sakamoto N, Enomoto N, Ueno Y, Kawada N, Kaneko S, Nishiguchi S, Chayama K, Tanaka J, Izumi N, Kanto T. Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis. J Gastroenterol 2021; 56:470-478. [PMID: 33791882 DOI: 10.1007/s00535-021-01782-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/18/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.
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Affiliation(s)
- Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroko Setoyama
- Department of Gastroenterology and Hepatology, Kumamoto Rosai Hospital, Yatsushiro, Japan
| | - Tetsuro Simakami
- Department of Gastroenterology, Saga Medical Center Kouseikan, Saga, Japan
| | - Noriko Oza
- Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Masaaki Korenaga
- Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan
| | - Motohiko Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Saga Medical Center Kouseikan, Saga, Japan
| | - Shuhei Nishiguchi
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tatsuya Kanto
- Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan.
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15
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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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Yunihastuti E, Wicaksana B, Wiraguna A, Hidayah AJ, Amelia F, Natali V, Widhani A, Sulaiman AS, Kurniawan J. Diagnostic performance of APRI and FIB-4 for confirming cirrhosis in Indonesian HIV/HCV co-infected patients. BMC Infect Dis 2020; 20:372. [PMID: 32450844 PMCID: PMC7249442 DOI: 10.1186/s12879-020-05069-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 05/04/2020] [Indexed: 02/06/2023] Open
Abstract
Background After successful of antiretroviral therapy, highly effective direct acting antiviral (DAA) make HCV elimination reasonable in HIV/HCV co-infected patients. However, in achieving this target, there are still barriers to start DAA treatment, particularly in the area of liver fibrosis assessment that determine the duration of therapy. We aimed to assess the diagnostic performance of APRI and FIB-4 for diagnosing cirrhosis in HIV/HCV co-infected patients using hepatic transient elastography (TE) as gold standard. Method This is a retrospective study on HIV/HCV co-infected patients who concomitantly performed hepatic TE measurement, APRI, and FIB-4 evaluation before HCV treatment initiation at a tertiary hospital in Jakarta from 2014 to 2019. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) ≥ 12.5 kPa was determined by receiver operator characteristics curves. Results 223 HIV/HCV co-infected patients on stable antiretroviral therapy were included, of whom 91.5% were male with mean age of 37 (SD 5) years. Only 28.7% of patients were classified as cirrhosis (F4). Using TE as gold standard (≥12.5 kPa), the low threshold of APRI (1) had specificity 95%, sensitivity 48.4%, correctly classified 81.6% of patients, with moderate performance, AUC at 0.72 (95% CI 0.63–0.80). The optimal cut-off of FIB-4 was 1.66 [specificity 92.5%, sensitivity 53.1%, AUC at 0.73 (95% CI 0.65–0.81)] and correctly classified 81.1% of the patients. Conclusion APRI score ≥ 1 and FIB-4 score ≥ 1.66 had moderate performance with high specificity in diagnosing cirrhosis. These biochemical markers could be used while TE is not available.
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Affiliation(s)
- Evy Yunihastuti
- HIV integrated services, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. .,Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Diponegoro, Jakarta, 71, Indonesia.
| | | | - Andrian Wiraguna
- HIV integrated services, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | | | - Fhadilla Amelia
- HIV integrated services, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Veritea Natali
- HIV integrated services, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Alvina Widhani
- HIV integrated services, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.,Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Diponegoro, Jakarta, 71, Indonesia
| | - Andri Sanityoso Sulaiman
- Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Diponegoro, Jakarta, 71, Indonesia
| | - Juferdy Kurniawan
- Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Diponegoro, Jakarta, 71, Indonesia
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Maev IV, Kuznetsova EI, Andreev DN, Dicheva DT. [Diagnostic accuracy of predictive indexes of liver fibrosis in patients with chronic hepatitis C]. TERAPEVT ARKH 2020; 92:24-28. [PMID: 32598714 DOI: 10.26442/00403660.2020.02.000261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Indexed: 12/14/2022]
Abstract
AIM Assessment of the diagnostic accuracy of predictive indexes of liver fibrosis for the identification of severe fibrosis and cirrhosis (F3F4) in patients with chronic hepatitis C (CHC). MATERIALS AND METHODS The retrospective design study included 127 patients with chronic hepatitis C (mean age 44.511.1 years). To assess the degree of liver fibrosis, all patients underwent transient elastography using a Fibroscan (EchoSens, France) and predictive indexes of liver fibrosis were calculated (APRI, FIB-4, discriminant Bonacini score). Transient elastography was considered as a reference method for assessing the degree of liver fibrosis for subsequent comparison of results with predictive fibrosis indixes. RESULTS The sensitivity of the APRI index for the identification of severe fibrosis and cirrhosis of the liver (F3F4) was 79%, and specificity was 69%. The FIB-4 index showed greater specificity (86%), but less sensitivity (68%). The sensitivity of the discriminant Bonacini scale was 81%, and the specificity was 77%. The positive predictive value of the APRI index, FIB-4 and the Bonacini scale for the identification of severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C was 66; 78 and 72% respectively, and negative predictive value 82; 78 and 84% respectively. CONCLUSION The results of this study indicate the relatively high diagnostic accuracy of a number of predictive indexes for evaluating liver fibrosis (APRI, FIB-4, discriminant Bonachini scale) in identifying severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E I Kuznetsova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D T Dicheva
- Yevdokimov Moscow State University of Medicine and Dentistry
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Hussain A, Gul MA, Khalid MU. Validation of Novel Fibrosis Index (NFI) for assessment of liver fibrosis: comparison with transient elastography (FibroScan). BMJ Open Gastroenterol 2019; 6:e000316. [PMID: 31749977 PMCID: PMC6827736 DOI: 10.1136/bmjgast-2019-000316] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 06/26/2019] [Accepted: 07/04/2019] [Indexed: 12/12/2022] Open
Abstract
Background In this study, we collated cheap and readily available non-invasive biomarkers and FibroScan score in predicting fibrosis stages in chronic hepatitis C virus (HCV) infection. Methods We studied 1898 patients with HCV infection confirmed by presence of HCV RNA in their serum. We compared the FibroScan score and fibrosis indices (FIs): aspartate transaminase (AST) to alanine transaminase (ALT) ratio (AAR), AST to Platelet Ratio Index (APRI), FI, fibrosis-4 (FIB-4), Age-Platelet Index (API), Pohl score, Fibrosis Cirrhosis Index (FCI). We developed a new FI, named Novel Fibrosis Index (NFI) calculated by the following formula: NFI=[(bilirubin×(ALP)2)/(platelet count (albumin)2)]−n. Results AAR, APRI, FI, FIB-4, API, Pohl score, FCI and NFI were able to predict fibrosis stage with correlation coefficient indices 0.848, 0.711, 0.618, 0.741, 0.529, 0.360, 0.477 and 0.26, respectively. Receiver operating characteristic curves showed sensitivity and specificity for predicting F3 by NFI=75.1% and 41.1% and F4 for NFI=72.1% and 47.1%, AAR=62.8% and 37.6%, APRI=74.6% and 87.6%, FIB-4=53.2% and 72.3%, FI=78.1% and 92.3%, API=78.1% and 60%, Pohl score=38.1% and 78.1% and FCI=78.1% and 88.1%. Conclusions Our NFI predicted F3 and has been found to have more sensitivity and specificity in predicting F4 fibrosis stage than other FIs.
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Affiliation(s)
- Azhar Hussain
- Ameer-ud-Din Medical College, PGMI, Lahore, Pakistan
| | - Muhammad Asif Gul
- Gastroenterology, Nishtar Medical College and Hospital, Multan, Pakistan
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Barakat NH, Barakat SH, Ahmed N. Prediction and Staging of Hepatic Fibrosis in Children with Hepatitis C Virus: A Machine Learning Approach. Healthc Inform Res 2019; 25:173-181. [PMID: 31406609 PMCID: PMC6689505 DOI: 10.4258/hir.2019.25.3.173] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 05/05/2019] [Accepted: 07/17/2019] [Indexed: 12/15/2022] Open
Abstract
Objectives The aim of this study is to develop an intelligent diagnostic system utilizing machine learning for data cleansing, then build an intelligent model and obtain new cutoff values for APRI (aspartate aminotransferase-to-platelet ratio) and FIB-4 (fibrosis score) for the prediction and staging of fibrosis in children with chronic hepatitis C (CHC). Methods Random forest (RF) was utilized in this study for data cleansing; then, prediction and staging of fibrosis, APRI and FIB-4 scores and their areas under the ROC curve (AUC) have been obtained on the cleaned dataset. A cohort of 166 Egyptian children with CHC was studied. Results RF, APRI, and FIB-4 achieved high AUCs; where APRI had AUCs of 0.78, 0.816, and 0.77; FIB-4 had AUCs of 0.74, 0.828, and 0.78; and RF had AUCs of 0.903, 0.894, and 0.822, for the prediction of any type of fibrosis, advanced fibrosis, and differentiating between mild and advanced fibrosis, respectively. Conclusions Machine learning is a valuable addition to non-invasive methods of liver fibrosis prediction and staging in pediatrics. Furthermore, the obtained cutoff values for APRI and FIB-4 showed good performance and are consistent with some previously obtained cutoff values. There was some agreement between the predictions of RF, APRI and FIB-4 for the prediction and staging of fibrosis.
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Affiliation(s)
- Nahla H Barakat
- Faculty of Informatics and Computer Science, The British University in Egypt, Cairo, Egypt
| | - Sana H Barakat
- Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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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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Abstract
BACKGROUND Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. DESIGN AND METHODS HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤ 1.45 and > 1.45 were examined using multistate Markov models. RESULTS Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range = 8-18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95-1.05] before AHCVI, 1.31 (95% CI = 1.25-1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and ≥ 3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤ 1.45. CONCLUSION In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥ 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression.
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Yoshimoto T, Eguchi S, Natsuda K, Hidaka M, Adachi T, Ono S, Hamada T, Huang Y, Kanetaka K, Takatsuki M. Relationship between various hepatic function scores and the formation of esophageal varices in patients with HIV/hepatitis C virus co-infection due to contaminated blood products for hemophilia. Hepatol Res 2019; 49:147-152. [PMID: 30358037 DOI: 10.1111/hepr.13279] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 09/30/2018] [Accepted: 10/14/2018] [Indexed: 02/08/2023]
Abstract
AIM It is reportedly difficult to accurately assess the liver reserve capacity of patients with HIV/hepatitis C virus (HCV) co-infection through contaminated blood products by the Child-Pugh (CP) classification. Therefore, we investigated a clinically applicable scoring system in determining the risk of esophageal varices in HIV/HCV co-infected patients, known as latent portal hypertension leading to esophageal varices. METHODS Forty-three patients with HIV/HCV co-infection underwent clinical examinations, including endoscopy and assessment of hepatic reserve, in our department between 2009 and 2017. Child-Pugh score, the recently developed albumin-bilirubin (ALBI) grade, and the albumin-indocyanine green evaluation (ALICE) were compared to evaluate their diagnostic accuracy for the detection of esophageal varices using the area under the receiver operating characteristic curve (AUROC). RESULTS The patients were all male hemophiliacs and were positive for both HIV and HCV antibodies, with a median age of 45 years (range, 29-66 years). Thirty-seven patients (84.1%) were classified as CP A at the examination. The comparison of AUROCs showed a superior diagnostic accuracy for ALICE (AUROC = 0.814) to detect esophageal varices. The positive prediction rate was the highest with ALICE if -2.325 was set, and the negative prediction rate was the highest with ALBI if -2.575 was set. The ALICE showed the highest accuracy compared to other two scores. CONCLUSION The ALICE score was found to be the most valuable system for portal hypertension in HIV/HCV co-infected hemophilia patients. Because of its high specificity, ALICE for secondary surveillance could be used after other markers such as the aspartate aminotransferase to platelet ratio index and Fibrosis-4 index.
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Affiliation(s)
- Tomoko Yoshimoto
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Koji Natsuda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinichiro Ono
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takashi Hamada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yu Huang
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kengo Kanetaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Shili-Masmoudi S, Sogni P, de Ledinghen V, Esterle L, Valantin MA, Poizot-Martin I, Simon A, Rosenthal E, Lacombe K, Pialoux G, Bouchaud O, Gervais-Hasenknoff A, Goujard C, Piroth L, Zucman D, Dominguez S, Raffi F, Alric L, Bani-Sadr F, Lascoux-Combe C, Garipuy D, Miailhes P, Vittecoq D, Duvivier C, Aumaître H, Neau D, Morlat P, Dabis F, Salmon D, Wittkop L. Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study. PLoS One 2019; 14:e0211286. [PMID: 30682180 PMCID: PMC6347250 DOI: 10.1371/journal.pone.0211286] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 01/10/2019] [Indexed: 12/22/2022] Open
Abstract
Background The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. Methods HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. Results 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. Conclusion Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.
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Affiliation(s)
- Sarah Shili-Masmoudi
- Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France
- Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d’Hépatologie, Bordeaux, France
| | - Philippe Sogni
- Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service d’Hépatologie, Paris, France
- INSERM U-1223 –Institut Pasteur, Paris, France
- Université Paris Descartes, Paris, France
| | - Victor de Ledinghen
- Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d’Hépatologie, Bordeaux, France
- Univ Bordeaux, Inserm, UMR 1053, Bordeaux, France
| | - Laure Esterle
- Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France
| | - Marc-Antoine Valantin
- Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Service Maladies infectieuses et tropicales, Paris, France
| | - Isabelle Poizot-Martin
- Aix Marseille Univ, APHM Sainte-Marguerite, Service d’Immuno-hématologie clinique, Marseille, France
- Inserm U912 (SESSTIM) Marseille, France
| | - Anne Simon
- Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Département de Médecine Interne et Immunologie Clinique, Paris, France
| | - Eric Rosenthal
- Centre Hospitalier Universitaire de Nice, Service de Médecine Interne et Cancérologie, Hôpital l’Archet, Nice, France
- Université de Nice-Sophia Antipolis, Nice, France
| | - Karine Lacombe
- Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Antoine, Service Maladies infectieuses et tropicales, Paris, France
- UMPC (Université Pierre et Marie Curie), UMR S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Gilles Pialoux
- Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service Maladies infectieuses et tropicales, Paris, France
| | - Olivier Bouchaud
- Assistance Publique des Hôpitaux de Paris, Hôpital Avicenne, Service Maladies infectieuses et tropicales, Bobigny, France
- Université Paris 13 Nord, Bobigny, France
| | - Anne Gervais-Hasenknoff
- Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des maladies infectieuses et tropicales, Paris, France
| | - Cécile Goujard
- Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Médecine interne et Immunologie clinique, Le Kremlin-Bicêtre, France
- Université Paris Sud, Le Kremlin-Bicêtre, France
| | - Lionel Piroth
- Centre Hospitalier Universitaire de Dijon, Département d’Infectiologie, Dijon, France
- Université de Bourgogne, Dijon, France
| | | | - Stéphanie Dominguez
- Assistance Publique des Hôpitaux de Paris, Hôpital Henri Mondor, Service Immunologie clinique et maladies infectieuses, Immunologie clinique, Créteil, France
| | - François Raffi
- Centre Hospitalier Universitaire de Nantes, Service Maladies infectieuses et tropicales, Nantes, France
| | - Laurent Alric
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Médecine interne, Toulouse, France
- Université Toulouse III, Paul Sabatier, Toulouse, France
| | - Firouzé Bani-Sadr
- Centre Hospitalier Universitaire de Reims, Service de médecine interne, maladies infectieuses et immunologie clinique, Reims, France
- Université de Reims, Champagne-Ardenne, Reims, France
| | - Caroline Lascoux-Combe
- Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service Maladies infectieuses et tropicales, Paris, France
| | - Daniel Garipuy
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Maladies infectieuses et tropicales, Toulouse, France
| | - Patrick Miailhes
- Service des Maladies Infectieuses et Tropicales, CHU Lyon, Hôpital de la Croix Rousse, Lyon, France
| | - Daniel Vittecoq
- Université Paris Sud, Le Kremlin-Bicêtre, France
- Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Maladies infectieuses et tropicales, Le Kremlin-Bicêtre, France
| | - Claudine Duvivier
- APHP-Hôpital Necker-Enfants malades, Service de Maladies Infectieuses et Tropicales, Paris, France
- Centre d'Infectiologie Necker-Pasteur, Paris, France
| | - Hugues Aumaître
- Centre Hospitalier de Perpignan, Service Maladies infectieuses et tropicales, Perpignan, France
| | - Didier Neau
- Centre Hospitalier Universitaire de Bordeaux, Service Maladies infectieuses et tropicales Bordeaux, Hôpital Pellegrin, Bordeaux, France
| | - Philippe Morlat
- Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France
- Centre Hospitalier Universitaire de Bordeaux, Service de médecine interne, hôpital Saint-André, Bordeaux, France
| | - François Dabis
- Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France
- Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Bordeaux, France
| | - Dominique Salmon
- Université Paris Descartes, Paris, France
- Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service Maladies infectieuses et tropicales, Paris, France
| | - Linda Wittkop
- Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France
- Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Bordeaux, France
- * E-mail:
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Mazzola G, Adamoli L, Calvaruso V, Macaluso FS, Colletti P, Mazzola S, Cervo A, Trizzino M, Di Lorenzo F, Iaria C, Prestileo T, Orlando A, Di Marco V, Cascio A. Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients. Infection 2018; 47:409-415. [PMID: 30519966 DOI: 10.1007/s15010-018-1258-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 11/27/2018] [Indexed: 12/16/2022]
Abstract
PURPOSE We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. METHODS This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. RESULTS 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. CONCLUSIONS Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.
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Affiliation(s)
- Giovanni Mazzola
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Lucia Adamoli
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | | | - Pietro Colletti
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Sergio Mazzola
- Clinical Epidemiology and Cancer Registry Unit, A.O.U.P. "Paolo Giaccone", Palermo, Italy
| | - Adriana Cervo
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Marcello Trizzino
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | | | - Chiara Iaria
- ARNAS "Civico-Benefratelli" Hospital, Palermo, Italy
| | | | - Ambrogio Orlando
- IBD Unit, "Villa Sofia-Cervello" Hospital, Via Trabucco 180, 90146, Palermo, Italy
| | - Vito Di Marco
- Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | - Antonio Cascio
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
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Hansen S, Kronborg G, Benfield T. Prediction of Liver Disease, AIDS, and Mortality Based on Discordant Absolute and Relative Peripheral CD4 T Lymphocytes in HIV/Hepatitis C Virus-Coinfected Individuals. AIDS Res Hum Retroviruses 2018; 34:1058-1066. [PMID: 30205696 DOI: 10.1089/aid.2017.0058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Hepatitis C virus (HCV)-induced liver fibrosis and splenomegaly may lead to discordance between absolute numbers and percentages of lymphocytes and subpopulations because of sequestration. We investigated lymphocyte discordance in HIV/HCV-coinfected individuals and its relationship to progression to liver disease, AIDS, and all-cause mortality. This is an observational retrospective cohort study. Adjusted hazard ratios (aHRs) with 95% confidence intervals (95% CIs) associated with liver disease, AIDS, or mortality were computed by time-updated Cox proportional hazards regression. Of 380 HIV/HCV-coinfected adult individuals followed for a median of 8.2 years, 360 individuals had a median of 11 discordant measurements corresponding to 5,080 of 9,091 paired samples (56%). Discordance alone was not associated with any of the outcomes. By multivariable analysis, a doubling of absolute or percentage CD4 cells was associated with comparable lower risks of mortality (aHR: 0.60, 95% CI: 0.53-0.67, p < .0001 and aHR: 0.67, 95% CI: 0.56-0.79, p < .0001, respectively). Higher CD4/CD8 ratio was associated with a lower mortality risk (aHR: 0.39, 95% CI: 0.22-0.71 per doubling, p = .002). Only absolute CD4 cell measurements predicted AIDS. Development of liver disease was not predicted by total lymphocyte count or subpopulations. Despite a high prevalence of lymphocyte-subpopulation discordance with HIV/HCV coinfection, absolute CD4 cell count predicted mortality and AIDS, whereas CD4 percentage only predicted mortality. Neither CD4 T lymphocyte count nor CD4 percentage was associated with liver disease in this cohort. These findings may be necessary and useful in countries where antiretroviral treatment is not initiated for all HIV-infected individuals.
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Affiliation(s)
- Sandra Hansen
- 1 Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen , Hvidovre, Denmark
| | - Gitte Kronborg
- 1 Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen , Hvidovre, Denmark
- 2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark
| | - Thomas Benfield
- 1 Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen , Hvidovre, Denmark
- 2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark
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Kelly EM, Dodge JL, Bacchetti P, Sarkar M, French AL, Tien PC, Glesby MJ, Golub ET, Augenbraun M, Plankey M, Peters MG. Moderate Alcohol Use Is Not Associated With Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women: A Prospective Cohort Study. Clin Infect Dis 2018; 65:2050-2056. [PMID: 29020382 DOI: 10.1093/cid/cix716] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 08/15/2017] [Indexed: 02/07/2023] Open
Abstract
Background Heavy alcohol use can lead to progressive liver damage, especially in individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use is not clear. We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of women coinfected with human immunodeficiency virus (HIV)/HCV. Methods Alcohol intake was ascertained every 6 months and use categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week), heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units per year using random-intercept, random-slope mixed modeling. Results Among 686 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0% had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between groups. On multivariable analysis, compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression (0.004 [95% confidence interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year, respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining, whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year). Conclusions Light/moderate alcohol use was not substantially associated with accelerated fibrosis progression, whereas drinking >14 drinks per week showed increased rates of fibrosis progression. Women with HIV/HCV infection should be counseled against heavy alcohol consumption, but complete abstinence may not be required to prevent accelerated liver fibrosis progression.
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Affiliation(s)
- Erin M Kelly
- Department of Medicine, University of Ottawa, Ontario, Canada
| | | | | | | | - Audrey L French
- Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, Illinois
| | - Phyllis C Tien
- Medicine, University of California, San Francisco.,Department of Veterans Affairs Medical Center, San Francisco, California
| | - Marshall J Glesby
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Elizabeth T Golub
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael Augenbraun
- Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn
| | - Michael Plankey
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia
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27
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Kennedy P, Wagner M, Castéra L, Hong CW, Johnson CL, Sirlin CB, Taouli B. Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology 2018; 286:738-763. [PMID: 29461949 DOI: 10.1148/radiol.2018170601] [Citation(s) in RCA: 188] [Impact Index Per Article: 26.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and limitations of US- and MR-based elastography techniques. Diagnostic performance in the most common etiologies of chronic liver disease will be presented. Reliability, reproducibility, failure rate, and emerging advances will be discussed. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Paul Kennedy
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Mathilde Wagner
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Laurent Castéra
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Cheng William Hong
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Curtis L Johnson
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Claude B Sirlin
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Bachir Taouli
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
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Tana MM, Muir AJ. Diagnosing Liver Fibrosis and Cirrhosis: Serum, Imaging, or Tissue? Clin Gastroenterol Hepatol 2018; 16:16-18. [PMID: 28694131 DOI: 10.1016/j.cgh.2017.06.050] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 06/30/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Michele M Tana
- Division of Gastroenterology, Duke University Hospital, Durham, North Carolina
| | - Andrew J Muir
- Division of Gastroenterology, Duke University Hospital, Durham, North Carolina.
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Abstract
Patients with HIV have a proclivity to develop liver fibrosis, especially when associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV-infected patients with significant fibrosis or cirrhosis plays an important role in clinical and therapeutic decision-making. Liver biopsy is currently considered as the gold standard for fibrosis assessment but carries many shortcomings (cost, invasiveness, complications, false negative rate of 20 %). Multiple non-invasive methods of liver fibrosis assessment have been developed, but not all have been studied in HIV-infected individuals. Non-invasive liver fibrosis tools include both serologic-based testing scores (rely on direct and/or indirect markers) such as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such as vibration controlled liver elastography. There is validated data to support the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected individuals for the exclusion of cirrhosis, but may be poorly reliable or not enough data exists for the assessment of other co-morbid disease processes.
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Natsuda K, Takatsuki M, Tanaka T, Soyama A, Adachi T, Ono S, Hara T, Baimakhanov Z, Imamura H, Okada S, Hidaka M, Eguchi S. Aspartate transaminase-platelet ratio and Fibrosis-4 indices as effective markers for monitoring esophageal varices in HIV/hepatitis C virus co-infected patients due to contaminated blood products for hemophilia. Hepatol Res 2017; 47:1282-1288. [PMID: 28130908 DOI: 10.1111/hepr.12866] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 12/25/2016] [Accepted: 01/23/2017] [Indexed: 02/08/2023]
Abstract
AIM We examined the feasibility of the aspartate transaminase (AST)-platelet ratio index (APRI) and Fibrosis-4 (FIB4) score, which are well-established markers for liver fibrosis, as indicators for monitoring esophageal varices in patients who were co-infected with HIV and hepatitis C virus (HCV) due to contaminated blood products for hemophilia in Japan. METHODS Forty-three HIV/HCV co-infected patients were enrolled. All were hemophilic men (median age 41 years; range, 29-66 years). We analyzed the correlations between fibrosis indices (APRI, FIB4) and various liver function tests, fibrosis markers, liver stiffness measured by acoustic radiation force impulse elastography, and the findings of gastrointestinal endoscopy. RESULTS Both APRI and FIB4 were well correlated with several of the factors related to liver fibrosis and the existence of esophageal varices in the patients. The cut-off values for detecting esophageal varices estimated as the area under the receiver operating characteristic curve were 0.85 for APRI and 1.85 for FIB4. CONCLUSION In patients co-infected with HIV/HCV due to contaminated blood products for hemophilia, APRI and FIB4 are effective for monitoring esophageal varices, even among patients who are apparently doing well with good liver function as Child-Pugh grade A.
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Affiliation(s)
- Koji Natsuda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takayuki Tanaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinichiro Ono
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Zhassulan Baimakhanov
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hajime Imamura
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Satomi Okada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Pembroke T, Deschenes M, Lebouché B, Benmassaoud A, Sewitch M, Ghali P, Wong P, Halme A, Vuille-Lessard E, Pexos C, Klein MB, Sebastiani G. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis. J Hepatol 2017; 67:801-808. [PMID: 28527666 DOI: 10.1016/j.jhep.2017.05.011] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 04/07/2017] [Accepted: 05/10/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.
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Affiliation(s)
- Thomas Pembroke
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada; School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
| | - Marc Deschenes
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Bertrand Lebouché
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Amine Benmassaoud
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Maida Sewitch
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Peter Ghali
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Philip Wong
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Alex Halme
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | | | - Costa Pexos
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Marina B Klein
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Giada Sebastiani
- Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada.
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Parisi SG, Basso M, Mengoli C, Scaggiante R, Andreis S, Franzetti MM, Cattelan AM, Zago D, Cruciani M, Andreoni M, Piovesan S, Palù G, Alberti A. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection. Ann Gastroenterol 2017; 30:534-541. [PMID: 28845109 PMCID: PMC5566774 DOI: 10.20524/aog.2017.0175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 06/06/2017] [Indexed: 12/24/2022] Open
Abstract
Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients.
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Affiliation(s)
- Saverio Giuseppe Parisi
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Monica Basso
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Carlo Mengoli
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Renzo Scaggiante
- Infectious Disease Unit, Padova Hospital, Padova (Renzo Scaggiante, Marzia Maria Franzetti, Anna Maria Cattelan), Italy
| | - Samantha Andreis
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Marzia Maria Franzetti
- Infectious Disease Unit, Padova Hospital, Padova (Renzo Scaggiante, Marzia Maria Franzetti, Anna Maria Cattelan), Italy
| | - Anna Maria Cattelan
- Infectious Disease Unit, Padova Hospital, Padova (Renzo Scaggiante, Marzia Maria Franzetti, Anna Maria Cattelan), Italy
| | - Daniela Zago
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Mario Cruciani
- Center of Diffusive Diseases, ULSS 20, Verona (Mario Cruciani), Italy
| | - Massimo Andreoni
- Clinical Infectious Diseases, Tor Vergata University of Rome, Rome (Massimo Andreoni), Italy
| | - Sara Piovesan
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Giorgio Palù
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
| | - Alfredo Alberti
- Department of Molecular Medicine, University of Padova, Padova (Saverio Giuseppe Parisi, Monica Basso, Carlo Mengoli, Samantha Andreis, Daniela Zago, Sara Piovesan, Giorgio Palù, Alfredo Alberti), Italy
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Wei Q, Lin H, Ding Y, Liu X, Wu Q, Shen W, Gao M, He N. Liver fibrosis after antiretroviral therapy in a longitudinal cohort of sexually infected HIV patients in eastern China. Biosci Trends 2017; 11:274-281. [PMID: 28484111 DOI: 10.5582/bst.2017.01071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We assessed the factors that influenced improvement or progression in human immunodeficiency virus (HIV)-infected patients who were receiving combination antiretroviral therapy (cART). This was a retrospective cohort study of HIV-infected patients receiving cART in Taizhou, Zhejiang, China, 2009-2015. Liver fibrosis was assessed by Fibrosis-4 (FIB-4) score. Improvement of liver fibrosis was defined as having > 30% decrease in FIB-4 from baseline, whereas progression of liver fibrosis was defined as having > 30% increase in FIB-4 score from baseline. A total of 955 HIV-infected patients were included. Of these, 808 (84.6%) were HIV-monoinfection, 125 (13.1%) were HIV/hepatitis B virus (HBV) coinfection and 29 (3.0%) were HIV/hepatitis C virus (HCV) coinfection. The median duration of treatment was 15 months. After treatment, 37.1% participants had > 30% decreases in FIB-4 index, 14.8% had > 30% increases in FIB-4 index, while the remaining 48.2% had stabilized FIB-4 index. In multivariate analysis, improvement of liver fibrosis was negatively associated with an older age, but was positively associated with baseline FIB-4 index and > 30% increases in CD4 cell count after ART. Progression of liver fibrosis was positively associated with an older age, but was negatively associated with gender and HIV transmission mode (male homosexual vs. male heterosexual, female heterosexual vs. male heterosexual), and baseline FIB-4 index. Our findings indicate that improvement of liver fibrosis could be achieved by early initiation of ART through better CD4 cell recovery. Liver fibrosis and hepatotoxicity associated with ART should be monitored as early as possible and throughout till the end of treatment, with special attention to the elderly and heterosexual men.
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Affiliation(s)
- Qian Wei
- Department of Epidemiology, School of Public Health, Fudan University, and The Key Laboratory of Public Health Safety of Ministry of Education.,Key Laboratory of Health Technology Assessment of Ministry of Health, Fudan University
| | - Haijiang Lin
- Taizhou City Center for Disease Control and Prevention
| | - Yingying Ding
- Department of Epidemiology, School of Public Health, Fudan University, and The Key Laboratory of Public Health Safety of Ministry of Education
| | - Xing Liu
- Department of Epidemiology, School of Public Health, Fudan University, and The Key Laboratory of Public Health Safety of Ministry of Education
| | - Qionghai Wu
- Taizhou City Center for Disease Control and Prevention
| | - Weiwei Shen
- Taizhou City Center for Disease Control and Prevention
| | - Meiyang Gao
- Department of Epidemiology, School of Public Health, Fudan University, and The Key Laboratory of Public Health Safety of Ministry of Education
| | - Na He
- Department of Epidemiology, School of Public Health, Fudan University, and The Key Laboratory of Public Health Safety of Ministry of Education.,Key Laboratory of Health Technology Assessment of Ministry of Health, Fudan University
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Abstract
PURPOSE OF REVIEW Availability of direct acting antivirals (DAAs) that demonstrate remarkable clinical efficacy and safety has revolutionized the ability to treat chronic infection with hepatitis C virus (HCV). An equal measure of clinical success has now been achieved in persons coinfected with HCV and the HIV, a historically harder to cure cohort with interferon-based therapy. Global goals include identifying all HIV-HCV-infected persons, gaining access to DAA therapy, preventing de novo and reinfection, and managing the sequelae of chronic infection. This review will discuss advances in the field of HIV-HCV coinfection reported during the last 18 months, and will suggest areas for future investigation. RECENT FINDINGS An expanding body of literature has enhanced our understanding of the clinical and epidemiologic issues surrounding HIV-HCV coinfection. DAA therapy for HCV is highly efficacious in HIV-HCV-coinfected persons if drug-drug interactions are appropriately considered. SUMMARY Eradicating HCV infection in persons with HIV coinfection can be achieved safely and effectively with available DAAs. Economic and social approaches to enable access and delivery of curative HCV therapy to HIV-infected persons require continued research and resource allocation.
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Zhang CY, Yuan WG, He P, Lei JH, Wang CX. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 2016; 22:10512-10522. [PMID: 28082803 PMCID: PMC5192262 DOI: 10.3748/wjg.v22.i48.10512] [Citation(s) in RCA: 430] [Impact Index Per Article: 47.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 10/12/2016] [Accepted: 11/15/2016] [Indexed: 02/06/2023] Open
Abstract
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
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Zhang CY, Yuan WG, He P, Lei JH, Wang CX. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 2016. [PMID: 28082803 DOI: 10.3748/wjg.v22.i48.10512.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/29/2022] Open
Abstract
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
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Affiliation(s)
- Chong-Yang Zhang
- Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei-Gang Yuan
- Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Pei He
- Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jia-Hui Lei
- Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Chun-Xu Wang
- Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Debes JD, Bohjanen PR, Boonstra A. Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection. J Clin Transl Hepatol 2016; 4:328-335. [PMID: 28097102 PMCID: PMC5225153 DOI: 10.14218/jcth.2016.00034] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 10/14/2016] [Accepted: 10/21/2016] [Indexed: 12/23/2022] Open
Abstract
With the introduction of antiretroviral therapy (ART), a dramatic reduction in HIV-related morbidity and mortality has been observed. However, it is now becoming increasingly clear that liver-related complications, particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself, are of serious concern to HIV patients. The pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication, and bacterial translocation lead to chronic immune activation and inflammation, which ART is unable to fully suppress, promoting production of fibrinogenic mediators and fibrosis. In addition, mitochondrial toxicity, triggered by both ART and HIV, contributes to intrahepatic damage, which is even more severe in patients co-infected with viral hepatitis. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV has been obtained, and these are detailed and discussed in this review.
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Affiliation(s)
- Jose D. Debes
- Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN, USA
- *Correspondence to: Jose D. Debes, Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, 2001 6th Street SE, Minneapolis, MN 55455, USA. Tel: +1-612-624-6353, Fax: +1-612-301-1292, E-mail:
| | - Paul R. Bohjanen
- Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Andre Boonstra
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
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Lui G, Wong VWS, Wong GLH, Chu WCW, Wong CK, Yung IMH, Wong RYK, Yeung SL, Yeung DKW, Cheung CSK, Chan HY, Chan HLY, Lee N. Liver fibrosis and fatty liver in Asian HIV-infected patients. Aliment Pharmacol Ther 2016; 44:411-21. [PMID: 27301337 DOI: 10.1111/apt.13702] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 03/29/2016] [Accepted: 05/27/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. CONCLUSIONS HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.
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Affiliation(s)
- G Lui
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - V W-S Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - G L-H Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - W C-W Chu
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong
| | - C-K Wong
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong
| | - I M H Yung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - R Y K Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - S-L Yeung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - D K-W Yeung
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong
| | - C S K Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - H-Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - H L-Y Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - N Lee
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.,Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong
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Focà E, Fabbiani M, Prosperi M, Quiros Roldan E, Castelli F, Maggiolo F, Di Filippo E, Di Giambenedetto S, Gagliardini R, Saracino A, Di Pietro M, Gori A, Sighinolfi L, Pan A, Postorino MC, Torti C. Liver fibrosis progression and clinical outcomes are intertwined: role of CD4+ T-cell count and NRTI exposure from a large cohort of HIV/HCV-coinfected patients with detectable HCV-RNA: A MASTER cohort study. Medicine (Baltimore) 2016; 95:e4091. [PMID: 27442636 PMCID: PMC5265753 DOI: 10.1097/md.0000000000004091] [Citation(s) in RCA: 16] [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: 12/15/2022] Open
Abstract
INTRODUCTION Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) suffer from faster progression of liver fibrosis (LF) and have greater risk of worse clinical outcomes. We evaluated predictors and incidence of these events in a large multicentre cohort. METHODS We selected all HIV-infected patients starting a first-line combination antiretroviral therapy (cART), with detectable HCV-RNA, without exposure to interferon/ribavirin, with ≥2 fibrosis-4 index (FIB-4) classifications before cART. Kaplan-Meier analysis was used to estimate incidence of clinical events (AIDS, non-AIDS related, deaths) and LF progression (via transitions: from FIB-4 class 1 to 2 or 3, from class 2 to class 3, and worsening by 0.5 point). Multivariate Cox regression was used to assess predictors, baseline, or time updated. RESULTS One thousand four hundred thirty-three patients were selected. Overall, 745 clinical events occurred, with an incidence of 7.6% over 9811 person-year of follow-up (PYFU) and a median survival time of 9.36 years. Incidence of LF progression from FIB-4 class 1 to 2 or 3 was 12.4%, and from FIB-4 class 2 to 3 was 7% with a median survival time of 5.67 and 10.35 years, respectively. At multivariate analyses, intravenous drug use and time-updated gamma-glutamyl transferase (γGT) were negative predictors for any outcomes, either clinical or FIB-4 progression. Higher CD4+ T-cell protected from clinical events, and lower HIV-RNA and higher CD4+ T-cell appeared to protect from FIB-4 transitions. Moreover, independently from the viro-immunological status, current FIB-4 class 3 predicted clinical events. Occurrence of AIDS and cardiovascular/kidney events were significant predictors of 0.5 point worsening and transitions of FIB-4, respectively. Prolonged exposure to nucleos(t)ide reverse transcriptase inhibitors (NRTI) was a negative predictor for any outcomes. CONCLUSION Both clinical and LF progression in HIV/HCV-coinfected patients depend strongly on immune status. Intravenous drug users and patients with high γGT (a possible proxy for alcohol abuse) are most-at-risk for both outcomes, as well those who had prolonged exposures to the NRTI class. Therefore, these patients should be prioritized for the access to anti-HCV therapy and a test-and-treat strategy should be implemented for early initiation of cART. Possible benefits of NRTI sparing regimens in HIV/HCV-coinfected patients should be investigated.
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Affiliation(s)
- Emanuele Focà
- University Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Brescia
- Correspondence: Emanuele Focà, University Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili, 1, I-25123 Brescia, Italy (e-mail: )
| | | | - Mattia Prosperi
- Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, FL
| | - Eugenia Quiros Roldan
- University Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Brescia
| | - Francesco Castelli
- University Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Brescia
| | - Franco Maggiolo
- Clinic of Infectious Diseases of “Papa Giovanni XXIII” Hospital, Bergamo
| | - Elisa Di Filippo
- Clinic of Infectious Diseases of “Papa Giovanni XXIII” Hospital, Bergamo
| | | | - Roberta Gagliardini
- Institute of Clinical Infectious Diseases of Catholic University of Sacred Heart, Rome
| | | | - Massimo Di Pietro
- Clinic of Infectious Diseases of “Azienda Ospedaliera SM. Annunziata”, Firenze
| | - Andrea Gori
- Clinic of Infectious Diseases, “San Gerardo de’ Tintori” Hospital, Monza, Italy
| | - Laura Sighinolfi
- Clinic of Infectious Diseases of “Azienda Ospedaliera S. Anna”, Ferrara
| | - Angelo Pan
- Clinic of Infectious Diseases of “Istituti Ospitalieri”, Cremona
| | | | - Carlo Torti
- Infectious Diseases Unit, University “Magna Graecia”, Catanzaro, Italy
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