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Poynard T, Deckmyn O, Pais R, Aron-Wisnewsky J, Peta V, Bedossa P, Charlotte F, Ponnaiah M, Siksik JM, Genser L, Clement K, Leanour G, Valla D. Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Diagnostics (Basel) 2025; 15:1253. [PMID: 40428246 PMCID: PMC12110081 DOI: 10.3390/diagnostics15101253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 04/27/2025] [Accepted: 04/28/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis tests in patients with metabolic liver disease (MASLD). An unmet need is to reduce the uncertainty of biomarkers for the diagnosis of the early stage of clinically significant fibrosis (eF). This can be achieved if three essential but neglected STARD methods (3M) are used, which have a more sensitive histological score than the standard comparator (five-tiers), the weighted area under the characteristic curve (wAUROC) instead of the binary AUROC, and biopsy length. We applied 3M to FibroTest-T2D to demonstrate this reduction of uncertainty and constructed proxies predicting eF in large populations. Methods: For uncertainty, seven subsets were analyzed, four included biopsies (n = 1903), and to assess eF incidence, three MASLD-populations (n = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (n = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. Results: After BS (110 biopsies), reversal of eF was observed in 16/29 patients (84%) using seven-tier scores vs. 3/20 patients (47%) using five-tier scores (p = 0.005). When the biopsy length was above the median, FibroTest-T2D wAUROC was 0.90 (SD = 0.01), and the wAUROC was 0.88 (SD = 0.1) when the length was below the median (p < 0.001). For the first time, obesity was associated with eF before T2D (p < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (p < 0.0001). Conclusions: Validations of circulating biomarkers need to assess their uncertainty. FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance.
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Affiliation(s)
- Thierry Poynard
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- BioPredictive, 75007 Paris, France; (O.D.); (V.P.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
- Institut National de la Santé et de la Recherche Médicale, 75013 Paris, France;
- Nutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France
| | | | - Raluca Pais
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
- Institut National de la Santé et de la Recherche Médicale, 75013 Paris, France;
- Nutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France
| | - Judith Aron-Wisnewsky
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
- Institut National de la Santé et de la Recherche Médicale, 75013 Paris, France;
- Nutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938, 75012 Paris, France
| | | | - Pierre Bedossa
- UMR1149 (CRI), Inserm, Université Paris Cité, 75018 Paris, France; (P.B.)
- Liverpat, 75116 Paris, France
| | - Frederic Charlotte
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
| | - Maharajah Ponnaiah
- Institut National de la Santé et de la Recherche Médicale, 75013 Paris, France;
| | - Jean-Michel Siksik
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
| | - Laurent Genser
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
- Nutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France
| | - Karine Clement
- Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, France; (R.P.); (J.A.-W.); (F.C.); (L.G.); (K.C.)
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France;
- Nutrition Department, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France
| | - Gilles Leanour
- CNRS UMR8507, Laboratoire Génie Électrique et Électronique de Paris (GeePs), Sorbonne Université, 75252 Paris, France;
| | - Dominique Valla
- UMR1149 (CRI), Inserm, Université Paris Cité, 75018 Paris, France; (P.B.)
- Service d’Hépatologie, AP-HP, Hôpital Beaujon, 92110 Clichy-la-Garenne, France
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Pérez Compte D, Etourneau L, Hesse AM, Kraut A, Barthelon J, Sturm N, Borges H, Biennier S, Courçon M, de Saint Loup M, Mignot V, Costentin C, Burger T, Couté Y, Bruley C, Decaens T, Jaquinod M, Boursier J, Brun V. Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients. Biomark Res 2024; 12:44. [PMID: 38679739 PMCID: PMC11057169 DOI: 10.1186/s40364-024-00583-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world's population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy - an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages. METHODS A discovery study was performed on 158 plasma samples from histologically-characterised MASLD patients using mass spectrometry (MS)-based quantitative proteomics. Differentially abundant proteins were selected for verification by ELISA in the same cohort. They were subsequently validated in an independent MASLD cohort (n = 200). RESULTS From the 72 proteins differentially abundant between patients with early (F0-2) and advanced fibrosis (F3-4), we selected Insulin-like growth factor-binding protein complex acid labile subunit (ALS) and Galectin-3-binding protein (Gal-3BP) for further study. In our validation cohort, AUROCs with 95% CIs of 0.744 [0.673 - 0.816] and 0.735 [0.661 - 0.81] were obtained for ALS and Gal-3BP, respectively. Combining ALS and Gal-3BP improved the assessment of advanced liver fibrosis, giving an AUROC of 0.796 [0.731. 0.862]. The {ALS; Gal-3BP} model surpassed classic fibrosis panels in predicting advanced liver fibrosis. CONCLUSIONS Further investigations with complementary cohorts will be needed to confirm the usefulness of ALS and Gal-3BP individually and in combination with other biomarkers for diagnosis of liver fibrosis. With the availability of ELISA assays, these findings could be rapidly clinically translated, providing direct benefits for patients.
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Affiliation(s)
- David Pérez Compte
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Lucas Etourneau
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Anne-Marie Hesse
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Alexandra Kraut
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Justine Barthelon
- Université Grenoble Alpes, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble Alpes, 38000, Grenoble, France
| | - Nathalie Sturm
- Université Grenoble Alpes, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble Alpes, 38000, Grenoble, France
| | - Hélène Borges
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Salomé Biennier
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Marie Courçon
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Marc de Saint Loup
- Hepato-Gastroenterology Department, University Hospital, Angers, France
- HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France
| | - Victoria Mignot
- Université Grenoble Alpes, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble Alpes, 38000, Grenoble, France
- Univ. Grenoble Alpes, Institute for Advanced Biosciences-INSERM U1209/ CNRS UMR 5309, Grenoble, France
| | - Charlotte Costentin
- Université Grenoble Alpes, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble Alpes, 38000, Grenoble, France
- Univ. Grenoble Alpes, Institute for Advanced Biosciences-INSERM U1209/ CNRS UMR 5309, Grenoble, France
| | - Thomas Burger
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Yohann Couté
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Christophe Bruley
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France
| | - Thomas Decaens
- Université Grenoble Alpes, Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble Alpes, 38000, Grenoble, France
- Univ. Grenoble Alpes, Institute for Advanced Biosciences-INSERM U1209/ CNRS UMR 5309, Grenoble, France
| | - Michel Jaquinod
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France.
| | - Jérôme Boursier
- Hepato-Gastroenterology Department, University Hospital, Angers, France
- HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France
| | - Virginie Brun
- Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, FR2048 ProFI, EDyP team, 17 Avenue des Martyrs, 38000, Grenoble, France.
- Univ. Grenoble Alpes, CEA, Leti, 38000, Grenoble, France.
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Vinnitskaya EV, Sandler YG, Saliev KG, Ivanov AN, Sbikina ES, Khaymenova TY, Bordin DS. Efficacy of human placenta hydrolyzate in the treatment of patients with metabolic associated fatty liver disease at the stage of fibrosis (pilot study). TERAPEVT ARKH 2024; 96:107-116. [DOI: 10.26442/00403660.2024.02.202582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Background. Despite active research, drug treatment options for metabolic associated fatty liver disease (MAFLD) are limited, and there are no currently approved drugs for patients with MAFLD. Treatment of patients at risk of developing non-alcoholic steatohepatitis and progressive liver fibrosis (LF) is of particular relevance, since they determine the clinical outcomes of the disease.
Aim. To evaluate the clinical efficacy of complex polypeptide drug (CPD), human placenta hydrolyzate, containing low molecular weight regulatory peptides, amino acids, vitamins, macro- and microelements in patients with MAFLD at the LF stage.
Materials and methods. A single-center, placebo-controlled pilot study. Patients with MAFLD at LF stage 1≤F≤3 according to METAVIR were included (n=10, of which 8 were women, median age was 55 years old). Patients were randomized into 2 groups: 5 people received CPD therapy for 12 weeks (intravenous infusion of 6 ml 2 times a week); another 5 people initially received placebo x 2 times a week (12 weeks), with transfer to the open phase for CPD therapy in the same regimen. The dynamics laboratory and instrumental data was assessed, as well as determine the presence of fibrosis by non-invasive tests – measurement of liver stiffness by transient elastography and use of serum biomarker (SM) by FibroTest and detection of steatosis with controlled attenuation parameter for transient elastography and SM by SteatoTest. The quality of life of patients was assessed using questionnaire SF-36 and well-being via Visual Analogue Scale. Statistical processing of the material was carried out using the methods of nonparametric analysis, using the Statistica 13.3 software.
Results. Patients in the CPD group compared with the baseline data and with the placebo group showed a statistically significant improvement: 1) transaminases (ALT, AST), lipid profile indicators (cholesterol), ferritin; 2) indicators of LF, based on a decrease in liver stiffness by transient elastography and SM of Fibrotest, as well as the degree of steatosis based on controlled attenuation parameter and SM of Steatotest; 3) in well-being and quality of life (according to testing: SF-36 physical, mental well-being and general condition of the VAS). CPD was well tolerated, no side effects were noted.
Conclusion. In patients with MAFLD during CPD therapy, a decrease in the level of liver enzymes was noted, as well as in LF and liver steatosis according to noninvasive methods. Randomized controlled trials are required to confirm these findings.
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Affiliation(s)
| | | | | | | | | | | | - Dmitry S. Bordin
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
- Tver State Medical University
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López Tórrez SM, Ayala CO, Ruggiro PB, Costa CAD, Wagner MB, Padoin AV, Mattiello R. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants. Front Nutr 2024; 11:1284509. [PMID: 38419854 PMCID: PMC10899345 DOI: 10.3389/fnut.2024.1284509] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established. Objective The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD. Methods Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Results In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87. Conclusion The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].
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Affiliation(s)
- Sergio M. López Tórrez
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Camila O. Ayala
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Paula Bayer Ruggiro
- School of Medicine, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Caroline Abud Drumond Costa
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Mario B. Wagner
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Alexandre Vontobel Padoin
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rita Mattiello
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- School of Medicine, Postgraduate Program in Epidemiology, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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6
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Bischoff SC, Barazzoni R, Busetto L, Campmans‐Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon‐Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J 2022; 10:663-720. [PMID: 35959597 PMCID: PMC9486502 DOI: 10.1002/ueg2.12280] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational SciencesUniversity of TriesteTriesteItaly
| | - Luca Busetto
- Department of MedicineUniversity of PadovaPadovaItaly
| | - Marjo Campmans‐Kuijpers
- Department of Gastroenterology and HepatologyUniversity Medical Centre GroningenGroningenThe Netherlands
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly
| | - Irit Chermesh
- Department of GastroenterologyRambam Health Care CampusAffiliated with Technion‐Israel Institute of TechnologyHaifaIsrael
| | - Ahad Eshraghian
- Department of Gastroenterology and HepatologyAvicenna HospitalShirazIran
| | - Haluk Tarik Kani
- Department of GastroenterologyMarmara UniversitySchool of MedicineIstanbulTurkey
| | - Wafaa Khannoussi
- Hepato‐Gastroenterology DepartmentMohammed VI University HospitalOujdaMorocco
- Laboratoire de Recherche des Maladies Digestives (LARMAD)Mohammed the First UniversityOujdaMorocco
| | - Laurence Lacaze
- Department of NutritionRennes HospitalRennesFrance
- Department of general surgeryMantes‐la‐Jolie HospitalFrance
- Department of clinical nutritionPaul Brousse‐Hospital, VillejuifFrance
| | - Miguel Léon‐Sanz
- Department of Endocrinology and NutritionUniversity Hospital Doce de OctubreMedical SchoolUniversity ComplutenseMadridSpain
| | - Juan M. Mendive
- La Mina Primary Care Academic Health Centre. Catalan Institute of Health (ICS)University of BarcelonaBarcelonaSpain
| | - Michael W. Müller
- Department of General and Visceral SurgeryRegionale Kliniken HoldingKliniken Ludwigsburg‐Bietigheim gGmbHBietigheim‐BissingenGermany
| | - Johann Ockenga
- Medizinische Klinik IIKlinikum Bremen‐MitteBremenGermany
| | - Frank Tacke
- Department of Hepatology & GastroenterologyCharité Universitätsmedizin BerlinCampus Virchow‐Klinikum and Campus Charité MitteBerlinGermany
| | - Anders Thorell
- Department of Clinical ScienceDanderyds HospitalKarolinska InstitutetStockholmSweden
- Department of SurgeryErsta HospitalStockholmSweden
| | - Darija Vranesic Bender
- Department of Internal MedicineUnit of Clinical NutritionUniversity Hospital Centre ZagrebZagrebCroatia
| | - Arved Weimann
- Department of General, Visceral and Oncological SurgerySt. George HospitalLeipzigGermany
| | - Cristina Cuerda
- Departamento de MedicinaUniversidad Complutense de MadridNutrition UnitHospital General Universitario Gregorio MarañónMadridSpain
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7
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Theel W, Boxma-de Klerk BM, Dirksmeier-Harinck F, van Rossum EFC, Kanhai DA, Apers J, van Dalen BM, de Knegt RJ, Holleboom AG, Tushuizen ME, Grobbee DE, Wiebolt J, Castro Cabezas M. Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques. Obes Rev 2022; 23:e13481. [PMID: 35692179 DOI: 10.1111/obr.13481] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 12/15/2022]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity.
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Affiliation(s)
- Willy Theel
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Obesity Center CGG, Rotterdam, The Netherlands
| | - Bianca M Boxma-de Klerk
- Department of Statistics and Education, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Femme Dirksmeier-Harinck
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Elisabeth F C van Rossum
- Obesity Center CGG, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Danny A Kanhai
- Department of Pediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Jan Apers
- Department of Bariatric Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Bas M van Dalen
- Department of Cardiology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Maarten E Tushuizen
- Department of Gastroenterology and Hepatology, Leiden UMC, Leiden, The Netherlands
| | - Diederick E Grobbee
- Julius Centre for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.,Julius Clinical, Zeist, The Netherlands
| | - Janneke Wiebolt
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Obesity Center CGG, Rotterdam, The Netherlands
| | - Manuel Castro Cabezas
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.,Julius Clinical, Zeist, The Netherlands
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8
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Liver Disease Assessment in Children with Fontan and Glenn Surgeries for Univentricular Hearts—The Role of Elastography and Biochemical Fibrosis Markers. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12157481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Children born with single-ventricle hearts require surgery in order to survive. Liver fibrosis is a known complication of Fontan surgery for univentricular hearts. Methods: In this study on 13 post-Fontan and 21 post-Glenn patients, we used elastography (shearwave and transient elastography) as well as serum biochemical fibrosis markers to evaluate the degree of liver fibrosis in comparison to 32 controls. Results: The mean Emedian and Vmedian values determined by shear wave elastography in the Fontan Group were significantly higher than the controls (4.85 kPa vs. 3.91 kPa and 1.25 m/s vs. 1.12 m/s, respectively). Fontan patients had significantly increased Fibrotest, Actitest, AST-to-Platelet Ratio index, ALT and GammaGT levels compared to controls. For post-Glenn patients, the mean Emedian and Vmedian values were similar to healthy controls, whereas the Fibrotest, Actitest and AST-to-Platelet Ratio index were significantly increased. Using transient elastography, we found significantly higher values for Emedian and Vmedian in Fontan patients compared to Glenn patients. Conclusions: Elastography and biochemical fibrosis markers are valuable non-invasive tools for screening and monitoring liver fibrosis in patients with Fontan and Glenn interventions.
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9
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Ismaiel A, Spinu M, Leucuta DC, Popa SL, Chis BA, Fadgyas Stanculete M, Olinic DM, Dumitrascu DL. Anxiety and Depression in Metabolic-Dysfunction-Associated Fatty Liver Disease and Cardiovascular Risk. J Clin Med 2022; 11:2488. [PMID: 35566616 PMCID: PMC9102968 DOI: 10.3390/jcm11092488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/21/2022] [Accepted: 04/24/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: The relationship between anxiety and depression in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular (CV) risk remains uncertain. Therefore, we aimed to assess whether anxiety and depression are associated with increased CV risk in MAFLD. (2) Methods: We conducted a cross-sectional observational study involving 77 subjects (39 MAFLD patients, 38 controls), between January and September 2020. Hepatic steatosis was assessed using a combination of hepatic ultrasonography and SteatoTestTM. CV parameters were evaluated using echocardiography and Doppler ultrasound. Self-reported questionnaires pertaining to symptoms of anxiety and depression were used. Anxiety was evaluated using Lehrer Woolfolk Anxiety Symptom Questionnaire (LWASQ), further divided into somatic, behavioral, and cognitive factors, as well as a global score, and depression using Beck Depression Inventory (BDI). (3) Results: MAFLD patients presented significantly higher BDI scores (p-value 0.009) and LWASQ global scores (p-value 0.045) than controls. LWASQ somatic factor was significantly associated with global longitudinal strain (GLS) in linear analysis (-0.0404, p-value = 0.002), while it lost significance following multivariate analysis (-0.0166, p-value = 0.124). Although group (MAFLD vs. controls) predicted BDI, LWASQ global score, and LWASQ somatic factor in linear regression, they lost significance in multivariate analysis. Moreover, the relationship between interventricular septal wall thickness (IVSWT) and BDI, LWASQ global score, and LWASQ somatic factor was significant in linear analysis, but statistical significance disappeared after multivariate analysis. (4) Conclusions: Although MAFLD patients presented increased anxiety and depression risk in univariate analysis, this association lost significance in multivariate analysis. A significant association between GLS levels and LWASQ somatic factor, in addition to IVSWT in anxiety and depression in univariate analysis, was observed, but was lost after multivariate analysis.
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Affiliation(s)
- Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (S.-L.P.); (B.A.C.); (D.L.D.)
| | - Mihail Spinu
- Medical Clinic No. 1, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (M.S.); (D.M.O.)
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (S.-L.P.); (B.A.C.); (D.L.D.)
| | - Bogdan Augustin Chis
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (S.-L.P.); (B.A.C.); (D.L.D.)
| | - Mihaela Fadgyas Stanculete
- Department of Neurosciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Institute of Advanced Studies in Science and Technology, Babes-Bolyai University, 400084 Cluj-Napoca, Romania
| | - Dan Mircea Olinic
- Medical Clinic No. 1, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (M.S.); (D.M.O.)
- Interventional Cardiology Department, Emergency Clinical Hospital, 400006 Cluj-Napoca, Romania
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (S.-L.P.); (B.A.C.); (D.L.D.)
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10
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Segura-Azuara NDLÁ, Varela-Chinchilla CD, Trinidad-Calderón PA. MAFLD/NAFLD Biopsy-Free Scoring Systems for Hepatic Steatosis, NASH, and Fibrosis Diagnosis. Front Med (Lausanne) 2022; 8:774079. [PMID: 35096868 PMCID: PMC8792949 DOI: 10.3389/fmed.2021.774079] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/10/2021] [Indexed: 12/12/2022] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is the most prevalent liver disorder worldwide. Historically, its diagnosis required biopsy, even though the procedure has a variable degree of error. Therefore, new non-invasive strategies are needed. Consequently, this article presents a thorough review of biopsy-free scoring systems proposed for the diagnosis of MAFLD. Similarly, it compares the severity of the disease, ranging from hepatic steatosis (HS) and nonalcoholic steatohepatitis (NASH) to fibrosis, by contrasting the corresponding serum markers, clinical associations, and performance metrics of these biopsy-free scoring systems. In this regard, defining MAFLD in conjunction with non-invasive tests can accurately identify patients with fatty liver at risk of fibrosis and its complications. Nonetheless, several biopsy-free scoring systems have been assessed only in certain cohorts; thus, further validation studies in different populations are required, with adjustment for variables, such as body mass index (BMI), clinical settings, concomitant diseases, and ethnic backgrounds. Hence, comprehensive studies on the effects of age, morbid obesity, and prevalence of MAFLD and advanced fibrosis in the target population are required. Nevertheless, the current clinical practice is urged to incorporate biopsy-free scoring systems that demonstrate adequate performance metrics for the accurate detection of patients with MAFLD and underlying conditions or those with contraindications of biopsy.
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11
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Garteiser P, Castera L, Coupaye M, Doblas S, Calabrese D, Dioguardi Burgio M, Ledoux S, Bedossa P, Esposito-Farèse M, Msika S, Van Beers BE, Jouët P. Prospective comparison of transient elastography, MRI and serum scores for grading steatosis and detecting non-alcoholic steatohepatitis in bariatric surgery candidates. JHEP Rep 2021; 3:100381. [PMID: 34786549 PMCID: PMC8578045 DOI: 10.1016/j.jhepr.2021.100381] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 08/27/2021] [Accepted: 09/17/2021] [Indexed: 12/15/2022] Open
Abstract
Background & Aims Tools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates. Methods Of 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated. Results The applicability of MRI was better than that of FibroScan (98% vs. 79%; p <0.0001). CAP had AUROCs of 0.83, 0.79, 0.73 and 0.69 for S>5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p <0.0003 and S>66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in "intention to diagnose" analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%). Conclusion MRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery. Lay summary Non-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery.
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Key Words
- AUROC, area under the receiver operating characteristic curve
- CAP
- CAP, controlled attenuation parameter
- FLI, fatty liver index
- FLIP, fatty liver inhibition of progression
- HSI, hepatic steatosis index
- LSM, liver stiffness measurement
- MRI-PDFF
- MRI-PDFF, MRI-proton density fat fraction
- NAFLD
- NAFLD, non-alcoholic fatty liver disease
- NAS, NAFLD activity score
- NASH
- NASH, non-alcoholic steatohepatitis
- NPV, negative predictive value
- Non-invasive diagnosis
- PPV, positive predictive value
- ST, SteatoTest
- Se, sensitivity
- Sp, specificity
- TE, transient elastography
- bariatric surgery
- steatosis
- transient elastography
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Affiliation(s)
- Philippe Garteiser
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France
| | - Laurent Castera
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, F-92110 Clichy, France
| | - Muriel Coupaye
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service des Explorations Fonctionnelles, Centre Intégré Nord Francilien de l'Obésité (CINFO), Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, F-92700 Colombes, France
| | - Sabrina Doblas
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France
| | - Daniela Calabrese
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service de chirurgie digestive, Centre Intégré Nord Francilien de l'Obésité (CINFO), Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, F-75018 Paris, France
| | - Marco Dioguardi Burgio
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service de Radiologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, F-92110 Clichy, France
| | - Séverine Ledoux
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service des Explorations Fonctionnelles, Centre Intégré Nord Francilien de l'Obésité (CINFO), Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, F-92700 Colombes, France
| | - Pierre Bedossa
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service de Pathologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, F-92110 Clichy, France
| | - Marina Esposito-Farèse
- Unité de Recherche Clinique, Hôpital Bichat, AP-HP.Nord - Université de Paris, Assistance Publique-Hôpitaux de Paris, Paris, F-75018, France.,INSERM CIC-EC 1425, Centre d'Investigation Clinique, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, F-75018, France
| | - Simon Msika
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service de chirurgie digestive, Centre Intégré Nord Francilien de l'Obésité (CINFO), Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, F-75018 Paris, France
| | - Bernard E Van Beers
- Centre de recherche sur l'Inflammation, Inserm U1149, Université de Paris, F-75018 Paris, France.,Service de Radiologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, F-92110 Clichy, France
| | - Pauline Jouët
- Service de Gastroentérologie, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, F-93000 Bobigny, France
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12
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Ismaiel A, Spinu M, Budisan L, Leucuta DC, Popa SL, Chis BA, Berindan-Neagoe I, Olinic DM, Dumitrascu DL. Relationship between Adipokines and Cardiovascular Ultrasound Parameters in Metabolic-Dysfunction-Associated Fatty Liver Disease. J Clin Med 2021; 10:5194. [PMID: 34768714 PMCID: PMC8584895 DOI: 10.3390/jcm10215194] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/02/2021] [Accepted: 11/05/2021] [Indexed: 12/12/2022] Open
Abstract
(1) Background: The role of adipokines such as adiponectin and visfatin in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease remains unclear. Therefore, we aim to assess serum adiponectin and visfatin levels in MAFLD patients and associated cardiovascular parameters. (2) Methods: A cross-sectional study involving 80 participants (40 MAFLD patients, 40 controls), recruited between January and September 2020, was conducted, using both hepatic ultrasonography and SteatoTestTM to evaluate hepatic steatosis. Echocardiographic and Doppler parameters were assessed. Serum adipokines were measured using ELISA kits. (3) Results: Adiponectin and visfatin levels were not significantly different in MAFLD vs. controls. Visfatin was associated with mean carotid intima-media thickness (p-value = 0.047), while adiponectin was associated with left ventricular ejection fraction (LVEF) (p-value = 0.039) and E/A ratio (p-value = 0.002) in controls. The association between adiponectin and E/A ratio was significant in the univariate analysis at 95% CI (0.0049-0.1331, p-value = 0.035), but lost significance after the multivariate analysis. Although LVEF was not associated with adiponectin in the univariate analysis, significant values were observed after the multivariate analysis (95% CI (-1.83--0.22, p-value = 0.015)). (4) Conclusions: No significant difference in serum adiponectin and visfatin levels in MAFLD patients vs. controls was found. Interestingly, although adiponectin levels were not associated with LVEF in the univariate analysis, a significant inversely proportional association was observed after the multivariate analysis.
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Affiliation(s)
- Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (B.A.C.); (D.L.D.)
| | - Mihail Spinu
- Medical Clinic No. 1, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (M.S.); (D.M.O.)
| | - Livia Budisan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (L.B.); (I.B.-N.)
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (B.A.C.); (D.L.D.)
| | - Bogdan Augustin Chis
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (B.A.C.); (D.L.D.)
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (L.B.); (I.B.-N.)
- Research Center for Advanced Medicine-Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
- Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania
| | - Dan Mircea Olinic
- Medical Clinic No. 1, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (M.S.); (D.M.O.)
- Interventional Cardiology Department, Emergency Clinical Hospital, 400006 Cluj-Napoca, Romania
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.I.); (B.A.C.); (D.L.D.)
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13
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Chang E, Chang JS, Kong ID, Baik SK, Kim MY, Park KS. Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease. Gut Liver 2021; 16:171-189. [PMID: 34420934 PMCID: PMC8924798 DOI: 10.5009/gnl210106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 11/22/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD.
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Affiliation(s)
- Eunha Chang
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jae Seung Chang
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - In Deok Kong
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Kyu-Sang Park
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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Codjia T, Rebibo L, François A, Lagnel C, Huet E, Bekri S, Pattou F, Régimbeau JM, Schwarz L. Evolution of Non-alcoholic Fatty Liver Disease (NAFLD) Biomarkers in Response to Weight Loss 1 Year After Bariatric Surgery-a Post Hoc Analysis of the FibroTest Prospective Study. Obes Surg 2021; 31:3548-3556. [PMID: 33844174 DOI: 10.1007/s11695-021-05402-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 03/27/2021] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Bariatric surgery is among the therapeutic options for non-alcoholic fatty liver disease (NAFLD), affecting 90% of patients with obesity. The aim of this study was to evaluate the evolution of NAFLD lesions 1 year after surgery using noninvasive markers. METHODS From November 2011 to November 2012, 253 patients with obesity undergoing bariatric surgery in three French University Hospitals were included. Histological data regarding intraoperative liver biopsy were collected at baseline, clinical, and biological data, including FibroTest®, SteatoTest®, and NASHTest®, before and after surgery. RESULTS Fibrosis' prevalence was 74.2% with a positive predictive value (PPV) for FibroTest® of 78.6% and 43.4% for significant fibrosis (Kleiner ≥ F2) with a negative predictive value (NPV) of 56.1%. NAFLD's prevalence was 84% with a PPV for SteatoTest® of 85.9% and 7.7% for NASH with an NPV for NASHTest® of 93.8%. One year after bariatric surgery, mean BMI had significantly decreased from 46.5 to 31.7 kg/m2 (p < 0.001). Fibrosis assessed by the FibroTest® showed that 82.5% of patients were F0 after surgery compared to 90.9% before. Using SteatoTest®, the percent of patient without steatosis (S0) increased from 1.6 to 49.6% after surgery, and rate of severe steatosis (S3) improved from 43.3 to 3.9%. NASHTest® revealed that the percent of patients without NASH increased from 12.8 to 73.6% and rates of NASH improved from 12 to 0.8%. CONCLUSIONS Validated noninvasive biomarkers SteatoTest® and NASHTest® suggested NAFLD and steatohepatitis improvement after bariatric surgery and might be useful tools for patient follow-up. Regarding fibrosis, FibroTest® was not accurate in patients with extreme obesity.
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Affiliation(s)
- Tatiana Codjia
- Department of Digestive Surgery, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France.
| | - Lionel Rebibo
- Department of Digestive Surgery, Amiens University Hospital, 1 Rond-point du Professeur Christian Cabrol, 80000, Amiens, France
| | - Arnaud François
- Department of Anatomo-pathology, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France
| | - Carole Lagnel
- Department of Biochemistry, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France
| | - Emmanuel Huet
- Department of Digestive Surgery, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France
| | - Soumeya Bekri
- Department of Biochemistry, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France
| | - François Pattou
- Department of Digestive Surgery, Lille University Hospital, Rue Michel Polonovski, 59037, Lille, France
| | - Jean-Marc Régimbeau
- Department of Digestive Surgery, Amiens University Hospital, 1 Rond-point du Professeur Christian Cabrol, 80000, Amiens, France
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France
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Rosso N, Stephenson AM, Giraudi PJ, Tiribelli C. Diagnostic management of nonalcoholic fatty liver disease: a transformational period in the development of diagnostic and predictive tools-a narrative review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:727. [PMID: 33987425 PMCID: PMC8106012 DOI: 10.21037/atm-20-4723] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
NAFLD is an emerging healthcare epidemic that is causing predictable adverse consequences for healthcare systems, societies and individuals. Whilst NAFLD is recognized as a multi-system disease with compound pathways that are both benign and pernicious in their unfolding; NASH is generally understood as a deleterious follow-on condition with path-specific tendencies that progress to cirrhosis, HCC and liver transplantation. Recent evidence is beginning to challenge this interpretation demanding more attention to the personalized nature of the disease and its pathogenesis across multiple different cohorts. This means that we need better diagnostic and prognostic tools not only to capture those 'at risk' disease phenotypes; but for better stratification and monitoring of patients according to their treatment strategies. With the advent of pipeline therapies for NASH underway, the medical profession looks to adopt more accurate non-invasive diagnostic tools that can help to delineate and eliminate NASH histology. This review looks at the search for the killer application revealing this particular moment in time as a transformational period; one that is pushing the boundaries of technology to integrate diverse panels of species through sensitive profiling and multi-omics approaches that cast wide, yet powerful diagnostic nets that have the potential to elucidate pathway specific biomarkers that are personalized and predictable.
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Affiliation(s)
- Natalia Rosso
- Fondazione Italiana Fegato, ONLUS Area Science Park Basovizza, Trieste, Italy
| | - Adam M Stephenson
- Helena Biosciences, Queensway South, Team Valley Trading Estate, Gateshead, UK
| | - Pablo J Giraudi
- Fondazione Italiana Fegato, ONLUS Area Science Park Basovizza, Trieste, Italy
| | - Claudio Tiribelli
- Fondazione Italiana Fegato, ONLUS Area Science Park Basovizza, Trieste, Italy
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16
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Netanel C, Goitein D, Rubin M, Kleinbaum Y, Katsherginsky S, Hermon H, Tsaraf K, Tachlytski I, Herman A, Safran M, Ben-Ari Z. The impact of bariatric surgery on nonalcoholic fatty liver disease as measured using non-invasive tests. Am J Surg 2020; 222:214-219. [PMID: 33309037 DOI: 10.1016/j.amjsurg.2020.11.045] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 08/28/2020] [Accepted: 11/22/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common in bariatric surgery candidates. We evaluated the effect of sleeve gastrectomy (SG) on NAFLD using validated non-invasive measures. METHODS Patients with morbid obesity and NAFLD, planned for SG, were evaluated before and after surgery. Data collected included anthropometrics, biochemistry, adiponectin, SteatoTest™, NashTest™, FibroTest™, OWLiver® test and real-time ShearWave™ elastography (SWE). RESULTS Twenty-six subjects were included in the study, mean age 44.1 ± 4.8 years, 69.2% males. One year following SG, body mass index decreased significantly from 41.7 ± 4.8 kg/m2 to 29.6 ± 4.5 kg/m2. Concomitantly, significant improvements in triglycerides, ALT, diabetes markers and adiponectin were observed. Mean steatosis, as measured by SteatoTest™, was significantly improved. Steatohepatitis score measured by NashTest™ and OWLiver® significantly decreased. Mean fibrosis, as measured by SWE liver stiffness and FibroTest™, did not change over time. CONCLUSION Steatosis and steatohepatitis are significantly improved by SG as measured by non-invasive measures.
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Affiliation(s)
- Carmit Netanel
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel.
| | - David Goitein
- Department of Surgery C, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Moshe Rubin
- Department of Surgery C, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Yeruham Kleinbaum
- Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel.
| | - Sima Katsherginsky
- Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel.
| | - Hila Hermon
- Department of Surgery C, Sheba Medical Center, Tel Hashomer, Israel.
| | - Keren Tsaraf
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel.
| | - Irina Tachlytski
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel.
| | - Amir Herman
- Department of Orthopaedic Surgery, Assuta Ashdod Medical Center, Ashdod, Israel; Goldman School of Medicine, Ben-Gurion University of the Negev, Beer Sheva, Israel.
| | - Michal Safran
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel.
| | - Ziv Ben-Ari
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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17
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Hernandez Roman J, Siddiqui MS. The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease. Endocrinol Diabetes Metab 2020; 3:e00127. [PMID: 33102796 PMCID: PMC7576290 DOI: 10.1002/edm2.127] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 02/28/2020] [Accepted: 02/29/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronically elevated liver enzymes. Diagnosis and risk stratification of NAFLD remains clinically challenge as patients with NAFLD are either asymptomatic or have nonspecific presenting complaints and may have normal liver enzymes. Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of NAFLD, is also difficult to differentiate noninvasively, and a liver biopsy is required to definitively diagnose NASH. Thus, the definitive diagnosis and risk stratification of NAFLD is embedded in histological assessment of the liver. Several clinical aides been investigated in an attempt to risk stratify and identify patients noninvasively as doing a liver biopsy in all patients with NAFLD are not feasible. Since these biomarkers are unable to differentiate NASH from non-NASH, they have leveraged biochemical changes within the liver as patients progress to varying degree of hepatic fibrosis to identify patients with moderate fibrosis (fibrosis stage 2 or greater) and advanced fibrosis (fibrosis stage 3 or greater) to help guide the need for additional and more definitive workup. These clinical aides span from by-products of apoptosis to statistical modelling of clinically available data to identify 'at-risk' patients with NAFLD. The current review will focus the diagnostic performance of these noninvasive serum-based biomarkers in NAFLD.
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Affiliation(s)
| | - Mohammad S. Siddiqui
- Division of Gastroenterology, Hepatology and NutritionDepartment of Internal MedicineVirginia Commonwealth University (VCU)RichmondVirginia
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Performance of liver biomarkers, in patients at risk of nonalcoholic steato-hepatitis, according to presence of type-2 diabetes. Eur J Gastroenterol Hepatol 2020; 32:998-1007. [PMID: 31789950 PMCID: PMC7337110 DOI: 10.1097/meg.0000000000001606] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE There is a controversy about the performance of blood tests for the diagnostic of metabolic liver disease in patients with type-2-diabetes in comparison with patients without type-2-diabetes. These indirect comparisons assumed that the gold-standard is binary, whereas fibrosis stages, steatosis and nonalcoholic-steato-hepatitis (NASH) grades use an ordinal scale. The primary aim was to compare the diagnostic performances of FibroTest in type-2-diabetes vs. controls matched on gender, age, fibrosis stages and obesity, and taking into account the spectrum effect by Obuchowski measure. METHODS Data were retrospectively compared among patients prospectively included, with simultaneous biopsy and blindly assessed FibroTest, SteatoTest-2 and NashTest-2. The secondary aim was to construct an index (SpectrumF3F4-Index) to predict an adjusted-area under the receiver operating curve (AUROC) for F3F4 diagnosis from the prevalences of fibrosis stages, permitting to reduce the spectrum effect when performances of FibroTest, transient elastography and magnetic resonance elastography are indirectly compared. RESULTS In 505 patients at risk of NASH, the Obuchowski measures [95% confidence interval (CI)] of FibroTest, SteatoTest-2 and NashTest-2 were all equivalent in 136 type-2-diabetes cases vs. 369 matched controls: 0.871 (0.837-0.905), vs. 0.880 (0.879-0.881), 0.835 (0.797-0.873) vs. 0.806 (0.780-0.832) and 0.829 (0.793-0.865) vs. 0.855 (0.829-0.869), respectively. Standard-AUROCs (95% CI) were 0.932 (0.898-0.965), 0.872 (0.837-0.907) and 0.834 (0.699-0.969) and reduced after adjustment by SpectrumF3F4-Index to 0.794 (0.749-0.838), 0.767 (0.750-0.783) and 0.773 (0.725-0.822) for transient, magnetic resonance elastography and FibroTest, respectively. CONCLUSIONS When compared by Obuchowski measures, the performances of tests were not different in patients with T2-diabetes vs. patients without T2-diabetes. When individual data are not available, adjusted-AUROCs reduced the spectrum effect.
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Jamialahmadi T, Nematy M, Jangjoo A, Goshayeshi L, Rezvani R, Ghaffarzadegan K, Nooghabi MJ, Shalchian P, Zangui M, Javid Z, Doaei S, Rajabzadeh F. Measurement of Liver Stiffness with 2D-Shear Wave Elastography (2D-SWE) in Bariatric Surgery Candidates Reveals Acceptable Diagnostic Yield Compared to Liver Biopsy. Obes Surg 2020; 29:2585-2592. [PMID: 31077025 DOI: 10.1007/s11695-019-03889-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common among severely obese patients. Two-dimensional shear wave elastography (2D-SWE) has been validated as a noninvasive diagnostic tool for liver stiffness measurement. However, the technical feasibility and accuracy of this method in severely obese patients are still under debate. OBJECTIVE We aimed to assess the diagnostic accuracy of 2D-SWE in bariatric surgery candidates in comparison with the gold standard liver biopsy. METHODS Ninety severely obese candidates for bariatric surgery were included. Liver stiffness was measured using 2D-SWE 14 days before liver biopsy. Liver biopsy was taken on the day of surgery. The area under the receiver operating curve (AUROC) was calculated for the staging of liver fibrosis. RESULTS 2D-SWE was performed in 97.3% of patients successfully. Histologic stages of fibrosis (F0-F4) were detected in 34.2%, 36%, 6.3%, 3.6%, and 0.9% of patients, respectively. The AUROC for 2D-SWE was 0.77 for F1, 0.72 for F2, 0.77 for F3, and 0.70 for F4. In univariate analysis, 2D-SWE values were correlated with BMI, waist circumference, NAFLD activity score (NAS), and steatosis, whereas these components did not affect liver stiffness in multivariate analysis. CONCLUSION Two-dimensional shear wave elastography of the liver can be feasible and has good accuracy in severely obese candidates for bariatric surgery. Therefore, 2D-SWE may be a good option for assessing liver fibrosis, especially in the early stages of fibrosis to lessen complications of surgery in this population. However, this method should be applied on a larger scale for late stage of fibrosis.
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Affiliation(s)
- Tannaz Jamialahmadi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Mohsen Nematy
- Biochemistry and Nutrition Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Ali Jangjoo
- Surgical Oncology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Ladan Goshayeshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Reza Rezvani
- Biochemistry and Nutrition Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Kamran Ghaffarzadegan
- Pathology Department, Education and Research Department, Razavi Hospital, Mashhad, 9177948564, Iran
| | - Mehdi Jabbari Nooghabi
- Department of Statistics, Faculty of Mathematical Sciences, Ferdowsi University of Mashhad, Mashhad, 9177948944, Iran
| | - Payman Shalchian
- Hazrat Zahra Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahtab Zangui
- Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Zeinab Javid
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran
| | - Saeid Doaei
- Research Center of Health and Environment, Guilan University of Medical Sciences, Rasht, 1313973476, Iran
| | - Farnood Rajabzadeh
- Department of Radiology, Faculty of Medicine, Islamic Azad University-Mashhad Branch, Mashhad, 9137714639, Iran.
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20
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Performance of Noninvasive Liver Fibrosis Scores in the Morbid Obese Patient, Same Scores but Different Thresholds. Obes Surg 2020; 30:2538-2546. [DOI: 10.1007/s11695-020-04509-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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21
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de Carli MA, de Carli LA, Correa MB, Junqueira G, Tovo CV, Coral GP. Performance of noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2020; 32:420-425. [PMID: 31464779 DOI: 10.1097/meg.0000000000001519] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Liver fibrosis is one of the most important predictors of mortality related to nonalcoholic fatty liver disease (NAFLD). The use of noninvasive markers has the advantage of a simple and low-cost evaluation. The aim of this study was to evaluate the performance of six noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese patients. MATERIAL AND METHODS A retrospective study validation included 323 morbidly obese patients undergoing bariatric surgery. Advance fibrosis was defined as stage 3 and 4 (septal fibrosis or cirrhosis). Accuracy, sensitivity, specificity, positive (PPV) or negative (NPV) predictive value, and positive (PLR) or negative (NLR) likelihood ratio test of the following noninvasive liver fibrosis scores were evaluated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR); AST to platelet ratio index (APRI); BARD; FIB4, NAFLD fibrosis score (NFS) and BAAT, which were compared with the histological findings of the intraoperative liver biopsy. The cutoff points established in the validation studies were used: AAR > 1; APRL > 0.98; BARD ≥ 2; FIB4 > 2.67; NFS > 0.676 and BAAT > 1. RESULTS Twenty-nine patients (8.97%) presented advanced fibrosis. APRI presented the higher specificity (99.61%), PPV (85.71%), PLR (62.5) and accuracy (0.93). FIB4 was the second test in accuracy (0.9) and in PLR (10.53). BAAT presented the highest sensitivity (73.08%) and NPV (94.78%); NFS the lowest sensitivity (12,5%), and BARD the lowest accuracy (0.44). CONCLUSION APRI and FIB-4 were the tests with best performance to predict advanced fibrosis.
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Affiliation(s)
- Maria Al de Carli
- Department of Internal Medicine - Gastroenterology Unit, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil and Santa Casa Hospital de Porto Alegre, Brazil
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Henry ZH, Argo CK. How to Identify the Patient with Nonalcoholic Steatohepatitis Who Will Progress to Cirrhosis. Gastroenterol Clin North Am 2020; 49:45-62. [PMID: 32033764 DOI: 10.1016/j.gtc.2019.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) figures prominently into the clinical hepatology landscape. NAFLD represents a disease spectrum comprising simple steatosis, steatosis with elevated liver enzymes, and non-alcoholic steatohepatitis (NASH), the entity with clear potential for fibrosis progression. Risk factors associated with fibrosis progression in NASH include histologic findings of lobular inflammation and any fibrosis as well as clinical comorbidities that include type 2 diabetes, obesity, and metabolic syndrome. Liver biopsy remains the gold standard in evaluating NASH; however, noninvasive methods are accumulating evidence for a growing role in identifying patients at increased risk to develop NASH, fibrosis, and potentially cirrhosis.
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Affiliation(s)
- Zachary H Henry
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Curtis K Argo
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA.
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23
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Differentiation between stages of non-alcoholic fatty liver diseases using surface-enhanced Raman spectroscopy. Anal Chim Acta 2020; 1110:190-198. [PMID: 32278395 DOI: 10.1016/j.aca.2020.02.040] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/11/2020] [Accepted: 02/19/2020] [Indexed: 12/25/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disorder progressing from an initial benign accumulation of fat (NAFL) towards steatohepatitis (NASH), a degenerative form that can lead to liver cirrhosis and cancer. The development of non-invasive, rapid and accurate method to diagnose NASH is of high clinical relevance. Surface-enhanced Raman spectroscopy (SERS) of plasma was tested as a method to distinguish NAFL from NASH. SERS spectra from plasma of female patients diagnosed with NAFL (n = 32) and NASH (n = 35) were obtained in few seconds, using a portable Raman spectrometer. The sample consisted of 5 μL of biofluid deposited on paper coated with Ag nanoparticles. The spectra show consistent differences between the NAFL and NASH patients, with the uric acid/hypoxanthine band area ratio statistically different (p-value <0.001) between the two groups. The average figures of merit for a diagnostic test based on these ratios, as derived from a repeated 4-fold cross-validation of a logistic regression model, are all between 0.73 and 0.79, with an average area under the curve of 0.81. We conclude that SERS may be a reliable and rapid method to discriminate NAFLD from NASH.
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24
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Shiha G, Mousa N. Noninvasive Biomarkers for Liver Fibrosis. LIVER DISEASES 2020:427-441. [DOI: 10.1007/978-3-030-24432-3_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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25
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Cansby E, Kulkarni NM, Magnusson E, Kurhe Y, Amrutkar M, Nerstedt A, Ståhlman M, Sihlbom C, Marschall HU, Borén J, Blüher M, Mahlapuu M. Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans. FASEB J 2019; 33:9974-9989. [PMID: 31173506 DOI: 10.1096/fj.201900356rr] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ectopic lipid storage in the liver is considered the main risk factor for nonalcoholic steatohepatitis (NASH). Understanding the molecular networks controlling hepatocellular lipid deposition is therefore essential for developing new strategies to effectively prevent and treat this complex disease. Here, we describe a new regulator of lipid partitioning in human hepatocytes: mammalian sterile 20-like (MST) 3. We found that MST3 protein coats lipid droplets in mouse and human liver cells. Knockdown of MST3 attenuated lipid accumulation in human hepatocytes by stimulating β-oxidation and triacylglycerol secretion while inhibiting fatty acid influx and lipid synthesis. We also observed that lipogenic gene expression and acetyl-coenzyme A carboxylase protein abundance were reduced in MST3-deficient hepatocytes, providing insight into the molecular mechanisms underlying the decreased lipid storage. Furthermore, MST3 expression was positively correlated with key features of NASH (i.e., hepatic lipid content, lobular inflammation, and hepatocellular ballooning) in human liver biopsies. In summary, our results reveal a role of MST3 in controlling the dynamic metabolic balance of liver lipid catabolism vs. lipid anabolism. Our findings highlight MST3 as a potential drug target for the prevention and treatment of NASH and related complex metabolic diseases.-Cansby, E., Kulkarni, N. M., Magnusson, E., Kurhe, Y., Amrutkar, M., Nerstedt, A., Ståhlman, M., Sihlbom, C., Marschall, H.-U., Borén, J., Blüher, M., Mahlapuu, M. Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans.
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Affiliation(s)
- Emmelie Cansby
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Nagaraj M Kulkarni
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Elin Magnusson
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Yeshwant Kurhe
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Manoj Amrutkar
- Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Annika Nerstedt
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Marcus Ståhlman
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Carina Sihlbom
- Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden
| | - Hanns-Ulrich Marschall
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jan Borén
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Matthias Blüher
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | - Margit Mahlapuu
- Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
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Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019; 156:1264-1281.e4. [PMID: 30660725 PMCID: PMC7505052 DOI: 10.1053/j.gastro.2018.12.036] [Citation(s) in RCA: 1009] [Impact Index Per Article: 168.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 12/02/2018] [Accepted: 12/24/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice.
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Affiliation(s)
- Laurent Castera
- Department of Hepatology, Hôpital Beaujon, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1149, University of Paris-VII, Clichy, France.
| | - Mireen Friedrich-Rust
- Department of Internal Medicine 1, Division of Gastroenterology, Hepatology, Goethe University Hospital, Frankfurt, Germany
| | - Rohit Loomba
- Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, California
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Lin B, Ma Y, Wu S, Liu Y, Liu L, Wu L. Novel Serum Biomarkers for Noninvasive Diagnosis and Screening of Nonalcoholic Fatty Liver Disease-Related Hepatic Fibrosis. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2019; 23:181-189. [PMID: 30932742 DOI: 10.1089/omi.2019.0035] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global public health concern and becoming the leading cause of liver disease worldwide. The estimated global prevalence of NAFLD is ∼25% depending on the country and the assessment method used to establish the diagnosis. Meta-analyses suggest that the highest prevalence is in the Middle East (31.8%) and South America (30.4%), and the lowest in Africa (13.5%). In the United States, between 75 and 100 million individuals were estimated to have NAFLD. This important disease is associated with increased incidence of liver-related deaths, hepatocarcinoma, and overall mortality. Fibrosis stage, among other histological characteristics, is the most critical factor in predicting all-cause and disease-specific mortality in NAFLD. The ability to detect fibrosis early in NAFLD patients is critical in controlling mortality associated with this highly prevalent disease. We present here an expert review on recent advances in novel blood biomarkers, for example, the Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP), type IV collagen 7S, chitinase 3 like 1 (CHI3L1; YKL-40), and insulin-like growth factor-1 (IGF-1). Algorithms using multiple biomarkers such as alpha-2-macroglobulin, mir34a, YKL-40, and hemoglobin A1c (HbA1c; NIS4), enhanced liver fibrosis (ELF), Hepascore, FibroMeter, FibroTest, FIBROSpect, FIB-C3, and ADPAPT are highlighted. Novel technologies such as tandem mass spectrometry to directly measure protein turnover rate of the key proteins involved in hepatic fibrosis, as an indicator of fibrogenesis, are also discussed. In conclusion, NAFLD is a growing global health problem that warrants long-term funding, research, and training of scholars across the fields of public health diagnostics, systems sciences, nutrition, hepatology, and clinical oncology.
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Affiliation(s)
- Biaoyang Lin
- 1 Zhejiang-California International Nanosystems Institute (ZCNI), Proprium Research Center, Zhejiang University, Hangzhou, China.,2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.,3 Department of Urology, University of Washington School of Medicine, Seattle, Washington
| | - Yingying Ma
- 1 Zhejiang-California International Nanosystems Institute (ZCNI), Proprium Research Center, Zhejiang University, Hangzhou, China.,2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Shengjun Wu
- 4 School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Yunhua Liu
- 5 Department of Liver Diseases, The Second Hospital of Yunnan Province, Kunming, China
| | - Longgen Liu
- 6 The Third People's Hospital of Changzhou, Changzhou, China
| | - Lihua Wu
- 7 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The Research Center for Clinical Pharmacy, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
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Non-invasive diagnosis of steatosis, inflammatory changes and liver fibrosis in patients with non-alcoholic fatty liver diseases. Pilot study. ACTA ACUST UNITED AC 2018; 3:e179-e183. [PMID: 30775610 PMCID: PMC6374567 DOI: 10.5114/amsad.2018.81184] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 12/11/2018] [Indexed: 01/01/2023]
Abstract
Introduction Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of abnormal liver enzymes in adult patients consulted by hepatologists. Due to the high prevalence of this disease, most often associated with obesity, it is necessary to assess the risk of NAFLD, monitoring the progression of the disease and the effectiveness of treatment. Material and methods We evaluated the intensity of steatosis, inflammatory activity and fibrosis in 36 patients with NAFLD (fatty liver in abdominal ultrasound examination), using non-invasive tests: SteatoTest, ActiTest and FibroTest. We compared the prevalence of metabolic disorders and hypertension between women and men. Results There were no significant differences in analysed parameters of metabolic disorders between women and men. In both studied groups, the intensity of steatosis and inflammatory changes was similar. However, in the male group, the intensity of liver fibrosis was higher. Conclusions The tests helped to detect advanced liver fibrosis in patients who were diagnosed with liver steatosis in ultrasound examination. Non-invasive diagnostics of liver injury may be useful in screening to select groups of patients requiring liver biopsy, as well as in monitoring the course of the disease and assessment of the treatment effectiveness. Early detection of liver disease may improve the prognosis of these patients.
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Zubajlo RE, Benjamin A, Grajo JR, Kaliannan K, Kang JX, Bhan AK, Thomenius KE, Anthony BW, Dhyani M, Samir AE. Experimental Validation of Longitudinal Speed of Sound Estimates in the Diagnosis of Hepatic Steatosis (Part II). ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2749-2758. [PMID: 30266215 PMCID: PMC6661157 DOI: 10.1016/j.ultrasmedbio.2018.07.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 07/23/2018] [Accepted: 07/23/2018] [Indexed: 05/12/2023]
Abstract
This study validates a non-invasive, quantitative technique to diagnose steatosis within tissue. The proposed method is based on two fundamental concepts: (i) the speed of sound in a fatty liver is lower than that in a healthy liver and (ii) the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium under examination. The method uses image brightness and sharpness as quantitative image-quality metrics to predict the true sound speed and capture the effects of fat infiltration, while accounting for the transmission through subcutaneous fat. Ex vivo testing on sheep liver, mouse livers and tissue-mimicking phantoms indicated the technique's ability to predict the true speed of sound with errors less than 0.5% and to quantify the inverse correlation between fat content and speed of sound.
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Affiliation(s)
- Rebecca E. Zubajlo
- Device Realization and Computational Instrumentation Laboratory, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Alex Benjamin
- Device Realization and Computational Instrumentation Laboratory, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Joseph R. Grajo
- Department of Radiology, Division of Abdominal Imaging, University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Kanakaraju Kaliannan
- Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
| | - Jing X. Kang
- Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
| | - Atul K. Bhan
- Department of Pathology, Massachusetts General Hospital, Boston, MA 02139, USA
| | - Kai E. Thomenius
- Device Realization and Computational Instrumentation Laboratory, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Brian W. Anthony
- Device Realization and Computational Instrumentation Laboratory, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Corresponding Author: Manish Dhyani: Tel: +1 617 852 8909,
| | - Manish Dhyani
- Center for Ultrasound Research and Translation, Department of Radiology, Massachusetts General Hospital, Boston, MA 02139, USA
- Department of Internal Medicine, Steward Carney Hospital, Dorchester, MA 02124, USA
| | - Anthony E. Samir
- Center for Ultrasound Research and Translation, Department of Radiology, Massachusetts General Hospital, Boston, MA 02139, USA
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Vilar-Gomez E, Chalasani N. Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers. J Hepatol 2018; 68:305-315. [PMID: 29154965 DOI: 10.1016/j.jhep.2017.11.013] [Citation(s) in RCA: 438] [Impact Index Per Article: 62.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 11/03/2017] [Accepted: 11/09/2017] [Indexed: 12/04/2022]
Abstract
The correct identification of patients at increased risk of non-alcoholic steatohepatitis (NASH) and advanced fibrosis is a critical step in the assessment of non-alcoholic fatty liver disease (NAFLD). Since liver biopsy is invasive, expensive and prone to sampling error, several clinical prediction rules and blood-based biomarkers have been developed as attractive and affordable alternatives for identification of patients at high risk of NASH and advanced fibrosis. Current biomarkers constitute predictive models (e.g. NAFLD fibrosis score, FIB-4 index and BARD score) or direct measures of inflammation (e.g. circulating keratin 18 fragments), or fibrosis (e.g. FibroTest®, ELF™ or Pro-C3 tests). In the clinical setting, biomarkers may discriminate between patients with NASH or advanced fibrosis, predict dynamic changes in NASH/fibrosis over time, and provide long-term prognostic information. Although clinically useful, current biomarker predictions may be influenced by hepatic and extrahepatic conditions (e.g. age, patient comorbidities, and fibrosis or NASH prevalence), which may lead to inaccurate estimates in small subsamples of patients. No highly sensitive and specific tests are available to differentiate NASH from simple steatosis. However, diagnostic accuracy can be improved by combining blood biomarkers. NAFLD fibrosis score and FIB-4 index are both cost-effective and highly sensitive tools to exclude patients with advanced fibrosis. Moreover, their higher scores may identify patients at higher risk of non-liver- and liver-related morbidity and mortality. More expensive tests such as FibroTest or ELF are more specific for detection of patients with significant and advanced fibrosis. Recent efforts have concentrated on "omics" approaches for developing and validating novel biomarkers. Herein, we describe currently available clinical prediction rules and blood-based biomarkers for identifying NASH and advanced fibrosis in patients with NAFLD, discussing their advantages and disadvantages, as well as their potential clinical utility for predicting dynamic changes over time and identifying patients at increased risk of adverse outcomes.
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Affiliation(s)
- Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, IN, USA.
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, IN, USA.
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Ooi GJ, Mgaieth S, Eslick GD, Burton PR, Kemp WW, Roberts SK, Brown WA. Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese. Obes Rev 2018; 19:281-294. [PMID: 29119725 DOI: 10.1111/obr.12628] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Revised: 09/11/2017] [Accepted: 09/15/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non-invasive NAFLD tests. We aimed to review current evidence for common non-invasive tests for NAFLD-related fibrosis in obesity. METHODS We systematically searched for studies assessing the diagnostic accuracy of 11 biomarker panels and elastography techniques for NAFLD-related fibrosis in obesity. Meta-analyses were performed where possible. RESULTS Thirty-eight studies were identified assessing the selected tests in obese populations. Simple biomarker panels (e.g. NAFLD fibrosis score) were the most validated. Evidence showed better accuracy of complex biomarker panels (NAFLD fibrosis score: summary receiver operator characteristic [SROC] 0.795-0.813 vs. enhanced liver fibrosis: SROC 0.962); however, these were poorly validated in obesity. Elastography techniques were better studied and had high diagnostic accuracy (transient elastography: SROC 0.859; magnetic resonance elastography: SROC 0.965) but were limited by BMI-dependent failure. Limited evidence was found to validate the accuracy of any test in exclusively obese populations. CONCLUSION In obese subjects, complex biomarker panels and elastography have been reasonable to good accuracy for NAFLD-related fibrosis; however, these methods have not been well validated. Further study in this high-risk population is needed.
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Affiliation(s)
- G J Ooi
- Centre for Obesity Research and Education, Monash University, Melbourne, Australia
- Department of Surgery, The Alfred Hospital, Melbourne, Australia
| | - S Mgaieth
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, Australia
| | - G D Eslick
- The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Nepean Hospital, Penrith, Australia
| | - P R Burton
- Centre for Obesity Research and Education, Monash University, Melbourne, Australia
- Department of Surgery, The Alfred Hospital, Melbourne, Australia
| | - W W Kemp
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - S K Roberts
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - W A Brown
- Centre for Obesity Research and Education, Monash University, Melbourne, Australia
- Department of Surgery, The Alfred Hospital, Melbourne, Australia
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Ooi GJ, Earnest A, Kemp WW, Burton PR, Laurie C, Majeed A, Johnson N, McLean C, Roberts SK, Brown WA. Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty liver disease in severe and morbid obesity. Int J Obes (Lond) 2018; 42:1900-1911. [PMID: 29463916 DOI: 10.1038/s41366-018-0007-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 12/13/2017] [Accepted: 12/21/2017] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In obese individuals, nonalcoholic fatty liver disease (NAFLD) is common but often goes undiagnosed, and therefore untreated. The presence of significant fibrosis is a key determinant of NAFLD progression, and liver steatosis has substantial cardiovascular implications. We aimed to determine the diagnostic accuracy of common noninvasive diagnostic tests for steatosis and fibrosis in the obese. METHODS We recruited 182 severely and morbidly obese individuals undergoing bariatric surgery (age 44 ± 12 years, body mass index 45.1 ± 8.3 kg/m2). Medical history, blood tests and liver biopsy were taken on the day of surgery. Serum steatosis and fibrosis scores were calculated. In a subgroup of patients, transient elastography with controlled attenuation parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy (1H-MRS) (n = 49) were performed. RESULTS 1H-MRS had excellent diagnostic accuracy for steatosis, with strong correlation to steatosis (r = 0.647, p < 0.001), good AUROC (0.852, p = 0.001), sensitivity (81.3%) and specificity (87.5%). However, due to low feasibility in this cohort (65.3% success), this was substantially decreased with intention-to-diagnose analysis (sensitivity 50.0%, specificity 60.9%). CAP had good feasibility (80.5%), and performed better in intention-to-diagnose analysis (AUROC 0.688, sensitivity 84.8%, specificity 47.2%). Serum steatosis scores performed poorly, with comparable accuracy to ALT. For significant fibrosis, TE had the best accuracy (AUROC 0.903, p = 0.007), which remained reasonable after intention-to-diagnose analysis (sensitivity 100%, specificity 59.0%). A combination approach using CAP with ALT for steatosis and TE with Forn index for fibrosis yielded reasonable overall accuracy. CONCLUSIONS 1H-MRS and TE/CAP had greatest accuracy for NAFLD-related steatosis and fibrosis. Failure rates in obesity significantly diminished diagnostic ability. Use of a combination of serum and imaging tests improved overall feasibility of assessment and diagnostic accuracy in obese individuals.
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Affiliation(s)
- Geraldine J Ooi
- Centre for Obesity Research and Education, Central Clinical School, Monash University, Melbourne, Australia. .,Department of General Surgery, The Alfred Hospital, Melbourne, Australia.
| | - Arul Earnest
- Department of Epidemiology and Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Clayton, VIC, Australia
| | - William W Kemp
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - Paul R Burton
- Centre for Obesity Research and Education, Central Clinical School, Monash University, Melbourne, Australia.,Department of General Surgery, The Alfred Hospital, Melbourne, Australia
| | - Cheryl Laurie
- Centre for Obesity Research and Education, Central Clinical School, Monash University, Melbourne, Australia
| | - Ammar Majeed
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - Nathan Johnson
- Faculty of Health Science, The University of Sydney, Sydney, Australia
| | - Catriona McLean
- Department of Pathology, The Alfred Hospital, Melbourne, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - Wendy A Brown
- Centre for Obesity Research and Education, Central Clinical School, Monash University, Melbourne, Australia.,Department of General Surgery, The Alfred Hospital, Melbourne, Australia
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Wong VWS, Chan WK, Chitturi S, Chawla Y, Dan YY, Duseja A, Fan J, Goh KL, Hamaguchi M, Hashimoto E, Kim SU, Lesmana LA, Lin YC, Liu CJ, Ni YH, Sollano J, Wong SKH, Wong GLH, Chan HLY, Farrell G. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment. J Gastroenterol Hepatol 2018; 33:70-85. [PMID: 28670712 DOI: 10.1111/jgh.13857] [Citation(s) in RCA: 354] [Impact Index Per Article: 50.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 05/30/2017] [Accepted: 06/25/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shiv Chitturi
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jiangao Fan
- Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Khean-Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Etsuko Hashimoto
- Departments of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | | | - Yu-Cheng Lin
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Hepatitis Research Center and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Hepatitis Research Center, National Taiwan University, Taipei, Taiwan
| | - Jose Sollano
- University of Santo Tomas, Manila, The Philippines
| | - Simon Kin-Hung Wong
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Geoff Farrell
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
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Saokaew S, Kanchanasuwan S, Apisarnthanarak P, Charoensak A, Charatcharoenwitthaya P, Phisalprapa P, Chaiyakunapruk N. Clinical risk scoring for predicting non-alcoholic fatty liver disease in metabolic syndrome patients (NAFLD-MS score). Liver Int 2017; 37:1535-1543. [PMID: 28294515 DOI: 10.1111/liv.13413] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 03/06/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS). METHODS A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance. RESULTS The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ2 =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively. CONCLUSIONS A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action.
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Affiliation(s)
- Surasak Saokaew
- Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.,School of Pharmacy, Monash University Malaysia, Selangor, Malaysia.,Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
| | - Shada Kanchanasuwan
- Clinical and Administrative Pharmacy, The University of Georgia College of Pharmacy, Athens, GA, USA
| | - Piyaporn Apisarnthanarak
- Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Aphinya Charoensak
- Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nathorn Chaiyakunapruk
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia.,Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.,School of Pharmacy, University of Wisconsin, Madison, WI, USA.,School of Population Health, University of Queensland, Brisbane, Qld, Australia
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Barbois S, Arvieux C, Leroy V, Reche F, Stürm N, Borel AL. Benefit–risk of intraoperative liver biopsy during bariatric surgery: review and perspectives. Surg Obes Relat Dis 2017; 13:1780-1786. [PMID: 28935200 DOI: 10.1016/j.soard.2017.07.032] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Revised: 07/24/2017] [Accepted: 07/28/2017] [Indexed: 02/06/2023]
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Visual Liver Score to Stratify Non-Alcoholic Steatohepatitis Risk and Determine Selective Intraoperative Liver Biopsy in Obesity. Obes Surg 2017; 28:427-436. [PMID: 28776153 DOI: 10.1007/s11695-017-2859-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Lonardo A, Nascimbeni F, Ponz de Leon M. Nonalcoholic fatty liver disease and COPD: is it time to cross the diaphragm? Eur Respir J 2017; 49:1700546. [PMID: 28596428 DOI: 10.1183/13993003.00546-2017] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 04/16/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Amedeo Lonardo
- Operating Unit of Internal Medicine, OCSAE, Modena, Italy
| | - Fabio Nascimbeni
- Operating Unit of Internal Medicine, OCSAE, Modena, Italy
- University of Modena and Reggio Emilia, Modena, Italy
| | - Maurizio Ponz de Leon
- Operating Unit of Internal Medicine, OCSAE, Modena, Italy
- University of Modena and Reggio Emilia, Modena, Italy
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38
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The Role of Allergy Testing in Eosinophilic Esophagitis: an Update of the Evidence. ACTA ACUST UNITED AC 2017; 15:26-34. [DOI: 10.1007/s11938-017-0125-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Munteanu M, Tiniakos D, Anstee Q, Charlotte F, Marchesini G, Bugianesi E, Trauner M, Romero Gomez M, Oliveira C, Day C, Dufour JF, Bellentani S, Ngo Y, Traussnig S, Perazzo H, Deckmyn O, Bedossa P, Ratziu V, Poynard T. Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference. Aliment Pharmacol Ther 2016; 44:877-889. [PMID: 27549244 PMCID: PMC5113673 DOI: 10.1111/apt.13770] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 07/19/2016] [Accepted: 07/27/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Blood tests of liver injury are less well validated in non-alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS We pre-included new NAFLD patients with biopsy and blood tests from a single-centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary-ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864-0.892) for FibroTest and fibrosis stages, 0.846 (0.830-0.862) for ActiTest and activity grades, and 0.822 (0.804-0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820-0.852; P = 0.0001), FIB4 (0.845; 0.829-0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850-0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non-invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis.
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Affiliation(s)
| | - D Tiniakos
- Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
- Laboratory of Histology & Embryology, Medical School, National & Kapodistrian University of Athens, Greece
| | - Q Anstee
- Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
| | - F Charlotte
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938 & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | | | - E Bugianesi
- Universita Degli Studi di Torino, Torino, Italy
| | - M Trauner
- Medizinischen Universitaet Wien, Vienna, Austria
| | - M Romero Gomez
- Valme University Hospital, University of Seville, Sevilla, Spain
| | - C Oliveira
- Department of Gastroenterology (LIM-07), University of São Paulo School of Medicine, São Paulo, Brazil
| | - C Day
- Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
| | | | - S Bellentani
- Gastroenterologia, Azienda USL di Modena Reggio Emilia, Modena, Italy
| | - Y Ngo
- BioPredictive, Paris, France
| | - S Traussnig
- Medizinischen Universitaet Wien, Vienna, Austria
| | - H Perazzo
- APHP UPMC Liver Center, Paris, France
| | | | - P Bedossa
- Assistance Publique-Hôpitaux de Paris, hôpital Beaujon, University Paris-Diderot, Paris, France
| | - V Ratziu
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938 & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - T Poynard
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938 & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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Kaswala DH, Lai M, Afdhal NH. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016. Dig Dis Sci 2016; 61:1356-64. [PMID: 27017224 DOI: 10.1007/s10620-016-4079-4] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 02/04/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.
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Affiliation(s)
- Dharmesh H Kaswala
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA
| | - Michelle Lai
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA
| | - Nezam H Afdhal
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA.
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Festi D, Schiumerini R, Marasco G, Scaioli E, Pasqui F, Colecchia A. Non-invasive diagnostic approach to non-alcoholic fatty liver disease: current evidence and future perspectives. Expert Rev Gastroenterol Hepatol 2016; 9:1039-53. [PMID: 25993881 DOI: 10.1586/17474124.2015.1049155] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease is a new epidemic liver disease, thus, its early diagnosis and the identification of those patients with the worst prognosis is mandatory. Liver biopsy is still the diagnostic gold standard, even if it is associated to a significant rate of complications; moreover, the interpretation of histological samples is not always univocal. Several non-invasive alternative scores have been proposed for the diagnostic approach to non-alcoholic fatty liver disease. This article evaluates the performance of the currently available non-invasive diagnostic strategies. The authors also suggest a potential diagnostic algorithm, with two or more non-invasive techniques, to increase the overall accuracy for identifying patients with worst prognosis, and to minimize the recourse to liver biopsy.
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Affiliation(s)
- Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, S.Orsola Hospital, Via Massarenti 9, 40138 Bologna, Italy
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Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg 2015; 260:893-8; discussion 898-9. [PMID: 25379859 DOI: 10.1097/sla.0000000000000945] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To compare the long-term benefit of gastric bypass [Roux-en-Y gastric bypass (RYGB)] versus adjustable gastric banding (AGB) on nonalcoholic fatty liver disease (NAFLD) in severely obese patients. BACKGROUND NAFLD improves after weight loss surgery, but no histological study has compared the effects of the various bariatric interventions. METHODS Participants consisted of 1236 obese patients (body mass index=48.4±7.6 kg/m), enrolled in a prospective longitudinal study for up to 5 years after RYGB (n=681) or AGB (n=555). Liver biopsy samples were available for 1201 patients (97.2% of those at risk) at baseline, 578 patients (47.2%) at 1 year, and 413 patients (68.9%) at 5 years. RESULTS At baseline, NAFLD was present in 86% patients and categorized as severe [NAFLD activity score (NAS)≥3] in 22% patients. RYGB patients had a higher body mass index (49.8±8.2 vs 46.8±6.5 kg/m, P<0.001) and more severe NAFLD (NAS: 2.0±1.5 vs 1.7±1.4, P=0.004) than AGB patients. Weight loss at 5 years was 25.5%±11.8% after RYGB versus 21.4%±12.7% after AGB (P<0.001). When analyzed with a mixed model, all NAFLD parameters improved after surgery (P<0.001) and improved significantly more after RYGB than after AGB [steatosis (%): 1 year, 7.9±13.7 vs 17.9±21.5, P<0.001/5 years, 8.7±7.1 vs 14.5±20.8, P<0.05; NAS: 1 year, 0.7±1.0 vs 1.1±1.2, P<0.001/5 years, 0.7±1.2 vs 1.0±1.3, P<0.05]. In multivariate analysis, the superiority of RYGB was primarily but not entirely explained by weight loss. CONCLUSIONS The improvement of NAFLD was superior after RYGB than after AGB.
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Dyson JK, McPherson S, Anstee QM. Republished: Non-alcoholic fatty liver disease: non-invasive investigation and risk stratification. Postgrad Med J 2015; 90:254-66. [PMID: 24737902 DOI: 10.1136/postgradmedj-2013-201620rep] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum of liver disease, from simple steatosis through to cirrhosis. As the worldwide rates of obesity have increased, NAFLD has become the commonest cause of liver disease in many developed countries, affecting up to a third of the population. The majority of patients have simple steatosis that carries a relatively benign prognosis. However, a significant minority have non-alcoholic steatohepatitis, and have increased liver related and cardiovascular mortality. Identifying those at risk of progressive disease is crucial. Liver biopsy remains the gold standard investigation for assessing stage of disease but its invasive nature makes it impractical for widespread use as a prognostic tool. Non-invasive tools for diagnosis and disease staging are required, reserving liver biopsy for those patients where it offers clinically relevant additional information. This review discusses the non-invasive modalities available for assessing steatosis, steatohepatitis and fibrosis. We propose a pragmatic approach for the assessment of patients with NAFLD to identify those at high risk of progressive disease who require referral to specialist services.
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Affiliation(s)
- J K Dyson
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, , Newcastle upon Tyne, UK
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44
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AlShaalan R, Aljiffry M, Al-Busafi S, Metrakos P, Hassanain M. Nonalcoholic fatty liver disease: Noninvasive methods of diagnosing hepatic steatosis. Saudi J Gastroenterol 2015; 21:64-70. [PMID: 25843191 PMCID: PMC4392577 DOI: 10.4103/1319-3767.153812] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD.
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Affiliation(s)
- Rasha AlShaalan
- Department of Surgery, Section of Hepatobiliary and Transplant Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Murad Aljiffry
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Said Al-Busafi
- Department of Medicine, Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada
| | - Peter Metrakos
- Department of Surgery, Section of Hepatobiliary and Transplant Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Mazen Hassanain
- Department of Surgery, King Saud University, Riyadh, Saudi Arabia,Department of Oncology, McGill University Health Center, Montreal Quebec, Canada,Address for correspondence: Dr. Mazen Hassanain, HPB, Royal Victoria Hospital, McGill University Health Center, 687 Pine Avenue West, S 10.26, H3A 1A1, Montreal, QC, Canada. E-mail:
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Buzzetti E, Lombardi R, De Luca L, Tsochatzis EA. Noninvasive Assessment of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease. Int J Endocrinol 2015; 2015:343828. [PMID: 26064107 PMCID: PMC4430647 DOI: 10.1155/2015/343828] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 04/17/2015] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is prevalent in 20-25% of the general population and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Histologically, NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As NASH develops in only 10-15% of patients with NAFLD, it is not practical to biopsy all patients who present with NAFLD. Noninvasive fibrosis tests have been extensively developed recently and offer alternatives for staging fibrosis. Despite their increasing use, such tests cannot adequately differentiate simple steatosis from NASH. At present, such tests can be used as first line tests to rule out patients without advanced fibrosis and thus prevent unnecessary secondary care referrals in a significant number of patients. In this review we present the evidence for the use of noninvasive fibrosis tests in patients with NAFLD.
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Affiliation(s)
- Elena Buzzetti
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London NW3 2QG, UK
| | - Rosa Lombardi
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London NW3 2QG, UK
| | - Laura De Luca
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London NW3 2QG, UK
| | - Emmanuel A. Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London NW3 2QG, UK
- *Emmanuel A. Tsochatzis:
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Elrazek AEMAA, Elbanna AEM, Bilasy SE. Medical management of patients after bariatric surgery: Principles and guidelines. World J Gastrointest Surg 2014; 6:220-228. [PMID: 25429323 PMCID: PMC4241489 DOI: 10.4240/wjgs.v6.i11.220] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 09/06/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index (BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients (BMI ≥ 30 kg/m2) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m2 and those with BMI > 35 kg/m2 with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.
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Sauerbruch T, Trebicka J. Future therapy of portal hypertension in liver cirrhosis - a guess. F1000PRIME REPORTS 2014; 6:95. [PMID: 25374673 PMCID: PMC4191223 DOI: 10.12703/p6-95] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In patients with chronic liver disease, portal hypertension is driven by progressive fibrosis and intrahepatic vasoconstriction. Interruption of the initiating and perpetuating etiology—mostly leading to necroinflammation—is possible for several underlying causes, such as autoimmune hepatitis, hepatitis B virus (HBV) infection, and most recently hepatitis C virus (HCV) infection. Thus, in the long run, lifestyle-related liver damage due to chronic alcoholism or morbid obesity will remain the main factor leading to portal hypertension. Both causes are probably more easily countered by socioeconomic measures than by individual approaches. If chronic liver injury supporting fibrogenesis and portal hypertension cannot be interrupted, a wide variety of tools are available to modulate and reduce intrahepatic resistance and therewith portal hypertension. Many of these have been evaluated in animal models. Also, some well-established drugs, which are used in humans for other indications (for example, statins), are promising if applied early and concomitantly to standard therapy. In the future, more individually tailored strategies must also be considered in line with the spectrum of portal hypertensive complications and risk factors defined by high-throughput analysis of the patient’s genome, transcriptome, metabolome, or microbiome.
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Hassan K, Bhalla V, Regal MEE, A-Kader HH. Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic. World J Gastroenterol 2014; 20:12082-12101. [PMID: 25232245 PMCID: PMC4161796 DOI: 10.3748/wjg.v20.i34.12082] [Citation(s) in RCA: 138] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 04/24/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.
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Kwok R, Tse YK, Wong GLH, Ha Y, Lee AU, Ngu MC, Chan HLY, Wong VWS. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 2014; 39:254-69. [PMID: 24308774 DOI: 10.1111/apt.12569] [Citation(s) in RCA: 292] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 10/22/2013] [Accepted: 11/11/2013] [Indexed: 12/16/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects 15-40% of the general population. Some patients have non-alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment. AIM To review current literature on the use of non-invasive tests to assess the severity of NAFLD. METHODS Systematic literature searching identified studies evaluating non-invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta-analysis was performed for areas with adequate number of publications. RESULTS Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low-risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin-18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH. CONCLUSIONS Current non-invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.
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Affiliation(s)
- R Kwok
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Department of Gastroenterology and Hepatology, Concord Repatriation Hospital, Sydney, Australia
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Dyson JK, McPherson S, Anstee QM. Non-alcoholic fatty liver disease: non-invasive investigation and risk stratification. J Clin Pathol 2013; 66:1033-45. [DOI: 10.1136/jclinpath-2013-201620] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum of liver disease, from simple steatosis through to cirrhosis. As the worldwide rates of obesity have increased, NAFLD has become the commonest cause of liver disease in many developed countries, affecting up to a third of the population. The majority of patients have simple steatosis that carries a relatively benign prognosis. However, a significant minority have non-alcoholic steatohepatitis, and have increased liver related and cardiovascular mortality. Identifying those at risk of progressive disease is crucial. Liver biopsy remains the gold standard investigation for assessing stage of disease but its invasive nature makes it impractical for widespread use as a prognostic tool. Non-invasive tools for diagnosis and disease staging are required, reserving liver biopsy for those patients where it offers clinically relevant additional information. This review discusses the non-invasive modalities available for assessing steatosis, steatohepatitis and fibrosis. We propose a pragmatic approach for the assessment of patients with NAFLD to identify those at high risk of progressive disease who require referral to specialist services.
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