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Gbadamosi SO, Evans KA, Brady BL, Hoovler A. Noninvasive tests and diagnostic pathways to MASH diagnosis in the United States: a retrospective observational study. J Med Econ 2025; 28:314-322. [PMID: 39963742 DOI: 10.1080/13696998.2025.2468582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/13/2025] [Accepted: 02/14/2025] [Indexed: 03/03/2025]
Abstract
AIM Although liver biopsy is considered the most reliable diagnostic tool for metabolic dysfunction-associated steatohepatitis (MASH), it is invasive and can be costly. Clinicians are increasingly relying on routine biomarkers and other noninvasive tests (NITs) for diagnosis. We examined real-world diagnostic pathways for patients newly diagnosed with MASH with a primary focus on NITs. MATERIALS AND METHODS This retrospective, observational study analyzed healthcare claims data (Merative MarketScan Commercial and Medicare Databases) from patients in the United States newly diagnosed with MASH from October 1, 2016, to March 31, 2023. Patients ≥18 years old with ≥12 months of continuous enrollment with medical and pharmacy benefits prior to diagnosis were included. Diagnostic pathways leading up to MASH diagnosis, including NITs (blood-based and imaging-based tests) and liver biopsies were assessed. Prevalence of comorbid conditions, MASH-associated medication use, and the diagnosing physician specialty were also examined. RESULTS A total of 18,396 patients were included in the analysis. Routine laboratory tests (alanine aminotransferase [ALT], albumin, aspartate aminotransferase [AST], cholesterol, complete blood count, and hemoglobin A1c) were performed among ≥70% of patients prior to MASH diagnosis, including 89% of patients with a liver enzyme test (ALT and/or AST). More than 75% of patients had necessary laboratory tests to calculate AST to platelet ratio index (APRI) and fibrosis-4 index (FIB-4) scores. The most common imaging performed was ultrasound (62%); liver biopsy was only performed in 10% of patients. There was a high prevalence of cardio metabolic risk factors such as hyperlipidemia (66%), hypertension (62%), obesity (58%), type 2 diabetes (40%), and cardiovascular disease (21%). Nearly half of the patients (49%) were diagnosed by a primary care physician. LIMITATIONS AND CONCLUSIONS This study highlights real-world diagnostic pathways among patients newly diagnosed with MASH, supporting previous findings that liver biopsies are infrequently used in favor of noninvasive methods.
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Mayengbam S, Raman M, Parnell JA, Eksteen B, Lambert JE, Eller LK, Nicolucci AC, Aktary ML, Reimer RA. Effects of combined prebiotic fiber supplementation and weight loss counseling in adults with metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Eur J Nutr 2025; 64:144. [PMID: 40172664 DOI: 10.1007/s00394-025-03660-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 03/22/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE Our aim was to examine the effects of combined prebiotic fiber supplementation and weight loss counseling on liver fat, body composition, subjective appetite, serum metabolomics, and intestinal microbiota in adults with MASLD. METHODS In a double blind, placebo-controlled trial, adult participants aged 18-70 years old with MASLD were randomized to receive prebiotic (oligofructose-enriched inulin, 16 g/day; n = 22) or isocaloric placebo (maltodextrin; n = 20) for 24 weeks alongside weight loss counseling from a registered dietitian. Primary outcomes were change in intrahepatic fat % (IHF%) and hepatic injury from baseline to 24 weeks. Secondary outcomes included body composition, subjective appetite, serum lipids and cytokines, fecal microbiota, and serum metabolomics. RESULTS At baseline, participants had IHF of 14.4 ± 8.4%. The change in IHF from baseline to 24 weeks did not differ between prebiotic and placebo. Prebiotic participants had a greater decrease (p = 0.029) in percent trunk fat compared to placebo. Compared to placebo, prebiotic significantly decreased desire to eat and hunger ratings over the course of the intervention. Fecal microbiota analysis showed a significant increase in Bifidobacterium abundance with prebiotic. A pathway analysis based on untargeted serum metabolomics revealed a downregulation of taurine and hypotaurine metabolism in the placebo group which was conserved in the prebiotic group. CONCLUSION Adding prebiotic fiber supplementation to weight loss counseling for adults with MASLD enhanced reductions in trunk fat and had a beneficial effect on subjective appetite compared to placebo. Improvements in fecal microbial profile and taurine metabolism revealed specific beneficial effects of prebiotics in the management of MASLD. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov/study/NCT02568605.
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Affiliation(s)
- Shyamchand Mayengbam
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Maitreyi Raman
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Jill A Parnell
- Department of Health and Physical Education, Mount Royal University, Calgary, AB, Canada
| | | | - Jennifer E Lambert
- Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
| | - Lindsay K Eller
- Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
| | - Alissa C Nicolucci
- Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
| | - Michelle L Aktary
- Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
| | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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Rigor J, Martins ME, Passos B, Oliveira R, Martins-Mendes D. Noninvasive tools for the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease. Minerva Med 2024; 115:660-670. [PMID: 39283245 DOI: 10.23736/s0026-4806.24.09290-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously nonalcoholic fatty liver disease (NAFLD), is the number one chronic liver disorder worldwide. Progression to advanced fibrosis marks the emergence of a significant risk of liver-related negative outcomes. However, only a minority of patients will present at this stage. Since widespread liver biopsy in unfeasible at such high disease prevalence, there was a need to develop noninvasive tests (NITs) that could easily and reliably be applied to patients with MASLD, regardless of clinical setting. The NITs include simple scores, like the fibrosis-4 (FIB-4) Index, patented serum tests, like the Enhanced Liver Fibrosis test (ELF™), and imaging-based modalities, like the vibration-controlled transient elastography (VCTE). Guidelines suggests a stepwise approach that utilizes more than one NIT, with FIB-4 <1.30 being used as a first step to rule out patients that do not need further testing. Subsequent choice of NIT will be influenced by setting, cost, and local availability. While these NITs are accurate, they are not perfect. As such, research is ongoing. A promising avenue is that of omics, a group of technologies that provide concomitant results on a large number of molecules (and other variables). With the advance of artificial intelligence, new NITs may arise from large demographic, biochemical, and radiological data sets.
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Affiliation(s)
- Joana Rigor
- Internal Medicine Department, Unidade Local de Saúde de Póvia de Varzim/Vila do Conde, Vila do Conde, Portugal -
- RISE-UFP, Network of Health Investigation, Fernando Pessoa University, Porto, Portugal -
| | - Maria E Martins
- Internal Medicine Department, Unidade Local de Saúde de Póvia de Varzim/Vila do Conde, Vila do Conde, Portugal
| | - Beatriz Passos
- Internal Medicine Department, Unidade Local de Saúde de Póvia de Varzim/Vila do Conde, Vila do Conde, Portugal
| | - Raquel Oliveira
- Internal Medicine Department, Unidade Local de Saúde de Póvia de Varzim/Vila do Conde, Vila do Conde, Portugal
| | - Daniela Martins-Mendes
- RISE-UFP, Network of Health Investigation, Fernando Pessoa University, Porto, Portugal
- School of Medicine and Biomedical Sciences, Fernando Pessoa University, Porto, Portugal
- FP-I3ID, Fernando Pessoa University, Porto, Portugal
- Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
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Zambon Azevedo V, Bel Lassen P, Aron-Wisnewsky J, Genser L, Charlotte F, Bedossa P, Ponnaiah M, Pais R, Clément K, Oppert JM, Ratziu V. Metabolic and hepatic phenotypes in sarcopenic obesity and impact of bariatric surgery. Clin Nutr 2024; 43:254-264. [PMID: 39536396 DOI: 10.1016/j.clnu.2024.10.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 10/25/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND & AIMS Sarcopenic obesity (SO) is associated with cardiometabolic disorders and steatotic liver disease and carries major health risks. We assessed the hepatic and metabolic clinical phenotype associated with SO in patients with obesity undergoing bariatric surgery (BS). We also evaluated whether weight-loss and metabolic improvement post-surgery differ between patients with and without SO. METHODS 972 consecutive patients from a single-center BS cohort who underwent whole-body dual-energy X-ray absorptiometry (DXA) and peri-operative liver biopsy were included. SO was diagnosed using the AIM-SO score, an AI-assisted unbiased clustering algorithm based on body composition. One-year post-surgery, 862 patients were reassessed for AIM-SO score changes. RESULTS Pre-operatively, 207 (21.3 %) patients were diagnosed with SO. These patients had significantly higher prevalence of type-2 diabetes (T2D), arterial hypertension and obstructive sleep apnea (OSA) compared to patients without SO (all p ≤ 0.003). Patients with SO had more severe liver damage: higher grades of moderate/advanced steatosis (64.2 % vs. 47.3 %), steatohepatitis (44.4 % vs. 32.3 %) and advanced fibrosis (12.1 % vs. 6.0 %) (all p ≤ 0.01). One-year post-BS, 58.5 % of patients had remission of SO. Patients with persistent SO exhibited less weight-loss than those with SO remission (-23.8 kg vs. -29.1 kg, p < 0.001) and had lower rates of remission for T2D (41.9 % vs. 69.8 %), arterial hypertension (20.8 % vs. 45.3 %), and metabolic syndrome (47.6 % vs. 75.0 %) (all p ≤ 0.009). CONCLUSION The DXA-based AIM-SO score identifies patients with SO who are at greater risk of hepatic and cardiometabolic comorbidities, and predicts less favorable weight-loss and metabolic improvements post-BS.
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Affiliation(s)
- Vittoria Zambon Azevedo
- Sorbonne Université, Paris, France; Foundation for Innovation in Cardiometabolism and Nutrition, IHU ICAN, Paris, France; Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Pierre Bel Lassen
- Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches, NutriOmics, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service de Nutrition, Hôpital Pitié-Salpêtrière, Paris, France
| | - Judith Aron-Wisnewsky
- Sorbonne Université, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches, NutriOmics, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service de Nutrition, Hôpital Pitié-Salpêtrière, Paris, France
| | - Laurent Genser
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris, AP-HP, Department of Hepato-Biliary and Pancreatic Surgery, France
| | - Frederic Charlotte
- Sorbonne Université, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service d'Anatomie et Cytologie Pathologiques, Hôpital Pitié-Salpêtrière, Paris, France
| | | | - Maharajah Ponnaiah
- Foundation for Innovation in Cardiometabolism and Nutrition, IHU ICAN, Paris, France
| | - Raluca Pais
- Foundation for Innovation in Cardiometabolism and Nutrition, IHU ICAN, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service d'Hépatologie et Gastro-entérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Karine Clément
- Sorbonne Université, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches, NutriOmics, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service de Nutrition, Hôpital Pitié-Salpêtrière, Paris, France
| | - Jean-Michel Oppert
- Sorbonne Université, Paris, France; Foundation for Innovation in Cardiometabolism and Nutrition, IHU ICAN, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service de Nutrition, Hôpital Pitié-Salpêtrière, Paris, France.
| | - Vlad Ratziu
- Sorbonne Université, Paris, France; Foundation for Innovation in Cardiometabolism and Nutrition, IHU ICAN, Paris, France; Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France; Assistance Publique Hôpitaux de Paris, AP-HP, Service d'Hépatologie et Gastro-entérologie, Hôpital Pitié-Salpêtrière, Paris, France
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Kim BK. [Serological Markers to Assess Liver Fibrosis and Their Roles]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:195-200. [PMID: 39582306 DOI: 10.4166/kjg.2024.123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 10/24/2024] [Indexed: 11/26/2024]
Abstract
Chronic liver disease is a significant public health issue worldwide, with the degree of liver fibrosis and its progression significantly influencing the treatment and prognosis. A liver biopsy is the standard diagnostic method, but it is invasive and presents various issues. Therefore, numerous non-invasive diagnostic methods have been developed. Serum markers are categorized into indirect markers, which reflect liver damage, inflammation, or functional changes, and direct markers, which measure the components released into the bloodstream during fibrosis. In addition, various kinds of formulas that combined direct/indirect markers and demographic variables were developed and validated with encouraging outcomes. Nevertheless, despite their convenience, serum indicators require cautious interpretation because they are affected by a number of factors. More research will be needed to determine if the clinical course of chronic liver disease under a disease-specific treatment could be monitored appropriately using serological markers.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Chadha N, Sterling RK. A Clinical Review of Noninvasive Tests for Hepatic Fibrosis. Gastroenterol Hepatol (N Y) 2024; 20:322-329. [PMID: 39193269 PMCID: PMC11346005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Identifying hepatic fibrosis is paramount in managing patients with chronic liver disease. The etiology of liver disease can be owing to many factors, including chronic viral hepatitis, steatotic liver diseases such as alcohol-associated liver disease or metabolic dysfunction-associated steatotic liver disease, autoimmune hepatitis, and cholestatic liver diseases. Currently, invasive liver biopsy with histopathologic evaluation is the gold standard; however, noninvasive tests are becoming more prevalent, especially because they do not carry the risks of invasive procedures such as biopsy. This article reviews noninvasive tests for fibrosis, separating them into blood-based and imaging-based tests.
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Affiliation(s)
- Nikita Chadha
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Richard K. Sterling
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Health System, Richmond, Virginia
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Bitterer F, Kupke P, Adenugba A, Evert K, Glehr G, Riquelme P, Scheibert L, Preverin G, Böhm C, Hornung M, Schlitt HJ, Wenzel JJ, Geissler EK, Safinia N, Hutchinson JA, Werner JM. Soluble CD46 as a diagnostic marker of hepatic steatosis. EBioMedicine 2024; 104:105184. [PMID: 38838471 PMCID: PMC11179574 DOI: 10.1016/j.ebiom.2024.105184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 05/21/2024] [Accepted: 05/21/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) incurs substantial morbidity, mortality and healthcare costs. Detection and clinical intervention at early stages of disease improves prognosis; however, we are currently limited by a lack of reliable diagnostic tests for population screening and monitoring responses to therapy. To address this unmet need, we investigated human invariant Natural Killer T cell (iNKT) activation by fat-loaded hepatocytes, leading to the discovery that circulating soluble CD46 (sCD46) levels accurately predict hepatic steatosis. METHODS sCD46 in plasma was measured using a newly developed immuno-competition assay in two independent cohorts: Prospective living liver donors (n = 156; male = 66, female = 90) and patients with liver tumours (n = 91; male = 58, female = 33). sCD46 levels were statistically evaluated as a predictor of hepatic steatosis. FINDINGS Interleukin-4-secreting (IL-4+) iNKT cells were over-represented amongst intrahepatic lymphocytes isolated from resected human liver samples. IL-4+ iNKT cells preferentially developed in cocultures with a fat-loaded, hepatocyte-like cell line, HepaRG. This was attributed to induction of matrix metalloproteases (MMP) in fat-loaded HepaRG cells and primary human liver organoids, which led to indiscriminate cleavage of immune receptors. Loss of cell-surface CD46 resulted in unrepressed differentiation of IL-4+ iNKT cells. sCD46 levels were elevated in patients with hepatic steatosis. Discriminatory cut-off values for plasma sCD46 were found that accurately classified patients according to histological steatosis grade. INTERPRETATION sCD46 is a reliable clinical marker of hepatic steatosis, which can be conveniently and non-invasively measured in serum and plasma samples, raising the possibility of using sCD46 levels as a diagnostic method for detecting or grading hepatic steatosis. FUNDING F.B. was supported by the Else Kröner Foundation (Award 2016_kolleg.14). G.G. was supported by the Bristol Myers Squibb Foundation for Immuno-Oncology (Award FA-19-009). N.S. was supported by a Wellcome Trust Fellowship (211113/A/18/Z). J.A.H. received funding from the European Union's Horizon 2020 research and innovation programme (Award 860003). J.M.W. received funding from the Else Kröner Foundation (Award 2015_A10).
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Affiliation(s)
- Florian Bitterer
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Paul Kupke
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Akinbami Adenugba
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Katja Evert
- Institute of Pathology, University of Regensburg, Regensburg 93053, Germany
| | - Gunther Glehr
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Paloma Riquelme
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Lena Scheibert
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Giulia Preverin
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Christina Böhm
- Oxford Nanopore Technologies PLC, Oxford Science Park, Oxford OX4 4DQ, United Kingdom
| | - Matthias Hornung
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Hans J Schlitt
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg 93053, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany
| | - Niloufar Safinia
- Department of Hepatology, King's College London, London SE5 8AF, United Kingdom
| | - James A Hutchinson
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany.
| | - Jens M Werner
- Department of Surgery, University Hospital Regensburg, Regensburg 93053, Germany.
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Huang CF, Liang PC, Wang CW, Jang TY, Hsu PY, Tsai PC, Wei YJ, Yeh ML, Hsieh MY, Lin YH, Huang CK, Dai CY, Huang JF, Chuang WL, Yu ML. Performance of noninvasive seromarkers in predicting liver fibrosis among MAFLD patients with or without viral hepatitis. Kaohsiung J Med Sci 2024; 40:374-383. [PMID: 38234005 DOI: 10.1002/kjm2.12804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/11/2023] [Accepted: 12/25/2023] [Indexed: 01/19/2024] Open
Abstract
The accuracy of noninvasive seromarkers in predicting liver fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) patients with or without viral hepatitis is elusive. The AST to platelet ratio index (APRI), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were assessed in 871 MAFLD patients who received elastography in a viral hepatitis-endemic area. The area under the receiver operating characteristic (AUROC) curve increased substantially with increasing fibrotic stage across the three biomarkers. APRI (AUROC range 0.73-0.80) and FIB-4 (AUROC range 0.66-0.82) performed better than NFS (AUROC range 0.63-0.75). When patients were divided into viral and non-viral MAFLD groups, a better AUROC of APRI (range 0.76-0.80) and FIB-4 (range 0.68-0.78) than NFS (range 0.62-70) existed only in viral MALFD but not in non-viral MAFLD. Regarding the NFS, the AUROC was higher in non-viral MAFLD (range 0.69-0.86) and outperformed viral MAFLD at all fibrotic stages. The accuracy in predicting liver fibrosis increased with the advancement of liver disease for the three biomarkers. NFS exerted better diagnostic accuracy in non-viral than in viral MAFLD patients across different fibrotic stages. The best accuracy was 91.1% using the cutoff value of -9.98 for the NFS in predicting liver cirrhosis in non-viral MAFLD patients. The APRI and FIB-4 performed better than the NFS in predicting liver fibrosis in MAFLD as a whole. The suboptimal performance and accuracy of the NFS existed only in viral MAFLD patients. Caution should be taken when assessing the NFS in MAFLD patients with viral hepatitis.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Academia Sinica, Taipei City, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chao-Kuan Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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10
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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: 0] [Impact Index Per Article: 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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11
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de Souza Echeverria L, Mounzer DLS, Gestic MA, Utrini MP, Chaim FDM, Callejas-Neto F, Chaim EA, Cazzo E. Fibrotic NASH in Individuals with Obesity: a Cross-sectional Analysis of the Prevalence of this Significant Milestone of Disease Progression and Accuracy of a Non-invasive Marker for its Screening. Obes Surg 2024; 34:389-395. [PMID: 38110785 DOI: 10.1007/s11695-023-06998-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 12/11/2023] [Accepted: 12/12/2023] [Indexed: 12/20/2023]
Abstract
BACKGROUND Fibrotic non-alcoholic steatohepatitis (NASH), i.e., the concomitant presence of active inflammation and fibrosis, represents a milestone in the natural history of NAFLD and a critical time point in its progression. The purpose of this study was to analyze the diagnostic accuracy of the non-invasive Fibrotic NASH Index (FNI) in individuals with obesity undergoing bariatric surgery. METHODS This is a cross-sectional study, enrolling individuals who underwent bariatric surgery with liver biopsy at a tertiary university hospital. FNI was calculated, and a cutoff value was determined. Its diagnostic accuracy was then calculated through comparison with the gold standard test for this analysis (histopathological examination). RESULTS Of 128 participants, 83.6% were female, and the average age was 39.8 ± 8.7 years. The mean BMI was 38.7 ± 5.7 kg/m2. NAFLD was histologically confirmed in 76.6%, of which 81.6% had NASH. Histologically confirmed fibrotic NASH was observed in 22.7% of the general study population, 29.6% of individuals with NAFLD, and 36.3% of those with NASH. The mean FNI was 0.18 ± 0.19. An optimal cutoff point of 0.21 was determined, with an overall accuracy of 90.1%, an 82.8% sensitivity, a 90.8% specificity, a 72.6% positive predictive value, and a 94.7% negative predictive value. CONCLUSIONS FNI provided adequate accuracy in detecting and ruling out fibrotic NASH. Considering the importance of fibrotic NASH within the natural history of NAFLD progression and the fact that this marker uses simple variables, it may be of great importance in high-risk populations, and its external validation and use should be encouraged.
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Affiliation(s)
| | | | | | | | | | | | | | - Everton Cazzo
- Dept. of Surgery, State University of Campinas (UNICAMP), Campinas, Brazil.
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12
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van Son K, te Nijenhuis-Noort L, Boone S, Mook-Kanamori D, Holleboom A, Roos P, Lamb H, Alblas G, Coenraad M, Rosendaal F, de Mutsert R, Tushuizen M. Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in a middle-aged population with overweight and normal liver enzymes, and diagnostic accuracy of noninvasive proxies. Medicine (Baltimore) 2024; 103:e34934. [PMID: 38181294 PMCID: PMC10766322 DOI: 10.1097/md.0000000000034934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 08/04/2023] [Indexed: 01/07/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Elevated liver enzymes are a primary reason to refer patients for further testing. However, liver enzymes within the normal range do not exclude the presence of MASLD. We examined the prevalence of MASLD in a middle-aged population with overweight and normal liver enzymes. In addition, we examined the accuracy of 4 sets of noninvasive proxies for MASLD. We included 1017 participants from the Netherlands epidemiology of obesity cohort study with body mass index ≥25 kg/m2 and liver enzymes (asparate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase) within normal range. The diagnostic accuracy of biomarker scores (fatty liver index, liver fat score [LFS], STEATO-ELSA, and hepatic steatosis index) was determined against elevated hepatic triglyceride content measured by 1proton magnetic resonance spectroscopy. Participants (mean age 56 years, 49% women), had a median body mass index of 29.6 kg/m2 and a median hepatic triglyceride content of 4.4%. MASLD was present in 42% of participants and was more common in men than women, with respectively 47% and 36% being affected. The LFS showed the highest accuracy with an area under the curve of 0.72. We identified metabolic syndrome as the prime predictor for MASLD with an odds ratio of 2.95 (95% confidence interval 2.20-3.98). The prevalence of MASLD in middle-aged men and women with overweight and liver enzymes within the normal range is over 40%. LFS showed the highest accuracy to detect MASLD, but, overall, biomarker scores performed relatively poor. The presence of metabolic syndrome was the prime predictor of MASLD.
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Affiliation(s)
- K.C. van Son
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | | | - S.C. Boone
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - D.O. Mook-Kanamori
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - A.G. Holleboom
- Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - P.R. Roos
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - H.J. Lamb
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - G. Alblas
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - M.J. Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - F.R. Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - R. de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - M.E. Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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13
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Kaya E, Yilmaz Y. Noninvasive, serum-based evaluation of liver fibrosis in metabolic (dysfunction)-associated fatty liver disease. METABOLIC STEATOTIC LIVER DISEASE 2024:137-150. [DOI: 10.1016/b978-0-323-99649-5.00012-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Boeriu A, Dobru D, Fofiu C. Non-Invasive Diagnostic of NAFLD in Type 2 Diabetes Mellitus and Risk Stratification: Strengths and Limitations. Life (Basel) 2023; 13:2262. [PMID: 38137863 PMCID: PMC10744403 DOI: 10.3390/life13122262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 10/26/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
The progressive potential of liver damage in type 2 diabetes mellitus (T2DM) towards advanced fibrosis, end-stage liver disease, and hepatocarcinoma has led to increased concern for quantifying liver injury and individual risk assessment. The combination of blood-based markers and imaging techniques is recommended for the initial evaluation in NAFLD and for regular monitoring to evaluate disease progression. Continued development of ultrasonographic and magnetic resonance imaging methods for accurate quantification of liver steatosis and fibrosis, as well as promising tools for the detection of high-risk NASH, have been noted. In this review, we aim to summarize available evidence regarding the usefulness of non-invasive methods for the assessment of NAFLD in T2DM. We focus on the power and limitations of various methods for diagnosis, risk stratification, and patient monitoring that support their implementation in clinical setting or in research field.
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Affiliation(s)
- Alina Boeriu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Daniela Dobru
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Crina Fofiu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Internal Medicine Department, Bistrita County Clinical Hospital, 420094 Bistrita, Romania
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15
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Gîlcă-Blanariu GE, Budur DS, Mitrică DE, Gologan E, Timofte O, Bălan GG, Olteanu VA, Ștefănescu G. Advances in Noninvasive Biomarkers for Nonalcoholic Fatty Liver Disease. Metabolites 2023; 13:1115. [PMID: 37999211 PMCID: PMC10672868 DOI: 10.3390/metabo13111115] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/15/2023] [Accepted: 10/24/2023] [Indexed: 11/25/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) currently represents one of the most common liver diseases worldwide. Early diagnosis and disease staging is crucial, since it is mainly asymptomatic, but can progress to nonalcoholic steatohepatitis (NASH) or cirrhosis or even lead to the development of hepatocellular carcinoma. Over time, efforts have been put into developing noninvasive diagnostic and staging methods in order to replace the use of a liver biopsy. The noninvasive methods used include imaging techniques that measure liver stiffness and biological markers, with a focus on serum biomarkers. Due to the impressive complexity of the NAFLD's pathophysiology, biomarkers are able to assay different processes involved, such as apoptosis, fibrogenesis, and inflammation, or even address the genetic background and "omics" technologies. This article reviews not only the currently validated noninvasive methods to investigate NAFLD but also the promising results regarding recently discovered biomarkers, including biomarker panels and the combination of the currently validated evaluation methods and serum markers.
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Affiliation(s)
- Georgiana-Emmanuela Gîlcă-Blanariu
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
| | - Daniela Simona Budur
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
| | - Dana Elena Mitrică
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
| | - Elena Gologan
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
| | - Oana Timofte
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
| | - Gheorghe Gh Bălan
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
| | - Vasile Andrei Olteanu
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
| | - Gabriela Ștefănescu
- Gastroenterology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-E.G.-B.); (D.E.M.); (E.G.); (O.T.); (G.G.B.); (V.A.O.)
- Department of Gastroenterology, “Sf Spiridon” County Clinical Emergency Hospital, 100115 Iași, Romania
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16
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Eskridge W, Cryer DR, Schattenberg JM, Gastaldelli A, Malhi H, Allen AM, Noureddin M, Sanyal AJ. Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective. J Clin Med 2023; 12:6216. [PMID: 37834859 PMCID: PMC10573476 DOI: 10.3390/jcm12196216] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage. Specifically, the paper dives into the issues patients and physicians experience, and, in turn, what is required to improve diagnosis and management, including tips and tools to empower patients and physicians dealing with MASLD.
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Affiliation(s)
| | | | - Jörn M. Schattenberg
- Metabolic Liver Research Program, Department of Medicine, University Medical Center of the Johannes Gutenberg University, 155131 Mainz, Germany
| | - Amalia Gastaldelli
- Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, Italian National Research Council CNR, 00133 Pisa, Italy
| | - Harmeet Malhi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55901, USA
| | - Alina M. Allen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55901, USA
| | - Mazen Noureddin
- Fatty Liver Program, Karsh Division of Gastroenterology and Hepatology, Cedar Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Arun J. Sanyal
- Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, VCU School of Medicine and Health System and Division of Gastroenterology, Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA
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17
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Garrafa E, Segala A, Vezzoli M, Bottani E, Zanini B, Vetturi A, Bracale R, Ricci C, Valerio A. Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers. Diagnostics (Basel) 2023; 13:2363. [PMID: 37510108 PMCID: PMC10378438 DOI: 10.3390/diagnostics13142363] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.
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Affiliation(s)
- Emirena Garrafa
- Department of Laboratory Diagnostics, ASST Spedali Civili, 25123 Brescia, Italy
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Agnese Segala
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Marika Vezzoli
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Emanuela Bottani
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Barbara Zanini
- Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
| | - Alice Vetturi
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Renata Bracale
- Department of Medicine and Sciences for Health, Molise University, 86100 Campobasso, Italy
| | - Chiara Ricci
- Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
- Division of Gastroenterology, ASST Spedali Civili, 25123 Brescia, Italy
| | - Alessandra Valerio
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
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Clark JM, Cryer DRH, Morton M, Shubrook JH. Nonalcoholic fatty liver disease from a primary care perspective. Diabetes Obes Metab 2023; 25:1421-1433. [PMID: 36789676 DOI: 10.1111/dom.15016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/31/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects up to one-third of the US population. Approximately one-fifth of patients with NAFLD have nonalcoholic steatohepatitis (NASH), characterized by hepatocyte damage and inflammation with or without fibrosis. NASH leads to greater risk of liver-related complications and liver-related mortality, with the poorest outcomes seen in patients with advanced fibrosis. NASH is also associated with other metabolic comorbidities and conveys an increased risk of adverse cardiovascular outcomes and extrahepatic cancers. Despite its high prevalence, NAFLD is frequently underdiagnosed. This is a significant concern, given that early diagnosis of NAFLD is a key step in preventing progression to NASH. In this review, we describe the clinical impact of NASH from the perspective of both the clinician and the patient. In addition, we provide practical guidance on the diagnosis and management of NASH for primary care providers, who play a pivotal role in the frontline care of patients with NASH, and we use case studies to illustrate real-world scenarios encountered in the primary care setting.
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Affiliation(s)
- Jeanne M Clark
- Department of Medicine, Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Donna R H Cryer
- Global Liver Institute, Washington, District of Columbia, USA
| | | | - Jay H Shubrook
- Primary Care Department, Touro University California College of Osteopathic Medicine, Vallejo, California, USA
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19
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Radu F, Potcovaru CG, Salmen T, Filip PV, Pop C, Fierbințeanu-Braticievici C. The Link between NAFLD and Metabolic Syndrome. Diagnostics (Basel) 2023; 13:diagnostics13040614. [PMID: 36832102 PMCID: PMC9955701 DOI: 10.3390/diagnostics13040614] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/02/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Most recent studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS' pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome. Taking into consideration the present pandemic of obesity and its tendency to drift towards a progressively earlier onset due to the Western lifestyle, it leads to an increased NAFLD incidence. Novel therapeutic resources are lifestyle intervention with physical activity, Mediterranean diet, or therapeutic surgical respective metabolic and bariatric surgery or drugs such as SGLT-2i, GLP-1 Ra or vitamin E. NAFLD early diagnosis is important due to its easily available diagnostic tools such as non-invasive tools: clinical and laboratory variables (serum biomarkers): AST to platelet ratio index, fibrosis-4, NAFLD Fibrosis Score, BARD Score, fibro test, enhanced liver fibrosis; imaging-based biomarkers: Controlled attenuation parameter, magnetic resonance imaging proton-density fat fraction, transient elastography (TE) or vibration controlled TE, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography; and the possibility to prevent its complications, respectively, fibrosis, hepato-cellular carcinoma or liver cirrhosis which can develop into end-stage liver disease.
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Affiliation(s)
- Fabiana Radu
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Claudia-Gabriela Potcovaru
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Correspondence:
| | - Teodor Salmen
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Petruța Violeta Filip
- Department of Gastroenterology and Internal Medicine, Clinical Emergency University Hospital, 050098 Bucharest, Romania
| | - Corina Pop
- Department of Gastroenterology and Internal Medicine, Clinical Emergency University Hospital, 050098 Bucharest, Romania
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Chee D, Ng CH, Chan KE, Huang DQ, Teng M, Muthiah M. The Past, Present, and Future of Noninvasive Test in Chronic Liver Diseases. Med Clin North Am 2023; 107:397-421. [PMID: 37001944 DOI: 10.1016/j.mcna.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Chronic liver disease is a major global health threat and is the 11th leading cause of death globally. A liver biopsy is frequently required in assessing the degree of steatosis and fibrosis, information that is important in diagnosis, management, and prognostication. However, liver biopsies have limitations and carry a considerable risk, leading to the development of various modalities of noninvasive testing tools. These tools have been developed in recent years and have improved markedly in diagnostic accuracy. Moving forward, they may change the practice of hepatology.
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Affiliation(s)
- Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Kai En Chan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Margaret Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore.
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21
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Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives. Nutrients 2023; 15:nu15030687. [PMID: 36771394 PMCID: PMC9921401 DOI: 10.3390/nu15030687] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/25/2023] [Accepted: 01/28/2023] [Indexed: 02/01/2023] Open
Abstract
While non-alcoholic fatty liver disease (NAFLD) is a prevalent and frequent cause of liver-related morbidity and mortality, it is also strongly associated with cardiovascular disease-related morbidity and mortality, likely driven by its associations with insulin resistance and other manifestations of metabolic dysregulation. However, few satisfactory pharmacological treatments are available for NAFLD due in part to its complex pathophysiology, and challenges remain in stratifying individual patient's risk for liver and cardiovascular disease related outcomes. In this review, we describe the development and progression of NAFLD, including its pathophysiology and outcomes. We also describe different tools for identifying patients with NAFLD who are most at risk of liver-related and cardiovascular-related complications, as well as current and emerging treatment options, and future directions for research.
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22
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Yongpisarn T, Namasondhi A, Iamsumang W, Rattanakaemakorn P, Suchonwanit P. Liver fibrosis prevalence and risk factors in patients with psoriasis: A systematic review and meta-analysis. Front Med (Lausanne) 2022; 9:1068157. [PMID: 36590962 PMCID: PMC9797863 DOI: 10.3389/fmed.2022.1068157] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/02/2022] [Indexed: 12/23/2022] Open
Abstract
Background Patients with psoriasis are more likely than matched controls in the general population to have advanced liver fibrosis; however, our understanding of these patients is limited. There is currently no systematic evaluation of the prevalence and risk factors of liver fibrosis in psoriasis patients. Objective To evaluate the prevalence of psoriasis patients who are at high or low risk for advanced liver fibrosis and determine the risk factors for developing liver fibrosis. Methods Electronic searches were conducted using the PubMed, Embase, Scopus, and Cochrane Library databases from the dates of their inception till May 2022, using the PubMed, Embase, Scopus, and Cochrane Library databases. Any observational study describing the prevalence and/or risk factors for liver fibrosis in patients with psoriasis was included. Results Patients with psoriasis at high risk for advanced liver fibrosis had a pooled prevalence of 9.66% [95% confidence interval (CI): 6.92-12.75%, I 2 = 76.34%], whereas patients at low risk for advanced liver fibrosis had a pooled prevalence of 77.79% (95% CI: 73.23-82.05%, I 2 = 85.72%). Studies that recruited methotrexate (MTX)-naïve patients found a lower prevalence of advanced liver fibrosis (4.44, 95% CI: 1.17-9.22%, I 2 = 59.34%) than those that recruited MTX-user cohorts (12.25, 95% CI: 6.02-20.08%, I 2 = 82.34%). Age, sex, BMI, PASI score, psoriasis duration, MTX cumulative dose, and the prevalence of obesity, MTX users, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were not identified as sources of heterogeneity by meta-regression analysis. The pooled odds ratios for age >50 years, BMI > 30, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were 2.20 (95% CI: 1.42-3.40, I 2 = 0%), 3.67 (95% CI: 2.37-5.68, I 2 = 48.8%), 6.23 (95% CI: 4.39-8.84, I 2 = 42.4%), 2.82 (95% CI: 1.68-4.74, I 2 = 0%), 3.08 (95% CI: 1.90-4.98, I 2 = 0%), and 5.98 (95% CI: 3.63-9.83, I 2 = 17%), respectively. Conclusion Approximately 10% of the population with psoriasis is at high risk for advanced liver fibrosis, while 78% are at low risk. Patients over the age of 50 with obesity, diabetes, hypertension, dyslipidemia, and/or metabolic syndrome have an increased risk of developing liver fibrosis, necessitating monitoring. Systematic review registration [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022303886], identifier [CRD42022303886].
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Wang J, Qin T, Sun J, Li S, Cao L, Lu X. Non-invasive methods to evaluate liver fibrosis in patients with non-alcoholic fatty liver disease. Front Physiol 2022; 13:1046497. [PMID: 36589424 PMCID: PMC9794751 DOI: 10.3389/fphys.2022.1046497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/15/2022] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease that is strongly related to insulin resistance and metabolic syndrome, and it has become the most common liver disorder in developed countries. NAFLD embraces the full pathological process of three conditions: steatosis, non-alcoholic steatohepatitis, and finally, cirrhosis. As NAFLD progresses, symptoms will become increasingly severe as fibrosis develops. Therefore, evaluating the fibrosis stage is crucial for patients with NAFLD. A liver biopsy is currently considered the gold standard for staging fibrosis. However, due to the limitations of liver biopsy, non-invasive alternatives were extensively studied and validated in patients with NAFLD. The advantages of non-invasive methods include their high safety and convenience compared with other invasive approaches. This review introduces the non-invasive methods, summarizes their benefits and limitations, and assesses their diagnostic performance for NAFLD-induced fibrosis.
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Affiliation(s)
- Jincheng Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tao Qin
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinyu Sun
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shiwu Li
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China
| | - Lihua Cao
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China,*Correspondence: Xiaojie Lu, ; Lihua Cao,
| | - Xiaojie Lu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,*Correspondence: Xiaojie Lu, ; Lihua Cao,
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Belcaro G, Cox DM, Cesarone MR, Gizzi G, Pellegrini L, Scipione C, Scipione V, Dugall M, Hu S, Corsi M, Feragalli B, Cotellese R. Effects of Robuvit® on the progression of non-alcoholic fatty liver disease. Minerva Gastroenterol (Torino) 2022; 68:434-441. [PMID: 36507829 DOI: 10.23736/s2724-5985.22.03201-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the effects of Robuvit® in preventing the progression of chronic hepatitis (CH) in non-alcoholic fatty liver disease (NAFLD) which encompasses the entire spectrum of fatty liver disease, from isolated steatosis to non-alcoholic steatohepatitis (NASH). METHODS One group of patients followed the Standard management (SM) and were assigned as controls while the supplementation group followed the SM and additionally took 2 Robuvit® capsules daily for 3 months (200 mg/day). RESULTS 34 subjects with NAFLD were included in the study. The two groups completing 90 days were comparable at baseline with 18 being supplemented with Robuvit® and 16 in the control group. The tolerability was very good, and no side effects were observed with the supplement. Fasting glucose levels were significantly lower after 3 months with Robuvit® (P<0.05) compared to controls. The increased serum aspartate aminotransferase levels (AST), considered the key metabolic value in these patients, decreased significantly with Robuvit® (P<0.05) compared to controls. Serum alanine aminotransferase levels (ALT) also decreased significantly with the supplement compared to controls (P<0.05). Platelet count and albumin levels improved significantly with Robuvit® (P<0.05) in comparison to standard management. No other significant changes were observed. The APRI score (the AST/platelet ratio index) was also decreased with the supplementation compared to controls (P<0.05). A high APRI score provides an estimate of the possibility of the liver to develop fibrosis and eventually cirrhosis. After Robuvit® supplementation, the ultrasound characterization showed a significant decrease in the size of the liver in association with a lower echogenicity, which represents less fibrotic changes due to collagen accumulation. CONCLUSIONS Robuvit® improved liver function in NAFLD and prevented progression to liver fibrosis by improving hepatic metabolism in a relatively short period of time. Numerous people are affected by NAFLD, many of them with subclinical symptoms. But to date, there are no specific, definite treatment options. Prolonged evaluations of Robuvit® in a larger group of subjects is suggested.
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Affiliation(s)
- Gianni Belcaro
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy -
| | - David M Cox
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - M Rosaria Cesarone
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Giuseppe Gizzi
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Luciano Pellegrini
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Claudia Scipione
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Valeria Scipione
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Mark Dugall
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Shu Hu
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | - Marcello Corsi
- Irvine3 Labs, San Valentino Vascular Screening Project and IA-PSS (International Agency for Pharma-Standard Supplements) Pescara, Italy
| | | | - Roberto Cotellese
- Dept.SMO-Biotec, Chieti University, Italy.,Outpatients Vascular Surgery, School of General Surgery, Ch-Pe University, Pescara, Italy
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25
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Kechagias S, Ekstedt M, Simonsson C, Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones (Athens) 2022; 21:349-368. [PMID: 35661987 PMCID: PMC9464753 DOI: 10.1007/s42000-022-00377-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 05/19/2022] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome and is characterized by ectopic accumulation of triglycerides in the cytoplasm of hepatocytes, i.e., steatosis. NAFLD has become the most common chronic liver disease, with an estimated global prevalence of 25%. Although the majority of NAFLD patients will never experience liver-related complications, the progressive potential of NAFLD is indisputable, with 5-10% of subjects progressing to cirrhosis, end-stage liver disease, or hepatocellular carcinoma. NAFLD patients with advanced fibrosis are at the highest risk of developing cardiovascular and cirrhosis-related complications. Liver biopsy has hitherto been considered the reference method for evaluation of hepatic steatosis and fibrosis stage. Given the limitations of biopsy for widescale screening, non-invasive tests (NITs) for assessment of steatosis and fibrosis stage, including serum-based algorithms and ultrasound- and magnetic resonance-based methods, will play an increasing role in the management of NAFLD patients. This comprehensive review presents the advantages and limitations of NITs for identification of steatosis and advanced fibrosis in NAFLD. The clinical implications of using NITs to identify and manage NAFLD patients are also discussed.
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Affiliation(s)
- Stergios Kechagias
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden.
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden.
| | - Mattias Ekstedt
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden
| | - Christian Simonsson
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
| | - Patrik Nasr
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden
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Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity. CHILDREN 2022; 9:children9081174. [PMID: 36010064 PMCID: PMC9406958 DOI: 10.3390/children9081174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 07/28/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an important health concern during childhood; indeed, it is the most frequent cause of chronic liver diseases in obese children. No valid pharmacological therapies for children affected by this condition are available, and the recommended treatment is lifestyle modification, usually including nutrition and exercise interventions. In this narrative review, we summarized up-to-date information on the benefits of physical exercise on NAFLD in children and adolescents with obesity. The role of exercise as non-pharmacological treatment was emphasized in order to provide recent advances on this topic for clinicians not deeply involved in the field. Several studies on obese children and adults confirm the positive role of physical activity (PA) in the treatment of NAFLD, but to date, there are no pediatric randomized clinical trials on exercise versus usual care. Among the pathogenic mechanisms involved in the PA effects on NAFLD, the main players seem to be insulin resistance and related inflammation, oxidative stress, and gut dysbiosis, but further evaluations are necessary to deeply understand whether these factors are correlated and how they synergistically act. Thus, a deeper research on this theme is needed, and it would be extremely interesting.
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27
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Dufour JF, Anstee QM, Bugianesi E, Harrison S, Loomba R, Paradis V, Tilg H, Wong VWS, Zelber-Sagi S. Current therapies and new developments in NASH. Gut 2022; 71:gutjnl-2021-326874. [PMID: 35710299 PMCID: PMC9484366 DOI: 10.1136/gutjnl-2021-326874] [Citation(s) in RCA: 118] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 04/26/2022] [Indexed: 12/13/2022]
Abstract
Non-alcoholic steatohepatitis is becoming the most important aetiology for advanced liver disease. There has been important progress in the field in recent years and the complexity of the pathophysiology of NASH is better understood. Multiple non-invasive circulating and imaging biomarkers have been tested. The importance of lifestyle has been recognised and several drugs are being tested in clinical trials. This review addresses the challenges that healthcare professionals face in the management of NASH patients.
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Affiliation(s)
| | - Quentin M Anstee
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
| | | | - Stephen Harrison
- Pinnacle clinical research, San Antonio, Texas, USA
- Visiting Professor of Hepatology, University of Oxford, Oxford, UK
| | - Rohit Loomba
- Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, California, USA
| | | | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa, Israel
- Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel
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28
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Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol 2022; 76:1362-1378. [PMID: 35589256 DOI: 10.1016/j.jhep.2022.03.026] [Citation(s) in RCA: 126] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 03/28/2022] [Indexed: 12/11/2022]
Abstract
Over the last two decades, there have been tremendous advances in the non-invasive diagnosis and risk stratification of chronic liver diseases (CLDs). Non-invasive approaches are based on the quantification of biomarkers in serum samples or on the measurement of liver stiffness, using either ultrasound- or magnetic resonance-based elastography techniques. The fibrosis-4 index (non-patented) and enhanced liver fibrosis test (patented) are the most widely adopted serum markers, whereas vibration-controlled transient elastography is the most widely adopted elastography technique. In this review, we discuss the role of non-invasive tests in the current era, as well as their accuracy and how their use in clinical practice has changed the practice of hepatology, including identification of early cirrhosis in patients with risk factors for CLD, diagnosis of portal hypertension, establishing prognosis in compensated cirrhosis, guiding antiviral treatment, and screening for fibrosis and cirrhosis in primary care.
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Affiliation(s)
- Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
| | - Laurent Castera
- Université de Paris, UMR1149 (CRI), Inserm, F-75018 Paris, France; Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, F-92110 Clichy-la-Garenne, France.
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, United States; Herbert Wertheim School of Public Health, University of California at San Diego, La Jolla, CA, United States.
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29
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Pipe SW, Reddy KR, Chowdary P. Gene therapy: Practical aspects of implementation. Haemophilia 2022; 28 Suppl 4:44-52. [PMID: 35521727 PMCID: PMC9324089 DOI: 10.1111/hae.14545] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/27/2022] [Accepted: 02/28/2022] [Indexed: 12/17/2022]
Abstract
The first wave of gene therapies for haemophilia submitted for regulatory review utilize a liver-directed approach in which a functional gene copy of factor VIII (FVIII) or factor IX (FIX) is packaged inside a recombinant adeno-associated viral vector (rAAV). Following a single treatment event, these particles are taken up into liver cells, where the rAAV uncoats and delivers the DNA to the nucleus of the cell, where genetic elements that accompany the gene allow for efficient expression and secretion of FVIII or FIX protein into the plasma. An immune response to the vector capsid has been manifest by elevations in common liver enzymes that must be diligently followed postinfusion for weeks and months afterward and if signs of toxicity appear, will trigger a course of immunosuppression. Despite this, the studies have shown that this works in the great majority of individuals and the immunosuppression course is either avoided or short-lived for many. Optimal outcomes in the haemophilia population will be dependent on proper screening assessment and maintenance of liver health prior to consideration of gene therapy, close short-term follow up and implementation of immunomodulatory strategies to identify and manage liver toxicity and preserve durable transgene expression. This review proposes best practices to assist clinical teams with overcoming the challenges this platform of therapy poses to the traditional clinical care models and infrastructure within the haemophilia treatment centres (HTCs) who will be coordinating the patient's journey through this potentially transformative therapy.
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Affiliation(s)
- Steven W Pipe
- Departments of Paediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - K Rajender Reddy
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Pratima Chowdary
- Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK
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Mózes FE, Lee JA, Selvaraj EA, Jayaswal ANA, Trauner M, Boursier J, Fournier C, Staufer K, Stauber RE, Bugianesi E, Younes R, Gaia S, Lupșor-Platon M, Petta S, Shima T, Okanoue T, Mahadeva S, Chan WK, Eddowes PJ, Hirschfield GM, Newsome PN, Wong VWS, de Ledinghen V, Fan J, Shen F, Cobbold JF, Sumida Y, Okajima A, Schattenberg JM, Labenz C, Kim W, Lee MS, Wiegand J, Karlas T, Yılmaz Y, Aithal GP, Palaniyappan N, Cassinotto C, Aggarwal S, Garg H, Ooi GJ, Nakajima A, Yoneda M, Ziol M, Barget N, Geier A, Tuthill T, Brosnan MJ, Anstee QM, Neubauer S, Harrison SA, Bossuyt PM, Pavlides M. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut 2022; 71:1006-1019. [PMID: 34001645 PMCID: PMC8995830 DOI: 10.1136/gutjnl-2021-324243] [Citation(s) in RCA: 281] [Impact Index Per Article: 93.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/23/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. CONCLUSION Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.
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Affiliation(s)
- Ferenc Emil Mózes
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Jenny A Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Emmanuel Anandraj Selvaraj
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK,Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Jerome Boursier
- Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Universite d'Angers, Angers, Pays de la Loire, France,Service d'Hepato-Gastroenterologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
| | | | - Katharina Staufer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria,Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, Bern, Switzerland,Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Rudolf E Stauber
- Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | | | - Ramy Younes
- Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
| | - Silvia Gaia
- Medical Sciences, University of Turin, Torino, Italy
| | - Monica Lupșor-Platon
- Department of Ultrasonography, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, Cluj Napoca, Romania
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, Palermo, Italy
| | - Toshihide Shima
- Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Sanjiv Mahadeva
- Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Wah-Kheong Chan
- Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Peter J Eddowes
- NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK,NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Philip Noel Newsome
- NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Victor de Ledinghen
- Centre d'Investigation de la Fibrose Hépatique, Hopital Haut-Leveque, Pessac, France,INSERM1053, Universite de Bordeaux, Talence, Aquitaine, France
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Feng Shen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jeremy F Cobbold
- Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | - Yoshio Sumida
- Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan
| | - Akira Okajima
- Department of Gastroenterology, Koseikai Takeda Hospital, Kyoto, Japan
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany
| | - Won Kim
- Department of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea
| | - Myoung Seok Lee
- Department of Radiology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, The Republic of Korea
| | - Johannes Wiegand
- Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany
| | - Thomas Karlas
- Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany
| | - Yusuf Yılmaz
- Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey,Institute of Gastroenterology, Marmara University, Istanbul, Turkey
| | - Guruprasad Padur Aithal
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Christophe Cassinotto
- Diagnostic and Interventional Radiology, University Hospital Centre Montpellier, Montpellier, Languedoc-Roussillon, France
| | - Sandeep Aggarwal
- Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India
| | - Harshit Garg
- Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India
| | - Geraldine J Ooi
- Department of Surgery, Monash University, Prahran, Victoria, Australia
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Marianne Ziol
- Service d'Anatomie Pathologique et Centre de Ressources Biologiques, Hopital Jean Verdier, Paris, France
| | - Nathalie Barget
- Centre de Ressources Biologiques, Hopitaux Universitaires Paris-Seine-Saint-Denis, Bondy, Île-de-France, France
| | - Andreas Geier
- Division of Hepatology, University Hospital Wurzburg, Wurzburg, Bayern, Germany
| | - Theresa Tuthill
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA
| | - M. Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA
| | - Quentin Mark Anstee
- Translational and Clinical Research Institute, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
| | - Stefan Neubauer
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Stephen A. Harrison
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Michael Pavlides
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK .,Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK.,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
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31
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Rinella ME, Dufour JF, Anstee QM, Goodman Z, Younossi Z, Harrison SA, Loomba R, Sanyal AJ, Bonacci M, Trylesinski A, Natha M, Shringarpure R, Granston T, Venugopal A, Ratziu V. Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study. J Hepatol 2022; 76:536-548. [PMID: 34793868 DOI: 10.1016/j.jhep.2021.10.029] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is a chronic, progressive fibrotic liver disease that can lead to cirrhosis. While liver biopsy is considered the reference standard for the histologic diagnosis of NASH and staging of fibrosis, its use in clinical practice is limited. Non-invasive tests (NITs) are increasingly being used to identify and stage liver fibrosis in patients with NASH, and several can assess liver-related outcomes. We report changes in various NITs in patients treated with obeticholic acid (OCA) or placebo in the phase III REGENERATE study. METHODS Patients with NASH and fibrosis stage F2 or F3 (n = 931) were randomized (1:1:1) to receive placebo, OCA 10 mg, or OCA 25 mg once daily. Various NITs based on clinical chemistry and/or imaging were evaluated at baseline and throughout the study. RESULTS Rapid, sustained reductions from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase levels, as well as in Fibrosis-4 (FIB-4), FibroTest, FibroMeter, and FibroScan-AST scores were observed in OCA-treated vs. placebo-treated patients. Reduction in liver stiffness by vibration-controlled transient elastography was observed in the OCA 25 mg group vs. the placebo group at Month 18. NIT changes were associated with shifts in histologic fibrosis stage. The greatest improvements were observed in patients with ≥1-stage fibrosis improvement; however, improvements in ALT, AST, FIB-4, and FibroTest were also observed in OCA-treated patients whose histologic fibrosis remained stable. CONCLUSIONS Based on the REGENERATE Month 18 interim analysis, rapid and sustained improvements in various NITs were observed with OCA treatment. Dynamic changes in selected NITs separated histologic responders from non-responders. These results suggest that NITs may be useful in assessing histologic response to OCA therapy. CLINICALTRIALS. GOV NUMBER NCT02548351 LAY SUMMARY: Non-alcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, non-invasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study, which is evaluating the effects of obeticholic acid vs. placebo in patients with NASH, various NITs were also evaluated. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients' response to therapy.
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Affiliation(s)
- Mary E Rinella
- Department of Medicine, Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jean-Francois Dufour
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; Hepatology, Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Quentin M Anstee
- The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Zachary Goodman
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Zobair Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | | | - Rohit Loomba
- Division of Gastroenterology, University of California San Diego, San Diego, CA, USA
| | - Arun J Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA
| | | | | | - Macky Natha
- Intercept Pharmaceuticals, San Diego, CA, USA
| | | | | | | | - Vlad Ratziu
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié - Salpêtrière, Institute for Cardiometabolism and Nutrition, INSERM UMRS 1138 CRC, Paris, France.
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32
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Ciardullo S, Perseghin G. Advances in fibrosis biomarkers in nonalcoholic fatty liver disease. Adv Clin Chem 2022; 106:33-65. [PMID: 35152974 DOI: 10.1016/bs.acc.2021.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult world population and the degree of liver fibrosis represents the best predictor of the development of liver-related outcomes. Easily applicable and well performing non-invasive fibrosis tests can overcome the limitations of liver biopsy and are of paramount importance to identify at-risk subjects in clinical practice. While tests with optimal performance and ease of use do not exist at this stage, available markers can be divided in three broad groups: simple serum tests, complex serum tests and elastographic methods. Simple scores (such as Fibrosis-4 and NAFLD Fibrosis Score) are based on readily available biochemical data and clinical features, while complex/proprietary tests (such as Fibrotest, Enhanced Liver Fibrosis and Hepascore) directly measure markers of fibrogenesis and fibrolysis, but have higher costs. Elastography techniques estimate the degree of fibrosis from liver stiffness and are based on either ultrasound or magnetic resonance (MR) imaging. MR elastography has better performance compared with sonographic techniques and is not affected by obesity and inflammation, but is highly costly and less available. In general, non-invasive tests are able to exclude the presence of fibrosis, but their positive predictive value is low to moderate and they lead to a high number of indeterminate results. In this context, a combination of different tests might increase accuracy while reducing gray-zone results. Their ability to predict future events and response to treatment is suboptimal and needs to be studied further. Finally, recent studies have tried different approaches, spanning from "omics" to the microbiome and micro-RNAs, with some promising results.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy.
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Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches. Diagnostics (Basel) 2022; 12:diagnostics12020407. [PMID: 35204498 PMCID: PMC8871470 DOI: 10.3390/diagnostics12020407] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/31/2022] [Accepted: 02/02/2022] [Indexed: 02/05/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.
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Meritsi A, Latsou D, Manesis E, Gatos I, Theotokas I, Zoumpoulis P, Rapti S, Tsitsopoulos E, Moshoyianni H, Manolakopoulos S, Pektasides D, Thanopoulou A. Noninvasive, Blood-Based Biomarkers as Screening Tools for Hepatic Fibrosis in People With Type 2 Diabetes. Clin Diabetes 2022; 40:327-338. [PMID: 35983425 PMCID: PMC9331611 DOI: 10.2337/cd21-0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is dramatically increasing in parallel with the pandemic of type 2 diabetes. Here, the authors aimed to assess the performance of the most commonly used noninvasive, blood-based biomarkers for liver fibrosis (FibroTest, NAFLD fibrosis score, BARD score, and FIB-4 Index) in subjects with type 2 diabetes. Liver stiffness measurement was estimated by two-dimensional shear wave elastography. Finally, the authors assessed the diagnostic role of ActiTest and NashTest 2 in liver fibrosis in the examined population.
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Affiliation(s)
- Angeliki Meritsi
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitra Latsou
- Department of Social and Educational Policy, University of Peloponnese, Corinth, Greece
| | | | - Ilias Gatos
- Diagnostic Echotomography, SA, Kifissia, Athens, Greece
| | | | | | - Stamatia Rapti
- Laboratory of Molecular Genetics, Biomedicine, SA, Athens, Greece
| | | | | | - Spilios Manolakopoulos
- Liver and Gastrointestinal Unit, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Pektasides
- 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Thanopoulou
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Meritsi A, Manesis E, Koussis P, Rapti S, Latsou D, Tsitsopoulos E, Moshoyianni H, Manolakopoulos S, Pektasides D, Thanopoulou A. PNPLA3 rs 738409 and Other Nongenetic Factors Associated with Hepatic Steatosis Estimated by Magnetic Resonance Imaging Proton Density Fat Fraction in Adult Greek Subjects with Type 2 Diabetes Mellitus. Metab Syndr Relat Disord 2021; 20:124-131. [PMID: 34962148 DOI: 10.1089/met.2021.0098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objectives: Nonalcoholic fatty liver disease is dramatically increasing in parallel with the pandemic of type 2 diabetes mellitus. We investigated factors associated with hepatic steatosis (HS) in adult Greek individuals with established type 2 diabetes mellitus. Materials and Methods: We investigated 120 consecutive people with type 2 diabetes attending the Diabetic Outpatient Clinic at an Academic Hospital in Athens, Greece. All of them had demographic, clinical, and biochemical data recorded. HS was estimated by magnetic resonance imaging determined by proton density fat fraction software and defined as the percentage of total liver fat divided by the liver volume. HS of >5% was considered abnormal. The PNPLA3 (I148M) variant was evaluated as a genetic factor by standard molecular techniques. FibroMax™ was also calculated. Results: Of the 120 participants, median age was 61.7, 46% were females, diabetes duration was 10 years, and HbA1c (glycated hemoglobin) was 6.7%. The median value of HS was 7.8. The PNPLA3 rs738409 CC/CG/GG genotype frequencies were 54.2%, 35%, and 10.8%, respectively. In multivariate analysis, PNPLA3 rs738409 (β = 0.425, P = 0.001), waist circumference (β = 2.448, P = 0.001), and female sex (β = 0.419, P = 0.002) had a direct association with HS, while duration of diabetes (β = -0.179, P = 0.011) had an inverse association with HS. Conclusions: HS in type 2 diabetes is the sum of interplay of various factors exerting a direct or an inverse association, the most prominent among them being abdominal obesity and PNPLA3 molecular variability.
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Affiliation(s)
- Angeliki Meritsi
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | - Stamatia Rapti
- Laboratory of Molecular Genetics, Biomedicine SA, Athens, Greece
| | - Dimitra Latsou
- Department of Social and Educational Policy, University of Peloponnese, Corinth, Greece
| | | | | | - Spilios Manolakopoulos
- Liver & Gastrointestinal Unit, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Pektasides
- 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Thanopoulou
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Kaur N, Goyal G, Garg R, Tapasvi C, Chawla S, Kaur R. Potential role of noninvasive biomarkers during liver fibrosis. World J Hepatol 2021; 13:1919-1935. [DOI: 10.4254/wjh.v13.i12.1919 kaur n, goyal g, garg r, tapasvi c, chawla s, kaur r. potential role of noninvasive biomarkers during liver fibrosis. world j hepatol 2021; 13(12): 1919-1935 [pmid: 35069998 doi: 10.4254/wjh.v13.i12.1919]] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/06/2024] Open
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37
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Kaur N, Goyal G, Garg R, Tapasvi C, Chawla S, Kaur R. Potential role of noninvasive biomarkers during liver fibrosis. World J Hepatol 2021; 13:1919-1935. [PMID: 35069998 PMCID: PMC8727215 DOI: 10.4254/wjh.v13.i12.1919] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/18/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
Various types of liver disease exist, such as hepatitis and alcoholic liver disease. These liver diseases can result in scarring of liver tissue, cirrhosis, and finally liver failure. During liver fibrosis, there is an excess and disorganized accumulation of extracellular matrix (ECM) components which cause the loss of normal liver cell functions. For patients with chronic liver disease, fibrosis prediction is an essential part of the assessment and management. To diagnose liver fibrosis, several invasive and noninvasive markers have been proposed. However, the adoption of invasive markers remains limited due to their inherent characteristics and poor patient acceptance rate. In contrast, noninvasive markers can expedite the clinical decision through informed judgment about disease stage and prognosis. These noninvasive markers are classified into two types: Imaging techniques and serum biomarkers. However, the diagnostic values of biomarkers associated with liver fibrosis have also been analyzed. For example, the serum levels of ECM proteins can react to either matrix accumulation or degradation. During virus-host interactions, several regulatory steps take place to control gene expression, such as the change in cellular microRNA expression profiles. MicroRNAs are a class of non-coding RNAs (18-20 long nucleotides) that function by post-transcriptional regulation of gene expression. Although various noninvasive markers have been suggested in recent years, certain limitations have restricted their clinical applications. Understanding the potential of non-invasive biomarkers as a therapeutic option to treat liver fibrosis is still in progress.
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Affiliation(s)
- Navneet Kaur
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Gitanjali Goyal
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Ravinder Garg
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Chaitanya Tapasvi
- Department of Radiodiagnosis, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Sonia Chawla
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Rajneet Kaur
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
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Petrtýl J, Dvořák K, Stříteský J, Leníček M, Jirásková A, Šmíd V, Haluzík M, Brůha R, Vítek L. Association of Serum Bilirubin and Functional Variants of Heme Oxygenase 1 and Bilirubin UDP-Glucuronosyl Transferase Genes in Czech Adult Patients with Non-Alcoholic Fatty Liver Disease. Antioxidants (Basel) 2021; 10:antiox10122000. [PMID: 34943103 PMCID: PMC8698489 DOI: 10.3390/antiox10122000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 12/29/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.
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Affiliation(s)
- Jaromír Petrtýl
- 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (J.P.); (K.D.); (V.Š.)
| | - Karel Dvořák
- 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (J.P.); (K.D.); (V.Š.)
| | - Jan Stříteský
- Institute of Pathology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic;
| | - Martin Leníček
- Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (M.L.); (A.J.); (M.H.)
| | - Alena Jirásková
- Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (M.L.); (A.J.); (M.H.)
| | - Václav Šmíd
- 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (J.P.); (K.D.); (V.Š.)
- Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (M.L.); (A.J.); (M.H.)
| | - Martin Haluzík
- Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (M.L.); (A.J.); (M.H.)
- Institute of Clinical and Experimental Medicine, 140 00 Prague, Czech Republic
| | - Radan Brůha
- 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (J.P.); (K.D.); (V.Š.)
- Correspondence: (R.B.); (L.V.); Tel.: +420-224-962-506 (R.B.); +420-224-964-203 (L.V.)
| | - Libor Vítek
- 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (J.P.); (K.D.); (V.Š.)
- Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague, Czech Republic; (M.L.); (A.J.); (M.H.)
- Correspondence: (R.B.); (L.V.); Tel.: +420-224-962-506 (R.B.); +420-224-964-203 (L.V.)
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Gluvic Z, Tomasevic R, Bojovic K, Obradovic M, Isenovic ER. Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines. EMERGENCY AND CRITICAL CARE MEDICINE 2021; 2:12-22. [DOI: 10.1097/ec9.0000000000000016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD's possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients.
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Affiliation(s)
- Zoran Gluvic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ksenija Bojovic
- Clinical Centre of Serbia, Clinic of Infectious and Tropical Diseases, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Alsowey AM, Shehata SM. Non-invasive staging of liver fibrosis by two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis C and B. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00502-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-invasive shear wave-based techniques have been developed for estimating liver fibrosis in patients with chronic liver diseases. Two-dimensional shear wave elastography provides in real-time, a tow dimensional quantitative map of tissue stiffness and enables measuring the stiffness by adjustment of a region of interest of tissue. The aim of this study was to highlight the role of tow dimensional shear wave elastography (2D-SWE) in detecting the degree of liver fibrosis in patients with chronic hepatitis C and B, in correlation with liver enzymes level and fibrotest.
Results
This study included 50 patients with chronic hepatitis C and B whose ages were (range, 30-65 years; mean, 48 years). Shear wave elastography cutoff values were 1.35 m/s, 5.48 KPa for (F>0); 1.66 m/s, 8.29 kPa for (F>1); 1.77 m/s, 9.40 kPa for (F>2); and 1.99 m/s, 11.9 kPa for (F>3). An excellent agreement was found between shear wave elastography and Fibrotest in staging of liver fibrosis in 88% of patients (κw=0.943, 95% CI, 0.88 to 1.00) achieving a highly statistical significance (P<0.001). There was a significant moderate positive concordance between US scoring and staging by 2D-SWE and staging by Fibrotest (rs, 0.49; P<0.01) and (rs, 0.48; P<0.01) respectively. However, no significant concordances were noticed between staging by AST and ALT and 2D-SWE and staging by Fibrotest (P>0.05).
Conclusions
2D shear wave elastography showed better diagnostic performance than visual assessment by conventional US for detection of chronic liver diseases, as well as for evaluation of their severity and prognosis. Elastograhy—Fibrotest combination gives best diagnostic performance in detecting the degree of fibrosis non-invasively and can be used reliably as a first-line pre-therapeutic evaluation of fibrosis in HCV and HBV-infected patients.
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Cervoni JP, Alby-Lepresle B, Weil D, Zhong P, Aubin F, Wendling D, Toussirot E, Vuitton L, Carbonnel F, Blondet R, Thévenot T, Calès P, Monnet E, Di Martino V. A pragmatic non-invasive assessment of liver fibrosis in patients with psoriasis, rheumatoid arthritis or Crohn's disease receiving methotrexate therapy. Clin Res Hepatol Gastroenterol 2021; 44S:100003. [PMID: 33602481 DOI: 10.1016/j.clirex.2020.100003] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 01/12/2020] [Accepted: 01/22/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The reported hepatotoxicity of methotrexate underlines the need for a repeated non-invasive and reliable evaluation of liver fibrosis. We estimated, using a non-invasive strategy, the prevalence of significant liver fibrosis in patients treated by methotrexate and the predictors of significant fibrosis (fibrosis≥F2). METHODS Fibrosis was prospectively evaluated using 9 non-invasive tests in consecutive patients with psoriasis, rheumatoid arthritis, or Crohn's disease. Significant fibrosis was assessed without liver biopsy by defining a "specific method" (result given by the majority of the tests) and a "sensitive method" (at least one test indicating a stage≥F2). RESULTS One hundred and thirty-one patients (66 Psoriasis, 40 rheumatoid arthritis, and 25 Crohn's disease) were enrolled, including 83 receiving methotrexate. Seven tests were performed on average per patient, with a complete concordance in 75% of cases. Fibroscan® was interpretable in only 61% of patients. The best performances (AUROC>0.9) for predicting significant fibrosis were obtained by tests dedicated to steatohepatitis (FibroMeter NAFLD, NFS and FPI). The prevalence of fibrosis≥F2 according to the "specific" or the "sensitive" assessment of fibrosis was 10% and 28%, respectively. Methotrexate exposure did not influence the fibrosis stage. Factors independently associated with significant fibrosis according our "sensitive method" were age, male gender, and metabolic syndrome. CONCLUSION We provided a non-invasive approach for identifying liver fibrosis≥F2 by using 8 biochemical tests and Fibroscan®. In this population, the risk of significant fibrosis was related to age, male gender, and presence of metabolic syndrome, but was not influenced by methotrexate.
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Affiliation(s)
- Jean-Paul Cervoni
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France; CIC-BT, CHRU Jean-Minjoz, 25030 Besançon cedex, France.
| | - Blandine Alby-Lepresle
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Delphine Weil
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Peng Zhong
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - François Aubin
- Service de dermatologie, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Daniel Wendling
- Service de rhumatologie, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Eric Toussirot
- CIC-BT, CHRU Jean-Minjoz, 25030 Besançon cedex, France; Service de rhumatologie, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Lucine Vuitton
- Service de gastroenterologie, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Franck Carbonnel
- Service de gastroenterologie, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | | | - Thierry Thévenot
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Paul Calès
- Service d'hépatologie et de gastroenterologie, CHRU Angers, 49100 Angers, France
| | - Elisabeth Monnet
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France; CIC-BT, CHRU Jean-Minjoz, 25030 Besançon cedex, France
| | - Vincent Di Martino
- Service d'hépatologie et de soins intensifs digestifs, CHRU Jean-Minjoz, 25030 Besançon cedex, France
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Poynard T, Paradis V, Mullaert J, Deckmyn O, Gault N, Marcault E, Manchon P, Si Mohammed N, Parfait B, Ibberson M, Gautier J, Boitard C, Czernichow S, Larger E, Drane F, Castille JM, Peta V, Brzustowski A, Terris B, Vallet‐Pichard A, Roulot D, Laouénan C, Bedossa P, Castera L, Pol S, Valla D. Prospective external validation of a new non-invasive test for the diagnosis of non-alcoholic steatohepatitis in patients with type 2 diabetes. Aliment Pharmacol Ther 2021; 54:952-966. [PMID: 34398492 PMCID: PMC8518776 DOI: 10.1111/apt.16543] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 06/14/2021] [Accepted: 07/11/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND One of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non-alcoholic liver disease by non-invasive blood tests, for each of the three main histological features, fibrosis, non-alcoholic steatohepatitis (NASH) and steatosis. AIMS To validate externally the performances of a recent panel, Nash-FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades. METHODS We prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest-2 and SteatoTest-2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve. RESULTS The diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest-2 and the SteatoTest-2 was 0.862 (0.012; P < 0.001), 0.827 (0.015; P < 0.001) and 0.794 (0.020; P < 0.01), respectively. For ballooning and lobular inflammation, OM was 0.794 (0.021; P < 0.001) and 0.821 (0.017; P < 0.001), respectively. In a post hoc analysis the FibroTest outperformed VCTE by 4.1% (2.5-6.5; P < 0.001) for reliability, with a non-significant difference for OM for fibrosis staging, 0.859 (0.012) for FibroTest vs 0.870 (0.009) for VCTE. CONCLUSIONS From a single blood sample, the panel provides non-invasive diagnosis of the stages of fibrosis, and the grades of NASH and steatosis in patients with T2DM. TRIAL REGISTRATION NUMBER NCT03634098.
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Dietrich CG, Rau M, Geier A. Screening for nonalcoholic fatty liver disease-when, who and how? World J Gastroenterol 2021; 27:5803-5821. [PMID: 34629804 PMCID: PMC8475001 DOI: 10.3748/wjg.v27.i35.5803] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/13/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming a frequent liver disease, especially in patients with metabolic syndrome and especially in Western countries. Complications of NAFLD comprise progressive fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD also represents an independent risk factor for cardiovascular disease, extrahepatic neoplasia and other organ damage, such as renal insufficiency. Given the epidemiological importance of the disease, new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis, NAFLD should be subject to screening programs, at least in countries with a high prevalence of the disease. The review discusses prerequisites for screening, cost-effectiveness, current guideline recommendations, suitability of techniques for screening and propositions for the following questions: Who should be screened? Who should perform screening? How should screening be performed? It is time for a screening program in patients at risk for NAFLD.
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Affiliation(s)
- Christoph G Dietrich
- Department of Internal Medicine, Bethlehem Health Center, Stolberg 52222, Germany
| | - Monika Rau
- Department of Internal Medicine II, University Hospital Würzburg, Würzburg 97080, Germany
| | - Andreas Geier
- Department of Medicine II, University Hospital Würzburg, Würzburg 97080, Germany
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Trindade AJ, Thaniyavarn T, Hashemi N, Coppolino A, Kennedy JC, Mallidi HR, El-Chemaly S, Goldberg HJ. 1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease. ERJ Open Res 2021; 7:00103-2021. [PMID: 34435032 PMCID: PMC8381158 DOI: 10.1183/23120541.00103-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/13/2021] [Indexed: 11/09/2022] Open
Abstract
Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [
1] However, whether fatty liver disease with mild–moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild–moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3–F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, β=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8–12 ng·mL−1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5–19.5 versus 12 days, IQR 0–18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild–moderate severity NAFLD may not be a contraindication to lung transplantation. In this single-centre, retrospective analysis of lung transplant recipients, we identified that mild–moderate non-alcoholic fatty liver disease is associated with acceptable perioperative and 1-year outcomeshttps://bit.ly/36WNzhi
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Affiliation(s)
- Anil J Trindade
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Tany Thaniyavarn
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Nikroo Hashemi
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Antonio Coppolino
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - John C Kennedy
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hari R Mallidi
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Cardiac Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Souheil El-Chemaly
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hilary J Goldberg
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
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Davison BA, Edwards C, Loomba R, Harrison SA, Cotter G, Alkhouri N, Koch GG, Dittrich HC. Noninvasive measure of treatment response in non-alcoholic steatohepatitis: Insights from EMMINENCE and meta-analysis. JGH Open 2021; 5:740-749. [PMID: 34263067 PMCID: PMC8264234 DOI: 10.1002/jgh3.12575] [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: 04/06/2021] [Revised: 05/07/2021] [Accepted: 05/14/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Liver histology changes are the current gold standard for evaluating non-alcoholic steatohepatitis (NASH), but are limited by their invasiveness and variability for sampling and interpretation. We evaluated noninvasive biomarkers as an indication of histologic changes in NASH. METHODS Associations between 12-month biomarker and NASH Clinical Research Network histologic score changes in 339 patients with NASH in the EMMINENCE trial was examined with multivariable models and partial canonical correlation. A meta-analysis of 17 NASH trials including 3717 patients examined associations between these same changes and histologic response within treatment groups, and treatment effects on biomarkers and on liver histology. Biopsy measures assessed were changes in ballooning, steatosis, inflammation, and fibrosis, NASH improvement without worsening of fibrosis, and fibrosis improvement without worsening of NASH. All analytic methods suggest that a combination of aspartate aminotransferase (AST), cytokeratin-18 (CK-18 [M30 or M65]), and hemoglobin A1C (HbA1c) changes best predicts overall liver biopsy changes in response to interventions. RESULTS The weighted average of standardized mean changes (0.403 × AST, 0.314 × CK-18, 0.283 × HbA1c) facilitated comparisons of within-group responses and treatment effects among studies included in the meta-analysis. This composite in EMMINENCE discriminated between patients with and without NASH resolution without worsening fibrosis with area under the receiver-operator characteristic curve of 0.7880, and for fibrosis improvement without NASH worsening of 0.7553. CONCLUSION A composite score based on changes in AST, HbA1c, and CK-18 could serve as a surrogate for liver histologic improvement and an effective objective, noninvasive tool for comparative assessment of treatment effects of novel interventions.
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Affiliation(s)
- Beth A Davison
- Momentum Research, Inc.North CarolinaUSA
- InsermU942 Cardiovascular Markers in Stressed Conditions (MASCOT)ParisFrance
| | | | - Rohit Loomba
- NAFLD Research Center Division of GastroenterologyUniversity of California at San DiegoLa JollaCaliforniaUSA
| | - Stephen A Harrison
- Hepatology, Radcliffe Department of MedicineUniversity of OxfordOxfordUK
| | - Gad Cotter
- Momentum Research, Inc.North CarolinaUSA
- InsermU942 Cardiovascular Markers in Stressed Conditions (MASCOT)ParisFrance
| | - Naim Alkhouri
- Metabolic Health CenterTexas Liver InstituteSan AntonioTexasUSA
| | - Gary G Koch
- Department of Biostatistics, School of Public HealthUniversity of North CarolinaChapel HillNorth CarolinaUSA
| | - Howard C Dittrich
- Chief Medical OfficerCirius Therapeutics, Inc.San DiegoCaliforniaUSA
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Seen TK, Sayed M, Bilal M, Reyes JV, Bhandari P, Lourdusamy V, Al-khazraji A, Syed U, Sattar Y, Bansal R. Clinical indicators for progression of nonalcoholic steatohepatitis to cirrhosis. World J Gastroenterol 2021; 27:3238-3248. [PMID: 34163108 PMCID: PMC8218360 DOI: 10.3748/wjg.v27.i23.3238] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/06/2020] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation, known as nonalcoholic steatohepatitis. Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma (HCC). Fatty liver disease prevalence has increased at alarming rates alongside obesity, diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide. Given this rise in prevalence, it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis. Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease. This article discusses the utility of current non-invasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available. Additionally, we summarize available treatment options including targeted medical therapy through four different pathways, surgical or endoscopic intervention.
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Affiliation(s)
- Tasur Kumar Seen
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Muntazir Sayed
- Division of Internal Medicine, R.C.S.M. Government College, Mahrashta 416013, India
| | - Muhammad Bilal
- Division of Gastroenterology, Hepatology and Endoscopy, Pakistan Institute of Medical Sciences, Islamabad 45710, Pakistan
| | - Jonathan Vincent Reyes
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Priyanka Bhandari
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Vennis Lourdusamy
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Ahmed Al-khazraji
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Umer Syed
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Yasar Sattar
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Raghav Bansal
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital, Elmhurst, NY 11375, United States
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Vali Y, Lee J, Boursier J, Spijker R, Verheij J, Brosnan MJ, Anstee QM, Bossuyt PM, Zafarmand MH. FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:jcm10112415. [PMID: 34072480 PMCID: PMC8198930 DOI: 10.3390/jcm10112415] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 05/23/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022] Open
Abstract
(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.
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Affiliation(s)
- Yasaman Vali
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
- Correspondence: ; Tel.: +31-(0)20-5668520
| | - Jenny Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
| | - Jérôme Boursier
- Hepato-Gastroenterology Department, Angers University Hospital, 49933 Angers, France;
- HIFIH Laboratory, UPRES EA3859, Angers University, 49035 Angers, France
| | - René Spijker
- Medical Library AMC, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
| | - M. Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139, USA;
| | - Quentin M. Anstee
- The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
- Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 7RU, UK
| | - Patrick M. Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
| | - Mohammad Hadi Zafarmand
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.L.); (P.M.B.); (M.H.Z.)
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Valoración bioquímica en la enfermedad hepática grasa asociada a la disfunción metabólica. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2021. [DOI: 10.1515/almed-2020-0062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Resumen
La enfermedad hepática grasa asociada a la disfunción metabólica (MAFLD) se define por el acúmulo de grasa en el hígado en presencia de alteraciones metabólicas. Suele cursar de forma asintomática y puede progresar a formas graves de enfermedad hepática, ligadas a la aparición de inflamación y/o fibrosis. Su prevalencia es muy elevada (26%), resultando en un alto número de pacientes con riesgo de presentar una enfermedad hepática avanzada. El presente documento describe los marcadores serológicos más relevantes en la caracterización y diagnóstico de la MAFLD, y se propone un ejemplo de su integración en un algoritmo diagnóstico en práctica clínica habitual. En la actualidad se dispone de índices serológicos útiles en el manejo de los pacientes con MAFLD, especialmente en la estratificación del riesgo de la presencia fibrosis. Una gran parte de la población está en riesgo de desarrollar enfermedad hepática grave. La integración de los marcadores serológicos no invasivos en la estratificación del riesgo de fibrosis hepática puede contribuir a un mejor control y manejo de los pacientes con MAFLD.
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Biochemical assessment of metabolic associated fatty liver disease. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2021. [DOI: 10.1515/almed-2021-0009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Abstract
Metabolic-associated fatty liver disease (MAFLD) is defined as fat accumulation in the liver in the presence of metabolic alterations. This disorder is generally asymptomatic and may progress to severe liver disease, which are linked to inflammation and/or fibrosis. MAFLD has a high prevalence (26%) and therefore a considerable number of patients are at high risk of having advanced liver disease. This document provides an overview of the most relevant serological markers in the characterization and diagnosis of MAFLD. An example is provided of a routine diagnostic algorithm that incorporates serological testing. A range of useful serological scores are currently available for the management of MAFLD patients, especially for the stratification of patients at risk of fibrosis. A large proportion of the population is at risk of developing severe liver disease. The integration of non-invasive serological markers in the stratification of patients at risk for liver fibrosis may contribute to improve the control and management of MAFLD patients.
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50
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Lonardo A, Arab JP, Arrese M. Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management. Adv Ther 2021; 38:2130-2158. [PMID: 33829368 PMCID: PMC8107169 DOI: 10.1007/s12325-021-01690-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023]
Abstract
Precision medicine defines the attempt to identify the most effective approaches for specific subsets of patients based on their genetic background, clinical features, and environmental factors. Nonalcoholic fatty liver disease (NAFLD) encompasses the alcohol-like spectrum of liver disorders (steatosis, steatohepatitis with/without fibrosis, and cirrhosis and hepatocellular carcinoma) in the nonalcoholic patient. Recently, disease renaming to MAFLD [metabolic (dysfunction)-associated fatty liver disease] and positive criteria for diagnosis have been proposed. This review article is specifically devoted to envisaging some clues that may be useful to implementing a precision medicine-oriented approach in research and clinical practice. To this end, we focus on how sex and reproductive status, genetics, intestinal microbiota diversity, endocrine and metabolic status, as well as physical activity may interact in determining NAFLD/MAFLD heterogeneity. All these factors should be considered in the individual patient with the aim of implementing an individualized therapeutic plan. The impact of considering NAFLD heterogeneity on the development of targeted therapies for NAFLD subgroups is also extensively discussed.
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Affiliation(s)
- Amedeo Lonardo
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria, Ospedale Civile di Baggiovara, 1135 Via Giardini, 41126, Modena, Italy.
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Biología Celular y Molecular, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Biología Celular y Molecular, Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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