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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [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: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Marti-Aguado D, Carot-Sierra JM, Villalba-Ortiz A, Siddiqi H, Vallejo-Vigo RM, Lara-Romero C, Martín-Fernández M, Fernández-Patón M, Alfaro-Cervello C, Crespo A, Coello E, Merino-Murgui V, Madamba E, Benlloch S, Pérez-Rojas J, Puglia V, Ferrández A, Aguilera V, Monton C, Escudero-García D, Lluch P, Aller R, Loomba R, Romero-Gomez M, Marti-Bonmati L. Identification of Candidates for MASLD Treatment With Indeterminate Vibration-Controlled Transient Elastography. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01037-1. [PMID: 39551253 DOI: 10.1016/j.cgh.2024.10.014] [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: 07/18/2024] [Revised: 09/15/2024] [Accepted: 10/09/2024] [Indexed: 11/19/2024]
Abstract
BACKGROUND AND AIMS A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis. METHODS This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization. RESULTS From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients. CONCLUSIONS To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain.
| | - José Miguel Carot-Sierra
- Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain
| | - Aida Villalba-Ortiz
- Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain
| | - Harris Siddiqi
- MASLD Research Center, Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Rose Marie Vallejo-Vigo
- Digestive Diseases Department, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, Department of Medicine, University of Seville, Seville, Spain
| | - Carmen Lara-Romero
- Digestive Diseases Department, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, Department of Medicine, University of Seville, Seville, Spain
| | - Marta Martín-Fernández
- Department of Cell Biology, Genetics, Histology and Pharmacology, University of Valladolid, Valladolid, Spain; BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Matías Fernández-Patón
- Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain
| | - Clara Alfaro-Cervello
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Ana Crespo
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Elena Coello
- Digestive Disease Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Merino-Murgui
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Egbert Madamba
- MASLD Research Center, Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Salvador Benlloch
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Judith Pérez-Rojas
- Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Puglia
- Pathology Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Antonio Ferrández
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Victoria Aguilera
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain; Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Cristina Monton
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Desamparados Escudero-García
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Paloma Lluch
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Rocío Aller
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Department of Medicine, Dermatology and Toxicology, Universidad de Valladolid, Valladolid, Spain; Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Rohit Loomba
- MASLD Research Center, Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California
| | - Manuel Romero-Gomez
- Digestive Diseases Department, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, Department of Medicine, University of Seville, Seville, Spain; University of Seville, Seville, Spain
| | - Luis Marti-Bonmati
- Biomedical Imaging Research Group (GIBI2(30)), La Fe Health Research Institute, Valencia, Spain; Imaging La Fe Node, Distributed Network for Biomedical Imaging Unique Scientific and Technical Infrastructures, Valencia, Spain; Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
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Yagmur V, Demeshkina L, Melanich S, Kyslova R. Influence of age, body mass index and gender on sonographic indicators of the liver in patients with metabolic dysfunction-associated steatotic liver disease. Gastroenterology 2024; 58:114-120. [DOI: 10.22141/2308-2097.58.2.2024.604] [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: 01/03/2025]
Abstract
Background. The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing along with the increasing prevalence of obesity. There are close relationships between these two pathologies due to the functioning of adipose tissue as an endocrine organ with a complex influence on various metabolic processes. It is known that premenopausal women are less prone to fatty liver disease than men. The aim was to study the influence of gender, body mass index (BMI) and age on sonographic indicators and the degree of liver steatosis in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Ninety-two patients with MASLD were included in the study, 48 women and 44 men. Inclusion criterion was metabolic dysfunction-associated steatotic liver disease, exclusion criteria were any non-metabolic factors of chronic diffuse liver disease. Patients were divided into groups by gender and age. Women were divided by age according to the presence and absence of menopause, men were divided into groups below and above 45 years — the conventional age of the beginning of the decline in gonadotropic function. The analysis of structural changes of the liver, namely the assessment of the size, contours, structure, echogenicity, and visualization of blood vessels in the B-mode was carried out with the help of ultrasound examination on Toshiba Xario 660 (Japan). The degree of steatosis was assessed by the controlled attenuation parameter. Results. In men, the right, left and caudate liver lobes were significantly larger (p < 0.05) than in women, which is due to the higher weight of men in the absence of a difference in the BMI. There was no significant difference between men and women in degree of steatosis (p > 0.05). A moderate positive correlation (r = 0.63) was found between BMI and the controlled attenuation parameter; in women, there was no connection between these indicators. Analysis of correlations in women of different ages, divided by the presence of menopause, found that before menopause, there was no dependence of steatosis indicators on BMI, while with the onset of menopause, the coefficient of correlation between these indicators was 0.39 (р < 0.02). Conclusions. No significant difference was found between the frequency of various degrees of steatosis in MASLD according to the controlled attenuation parameter in men and women. There was a dependence of the severity of liver steatosis on the BMI in men, the dependence of steatosis on the body mass index in women was manifested starting from the menopause period, which suggests the protective role of female sex hormones.
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Steinmann S, Hartl J, Weidemann S, Füssel K, Kroll C, Sebode M, Lohse AW, Schramm C. Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases. JHEP Rep 2023; 5:100898. [PMID: 37954487 PMCID: PMC10632533 DOI: 10.1016/j.jhepr.2023.100898] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 08/08/2023] [Accepted: 08/17/2023] [Indexed: 11/14/2023] Open
Abstract
Background & Aims Concurrent fatty liver disease represents an emerging challenge in the care of individuals with autoimmune liver diseases (AILD). Therefore, we aimed to validate the ultrasound-based method of controlled-attenuation parameter (CAP) as a non-invasive tool to detect hepatic steatosis in individuals with AILD. Methods The diagnostic performance of CAP to determine biopsy-proven hepatic steatosis (>5%) was assessed in individuals with AILD (autoimmune hepatitis [AIH], primary biliary cholangitis [PBC], primary biliary cholangitis [PSC], or variant syndromes) who underwent liver biopsy at the University Medical Center Hamburg-Eppendorf between 2015-2020 by calculating the area under the receiver operating characteristic (AUROC) curves. In AIH, the impact of disease activity was evaluated by assessment of CAP upon resolution of hepatic inflammation during follow-up. Results Overall, 433 individuals with AILD (AIH: 218, PBC: 51, PSC: 85, PBC/AIH: 63, PSC/AIH: 16) were included. Histologically proven steatosis was present in 90 individuals (20.8%). Steatosis was less frequently observed in people with PSC (14%) than in other AILD. CAP values correlated positively with grade of steatosis (ρ = 0.39) and the BMI (ρ = 0.53). In PBC and PSC, the ROC curves defined an AUROC of 0.81 and 0.93 for detecting steatosis at an optimal cut-off of 276 dB/m (sensitivity: 0.71; specificity: 0.82) and 254 dB/m (sensitivity: 0.91, specificity: 0.85), respectively. In AIH, the diagnostic performance of CAP was significantly lower (AUROC = 0.72, p = 0.009). However, resolution of hepatic inflammation under treatment was associated with a significant increase in CAP levels (median [IQR]: +38.0 [6-81] dB/m) and considerably improved diagnostic accuracy (AUROC = 0.85; cut-off: 288 dB/m; sensitivity: 0.67, specificity: 0.90). Conclusions In PBC and PSC, hepatic steatosis can be reliably detected by applying disease-specific thresholds of CAP. In AIH, the diagnostic accuracy of CAP is moderate at diagnosis, but improves after acute hepatitis has resolved. Impact and implications Non-invasive estimation of fat content in the liver can be performed with the ultrasound-based method of controlled-attenuation parameter (CAP). Here, we showed that the presence of a concomitant fatty liver is frequent in people with autoimmune liver diseases and we determined disease-specific thresholds of CAP to best predict the presence of a fatty liver. CAP measurement was shown to be a valid tool to detect fatty liver in individuals with PSC and PBC; however, in AIH, CAP had limited accuracy especially when significant inflammatory activity was present in the liver. In the context of substantial liver inflammation, therefore, CAP values should be interpreted with caution, and measurements should be repeated after acute hepatitis has resolved.
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Affiliation(s)
- Silja Steinmann
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN-RARE LIVER), Hamburg, Germany
| | - Johannes Hartl
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN-RARE LIVER), Hamburg, Germany
| | - Sören Weidemann
- Institute of Pathology, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Katja Füssel
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Claudia Kroll
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Marcial Sebode
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN-RARE LIVER), Hamburg, Germany
| | - Ansgar Wilhelm Lohse
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN-RARE LIVER), Hamburg, Germany
- Hamburg Centre for Translational Immunology (HCTI), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany
- European Reference Network for Hepatological Diseases (ERN-RARE LIVER), Hamburg, Germany
- Hamburg Centre for Translational Immunology (HCTI), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Hohmann N, Schröder F, Moreira B, Teng H, Burhenne J, Bruckner T, Mueller S, Haefeli WE, Seitz HK. Effect of Clomethiazole Vs. Clorazepate on Hepatic Fat and Serum Transaminase Activities in Alcohol-Associated Liver Disease: Results from a Randomized, Controlled Phase II Clinical Trial. Alcohol Alcohol 2023; 58:134-141. [PMID: 36562601 DOI: 10.1093/alcalc/agac068] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/27/2022] [Accepted: 11/21/2022] [Indexed: 12/24/2022] Open
Abstract
AIMS Alcohol-associated liver disease (ALD) is a global health problem caused, among other factors, by oxidative stress from the formation of reactive oxygen species (ROS). One important source of ROS is microsomal ethanol metabolism catalyzed by cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption. Inhibition of CYP2E1 by clomethiazole (CMZ) decreases oxidative stress in cell cultures and improves ALD in animal studies. Our study aimed to assess the benefits of a CYP2E1 inhibitor (clomethiazole) in detoxification of patients with ALD. METHODS Open label, randomized controlled clinical trial to study whether CYP2E1 inhibition improves ALD in the patients with alcohol use disorders admitted for alcohol detoxification therapy (ADT). Patients had to have a serum aspartate aminotransferase (AST) activity exceeding twice the upper normal limit at time of admission and be non-cirrhotic defined by fibroscan value <12 kPa. Sixty patients were randomly assigned to ADT with either CMZ or clorazepate (CZP) for 7-10 days in a 1:1 ratio. The chlorzoxazone test of CYP2E1 activity was performed at enrolment and at 2 points during the study. RESULTS ADT improved hepatic steatosis (controlled attenuation parameter) in both groups significantly. A trend towards a greater improvement in hepatic fat content during ADT (-21.5%) was observed in the CMZ group (252 ± 48 dB/m vs. 321 ± 38 dB/m; P < 0.0001) compared with the CZP group (-13.9%; 273 ± 38 dB/m vs. 317 ± 39 dB/m; P < 0.0001). As already reported, serum AST (P < 0.004) and alanine aminotransferase (ALT) activities (P < 0.0006) significantly decreased in CMZ patients as compared with patients on CZP by the end of hospitalization. A significant correlation was found between AST (P = 0.023), ALT (P = 0.009), GGT (P = 0.039) and CAP. CONCLUSION This study demonstrates that CMZ improves clinical biomarkers for ALD in humans most likely due to its inhibitory effect on CYP2E1. Because of its addictive potential, CMZ can only be given for a short period of time and therefore other CYP2E1 inhibitors to treat ALD are needed.
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Affiliation(s)
- Nicolas Hohmann
- Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg 69120, Germany
| | - Fabian Schröder
- Centre of Alcohol Research (CAR) University of Heidelberg, Germany, and Department of Medicine, Salem Medical Centre, Heidelberg 69121, Germany
| | - Bernardo Moreira
- Centre of Alcohol Research (CAR) University of Heidelberg, Germany, and Department of Medicine, Salem Medical Centre, Heidelberg 69121, Germany
| | - Haidong Teng
- Centre of Alcohol Research (CAR) University of Heidelberg, Germany, and Department of Medicine, Salem Medical Centre, Heidelberg 69121, Germany
| | - Jürgen Burhenne
- Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg 69120, Germany
| | - Thomas Bruckner
- Institute for Medical Biometry and Informatics, Heidelberg University, Heidelberg 69120, Germany
| | - Sebastian Mueller
- Centre of Alcohol Research (CAR) University of Heidelberg, Germany, and Department of Medicine, Salem Medical Centre, Heidelberg 69121, Germany
| | - Walter E Haefeli
- Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg 69120, Germany
| | - Helmut K Seitz
- Centre of Alcohol Research (CAR) University of Heidelberg, Germany, and Department of Medicine, Salem Medical Centre, Heidelberg 69121, Germany
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Becchetti C, Lange NF, Delgado MG, Brönnimann MP, Maurer MH, Dufour JF, Berzigotti A. 2D shear wave elastography of the rectus femoris muscle in patients with cirrhosis: Feasibility and clinical findings. A pilot study. Clin Res Hepatol Gastroenterol 2023; 47:102080. [PMID: 36657524 DOI: 10.1016/j.clinre.2023.102080] [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: 08/04/2022] [Revised: 11/11/2022] [Accepted: 12/29/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS Frailty is frequent in cirrhosis and associated with skeletal muscle abnormalities and worse prognosis. 2D shear-wave elastography (2D-SWE) could mirror biomechanical properties of skeletal muscle reflecting muscle quality. However, there is no data on 2D-SWE on skeletal muscle stiffness assessment in cirrhosis and on frailty. METHODS Outpatients with cirrhosis were prospectively included in a single center. Skeletal muscle stiffness was studied at the rectus femoris by 2D-SWE. Ileo-psoas area and index (area/height2), and antero-posterior diameter of rectus femoris (RF) was measured on ultrasound. RESULTS We included 44 patients (24 male, age 59 [IQR 49-66]) with a median liver frailty index (LFI) of 3.7 (IQR 3.2-4.0). Measurement of RF muscle stiffness (RFMS) was feasible in all with high inter-measurement reproducibility. RFMS did not correlate with LFI, liver function and skeletal muscle diameters. Ileo-psoas index was lower in frail patients (1.7 vs 1.0 cm2/m2, p = 0.024). RF antero-posterior diameter inversely correlated with LFI (r -0.578: p<0.001). CONCLUSION RFMS by 2D-SWE is feasible and reproducible in cirrhosis and is independent of liver function and LFI, and warrants further studies in this setting. RF antero-posterior diameter could be reported as an objective parameter mirroring sarcopenia and frailty.
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Affiliation(s)
- Chiara Becchetti
- Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Naomi F Lange
- Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Bern, Switzerland
| | - Maria Gabriela Delgado
- Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Michael P Brönnimann
- Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Martin H Maurer
- Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Jean-François Dufour
- Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Annalisa Berzigotti
- Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
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Hari A. Ultrasound-Based Diagnostic Methods: Possible Use in Fatty Liver Disease Area. Diagnostics (Basel) 2022; 12:diagnostics12112822. [PMID: 36428882 PMCID: PMC9689357 DOI: 10.3390/diagnostics12112822] [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: 10/02/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/19/2022] Open
Abstract
Liver steatosis is a chronic liver disease that is becoming one of the most important global health problems, due to its direct connection with metabolic syndrome, its significant impact on patients' socioeconomic status and frailty, and the occurrence of advanced chronic liver disease. In recent years, there has been rapid technological progress in the ultrasound-based diagnostics field that can help us to quantitatively assess liver steatosis, including continuous attenuation parameters in A and B ultrasound modes, backscatter coefficients (e.g., speed of sound) and ultrasound envelope statistic parametric imaging. The methods used in this field are widely available, have favorable time and financial profiles, and are well accepted by patients. Less is known about their reliability in defining the presence and degree of liver steatosis. Numerous study reports have shown the methods' favorable negative and positive predictive values in comparison with reference investigations (liver biopsy and MRI). Important research has also evaluated the role of these methods in diagnosing and monitoring non-alcoholic fatty liver disease (NAFLD). Since NAFLD is becoming the dominant global cause of liver cirrhosis, and due to the close but complex interplay of liver steatosis with the coexistence of liver fibrosis, knowledge regarding NAFLD's influence on the progression of liver fibrosis is of crucial importance. Study findings, therefore, indicate the possibility of using these same diagnostic methods to evaluate the impact of NAFLD on the patient's liver fibrosis progression risk, metabolic risk factors, cardiovascular complications, and the occurrence of hepatocellular carcinoma. The mentioned areas are particularly important in light of the fact that most of the known chronic liver disease etiologies are increasingly intertwined with the simultaneous presence of NAFLD.
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Affiliation(s)
- Andrej Hari
- Oddelek za Bolezni Prebavil, Splošna Bolnišnica Celje, Oblakova Cesta 3, 3000 Celje, Slovenia
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Zhuang RH, Weinstock AK, Ganesh S, Behari J, Malik SM, Bataller R, Furlan A, Hughes CB, Humar A, Duarte-Rojo A. Characterization of hepatic steatosis using controlled attenuation parameter and MRI-derived proton density fat fraction in living donor liver transplantation. Clin Transplant 2022; 36:e14786. [PMID: 35993599 DOI: 10.1111/ctr.14786] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The increasingly favorable outcomes of live donor liver transplant warrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD). STUDY DESIGN In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference. RESULTS One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233 dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270 dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P = .26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis. CONCLUSION The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.
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Affiliation(s)
- Rachel H Zhuang
- Internal Medicine Program, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Allison K Weinstock
- Department of Radiology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Swaytha Ganesh
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Jaideep Behari
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Shahid M Malik
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Ramon Bataller
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Alessandro Furlan
- Department of Radiology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Christopher B Hughes
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Abhinav Humar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Andres Duarte-Rojo
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
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10
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Mendoza YP, Shengir M, Bosch J, Sebastiani G, Berzigotti A. FIB-4 Improves LSM-Based Prediction of Complications in Overweight or Obese Patients With Compensated Advanced Chronic Liver Disease. Clin Gastroenterol Hepatol 2022; 20:2396-2398.e3. [PMID: 33716139 DOI: 10.1016/j.cgh.2021.03.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 03/01/2021] [Accepted: 03/05/2021] [Indexed: 02/07/2023]
Abstract
Liver stiffness measurement (LSM) by transient elastography (TE) is able to stratify the risk of decompensation in patients with compensated advanced chronic liver disease (cACLD).1 Recently, we demonstrated that this holds true also in overweight or obese patients with cACLD due to nonalcoholic steatohepatitis (NASH) studied by the XL probe. An LSM cutoff of ≥21 kPa remained associated with a high risk of complications in this population.2.
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Affiliation(s)
- Yuly P Mendoza
- University Clinic for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Bern, Switzerland
| | - Mohamed Shengir
- Division of Experimental Medicine, McGill University, Montreal, Canada
| | - Jaime Bosch
- August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Hospital Clínic, University of Barcelona, Barcelona, Spain; Hepatology Group, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Giada Sebastiani
- Division of Experimental Medicine, McGill University, Montreal, Canada; Division of Gastroenterology and Hepatology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada
| | - Annalisa Berzigotti
- University Clinic for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland; Hepatology Group, Department of Biomedical Research, University of Bern, Bern, Switzerland.
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11
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Schulz M, Wilde ACB, Demir M, Müller T, Tacke F, Wree A. Shear wave elastography and shear wave dispersion imaging in primary biliary cholangitis-a pilot study. Quant Imaging Med Surg 2022; 12:1235-1242. [PMID: 35111619 DOI: 10.21037/qims-21-657] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/09/2021] [Indexed: 12/20/2022]
Abstract
Background Primary biliary cholangitis (PBC) is a chronic liver disease that can lead to liver fibrosis and cirrhosis. Two-dimensional shear wave elastography (2D-SWE) is a modern technique for fibrosis assessment. However, data regarding its performance in PBC is sparse. We aimed to characterize severity of liver disease in PBC patients using non-invasive 2D-SWE and the new methods of attenuation imaging (ATI) and shear wave dispersion imaging (SWD). Methods Twenty two PBC patients were examined with 2D-SWE, SWD and ATI, alongside established non-invasive fibrosis and steatosis assessment methods as well as liver function tests. Results Median 2D-SWE values were 1.48 m/s (range, 1.14-2.13 m/s) and 6.7 kPa (range, 3.8-14.7 kPa), respectively. Median SWD, ATI, transient elastography (TE) and controlled attenuation parameter (CAP) values were 13.9 m/s/kHz (range, 11.6-21 m/s/kHz), 0.57 dB/cm/MHz (range, 0.5-0.68 dB/cm/MHz), 7 kPa (range, 3.7-14.6 kPa), and 208 dB/m (range, 107-276 dB/m), respectively. 2D-SWE displayed a significant correlation with spleen length, platelet count, non-invasive fibrosis scores (FIB-4, APRI) and with TE. SWD correlated with alkaline phosphatase (ALP) levels, which is a prognostic marker in PBC. Conclusions Our findings add further evidence that 2D-SWE is a reliable method for fibrosis assessment in PBC. Even though the cohort size was small, the correlation of SWD with the prognostic marker ALP suggests a potentially valuable role of this new non-invasive method in evaluating liver disease activity in PBC.
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Affiliation(s)
- Marten Schulz
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Anne-Christin B Wilde
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Tobias Müller
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | - Alexander Wree
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
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12
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Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021; 75:659-689. [PMID: 34166721 DOI: 10.1016/j.jhep.2021.05.025] [Citation(s) in RCA: 998] [Impact Index Per Article: 249.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.
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13
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Liu F. Ultrasound-based techniques for noninvasive diagnosis of liver steatosis in nonalcoholic fatty liver disease. Shijie Huaren Xiaohua Zazhi 2021; 29:543-549. [DOI: 10.11569/wcjd.v29.i10.543] [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] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a worldwide medical and social problem. Although nonalcoholic steatosis can be reversed, some patients still progress to nonalcoholic steatohepatitis, liver cirrhosis, and even liver cancer. Therefore, early diagnosis and accurate disease assessment of NAFLD have become an important basis for its intervention treatment and prognosis improvement. Although liver biopsy is the gold standard for the diagnosis of NAFLD, it is not an ideal reference standard, and MRI-PDFF is more often used in clinical research. The non-invasive examination based on ultrasound detection has also become a hot spot of NAFLD research. This paper discusses the ultrasonic diagnosis technology for liver steatosis in NAFLD, with an aim to provide a safe and practical basis for the diagnosis, disease evaluation, and treatment intervention of NAFLD.
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Affiliation(s)
- Fang Liu
- Tianjin Third Central Hospital, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Technology Research Center, Tianjin 300170, China
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14
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Hari A. Ultrasound Elastography-Cornerstone of Non-Invasive Metabolic Dysfunction-Associated Fatty Liver Disease Assessment. ACTA ACUST UNITED AC 2021; 57:medicina57060516. [PMID: 34064124 PMCID: PMC8224344 DOI: 10.3390/medicina57060516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/16/2021] [Accepted: 05/20/2021] [Indexed: 12/02/2022]
Abstract
Metabolic dysfunction-associated fatty liver disease has become the most common chronic liver disease as well as the most common cause for liver transplantation. With its different methods types, elastography of the liver can be used for non-invasive evaluation of the liver fibrosis and steatosis degree. The article focuses on the description, use, advantages, and limitations of the currently known elastographic techniques. It proposes a simple risk assessment algorithm for the liver fibrosis progress evaluation. The following is an overview of the use of liver and spleen elastography in the detection of clinically relevant portal hypertension. It concludes with research and technological possibilities that could be important to the field in the upcoming years.
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Affiliation(s)
- Andrej Hari
- Department of Gastroenterology, General Hospital Celje, 3000 Celje, Slovenia
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15
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Schulz M, Kleinjans M, Strnad P, Demir M, Holtmann TM, Tacke F, Wree A. Shear Wave Elastography and Shear Wave Dispersion Imaging in the Assessment of Liver Disease in Alpha1-Antitrypsin Deficiency. Diagnostics (Basel) 2021; 11:diagnostics11040629. [PMID: 33807358 PMCID: PMC8066059 DOI: 10.3390/diagnostics11040629] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/17/2021] [Accepted: 03/27/2021] [Indexed: 12/19/2022] Open
Abstract
Liver affection of Alpha1-antitrypsin deficiency (AATD) can lead to cirrhosis and hepatocellular carcinoma (HCC). A noninvasive severity assessment of liver disease in AATD is urgently needed since laboratory parameters may not accurately reflect the extent of liver involvement. Preliminary data exist on two-dimensional shear wave elastography (2D-SWE) being a suitable method for liver fibrosis measurement in AATD. AATD patients without HCC were examined using 2D-SWE, shear wave dispersion imaging (SWD) and transient elastography (TE). Furthermore, liver steatosis was assessed using the controlled attenuation parameter (CAP) and compared to the new method of attenuation imaging (ATI). 29 AATD patients were enrolled, of which 18 had the PiZZ genotype, eight had PiMZ, two had PiSZ and one had a PiZP-Lowell genotype. 2D-SWE (median 1.42 m/S, range 1.14–1.83 m/S) and TE (median 4.8 kPa, range 2.8–24.6 kPa) values displayed a significant correlation (R = 0.475, p < 0.05). 2D-SWE, ATI (median 0.56 dB/cm/MHz, range 0.43–0.96 dB/cm/MHz) and CAP (median 249.5 dB/m, range 156–347 dB/m) values were higher in PiZZ when compared to other AATD genotypes. This study provides evidence that 2D-SWE is a suitable method for the assessment of liver disease in AATD. The newer methods of SWD and ATI require further evaluation in the context of AATD.
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Affiliation(s)
- Marten Schulz
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (M.D.); (T.M.H.); (F.T.); (A.W.)
- Correspondence:
| | - Moritz Kleinjans
- Medical Clinic III, Gastroenterology, Metabolic Diseases, and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany; (M.K.); (P.S.)
- Coordinating Center for Alpha1-Antitrypsin Deficiency-Related Liver Disease of the European Reference Network (ERN) “Rare Liver” and the European Association for the Study of the Liver (EASL) Registry Group “Alpha1-Liver”, 52074 Aachen, Germany
| | - Pavel Strnad
- Medical Clinic III, Gastroenterology, Metabolic Diseases, and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany; (M.K.); (P.S.)
- Coordinating Center for Alpha1-Antitrypsin Deficiency-Related Liver Disease of the European Reference Network (ERN) “Rare Liver” and the European Association for the Study of the Liver (EASL) Registry Group “Alpha1-Liver”, 52074 Aachen, Germany
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (M.D.); (T.M.H.); (F.T.); (A.W.)
| | - Theresa M. Holtmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (M.D.); (T.M.H.); (F.T.); (A.W.)
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (M.D.); (T.M.H.); (F.T.); (A.W.)
| | - Alexander Wree
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (M.D.); (T.M.H.); (F.T.); (A.W.)
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16
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Grgurevic I, Salkic N, Mustapic S, Bokun T, Podrug K, Marusic S, Rahelic D, Matic T, Skurla V, Mikolasevic I. Liver and Nonliver-Related Outcomes at 2 Years Are Not Influenced by the Results of the FIB-4 Test and Liver Elastography in a Real-Life Cohort of Patients with Type 2 Diabetes. Can J Gastroenterol Hepatol 2021; 2021:5582813. [PMID: 33763391 PMCID: PMC7964120 DOI: 10.1155/2021/5582813] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 02/27/2021] [Indexed: 01/14/2023] Open
Abstract
AIMS To investigate morbidity and mortality in a real-life cohort of patients with type 2 diabetes (T2D) in relation to prevalence and severity of nonalcoholic fatty liver disease (NAFLD). METHODS Patients with T2D were referred for assessment of liver fibrosis by the FIB-4 test and liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). Liver steatosis was quantified by the controlled attenuation parameter (CAP). These patients were followed until death or censored date. RESULTS Among 454 patients (52% males, mean age 62.5 years, BMI 30.9 kg/m2), 82.6% was overweight, 77.8% had fatty liver, and 9.9% and 3.1% had LSM and FIB-4 values suggestive of advanced fibrosis, respectively. During the follow-up period of median 2 years, 106 (23%) patients experienced adverse event (11% cardiovascular) and 17 (3.7%) died, whereas no liver-related morbidity or mortality was observed. Independent predictors of adverse outcomes were age and higher platelet count, while FIB-4, LSM, and CAP were not. CONCLUSION In a cohort of T2D patients, no liver-related morbidity or mortality occurred during 2 years. Our patients probably have low real prevalence of advanced fibrosis which is likely overestimated by LSM ≥ 9.6 kPa. Liver fibrosis may be safely reassessed in the 2 years interval in noncirrhotic patients with T2D.
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Affiliation(s)
- Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Nermin Salkic
- Department of Gastroenterology and Hepatology, University Hospital Centre Tuzla, Tuzla, Bosnia and Herzegovina
| | - Sanda Mustapic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Tomislav Bokun
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Kristian Podrug
- Department of Gastroenterology and Hepatology, University Hospital Split, Split, Croatia
| | - Srecko Marusic
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Dario Rahelic
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, University of Zagreb School of Medicine, Zagreb, Croatia
- School of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Tomas Matic
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, University of Zagreb School of Medicine, Zagreb, Croatia
| | | | - Ivana Mikolasevic
- Department of Gastroenterology and Hepatology, University Hospital Merkur, Zagreb, Croatia
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17
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Nascimbeni F, Lugari S, Cassinerio E, Motta I, Cavicchioli A, Dalla Salda A, Bursi S, Donatiello S, Spina V, Cappellini MD, Andreone P, Carubbi F. Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease. Liver Int 2020; 40:3061-3070. [PMID: 32810900 DOI: 10.1111/liv.14640] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 07/24/2020] [Accepted: 08/08/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. METHODS Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. RESULTS Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024). CONCLUSIONS Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications.
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Affiliation(s)
- Fabio Nascimbeni
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Simonetta Lugari
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Elena Cassinerio
- Rare Diseases Centre, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS, Milan, Italy
| | - Irene Motta
- Rare Diseases Centre, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS, Milan, Italy
| | - Alessia Cavicchioli
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Annalisa Dalla Salda
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Serena Bursi
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Vincenzo Spina
- Radiology Division, Civil Hospital, AOU of Modena, Modena, Italy
| | - Maria Domenica Cappellini
- Rare Diseases Centre, Department of Medicine and Medical Specialities, "Ca' Granda" Foundation IRCCS, Milan, Italy
| | - Pietro Andreone
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesca Carubbi
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
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18
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Applicability and Results of Liver Stiffness Measurement and Controlled Attenuation Parameter Using XL Probe for Metabolic-Associated Fatty Liver Disease in Candidates to Bariatric Surgery. A Single-Center Observational Study. Obes Surg 2020; 31:702-711. [PMID: 32959331 DOI: 10.1007/s11695-020-04971-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 09/06/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Patients with morbid obesity are at high risk of liver fibrosis due to metabolic-associated fatty liver disease. Data on liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by vibration-controlled transient elastography (VCTE, FibroScan®) XL probe for liver fibrosis and steatosis assessment in morbid obesity are needed. MATERIALS AND METHODS LSM and CAP were measured in candidates to bariatric surgery at a single center during 12 months. In patients who underwent an intraoperative liver biopsy, we compared LSM and CAP with histology findings. Comorbidities, body mass index, type of surgery, and infections after surgery were collected and analyzed. RESULTS Of the eighty-three patients assessed by XL probe, 49 (59%; female in 63%, BMI 42.6 ± 5.1 kg/m2) had a valid LSM and CAP measurement. LSM was 7.0 ± 3.9 kPa and CAP 329 ± 57 dB/m. In the 14 patients undergoing intraoperative liver biopsy, all had steatosis (severe in 50%), 6 (43%) had NASH (NAS ≥ 5), and 4 (29%) showed significant or bridging fibrosis. LSM accurately discriminated between patients with and without significant or severe fibrosis (AUROC 0.833) and CAP well-identified patients with or without ≥S2 steatosis (AUROC 0.896). Nine of 49 patients (18%) tested positive for significant/severe fibrosis by LSM (cut-off 8.9 kPa). CONCLUSION Applicability of LSM and CAP by XL probe in patients candidate to bariatric surgery was moderate. However, when technically successful, their reliability to diagnose severe steatosis and fibrosis related to MAFLD was good.
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19
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Schulz M, Tacke F. Identifying High-Risk NASH Patients: What We Know so Far. ACTA ACUST UNITED AC 2020; 12:125-138. [PMID: 32982495 PMCID: PMC7493213 DOI: 10.2147/hmer.s265473] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022]
Abstract
Steatosis is a condition of hepatic fat overload that is associated with overweight and the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease with a global impact on healthcare. A proportion of NAFLD patients develops nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis or hepatocellular carcinoma (HCC). Identifying patients at risk for potentially life-threatening complications is crucial in their prevention, surveillance and treatment. In addition to hepatic disease progression (cirrhosis, portal hypertension, HCC), NAFLD patients are also at risk of cardiovascular and metabolic diseases as well as extrahepatic malignancies. Liver fibrosis is related to morbidity and mortality in NASH patients, and biomarkers, imaging techniques (ultrasound, elastography, MRI) as well as liver biopsy help in diagnosing fibrosis. In this review, we discuss the tools for identifying patients at risk and their reasonable application in clinical routine in order to stratify prevention and treatment of this emerging disease.
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Affiliation(s)
- Marten Schulz
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) Und Campus Charité Mitte (CCM), Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) Und Campus Charité Mitte (CCM), Berlin, Germany
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Grgurevic I, Salkic N, Madir A, Aralica G. Steatosis assessment by controlled attenuation parameter in patients with compensated advanced chronic liver disease. Liver Int 2020; 40:1784-1785. [PMID: 32145702 DOI: 10.1111/liv.14426] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Nermin Salkic
- Department of Gastroenterology and Hepatology, University Hospital Centre Tuzla, Tuzla, Bosnia and Herzegovina
| | - Anita Madir
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Gorana Aralica
- Department of Pathology and Cytology, University Hospital Dubrava, University of Zagreb School of Medicine, Zagreb, Croatia
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