|
1
|
Giuffrè M, Dupont J, Visintin A, Masutti F, Monica F, You K, Shung DL, Crocè LS. Predicting response to non-selective beta-blockers with liver-spleen stiffness and heart rate in patients with liver cirrhosis and high-risk varices. Hepatol Int 2025; 19:460-471. [PMID: 38664292 PMCID: PMC12003444 DOI: 10.1007/s12072-024-10649-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/20/2024] [Indexed: 02/08/2025]
Abstract
INTRODUCTION Non-selective beta-blockers (NSBB) are used for primary prophylaxis in patients with liver cirrhosis and high-risk varices (HRVs). Assessing therapeutic response is challenging due to the invasive nature of hepatic venous pressure gradient (HVPG) measurement. This study aims to define a noninvasive machine-learning based approach to determine response to NSBB in patients with liver cirrhosis and HRVs. METHODS We conducted a prospective study on a cohort of cirrhotic patients with documented HRVs receiving NSBB treatment. Patients were followed-up with clinical and elastography appointments at 3, 6, and 12 months after NSBB treatment initiation. NSBB response was defined as stationary or downstaging variceal grading at the 12-month esophagogastroduodenoscopy (EGD). In contrast, non-response was defined as upstaging variceal grading at the 12-month EGD or at least one variceal hemorrhage episode during the 12-month follow-up. We chose cut-off values for univariate and multivariate model with 100% specificity. RESULTS According to least absolute shrinkage and selection operator (LASSO) regression, spleen stiffness (SS) and liver stiffness (LS) percentual decrease, along with changes in heart rate (HR) at 3 months were the most significant predictors of NSBB response. A decrease > 11.5% in SS, > 16.8% in LS, and > 25.3% in HR was associated with better prediction of clinical response to NSBB. SS percentual decrease showed the highest accuracy (86.4%) with high sensitivity (78.8%) when compared to LS and HR. The multivariate model incorporating SS, LS, and HR showed the highest discrimination and calibration metrics (AUROC = 0.96), with the optimal cut-off of 0.90 (sensitivity 94.2%, specificity 100%, PPV 95.7%, NPV 100%, accuracy 97.5%).
Collapse
Affiliation(s)
- Mauro Giuffrè
- Department of Internal Medicine (Digestive Diseases), Yale School of Medicine, Yale University, New Haven, CT, USA.
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
- Liver Clinic, Trieste University Hospital, Trieste, Italy.
| | - Johannes Dupont
- Department of Internal Medicine (Digestive Diseases), Yale School of Medicine, Yale University, New Haven, CT, USA
- Faculty of Medicine, University of Cologne, Cologne, Germany
| | | | - Flora Masutti
- Liver Clinic, Trieste University Hospital, Trieste, Italy
| | - Fabio Monica
- Gastroenterology and Endoscopy Unit, Trieste University Hospital, Trieste, Italy
| | - Kisung You
- Barauch College, Department of Mathematics, City University of New York, New York, NY, USA
| | - Dennis L Shung
- Department of Internal Medicine (Digestive Diseases), Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
- Liver Clinic, Trieste University Hospital, Trieste, Italy
| |
Collapse
|
|
2
|
Balcar L, Dominik N, Mozayani B, Semmler G, Halilbasic E, Mandorfer M, Reiberger T, Trauner M, Scheiner B, Stättermayer AF. Elevated Hepatic Copper Content in Porto-Sinusoidal Vascular Disorder (PSVD): Leading Down a Wrong Track. Liver Int 2025; 45:e16175. [PMID: 39807082 PMCID: PMC11730389 DOI: 10.1111/liv.16175] [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: 08/14/2024] [Revised: 10/23/2024] [Accepted: 11/05/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND AND AIMS Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD. METHODS Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included. Elevated hepatic copper content was correlated with cholestatic changes and WD diagnostics in PSVD and analysed for liver-related outcomes (first/further hepatic decompensation/liver-related death). RESULTS Overall, 92 patients were included into this study (mean age 49 ± 16; 57% male; median hepatic copper content was 30 [IQR: 18-55] μg/g) of whom 29 (32%) had moderately (≥ 50 μg/g) and 4 (4%) strongly (≥ 250 μg/g) elevated hepatic copper content. Elevated levels of hepatic copper were associated with younger age in multivariable linear regression analysis. After adjusting for age, decompensation status and albumin, hepatic copper content was significantly associated with the outcome of interest (log, per 10; aHR: 1.60 [95% CI: 1.14-2.25]; p = 0.007). A hepatic copper cut-off at ≥ 90 μg/g identified PSVD patients with considerable risk of liver-related outcomes (at 2 years: 51% vs. 12%). CONCLUSION Elevated hepatic copper seems frequent in patients with PSVD even in the absence of cholestatic features, especially in young patients, which makes differential diagnosis to WD challenging. Since PSVD patients with elevated hepatic copper content had increased risk for liver-related outcomes, the pathomechanisms underlying hepatic copper accumulation in PSVD should be investigated as this may open new therapeutic avenues.
Collapse
Affiliation(s)
- Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Nina Dominik
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Behrang Mozayani
- Department of PathologyMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Emina Halilbasic
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Clinical Research Group MOTIONMedical University of ViennaViennaAustria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| |
Collapse
|
|
3
|
Semmler G, Petrenko O, Lozano JJ, Shalaby S, Sánchez-Avila JI, Marella N, Hannich T, Wöran K, Balcar L, Simbrunner B, Lampichler K, Mozayani B, Trauner M, Mandorfer M, Reiberger T, García-Pagán JC, Scheiner B. Metabolomic profiles differentiate between porto-sinusoidal vascular disorder, cirrhosis, and healthy individuals. JHEP Rep 2024; 6:101208. [PMID: 39624234 PMCID: PMC11609546 DOI: 10.1016/j.jhepr.2024.101208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 07/30/2024] [Accepted: 08/27/2024] [Indexed: 04/03/2025] Open
Abstract
Background & Aims Porto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD or cirrhosis to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways. Methods Serum samples from 20 healthy volunteers (HVs), 20 patients with histologically confirmed PSVD or 20 patients with cirrhosis were analyzed. Metabolites were measured using liquid chromatography-mass spectrometry. Differential abundance was evaluated with Limma's moderated t-statistics. Artificial neural network and support vector machine models were developed to classify PSVD against cirrhosis or HV metabolomic profiles. An independent cohort was used for validation. Results A total of 283 metabolites were included for downstream analysis. Clustering effectively separated PSVD from HV metabolomes, although a subset of patients with PSVD (n = 5, 25%) overlapped with those with cirrhosis. Differential testing revealed significant PSVD-linked metabolic perturbations, including pertubations in taurocholic and adipic acids, distinguishing patients with PSVD from both HVs and those with cirrhosis. Alterations in pyrimidine, glycine, serine, and threonine pathways were exclusively associated with PSVD. Machine learning models utilizing selected metabolic signatures reliably differentiated the PSVD group from HVs or patients with cirrhosis using only 4 to 6 metabolites. Validation in an independent cohort demonstrated the high discriminative ability of taurocholic acid (AUROC 0.899) for patients with PSVD vs. HVs and the taurocholic acid/aspartic acid ratio (AUROC 0.720) for PSVD vs. cirrhosis. Conclusions High-throughput metabolomics enabled the identification of distinct metabolic profiles that differentiate between PSVD, cirrhosis, and healthy individuals. Unique alterations in the glycine, serine, and threonine pathways suggest their potential involvement in PSVD pathogenesis. Impact and implications Porto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in patients with PSVD, including alterations in the pyrimidine, glycine, serine and threonine pathways, potentially shedding light on the disease's underlying pathways. These findings could enable earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.
Collapse
Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
| | - Oleksandr Petrenko
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | | | - Sarah Shalaby
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Spain
| | - Juan I. Sánchez-Avila
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Nara Marella
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Thomas Hannich
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Katharina Wöran
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
| | - Katharina Lampichler
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Behrang Mozayani
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Juan-Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE-Liver). Departament de Medicina i Ciències de la Salut. Universitat de Barcelona, Spain
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Clinical Research Group MOTION, Medical University of Vienna, Vienna, Austria
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| |
Collapse
|
|
4
|
Clevert DA, Beyer G, Nieß H, Schlenker B. Ultrasound-New Techniques Are Extending the Applications. DEUTSCHES ARZTEBLATT INTERNATIONAL 2023; 120:41-47. [PMID: 36519209 DOI: 10.3238/arztebl.m2022.0380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 03/16/2022] [Accepted: 11/14/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Sonography is often the first imaging procedure to be used in diagnostic investigation of the abdomen. The aim of this article is to provide a new interdisciplinary overview of recent groundbreaking advances in this modality. METHODS A selective survey of the literature in PubMed was conducted. The literature search was carried out in 2021-2022 and included publications over the period 2004-2022. RESULTS The novel sonographic software techniques can be divided into algorithms that deal with conventional B-scan optimization and new programs that extend the scope of sonographic examination. The latter include elastography, contrast-enhanced sonography, and image fusion in combination with other cross-sectional imaging modalities. Elastography can be used to assess the presence of steatosis, fibrosis, or cirrhosis in patients with liver disease. One study reported diagnostic accuracy of 84-87% for the diagnosis of significant fibrosis (F2), 89-91% for the diagnosis of severe fibrosis (F3), and 92-93% for the diagnosis of liver cirrhosis (F4). Contrast-enhanced sonography is used for evaluation of tumors and trauma. A prospective multicenter study found sensitivity of 95.8% for the characterization of malignant lesions and specificity of 83.1% for benign lesions. Image fusion has the potential to improve the diagnostic assessment of parenchymatous organs, vascular conditions, and the prostate. CONCLUSION With continuous improvement of the B-scan and the development of high-frequency probes and novel investigation techniques, sonography has become established as an increasingly autonomous examination procedure.
Collapse
Affiliation(s)
- Dirk-André Clevert
- Department of Radiology, Interdisciplinary Ultrasound-Center, University Hospital of Ludwig-Maximilians-Universität Munich, Germany; Medical Department III,Interdisciplinary Ultrasound-Center, University Hospital of Ludwig-Maximilians-Universität Munich, Germany; Department of General, Visceral and Transplantation Surgery, University Hospital of Ludwig-Maximilians-Universität Munich, Germany; University Hospital of Ludwig-Maximilians-Universität Munich, Germany
| | | | | | | |
Collapse
|
|
5
|
Non-invasive tests for clinically significant portal hypertension after HCV cure. J Hepatol 2022; 77:1573-1585. [PMID: 36063968 DOI: 10.1016/j.jhep.2022.08.025] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 07/26/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting. METHODS A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort). RESULTS HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%). CONCLUSIONS NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment. LAY SUMMARY Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.
Collapse
|
|
6
|
Spleen and Liver Stiffness Evaluation by ARFI Imaging: A Reliable Tool for a Short-Term Monitoring of Portal Hypertension? Int J Hepatol 2022; 2022:7384144. [PMID: 36117519 PMCID: PMC9481411 DOI: 10.1155/2022/7384144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in diagnosis, but not in monitoring of portal hypertension. The aim of our prospective study was to determine the value of acoustic radiation force impulse (ARFI) elastography technique of the liver and spleen in diagnosis and monitoring of portal hypertension. METHODS We prospectively assessed portal hypertension by HVPG and corresponding elastography of the liver and spleen in 31 patients with liver cirrhosis and an indication for primary prophylaxis by non-cardio selective beta-blockers. Investigations were performed at baseline and a follow-up visit after 6-8 weeks. To address the known large variability of values for spleen elastography, well-defined corresponding areas in the spleen were used for baseline and follow-up elastography. Sensitivity, specificity, and AUC-ROC values for both spleen and liver elastography monitoring of portal hypertension were calculated. RESULTS Liver but not spleen elastography significantly correlated with HVPG results and was suitable for initial evaluation of portal hypertension. However, changes in HVPG results did not show any correlation with alterations of ARFI values from baseline to follow-up visits both for liver and spleen elastography. Spleen stiffness results were not homogeneous across the whole organ differing significantly between the upper, hilar, and bottom placed investigation areas. CONCLUSIONS In this prospective study ARFI-based assessment of liver elastography showed itself suitable for initial assessment but not for monitoring of portal hypertension. Spleen elastography was not appropriate for both, evaluation and monitoring of portal hypertension. A possible explanation for this new data that are in some contrast to previously published results is the degree of portal hypertension in our study, a comparatively short follow-up period, and well-defined investigation areas for spleen elastography in repetitive ARFI investigations. This trial is registered with NCT03315767.
Collapse
|
|
7
|
Wöran K, Semmler G, Jachs M, Simbrunner B, Bauer DJM, Binter T, Pomej K, Stättermayer AF, Schwabl P, Bucsics T, Paternostro R, Lampichler K, Pinter M, Trauner M, Mandorfer M, Stift J, Reiberger T, Scheiner B. Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension. Clin Gastroenterol Hepatol 2022; 20:e251-e266. [PMID: 33279774 DOI: 10.1016/j.cgh.2020.11.039] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/08/2020] [Accepted: 11/25/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.
Collapse
Affiliation(s)
- Katharina Wöran
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - David Josef Maria Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Teresa Binter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Pomej
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
8
|
Marynissen H, Lodeweyckx T, Bielen D, de Hoon J. Doppler ultrasound to assess the pharmacodynamic effects of splanchnic vasoactive compounds. Br J Clin Pharmacol 2021; 88:1785-1794. [PMID: 34558102 DOI: 10.1111/bcp.15095] [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: 01/21/2021] [Revised: 09/14/2021] [Accepted: 09/19/2021] [Indexed: 11/29/2022] Open
Abstract
AIMS In search of noninvasive biomarkers to assess the pharmacodynamic effects of portal pressure-lowering drugs, the reproducibility of flow measurements in the superior mesenteric artery was evaluated using Doppler ultrasound. METHODS A reproducibility study was conducted in 15 healthy male volunteers (18-50 y). Eight ultrasound measurements were performed for each subject: 2 observers each conducted 2 measurements during 2 separate visits. The following flow parameters were captured: peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), volume flow (VF) and vessel diameter. Reproducibility was assessed by the intraclass correlation coefficient. RESULTS Results are presented as intraclass correlation coefficient [95% confidence interval]. The flow parameters PSV, EDV, PI and VF correlated excellently within observer during visit 1 (0.888 [0.748-0.953], 0.910 [0.793-0.962], 0.844 [0.656-0.933] and 0.916 [0.857-0.951], respectively) and visit 2 (0.925 [0.829-0.968], 0.942 [0.863-0.976], 0.883 [0.719-0.954] and 0.915 [0.855-0.951], respectively). Measurements conducted during 2 separate visits by 1 observer correlated well to excellently for PSV, EDV, PI and VF (0.756 [0.552-0.875], 0.836 [0.694-0.916], 0.807 [0.631-0.904] and 0.839 [0.783-0.882], respectively). Measurements conducted by 2 distinct observers correlated well to excellently for PSV, EDV and VF during visit 1 (0.813 [0.584-0.922], 0.884 [0.597-0.945] and 0.786 [0.575-0.899], respectively) and visit 2 (0.779 [0.498-0.912], 0.861 [0.672-0.945], 0.810 [0.553-0.926], respectively). Vessel diameter measurements were poorly reproducible. CONCLUSION Doppler ultrasound is a reproducible method for flow measurements in the superior mesenteric artery in a standardized group of healthy volunteers. Therefore, it is a promising technique to assess pharmacodynamic effects of splanchnic vasoactive compounds in early clinical drug development.
Collapse
Affiliation(s)
- Heleen Marynissen
- Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium
| | - Thomas Lodeweyckx
- Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium
| | - Didier Bielen
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Jan de Hoon
- Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium
| |
Collapse
|
|
9
|
Sharma S, Chauhan A. MR elastography to predict haemodynamic response to beta-blockers-The story is still incomplete. Liver Int 2021; 41:2235. [PMID: 34269509 DOI: 10.1111/liv.15015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 07/12/2021] [Indexed: 02/13/2023]
Affiliation(s)
- Sanchit Sharma
- All India Institute of Medical Sciences, New Delhi, India
| | | |
Collapse
|
|
10
|
Danielsen KV, Hove JD, Nabilou P, Yin M, Chen J, Zhao M, Kallemose T, Teisner AS, Siebner HR, Ehman RL, Møller S, Bendtsen F. Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis. Liver Int 2021; 41:2149-2158. [PMID: 34060714 PMCID: PMC8373798 DOI: 10.1111/liv.14981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/18/2021] [Accepted: 05/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND MR elastography can determine organ-related stiffness, which reflects the degree of fibrosis. Liver stiffness increases in cirrhosis, and stiffness increases further post-prandially due to increased portal blood in-flow. Non-selective beta-blockers (NSBB) reduce the portal venous inflow, but their effect on liver and spleen stiffness are disputed. AIMS To assess whether MR elastography of the liver or spleen reflects the severity of cirrhosis, whether treatment with NSBB changes liver and spleen stiffness and whether changes in stiffness can predict the effect of NSBB on portal pressure. METHODS Fifty-two patients with cirrhosis underwent liver vein catheterization and two-dimensional (2D) MR elastography on separate days. Thirty-six of the patients had a hepatic venous pressure gradient (HVPG) of ≥12 mmHg and were tested prior to, and after, intravenous infusion of NSBB using HVPG measurement and MR elastography. RESULTS HVPG showed a strong, positive, linear relationship with liver stiffness (r2 = 0.92; P < .001) and spleen stiffness (r2 = 0.94; P < .001). The cut-off points for identifying patients with a HVPG ≥ 12 mmHg were 7.7 kPa for liver stiffness (sensitivity 0.78, specificity 0.64) and 10.5 kPa for spleen stiffness (sensitivity 0.8, specificity 0.79). Intravenous administration of NSBB significantly decreased spleen stiffness by 6.9% (CI: 3.5-10.4, P < .001), but NSBB had no consistent effect on liver stiffness. However, changes in spleen stiffness were not related to the HVPG response (P = .75). CONCLUSIONS Two-dimensional MR elastographic estimation of liver or spleen stiffness reflects the degree of portal hypertension in patients with liver cirrhosis, but changes in stiffness after NSBB do not predict the effect on HVPG.
Collapse
Affiliation(s)
- Karen Vagner Danielsen
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark,Dept. Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Dept. of Cardiology, Copenhagen University Hospital Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
| | - Puria Nabilou
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark
| | - Meng Yin
- Dept. of Radiology, Mayo Clinic, Rochester, cx USA
| | - Jun Chen
- Dept. of Radiology, Mayo Clinic, Rochester, cx USA
| | - Mirabella Zhao
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark
| | - Thomas Kallemose
- Clinical Research Department. Copenhagen University Hospital Hvidovre, Denmark
| | - Ane Søgaard Teisner
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Herlev, Denmark
| | - Hartwig Roman Siebner
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen,Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | | | - Søren Møller
- Dept. Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
| | - Flemming Bendtsen
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
| |
Collapse
|
|
11
|
Cicero G, Mazziotti S, Silipigni S, Blandino A, Cantisani V, Pergolizzi S, D'Angelo T, Stagno A, Maimone S, Squadrito G, Ascenti G. Dual-energy CT quantification of fractional extracellular space in cirrhotic patients: comparison between early and delayed equilibrium phases and correlation with oesophageal varices. LA RADIOLOGIA MEDICA 2021; 126:761-767. [PMID: 33715036 DOI: 10.1007/s11547-021-01341-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 02/22/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Fractional extracellular space has been validated as a marker of hepatic fibrotic in cirrhotic patients at CT-scan as well as on dual-energy CT, which takes advantage from iodine uptake. Since no consensus still exists between equilibrium phases performed at 3 or 10 min, the first aim of this work is to evaluate performances at the two different time points. Moreover, correlation between fractional extracellular space and oesophageal varices, directly related to liver fibrosis, has been assessed. MATERIALS AND METHODS Dual-Energy equilibrium phases at 3 and 10 min were performed within a follow-up CT-protocol scan in cirrhotic patients. Oesophageal varices were endoscopically assessed according to their size. At the two different time points, correlation between iodine density of the right and left liver lobes and correlation between the fractional extracellular space values were assessed. Correlation between fractional extracellular space and endoscopic grade of oesophageal varices was calculated. RESULTS No statistical differences were found between the iodine density values from the two liver lobes at the two time points (p = 0.8 at 3'; p = 0.5 at 10'). No statistical difference about fractional extracellular space estimation was found between the two time points (p = 0.17). Correlation between fractional extracellular space values and oesophageal varices was moderate (ρ = 0.45, IC 0.08-0.71, p < 0.05). CONCLUSION Fractional extracellular space assessed on dual-energy CT at equilibrium phases with different timing was substantially similar. The moderate correlation found between fractional extracellular space and endoscopic grade of oesophageal varices confirms that CT-scan is not currently reliable as endoscopy.
Collapse
Affiliation(s)
- Giuseppe Cicero
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy.
| | - Silvio Mazziotti
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Salvatore Silipigni
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Alfredo Blandino
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Vito Cantisani
- Department of Radiology, "Sapienza" University of Rome, Rome, Italy
| | - Stefano Pergolizzi
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Tommaso D'Angelo
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Alberto Stagno
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Giovanni Squadrito
- Division of Clinical and Molecular Hepatology, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| | - Giorgio Ascenti
- Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy
| |
Collapse
|
|
12
|
Vuille-Lessard É, Rodrigues SG, Berzigotti A. Noninvasive Detection of Clinically Significant Portal Hypertension in Compensated Advanced Chronic Liver Disease. Clin Liver Dis 2021; 25:253-289. [PMID: 33838850 DOI: 10.1016/j.cld.2021.01.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with compensated advanced chronic liver disease have different prognoses depending on the presence of portal hypertension. Current non-invasive diagnostic methods allow identification of clinically significant portal hypertension. Portosystemic collaterals on imaging or liver stiffness of more than 20 to 25 kPa by using transient elastography identifies patients with clinically significant portal hypertension. Patients with liver stiffness of less than 20 kPa and platelet count of greater than 150 g/L can avoid endoscopy. This rule could be expanded using spleen stiffness. Methods to risk stratify for portal hypertension in compensated advanced chronic liver disease and successfully treated chronic hepatitis C and B are subject of research.
Collapse
Affiliation(s)
- Élise Vuille-Lessard
- Hepatology, University Clinic for Visceral Surgery and Medicine (UVCM), Inselspital, University Hospital of Bern, Freiburgstrasse, 3010 Bern, Switzerland; Department of Biomedical Research, University of Bern, Switzerland
| | - Susana G Rodrigues
- Hepatology, University Clinic for Visceral Surgery and Medicine (UVCM), Inselspital, University Hospital of Bern, Freiburgstrasse, 3010 Bern, Switzerland; Department of Biomedical Research, University of Bern, Switzerland
| | - Annalisa Berzigotti
- Hepatology, University Clinic for Visceral Surgery and Medicine (UVCM), Inselspital, University Hospital of Bern, Freiburgstrasse, 3010 Bern, Switzerland; Department of Biomedical Research, University of Bern, Switzerland.
| |
Collapse
|
|
13
|
Balcar L, Semmler G, Pomej K, Simbrunner B, Bauer D, Hartl L, Jachs M, Paternostro R, Bucsics T, Pinter M, Trauner M, Mandorfer M, Reiberger T, Scheiner B. Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute-on-chronic liver failure. United European Gastroenterol J 2021; 9:427-437. [PMID: 34050619 PMCID: PMC8259248 DOI: 10.1002/ueg2.12089] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/22/2021] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on-chronic liver failure (pre-ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real-life cohort of hospitalized patients with cirrhosis. METHODS Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis. RESULTS Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre-ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1-year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90-day mortality: pre-ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C-reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre-ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre-ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis. DISCUSSION The recently proposed pathophysiological/prognostic EF-CLIF subgroups are also reproduceable in a real-life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre-ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
Collapse
Affiliation(s)
- Lorenz Balcar
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Georg Semmler
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Katharina Pomej
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
- Christian‐Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
- Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - David Bauer
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Lukas Hartl
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Mathias Jachs
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Theresa Bucsics
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Matthias Pinter
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Michael Trauner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
- Christian‐Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
- Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Bernhard Scheiner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| |
Collapse
|
|
14
|
Pons M, Augustin S, Scheiner B, Guillaume M, Rosselli M, Rodrigues SG, Stefanescu H, Ma MM, Mandorfer M, Mergeay-Fabre M, Procopet B, Schwabl P, Ferlitsch A, Semmler G, Berzigotti A, Tsochatzis E, Bureau C, Reiberger T, Bosch J, Abraldes JG, Genescà J. Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease. Am J Gastroenterol 2021; 116:723-732. [PMID: 33038131 DOI: 10.14309/ajg.0000000000000994] [Citation(s) in RCA: 142] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION:
We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice.
METHODS:
This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH.
RESULTS:
A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 109/L ruled out CSPH in most etiologies.
DISCUSSION:
Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.
Collapse
Affiliation(s)
- Monica Pons
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Salvador Augustin
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Maeva Guillaume
- Service d'Hépatologie CHU Toulouse Rangueil, Institut Cardiomet et Université Paul Sabatier, Toulouse, France
| | - Matteo Rosselli
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Centre, Royal Free Hospital and UCL, London, United Kingdom
| | - Susana G. Rodrigues
- Swiss Liver Center, UVCM, Inselspital, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Horia Stefanescu
- Liver Unit, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor,” University of Medicine and Pharmacy “Iuliu Hatieganu,” Cluj-Napoca, Romania
| | - Mang M. Ma
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Mayka Mergeay-Fabre
- Service d'Hépatologie CHU Toulouse Rangueil, Institut Cardiomet et Université Paul Sabatier, Toulouse, France
| | - Bogdan Procopet
- Liver Unit, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor,” University of Medicine and Pharmacy “Iuliu Hatieganu,” Cluj-Napoca, Romania
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
- Division of Internal Medicine II, Krankenhaus Barmherzige Brüder, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Annalisa Berzigotti
- Swiss Liver Center, UVCM, Inselspital, Department of Biomedical Research, University of Bern, Bern, Switzerland
- Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Emmanuel Tsochatzis
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Centre, Royal Free Hospital and UCL, London, United Kingdom
| | - Christophe Bureau
- Service d'Hépatologie CHU Toulouse Rangueil, Institut Cardiomet et Université Paul Sabatier, Toulouse, France
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Jaime Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Swiss Liver Center, UVCM, Inselspital, Department of Biomedical Research, University of Bern, Bern, Switzerland
- Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan G. Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Joan Genescà
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
15
|
Agarwal S, Sharma S, Anand A, Gunjan D, Saraya A. Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study. JGH OPEN 2021; 5:73-80. [PMID: 33490616 PMCID: PMC7812463 DOI: 10.1002/jgh3.12449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/08/2020] [Accepted: 10/27/2020] [Indexed: 12/25/2022]
Abstract
Background and Aim Hepatic venous pressure gradient (HVPG), although an important determinant in predicting rebleeding after an episode of acute variceal bleed (AVB), is seldom utilized in clinical practice. We aimed to study the role of liver stiffness measurement (LSM) after variceal bleeding as a potential noninvasive predictor of rebleed. Methods This was a post hoc analysis of clinical trial of patients undergoing HVPG (postbleed HVPG) and LSM (postbleed LSM) assessment within 3–5 days of index AVB. HVPG response was assessed after 4 weeks of pharmacotherapy. Comparative assessment of long‐term rebleeding rates stratified using postbleed LSM, postbleed HVPG, and HVPG response was performed. Decision curve analysis (DCA) was conducted to identify the most appropriate tool for routine use. Results Long‐term clinical and HVPG response data were available for 48 patients post‐AVB, of whom 45 patients had valid postbleed LSM. Rebleeding occurred in 13 (28%) patients over a median follow‐up of 4 years with no early rebleeds. Postbleed LSM >30 kPa and baseline HVPG >15 mm Hg were optimal cutoffs for identifying patients at high risk of rebleeding. Time‐dependent receiver operating characteristic curves and competing risk analysis accounting for death showed similar discriminative values for all three stratification tools. At usual risk thresholds, HVPG response had maximum benefit on DCA followed by postbleed LSM. On DCA, 50–60 additional HVPGs were required to detect one additional patient at high risk of rebleed. Conclusion Liver stiffness measurement during AVB can potentially be used as an alternative to portal pressure indices in decompensated cirrhosis to identify those at high risk of late‐onset rebleed.
Collapse
Affiliation(s)
- Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| |
Collapse
|
|
16
|
Frankova S, Lunova M, Gottfriedova H, Senkerikova R, Neroldova M, Kovac J, Kieslichova E, Lanska V, Urbanek P, Spicak J, Jirsa M, Sperl J. Liver stiffness measured by two-dimensional shear-wave elastography predicts hepatic vein pressure gradient at high values in liver transplant candidates with advanced liver cirrhosis. PLoS One 2021; 16:e0244934. [PMID: 33411729 PMCID: PMC7790429 DOI: 10.1371/journal.pone.0244934] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/20/2020] [Indexed: 12/15/2022] Open
Abstract
Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis.
Collapse
Affiliation(s)
- Sona Frankova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Mariia Lunova
- Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Halima Gottfriedova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Renata Senkerikova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
| | - Magdalena Neroldova
- Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jozef Kovac
- Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Eva Kieslichova
- Anaesthesiology, Resuscitation and Intensive Care Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vera Lanska
- Department of Biostatistics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Petr Urbanek
- Charles University, First Faculty of Medicine, Prague, Czech Republic
- Department of Internal Medicine, Central Military Hospital, Prague, Czech Republic
| | - Julius Spicak
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Milan Jirsa
- Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
| | - Jan Sperl
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
- * E-mail:
| |
Collapse
|
|
17
|
Kennedy P, Bane O, Hectors SJ, Fischman A, Schiano T, Lewis S, Taouli B. Noninvasive imaging assessment of portal hypertension. Abdom Radiol (NY) 2020; 45:3473-3495. [PMID: 32926209 PMCID: PMC10124623 DOI: 10.1007/s00261-020-02729-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/16/2020] [Accepted: 08/30/2020] [Indexed: 02/07/2023]
Abstract
Portal hypertension (PH) is a spectrum of complications of chronic liver disease (CLD) and cirrhosis, with manifestations including ascites, gastroesophageal varices, splenomegaly, hypersplenism, hepatic hydrothorax, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. PH can vary in severity and is diagnosed via invasive hepatic venous pressure gradient measurement (HVPG), which is considered the reference standard. Accurate diagnosis of PH and assessment of severity are highly relevant as patients with clinically significant portal hypertension (CSPH) are at higher risk for developing acute variceal bleeding and mortality. In this review, we discuss current and upcoming noninvasive imaging methods for diagnosis and assessment of severity of PH.
Collapse
|
|
18
|
Marasco G, Dajti E, Ravaioli F, Alemanni LV, Capuano F, Gjini K, Colecchia L, Puppini G, Cusumano C, Renzulli M, Golfieri R, Festi D, Colecchia A. Spleen stiffness measurement for assessing the response to β-blockers therapy for high-risk esophageal varices patients. Hepatol Int 2020; 14:850-857. [PMID: 32557193 DOI: 10.1007/s12072-020-10062-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 06/06/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Non-selective β-blocker (NSBB) therapy is the treatment of choice for primary prophylaxis of cirrhotic patients with high-bleeding risk esophageal varices (HRV). The hemodynamic response to NSBB is assessed by the measurement of the hepatic venous pressure gradient (HVPG). Recently, liver and spleen stiffness measurements (LSM and SSM) were proposed as non-invasive surrogates of HVPG. We aimed to evaluate LSM and SSM changes for assessing hemodynamic response in these patients. METHODS Cirrhotic patients with HRV were prospectively enrolled and evaluated at our Department before starting NSBB and after 3 months. Correlation between changes (delta) of HVPG after NSBB treatment and those of LSM or SSM by transient elastography was performed. RESULTS From the initial 59 patients considered for the study, 20 were finally included in the analysis. Fifteen (15) patients reached hemodynamic response to NSBB according to HVPG. Changes in LSM did not correlate with changes in HVPG (r = 0.107, p value = 0.655), unlike changes in SSM (r = 0.784, p value < 0.0001). Delta SSM presented excellent accuracy in identifying HVPG responders (AUROC 0.973; 95% CI 0.912-1). The best cut-off for delta SSM to identify responders was -10% (sensitivity 100%, specificity 60%, NPV 100% and PPV 90%). CONCLUSIONS SSM could be a reliable non-invasive test for the assessment of hemodynamic response to NSBB therapy as primary prophylaxis for HRV. Similar to HVPG, SSM reduction ≥ 10% is able to assess hemodynamic response.
Collapse
Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
| | - Elton Dajti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Luigina Vanessa Alemanni
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Fabiana Capuano
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, P.le Aristide Stefani 1, 37126, Verona, Italy
| | - Kamela Gjini
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, P.le Aristide Stefani 1, 37126, Verona, Italy
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Giovanni Puppini
- Radiology Unit, Borgo Trento University Hospital, P.le Aristide Stefani 1, 37126, Verona, Italy
| | - Caterina Cusumano
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, P.le Aristide Stefani 1, 37126, Verona, Italy
| | - Matteo Renzulli
- Radiology Unit, Sant'Orsola Malpighi Hospital, Via Albertoni 4, 40126, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Sant'Orsola Malpighi Hospital, Via Albertoni 4, 40126, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Antonio Colecchia
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, P.le Aristide Stefani 1, 37126, Verona, Italy
| |
Collapse
|
|
19
|
Mandorfer M, Hernández-Gea V, García-Pagán JC, Reiberger T. Noninvasive Diagnostics for Portal Hypertension: A Comprehensive Review. Semin Liver Dis 2020; 40:240-255. [PMID: 32557480 DOI: 10.1055/s-0040-1708806] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Noninvasive diagnostics for portal hypertension include imaging and functional tests, as well as blood-based biomarkers, and capture different features of the portal hypertensive syndrome. Definitive conclusions regarding their clinical utility require assessment of their diagnostic value in specific clinical settings (i.e., diagnosing a particular hemodynamic condition within a well-defined target population). Several noninvasive methods are predictive of clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥ 10 mm Hg; the threshold for complications of portal hypertension); however, only a minority of them have been evaluated in compensated advanced chronic liver disease (i.e., the target population). Importantly, most methods correlate only weakly with HVPG at high values (i.e., in patients with CSPH). Nevertheless, selected methods show promise for diagnosing HVPG ≥ 16 mm Hg (the cut-off for increased risks of hepatic decompensation and mortality) and monitoring HVPG changes in response to nonselective beta-blockers or etiological treatments. Finally, we review established and potential future clinical applications of noninvasive methods.
Collapse
Affiliation(s)
- Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Barcelona, Spain
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
20
|
Simbrunner B, Marculescu R, Scheiner B, Schwabl P, Bucsics T, Stadlmann A, Bauer DJM, Paternostro R, Eigenbauer E, Pinter M, Stättermayer AF, Trauner M, Mandorfer M, Reiberger T. Non-invasive detection of portal hypertension by enhanced liver fibrosis score in patients with different aetiologies of advanced chronic liver disease. Liver Int 2020; 40:1713-1724. [PMID: 32358998 PMCID: PMC7383870 DOI: 10.1111/liv.14498] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/03/2020] [Accepted: 04/27/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS The enhanced liver fibrosis (ELF) score comprises serum markers of fibrogenesis and matrix remodelling and was developed to detect liver fibrosis, however, it may also be useful for the non-invasive detection of portal hypertension (PHT). METHODS ELF score and its single components (TIMP1/PIIINP/HA) were analysed in 201 patients with advanced chronic liver disease (ACLD; ie hepatic venous pressure gradient (HVPG) ≥6 mm Hg). Patients with pre-/post-hepatic PHT, hepatocellular carcinoma beyond Milan criteria, and history of TIPS implantation or liver transplantation were excluded. RESULTS ELF and its single components correlated with HVPG in the overall cohort: ELF: r = .443, TIMP1: r = .368, PIIINP:r = .332, and HA:r = .419 (all P < .001). The strength of the correlation between ELF and HVPG decreased in higher HVPG strata: 6-9 mm Hg:r = .569(P = .004), 10-19 mm Hg:r = .304 (P = .001) and ≥20 mm Hg:r = -.023(P = .853). Area under the receiver operating characteristics (AUROC) of ELF score to detect clinically significant PHT (CSPH; HVPG ≥ 10 mm Hg) was 0.833. Importantly, HA alone yielded an AUROC of 0.828. Detection of CSPH in strictly compensated ACLD (cACLD) patients was less accurate: AUROC: 0.759 (P < .001). CSPH was ruled-in by ELF ≥ 11.1 with a PPV of 98% (sensitivity: 61%/specificity: 92%/NPV:24%), but CSPH could not be ruled-out. ELF score had a low AUROC of 0.677 (0.60-0.75; P < .001) for the diagnosis of high-risk PHT (HRPH; HVPG ≥ 20mm Hg) and, thus, HRPH could not be ruled-in by ELF. However, ELF < 10.1 ruled-out HRPH with a NPV of 95% (sensitivity: 97%/specificity: 26%/PPV: 39%). CONCLUSION The ELF score correlates with HVPG at values <20 mm Hg. An ELF ≥ 11.1 identifies patients with a high probability of CSPH, while an ELF < 10.1 may be used to rule-out HRPH.
Collapse
Affiliation(s)
- Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Rodrig Marculescu
- Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Theresa Bucsics
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Alexander Stadlmann
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria,Hospital HietzingViennaAustria
| | - David J. M. Bauer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Ernst Eigenbauer
- IT‐Systems & CommunicationsMedical University of ViennaViennaAustria
| | - Matthias Pinter
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| |
Collapse
|
|
21
|
Mandorfer M, Kozbial K, Schwabl P, Chromy D, Semmler G, Stättermayer AF, Pinter M, Hernández‐Gea V, Fritzer‐Szekeres M, Steindl‐Munda P, Trauner M, Peck‐Radosavljevic M, García‐Pagán JC, Ferenci P, Reiberger T. Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy. Hepatology 2020; 71:1023-1036. [PMID: 31365764 PMCID: PMC7155089 DOI: 10.1002/hep.30885] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 07/27/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH. APPROACH AND RESULTS The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08-1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC], < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner. CONCLUSIONS Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An "immediate" HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.
Collapse
Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
- Barcelona Hepatic Hemodynamic Lab, Liver UnitHospital ClínicBarcelonaSpain
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Albert F. Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| | - Virginia Hernández‐Gea
- Barcelona Hepatic Hemodynamic Lab, Liver UnitHospital ClínicBarcelonaSpain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | | | - Petra Steindl‐Munda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Markus Peck‐Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
- Department of Internal Medicine and Gastroenterology (IMuG), Hepatology, Endocrinology, Rheumatology, and Nephrology with Centralized Emergency Service (ZAE)Klinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - Juan C. García‐Pagán
- Barcelona Hepatic Hemodynamic Lab, Liver UnitHospital ClínicBarcelonaSpain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LabMedical University of ViennaViennaAustria
| |
Collapse
|
|
22
|
Scheiner B, Semmler G, Maurer F, Schwabl P, Bucsics TA, Paternostro R, Bauer D, Simbrunner B, Trauner M, Mandorfer M, Reiberger T. Prevalence of and risk factors for anaemia in patients with advanced chronic liver disease. Liver Int 2020; 40:194-204. [PMID: 31444993 PMCID: PMC6973120 DOI: 10.1111/liv.14229] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 07/19/2019] [Accepted: 08/10/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Anaemia is common in advanced chronic liver disease (ACLD) as a result of various risk factors. AIMS & METHODS We evaluated the prevalence and severity of anaemia as well as the impact of anaemia on clinical outcomes in consecutive patients with ACLD and portal hypertension. RESULTS Among 494 patients, 324 (66%) patients had anaemia. Anaemic patients showed higher MELD (12 ± 4 vs 9 ± 3; P < .001), lower albumin (34 ± 6 vs 39 ± 5 g/dL; P < .001) and more often Child-Pugh B/C stage (56% vs 17%; P < .001). The prevalence of moderate-severe anaemia (haemoglobin <10 g/dL) increased with the degree of portal hypertension (HVPG: 6-9 mm Hg: 22% vs HVPG: 10-19 mm Hg: 24% vs HVPG ≥ 20 mm Hg: 36%; P = .031). The most common aetiologies of anaemia were gastrointestinal bleeding (25%) and iron deficiency (9%), while reason for anaemia remained unclear in 53% of cases. Male gender (odds ratio [OR]: 1.94 [95% CI: 1.09-3.47]; P = .025), MELD (OR: 1.20 [95% CI: 1.09-1.32]; P < .001), hepatic decompensation (OR: 4.40 [95% CI: 2.48-7.82]; P < .001) and HVPG (OR per mm Hg: 1.07 [95% CI: 1.02-1.13]; P = .004) were independent risk factors for anaemia. Anaemia was associated with hepatic decompensation (1 year: 25.1% vs 8.1%; 5 years: 60.3% vs 32.9%; P < .0001), hospitalization (73% vs 57%; P < .001) and a higher incidence rate of acute-on-chronic liver failure (0.05 [95% CI: 0.04-0.07] vs 0.03 [95% CI: 0.01-0.04]). Anaemic patients had worse overall survival (1 year: 87.1% vs 93.7%, 5 year survival: 50.5% vs 68.6%; P < .0001) and increased liver-related mortality (1 year mortality: 9.7% vs 5.7%, 5 year mortality: 38.0% vs 26.9%; P = .003). CONCLUSION Two-thirds of patients with ACLD suffer from anaemia. The degree of hepatic dysfunction and of portal hypertension correlate with severity of anaemia. Anaemia is associated with decompensation, ACLF and increased mortality in patients with ACLD.
Collapse
Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Florian Maurer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Theresa A. Bucsics
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - David Bauer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| |
Collapse
|
|
23
|
Semmler G, Scheiner B, Schwabl P, Bucsics T, Paternostro R, Chromy D, Stättermayer AF, Trauner M, Mandorfer M, Ferlitsch A, Reiberger T. The impact of hepatic steatosis on portal hypertension. PLoS One 2019; 14:e0224506. [PMID: 31693695 PMCID: PMC6834246 DOI: 10.1371/journal.pone.0224506] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/15/2019] [Indexed: 12/20/2022] Open
Abstract
Background and aims Studies in animal models have suggested that hepatic steatosis impacts on portal pressure, potentially by inducing liver sinusoidal endothelial dysfunction and thereby increasing intrahepatic resistance. Thus, we aimed to evaluate the impact of hepatic steatosis on hepatic venous pressure gradient (HVPG) in patients with chronic liver disease. Method 261 patients undergoing simultaneous HVPG measurements and controlled attenuation parameter (CAP)-based steatosis assessment were included in this retrospective study. Results The majority of patients had cirrhosis (n = 205; 78.5%) and n = 191 (73.2%) had clinically significant portal hypertension (CSPH; HVPG≥10mmHg). Hepatic steatosis (S1/2/3; CAP ≥248dB/m) was present in n = 102 (39.1%). Overall, HVPG was comparable between patients with vs. without hepatic steatosis (15.5±7.5 vs. 14.8±7.7mmHg; p = 0.465). Neither in patients with HVPG (<6mmHg; p = 0.371) nor in patients with mild portal hypertension (HVPG 6–9mmHg; p = 0.716) or CSPH (HVPG≥10mmHg; p = 0.311) any correlation between CAP and HVPG was found. Interestingly, in patients with liver fibrosis F2/3, there was a negative correlation between CAP and HVPG (Pearson’s ρ:-0.522; p≤0.001). In multivariate analysis, higher CAP was an independent ‘protective’ factor for the presence of CSPH (odds ratio [OR] per 10dB/m: 0.92, 95% confidence interval [CI]:0.85–1.00; p = 0.045), while liver stiffness was associated with the presence of CSPH (OR per kPa: 1.26, 95%CI: 1.17–1.36; p≤0.001). In 78 patients, in whom liver biopsy was performed, HVPG was neither correlated with percentage of histological steatosis (p = 0.714) nor with histological steatosis grade (p = 0.957). Conclusion Hepatic steatosis, as assessed by CAP and liver histology, did not impact on HVPG in our cohort comprising a high proportion of patients with advanced chronic liver disease. However, high CAP values (i.e. pronounced hepatic steatosis) might lead to overestimation of liver fibrosis by ‘artificially’ increasing transient elastography-based liver stiffness measurements.
Collapse
Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Department of Internal Medicine I, Hospital of St. John of God, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
24
|
Zaghloul SG, Wahab EA, Seleem WM, Hanafy AS, Gomaa AF, Lakouz K, Amin AI. Impact of non-selective beta blockers on portal hypertension and hepatic elasticity in hepatitis C virus-related liver cirrhosis. Drug Discov Ther 2019; 13:108-113. [PMID: 31080201 DOI: 10.5582/ddt.2019.01009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Portal hypertension and its complications are the leading causes of morbidity and mortality in patients with liver cirrhosis. Noninvasive assessment of liver stiffness had been an effective tool for assessment of fibrosis progression in chronic liver disease. It was intended to assess liver stiffness measurement (LSM), portal vein diameter (PVD), splenic bipolar diameter (SD), and the platelet count/spleen diameter (PC/SD) ratio in patients who test positive for the hepatitis C virus (HCV) and to study the impact of non-selective beta blockers (NSBB) on the grade of esophageal varices (EVs) and liver elasticity. Subjects were 80 patients with Child-Pugh grade A or B compensated cirrhosis who tested positive for HCV. All of the patients underwent a laboratory workup including AFP, HCV antibodies, HCV RNA, HBsAg, LSM according to real-time elastography, upper gastrointestinal endoscopy (UGIE) to detect and grade EVs, calculation of the PC/SD ratio, and measurement of the PVD and SD according to real-time abdominal ultrasonography. All patients were given the maximum tolerated dose of NSBB for three months, and UGIE, LSM, PC/SD, PVD, and SD were subsequently reassessed and reported. LSM and the PC/SD ratio were exceptional noninvasive tools for prediction of significant EVs (grade ≥ II, p < 0.001) with a sensitivity 82.4% and a specificity 82.6% at a cutoff point 18 kPa for LSM, and a sensitivity 94.1% and specificity 69.6% at a cutoff point 880 for the PC/SD ratio. LSM is highly correlated with PVD, the PC/SD ratio, SD, and the Child-Pugh score. NSBB significantly decreased PVD. The percent change in PVD significantly correlated with LSM, the grade of EVs, and SD. Findings indicated that LSM is a noninvasive, rapid, and reproducible tool with which to detect portal hypertension and EVs. NSBB therapy can effectively decrease PVD and may consequently improve the EV grade with no significant impact on LSM in patients with liver cirrhosis.
Collapse
Affiliation(s)
- Sahar G Zaghloul
- Hepato-gastroenterology Unit, Department of Internal Medicine, Zagazig University
| | - Essam A Wahab
- Hepato-gastroenterology Unit, Department of Internal Medicine, Zagazig University
| | - Waseem M Seleem
- Hepato-gastroenterology Unit, Department of Internal Medicine, Zagazig University
| | - Amr S Hanafy
- Hepato-gastroenterology Unit, Department of Internal Medicine, Zagazig University
| | - Ahmed Fathy Gomaa
- Hepato-gastroenterology Unit, Department of Internal Medicine, Zagazig University
| | - Kh Lakouz
- Department of Diagnostic Radiology, Faculty of Medicine, Zagazig University
| | - A I Amin
- Hepato-gastroenterology Unit, Department of Internal Medicine, Faculty of Medicine, Port Said University
| |
Collapse
|
|
25
|
Ling L, Li G, Wang G, Meng D, Li Z, Zhang C. Carvedilol improves liver cirrhosis in rats by inhibiting hepatic stellate cell activation, proliferation, invasion and collagen synthesis. Mol Med Rep 2019; 20:1605-1612. [PMID: 31257490 PMCID: PMC6625452 DOI: 10.3892/mmr.2019.10401] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 05/22/2019] [Indexed: 12/13/2022] Open
Abstract
Portal hypertension (PHT) is one of the most severe consequences of liver cirrhosis. Carvedilol is a first-line pharmacological treatment of PHT. However, the antifibrogenic effects of carvedilol on liver cirrhosis and the intrinsic mechanisms underlying these effects have not been thoroughly investigated. The present study aimed to investigate the antifibrogenic effects of carvedilol on liver cirrhosis in vivo and in vitro. Liver cirrhosis was induced in rats by carbon tetrachloride (CCl4) administration for 9 weeks; carvedilol was administered simultaneously in the experimental group. Blood samples were collected for serum biochemistry. Liver tissues were used for fibrosis evaluation, histological examination, immunohistochemistry and western blot analysis. The human hepatic stellate cell (HSC) line LX-2 was used for in vitro studies. The effects of carvedilol on LX-2 cell proliferation and invasion were evaluated by Cell Counting Kit-8 assay and Transwell invasion assays, respectively. The effect of carvedilol on transforming growth factor β1 (TGFβ1)-induced collagen synthesis in LX-2 cells and the molecular mechanisms were examined by western blot analysis. The results demonstrated that carvedilol improved CCl4-induced structural distortion and fibrosis in the liver. Carvedilol inhibited HSC activation, proliferation and invasion. Carvedilol inhibited HSC collagen synthesis through the TGFβ1/SMAD pathway. In conclusion, carvedilol may alleviate liver cirrhosis in rats by inhibiting HSC activation, proliferation, invasion and collagen synthesis. Carvedilol may be a potential treatment of early-stage liver cirrhosis.
Collapse
Affiliation(s)
- Liping Ling
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Guangqi Li
- Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256603, P.R. China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Dongxiao Meng
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Zhen Li
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| |
Collapse
|
|
26
|
Mandorfer M, Hernández-Gea V, Reiberger T, García-Pagán JC. Hepatic Venous Pressure Gradient Response in Non-Selective Beta-Blocker Treatment—Is It Worth Measuring? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00469-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
27
|
Qi X, Berzigotti A, Cardenas A, Sarin SK. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol 2019; 3:708-719. [PMID: 30215362 DOI: 10.1016/s2468-1253(18)30232-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 05/13/2018] [Accepted: 06/25/2018] [Indexed: 02/08/2023]
Abstract
Clinically significant portal hypertension is associated with an increased risk of developing gastro-oesophageal varices and hepatic decompensation. Hepatic venous pressure gradient measurement and oesophagogastroduodenoscopy are the gold-standard methods for assessing clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mm Hg) and gastro-oesophageal varices, respectively. However, invasiveness, cost, and feasibility limit their widespread use, especially if repeated and serial evaluations are required to assess the efficacy of pharmacotherapy. Although new techniques for non-invasive portal pressure measurement have been pursued for many decades, only recently have new tools been assessed and validated for larger clinical application. This Review focuses on the recent advances in non-invasive approaches for the diagnosis and serial monitoring of portal hypertension and varices for clinical practice.
Collapse
Affiliation(s)
- Xiaolong Qi
- CHESS Group, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; CHESS Frontier Center, Lanzhou University, Lanzhou, China.
| | - Annalisa Berzigotti
- Hepatology Group, Swiss Liver Center, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
| | - Andres Cardenas
- GI/Liver Unit, Institute of Digestive Diseases and Metabolism, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| |
Collapse
|
|
28
|
Malayeri AA. Virtual Hepatic Venous Pressure Gradient with CT: Ready for Prime Time? Radiology 2019; 290:378-379. [PMID: 30457481 DOI: 10.1148/radiol.2018182351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- Ashkan A Malayeri
- From the Department of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115
| |
Collapse
|
|
29
|
Scheiner B, Steininger L, Semmler G, Unger LW, Schwabl P, Bucsics T, Paternostro R, Ferlitsch A, Trauner M, Reiberger T, Mandorfer M. Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease. Liver Int 2019; 39:127-135. [PMID: 30107095 PMCID: PMC6585636 DOI: 10.1111/liv.13943] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 07/24/2018] [Accepted: 08/08/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Assessment of hepatic steatosis by transient elastography (TE)-based controlled attenuation parameter (CAP) might predict hepatic decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in patients with compensated advanced chronic liver disease (cACLD) and decompensated cirrhosis (DC). METHODS A total of 430 patients who underwent TE (liver stiffness ≥10 kPa) and CAP measurements were included in this retrospective analysis. Half of patients (n = 189) underwent simultaneous HVPG measurement. In cACLD patients, first hepatic decompensation was defined by new onset of ascites, hepatic encephalopathy or variceal bleeding. In patients with DC, the following events were considered as further hepatic decompensation: requirement of paracentesis, admission for/development of grade 3/4 hepatic encephalopathy, variceal (re-)bleeding or liver-related death. RESULTS First hepatic decompensation occurred in 25 of 292 (9%) cACLD patients, while 46 of 138 (33%) DC patients developed further hepatic decompensation during a median follow-up of 22 and 12 months respectively. CAP was not predictive of first (cACLD; per 10 dB/m; hazard ratio [HR]: 0.97, 95% confidence interval [95% CI]: 0.91-1.03, P = 0.321) or further hepatic decompensation (DC; HR: 0.99, 95% CI: 0.94-1.03, P = 0.554) in adjusted analysis. Using the well-established CAP cut-off of ≥248 dB/m for hepatic steatosis, the incidence of first (cACLD; P = 0.065) and further hepatic decompensation (DC; P = 0.578) was similar in patients with hepatic steatosis or without. Serum albumin levels (per mg/dL; HR: 0.83, 95% CI: 0.77-0.89, P < 0.001) and MELD-Na (per point; HR: 1.15, 95% CI: 1.04-1.28, P = 0.006) in cACLD and MELD-Na (per point; HR: 1.12, 95% CI: 1.05-1.19, P < 0.0001) in DC patients were the only parameters independently associated with first and further hepatic decompensation, respectively. CONCLUSION Controlled attenuation parameter does not predict the development of first (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD-Na are of prognostic value.
Collapse
Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Lisa Steininger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Lukas W. Unger
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria,Department of SurgeryMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Theresa Bucsics
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| |
Collapse
|
|
30
|
Li Q, Wang R, Guo X, Li H, Shao X, Zheng K, Qi X, Li Y, Qi X. Contrast-Enhanced CT May Be a Diagnostic Alternative for Gastroesophageal Varices in Cirrhosis with and without Previous Endoscopic Variceal Therapy. Gastroenterol Res Pract 2019; 2019:6704673. [PMID: 31781196 PMCID: PMC6855090 DOI: 10.1155/2019/6704673] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 08/20/2019] [Accepted: 09/06/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS Liver fibrosis blood tests, platelet count/spleen diameter ratio (PSR), and contrast-enhanced CT are diagnostic alternatives for gastroesophageal varices, but they have heterogeneous diagnostic performance among different study populations. Our study is aimed at evaluating their diagnostic accuracy for esophageal varices (EVs) and gastric varices (GVs) in cirrhotic patients with and without previous endoscopic variceal therapy. METHODS Patients with liver cirrhosis who underwent blood tests and contrast-enhanced CT scans as well as endoscopic surveillance should be potentially eligible. EVs needing treatment (EVNTs) and GVs needing treatment (GVNTs) were recorded according to the endoscopic results. Area under the curves (AUCs) were calculated. RESULTS Overall, 279 patients were included. In 175 patients without previous endoscopic variceal therapy, including primary prophylaxis population (n = 70), acute bleeding population (n = 38), and previous bleeding population (n = 67), the diagnostic accuracy of contrast-enhanced CT for EVNTs was higher (AUCs = 0.816-0.876) as compared to blood tests and PSR; by comparison, the diagnostic accuracy of contrast-enhanced CT for GVNTs was statistically significant among primary prophylaxis population (AUC = 0.731, P = 0.0316), but not acute or previous bleeding population. In 104 patients with previous endoscopic variceal therapy (i.e., secondary prophylaxis population), contrast-enhanced CT was the only statistically significant alternative for diagnosing EVNTs and GVNTs but with modest accuracy (AUCs = 0.673 and 0.661, respectively). CONCLUSIONS Contrast-enhanced CT might be a diagnostic alternative for EVNTs in cirrhotic patients, but its diagnostic performance was slightly weakened in secondary prophylaxis population. Additionally, contrast-enhanced CT may be considered for diagnosis of GVNTs in primary prophylaxis population without previous endoscopic variceal therapy and secondary prophylaxis population.
Collapse
Affiliation(s)
- Qianqian Li
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- 2Postgraduate College, Dalian Medical University, Dalian 116044, China
| | - Ran Wang
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Xiaozhong Guo
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Hongyu Li
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Xiaodong Shao
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Kexin Zheng
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- 3Postgraduate College, Jinzhou Medical University, Jinzhou 121001, China
| | - Xiaolong Qi
- 4CHESS Group, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yingying Li
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- 3Postgraduate College, Jinzhou Medical University, Jinzhou 121001, China
| | - Xingshun Qi
- 1Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
- 4CHESS Group, Hepatic Hemodynamic Lab, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
31
|
Bucsics T, Grasl B, Ferlitsch A, Schwabl P, Mandorfer M, Zinober K, Stern R, Chromy D, Scheiner B, Sieghart W, Peck-Radosavljevic M, Trauner M, Reiberger T. Point Shear Wave Elastography for Non-invasive Assessment of Liver Fibrosis in Patients with Viral Hepatitis. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2578-2586. [PMID: 30241728 DOI: 10.1016/j.ultrasmedbio.2018.07.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 07/19/2018] [Accepted: 07/28/2018] [Indexed: 06/08/2023]
Abstract
Elastography point quantification (ElastPQ) is a new ultrasound-based shear wave elastography method for non-invasive assessment of liver fibrosis. We evaluated the diagnostic accuracy of ElastPQ in patients with chronic viral hepatitis. Fibrosis stage (F) was determined by transient elastography (F0/F1: <7.1 kPa, F2: 7.1-9.4 kPa, F3: 9.5-12.4 kPa, F4: ≥12.5 kPa). Area under the receiver operator characteristics curve (AUROC) analysis was performed to assess ElastPQ cutoffs for significant fibrosis (≥F2) and cirrhosis (F4). Paired transient elastography and ElastPQ measurements were obtained from 217 patients (mean age ± SEM: 49 ± 0.79 years, 68.2% male, F0/F1: n = 98 [45.0%], F2: 47 [21.6%], F3: 22 [10.1%], F4: 50 [22.9%]). AUROC for ≥F2 was 0.843 (95% confidence interval: 0.791-0.895), and for F4, 0.933 (95% confidence interval: 0.894-0.972). The optimal ElastPQ cutoff for F2 was 6.68 kPa (sensitivity: 80.7%, specificity: 70.4%, positive predictive value: 78.5%, negative predictive value: 72.3%), and for F4 11.28 kPa (sensitivity: 86.0%, specificity: 85.6%, positive predictive value: 60.52%, negative predictive value: 97.16%). In conclusion, ElastPQ represents an accurate tool for non-invasive staging of liver fibrosis in patients with viral hepatitis.
Collapse
Affiliation(s)
- Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Benjamin Grasl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Kerstin Zinober
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Rafael Stern
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
32
|
Ferraioli G, Wong VWS, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2419-2440. [PMID: 30209008 DOI: 10.1016/j.ultrasmedbio.2018.07.008] [Citation(s) in RCA: 352] [Impact Index Per Article: 50.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/02/2018] [Accepted: 07/13/2018] [Indexed: 06/08/2023]
Abstract
The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.
Collapse
Affiliation(s)
- Giovanna Ferraioli
- Ultrasound Unit, Department of Clinical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, School of Medicine, University of Pavia, Pavia, Italy
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Laurent Castera
- Service d'Hepatologie, Hopital Beaujon, Clichy, Assistance Publique-Hopitaux de Paris, INSERM UMR 1149 CRI, Universite Denis Diderot Paris-VII, Paris, France
| | - Annalisa Berzigotti
- Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Switzerland
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania
| | | | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Stephanie R Wilson
- Department of Diagnostic Imaging, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka Sayama, Japan
| | - Richard G Barr
- Department of Radiology, Northeastern Ohio Medical University and Southwoods Imaging, Youngstown, Ohio, USA.
| |
Collapse
|
|
33
|
Piyachaturawat P, Siramolpiwat S, Sonsiri K, Tangkijvanich P, Treeprasertsuk S. Changes in transient elastography in early cirrhotic patients after receiving nonselective B-blocker for primary variceal bleeding prophylaxis: Three-month follow up. JGH Open 2018; 2:172-177. [PMID: 30483585 PMCID: PMC6206988 DOI: 10.1002/jgh3.12063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 04/29/2018] [Accepted: 05/07/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM A nonselective B-blocker (NSBB) is recommended for primary prophylaxis of variceal bleeding. The impact of treatment with NSBB on modulating transient elastography (TE) has not been reported. The aim of the study is to investigate the effect of NSBB treatment on TE in early cirrhotic patients. METHODS In this prospective study, we enrolled all early cirrhotic patients who underwent esophagogastroduodenoscopy (EGD) and showed small esophageal varices (EV) at our institute for a period of 1 year. The TE and heart rate (HR) of all participants were measured before and 3 months after receiving NSBB. RESULTS Thirty-nine patients receiving propanolol for 3 months were analyzed. There were 16 patients in the HR responder group (41%) and 23 patients in the HR nonresponder group (59%). The reduction of TE was preferably found in the HR responder group compared with the HR nonresponder group, in which mean changes in TE were -5.6 and -0.7 kPa, respectively (P = 0.23). In addition, we categorized the patients using their TE responses. Twenty-five patients (64.1%) showed reduced TE during the follow-up period, in which the mean TE value change was -2.94 kPa. Using correlation analysis, TE and HR responses were insignificantly correlated (r = 0.23, P = 0.15). CONCLUSION The NSBB administered for 3 months mainly improved TE value in early cirrhotic patients even though the changes of HR and TE did not correlate. Further study is needed to confirm whether the monitoring of TE change may be a better predictor for pharmacological response than the HR response.
Collapse
Affiliation(s)
- Panida Piyachaturawat
- Department of Medicine, Faculty of MedicineChulalongkorn UniversityBangkokThailand
- Gastroenterology Unit, Faculty of MedicineChulalongkorn UniversityBangkokThailand
| | - Sith Siramolpiwat
- Division of Gastroenterology, Department of Internal Medicine, Faculty of MedicineThammasat UniversityPathumthaniThailand
| | - Kanokwan Sonsiri
- Gastroenterology Unit, Faculty of MedicineChulalongkorn UniversityBangkokThailand
| | - Pisit Tangkijvanich
- Liver Research Unit, Faculty of MedicineChulalongkorn UniversityBangkokThailand
| | - Sombat Treeprasertsuk
- Department of Medicine, Faculty of MedicineChulalongkorn UniversityBangkokThailand
- Gastroenterology Unit, Faculty of MedicineChulalongkorn UniversityBangkokThailand
| |
Collapse
|
|
34
|
Piecha F, Mandorfer M, Peccerella T, Ozga AK, Poth T, Vonbank A, Seitz HK, Rausch V, Reiberger T, Mueller S. Pharmacological decrease of liver stiffness is pressure-related and predicts long-term clinical outcome. Am J Physiol Gastrointest Liver Physiol 2018; 315:G484-G494. [PMID: 29746172 DOI: 10.1152/ajpgi.00392.2017] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver stiffness (LS) as measured by transient elastography is increasingly used to noninvasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, nitric oxide donors, and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n = 38 cirrhotic patients. In the animal model, cirrhosis induction resulted in a significant increase of LS and PP. After losartan or NO application, a LS decrease of 25% was strongly correlated with a concomitant decrease of mean arterial pressure (MAP) and PP. In contrast, acute propranolol administration decreased heart rate but not MAP resulting in stable LS. In the human cohort, most patients ( n = 25, 66%) showed a LS decrease after propranolol treatment initiation which significantly correlated to HVPG ( r = 0.518, P < 0.01) but was not accompanied by statistically significant changes in transaminases or model of end-stage liver disease (MELD). On multivariate analysis, patients with decreasing LS on propranolol had a decreased risk for experiencing a transplantation or death than patients with increasing LS irrespective of HVPG. In conclusion, LS changes after pharmacological interventions are influenced by hemodynamic effects on arterial and portal pressure. In humans, a LS decrease may be predictive of improved outcome irrespective of MELD scores and may serve as an additional follow-up tool in the future. NEW & NOTEWORTHY Liver stiffness (LS) is efficiently modulated by changes in portal venous and systemic pressures in an animal model of liver cirrhosis irrespective of baseline LS and portal pressure values. In humans, most patients show a decrease in LS after propranolol treatment initiation without statistically significant changes in transaminases or model of end-stage liver disease (MELD) scores. A decrease in LS may be associated with improved outcome and thus another valuable tool in the follow-up of patients after propranolol treatment initiation.
Collapse
Affiliation(s)
- Felix Piecha
- Department of Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg , Heidelberg , Germany
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna , Austria
| | - Teresa Peccerella
- Department of Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg , Heidelberg , Germany
| | - Ann-Kathrin Ozga
- Center for Experimental Medicine, Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany
| | - Tanja Poth
- Center for Model System and Comparative Pathology, Institute of Pathology, University Hospital Heidelberg , Heidelberg , Germany
| | - Anna Vonbank
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna , Austria
| | - Helmut Karl Seitz
- Department of Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg , Heidelberg , Germany
| | - Vanessa Rausch
- Department of Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg , Heidelberg , Germany
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna , Austria
| | - Sebastian Mueller
- Department of Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg , Heidelberg , Germany
| |
Collapse
|
|
35
|
Wang HW, Shi HN, Cheng J, Xie F, Luo YK, Tang J. Real-time shear wave elastography (SWE) assessment of short- and long-term treatment outcome in Budd-Chiari syndrome: A pilot study. PLoS One 2018; 13:e0197550. [PMID: 29847588 PMCID: PMC5976180 DOI: 10.1371/journal.pone.0197550] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 04/19/2018] [Indexed: 12/12/2022] Open
Abstract
Purpose The first aim of this study was to analyze the relationships between liver stiffness measurement, hepatic venous pressure and liver fibrosis. The second aim was to demonstrate the utility of real-time shear wave elastography for evaluation of Budd-Chiari syndrome patients before and after balloon hepatic venous angioplasty. Materials and methods A total of 32 patients with Budd-Chiari syndrome slated for successful balloon angioplasty met the inclusion and exclusion criteria. Shear wave elastography was used to generate dynamic liver stiffness measurement 2 days before angioplasty and 2 days, 3 months, and 6 months after angioplasty. Hepatic venous pressures were measured during balloon angioplasty. Correlations among liver stiffness, hepatic venous pressure, and fibrosis were assessed. Result Mean liver stiffness was 35.17 ± 10.60 kPa, 20.15 ± 5.47 kPa, 15.36 ± 4.34 kPa and 15.68 ± 5.58 kPa at baseline and 2 days, 3 months, and 6 months after angioplasty, respectively. Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P < 0.001); liver stiffness measured at 6 months after angioplasty was not significantly different from that measured at 3 months after angioplasty (P = 0.636). Analysis of liver stiffness measurement and hepatic venous pressure before balloon angioplasty yielded a coefficient of correlation r = 0.701 (P < 0.001). Before and 2d after angioplasty, liver stiffness measurement did not correlated with fibrosis (r = − 0.170, P = 0.22), (r = 0.223, P = 0.220), respectively, while the LSM difference before and 2 days after angioplasty negatively correlated with stiffness severity (r = − 0.502, P = 0.003). Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P < 0.001), remaining stable at 3 months, though still in the cirrhotic range. Conclusions The liver stiffness of Budd-Chiari syndrome patients, measured by shear wave elastography, decreased considerably after hepatic venous recanalization, and significantly correlated with hepatic venous pressure though not with degree of fibrosis. Shear wave elastography may be effective in monitoring short- and long-term treatment outcomes in Budd-Chiari syndrome.
Collapse
Affiliation(s)
- Hong-Wei Wang
- Department of Ultrasound, Chinese PLA General Hospital, Beijing, China
- Department of Ultrasound, Yong Liang Hospital, Baoding, China
| | - Hua-Ning Shi
- Department of Ultrasound, Affiliated Hospital of Chengde Medical College, Chengde, China
| | - Jia Cheng
- Department of Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Fang Xie
- Department of Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Yu-Kun Luo
- Department of Ultrasound, Chinese PLA General Hospital, Beijing, China
- * E-mail: (YKL); (JT)
| | - Jie Tang
- Department of Ultrasound, Chinese PLA General Hospital, Beijing, China
- * E-mail: (YKL); (JT)
| |
Collapse
|
|
36
|
Abstract
CLINICAL ISSUE In the daily clinical routine characterization of focal lesions using native B‑mode classical ultrasound and color Doppler can be difficult or insufficient; therefore, additional diagnostic information must be taken into consideration. STANDARD RADIOLOGICAL METHODS Standard radiological methods in the daily clinical routine include native B‑mode ultrasound and color Doppler ultrasound. METHODICAL INNOVATIONS Using sonoelastography it is possible to evaluate and characterize tissue properties and focal lesions regarding their stiffness to acquire additional information on a noninvasive basis. PERFORMANCE Sonoelastography enables the differentiation between benign and malignant lesions especially in organs that can be easily evaluated using ultrasound. This particularly includes the liver, the thyroid gland, the breasts and the testicles. Regarding the liver, sonoelastography techniques can also be used for evaluation of the tissue flexibility in the diagnostics of fibrosis and cirrhosis. ACHIEVEMENTS Nowadays, elastography is implemented into every modern ultrasound system and has been established as a supplementary examination technique to the conventional ultrasound techniques. PRACTICAL RECOMMENDATIONS Sonoelastography should be used in cases with unclear findings as an additional noninvasive tool for the differentiation between benign and malignant lesions.
Collapse
|
|
37
|
Jansen C, Möller P, Meyer C, Kolbe CC, Bogs C, Pohlmann A, Schierwagen R, Praktiknjo M, Abdullah Z, Lehmann J, Thomas D, Strassburg CP, Latz E, Mueller S, Rössle M, Trebicka J. Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality. Hepatology 2018; 67:1472-1484. [PMID: 29059466 DOI: 10.1002/hep.29612] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 09/05/2017] [Accepted: 10/18/2017] [Indexed: 12/15/2022]
Abstract
UNLABELLED Transjugular intrahepatic portosystemic shunt (TIPS) efficiently treats complications of portal hypertension. Liver and spleen stiffness might predict clinically significant portal hypertension. This prospective study investigated liver stiffness in patients receiving TIPS regardless of indication. Of 83 included patients, 16 underwent transient elastography immediately before and 30 minutes after TIPS (acute group), while 67 received shear wave elastography of liver and spleen 1 day before and 7 days after TIPS (chronic group) and were followed further. In blood samples obtained before TIPS from cubital, portal, and hepatic veins, levels of several interleukins (IL1b, IL6, IL8, IL10, IL18) and interferon-gamma were analyzed. In 27 patients (5 acute, 22 chronic), it resulted in an increase in liver stiffness of >10%. In 56 patients, liver stiffness decreased or remained unchanged (<10%). Importantly, spleen stiffness measured by shear wave elastography decreased in all patients (chronic group). None of the clinical or laboratory parameters differed between patients with increase in liver stiffness and those without. Of note, patients with increased liver stiffness showed higher overall and/or hepatic venous levels of proinflammatory cytokines at TIPS and higher incidence of organ failure and worse survival after TIPS. C-reactive protein values and increase of >10% in liver stiffness after TIPS were the only independent predictors of mortality in these patients. CONCLUSION This study demonstrates that the presence of systemic inflammation predisposes patients to develop increased liver stiffness after TIPS, a predictor of organ failure and death. (NCT03072615) (Hepatology 2018;67:1472-1484).
Collapse
Affiliation(s)
- Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Philipp Möller
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Carsten Meyer
- Department of Radiology, University of Bonn, Bonn, Germany
| | | | - Christopher Bogs
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | | | | | - Zeinab Abdullah
- Institute of Experimental Immunology, University of Bonn, Bonn, Germany
| | - Jennifer Lehmann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Daniel Thomas
- Department of Radiology, University of Bonn, Bonn, Germany
| | | | - Eicke Latz
- Institute of Innate Immunity, University of Bonn, Bonn, Germany.,University of Massachusetts Medical School, Worcester, MA
| | - Sebastian Mueller
- Center for Alcohol Research, University of Heidelberg and Salem Medical Center, Heidelberg, Germany
| | - Martin Rössle
- Department of Gastroenterology, University Hospital Freiburg, Freiburg, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.,Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.,Institute for Bioengineering of Catalonia, Barcelona, Spain
| |
Collapse
|
|
38
|
Mandorfer M, Reiberger T, Peck-Radosavljevic M. Monitoring the Evolution of Portal Hypertension After Sustained Virologic Response. Gastroenterology 2018. [PMID: 29526728 DOI: 10.1053/j.gastro.2017.08.078] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna and Department of Gastroenterology and Hepatology, Endocrinology, and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| |
Collapse
|
|
39
|
Roccarina D, Rosselli M, Genesca J, Tsochatzis EA. Elastography methods for the non-invasive assessment of portal hypertension. Expert Rev Gastroenterol Hepatol 2018; 12:155-164. [PMID: 28856972 DOI: 10.1080/17474124.2017.1374852] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The gold standard to assess the presence and severity of portal hypertension remains the hepatic vein pressure gradient, however the recent development of non-invasive assessment using elastography techniques offers valuable alternatives. In this review, we discuss the diagnostic accuracy and utility of such techniques in patients with portal hypertension due to cirrhosis. Areas covered: A literature search focused on liver and spleen stiffness measurement with different elastographic techniques for the assessment of the presence and severity of portal hypertension and oesophageal varices in people with chronic liver disease. The combination of elastography with parameters such as platelet count and spleen size is also discussed. Expert commentary: Non-invasive assessment of liver fibrosis and portal hypertension is a validated tool for the diagnosis and follow-up of patients. Baveno VI recommended the combination of transient elastography and platelet count for ruling out varices needing treatment in patients with compensated advanced chronic liver disease. Assessment of aetiology specific cut-offs for ruling in and ruling out clinically significant portal hypertension is an unmet clinical need. The incorporation of spleen stiffness measurements in non-invasive algorithms using validated software and improved measuring scales might enhance the non-invasive diagnosis of portal hypertension in the next 5 years.
Collapse
Affiliation(s)
- Davide Roccarina
- a UCL Institute for Liver and Digestive Health , Royal Free Hospital and UCL , London , UK
| | - Matteo Rosselli
- a UCL Institute for Liver and Digestive Health , Royal Free Hospital and UCL , London , UK
| | - Joan Genesca
- b Liver Unit, Department of Internal Medicine , Valld'Hebron University Hospital, VHIR, Universitat Autònoma de Barcelona, CIBERehd , Barcelona , Spain
| | - Emmanuel A Tsochatzis
- a UCL Institute for Liver and Digestive Health , Royal Free Hospital and UCL , London , UK
| |
Collapse
|
|
40
|
Berzigotti A, Ferraioli G, Bota S, Gilja OH, Dietrich CF. Novel ultrasound-based methods to assess liver disease: The game has just begun. Dig Liver Dis 2018; 50:107-112. [PMID: 29258813 DOI: 10.1016/j.dld.2017.11.019] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 11/08/2017] [Accepted: 11/27/2017] [Indexed: 12/11/2022]
Abstract
In the last 10 years the availability of ultrasound elastography allowed to diagnose and stage liver fibrosis in a non-invasive way and changed the clinical practice of hepatology. Newer ultrasound-based techniques to evaluate properties of the liver tissue other than fibrosis are emerging and will lead to a more complete characterization of the full spectrum of diffuse and focal liver disease. Since these methods are currently undergoing validation and go beyond elastography for liver tissue evaluation, they were not included in the recent guidelines regarding elastography issued by the European Federation of Societies in Ultrasound in Medicine and Biology. In this review paper, we outline the major advances in the field of ultrasound for liver applications, with special emphasis on techniques that could soon be part of the future armamentarium of ultrasound specialists devoted to the assessment of liver disease. Specifically, we discuss current and future ultrasound assessment of steatosis, spleen stiffness for portal hypertension, and elastography for the evaluation of focal liver lesions; we also provide a short glimpse into the next generation of ultrasound diagnostic methods.
Collapse
Affiliation(s)
- Annalisa Berzigotti
- Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Berne, Switzerland.
| | - Giovanna Ferraioli
- Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
| | - Simona Bota
- Department of Gastroenterology, Hepatology, Nephrology and Endocrinology, Klinikum Klagenfurt, Klagenfurt am Wörthersee, Austria.
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen and Department of Clinical Medicine, University of Bergen, Norway.
| | - Christoph F Dietrich
- Department of Internal Medicine 2, Caritas Krankenhaus, Bad Mergentheim, Germany.
| |
Collapse
|
|
41
|
Castera L. Liver Stiffness by Ultrasound Elastography. DIAGNOSTIC METHODS FOR CIRRHOSIS AND PORTAL HYPERTENSION 2018:95-111. [DOI: 10.1007/978-3-319-72628-1_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
42
|
Platelet Count/Spleen Diameter Ratio and Shear-Wave Elastography for Non-Invasive Prediction of High-Risk Varices: Can We Delay Screening Endoscopy for Compensated Cirrhosis? HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
|
|
43
|
Scheiner B, Parada-Rodriguez D, Bucsics T, Schwabl P, Mandorfer M, Pfisterer N, Riedl F, Sieghart W, Ferlitsch A, Trauner M, Peck-Radosavljevic M, Reiberger T. Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices. Scand J Gastroenterol 2017; 52:1008-1015. [PMID: 28532189 DOI: 10.1080/00365521.2017.1329456] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
GOALS AND BACKGROUND Non-selective beta-blockers (NSBBs) are used for bleeding prophylaxis in cirrhotic patients with gastroesophageal varices (GEVs). Recent data suggested that NSBB treatment might increase the risk of renal dysfunction in patients with refractory ascites due to an impaired response to acute haemodynamic stress. STUDY Retrospective longitudinal assessment of kidney function in a cohort of cirrhotic patients with GEVs with vs. without NSBB therapy. Serum creatinine (SCre), estimated glomerular filtration rate (eGFR), incidence of acute kidney injury (AKI), new onset of large volume ascites and TIPS-/transplant-free survival were compared. RESULTS Among 176 patients, 93 patients received NSBBs, while 83 did not. Most patients were male (77.8%), had alcoholic aetiology (52.3%) and compensated cirrhosis (51.1% Child-A, MELD: 12.1 ± 3.8). Over a 3-year follow-up, renal function was comparable between patients with and without NSBB treatment. Incidence of AKI was similar in NSBB vs. no-NSBB patients (p = .323). Even in potential risk groups (ascites, MAP <90 mmHg, baseline creatinine > ULN, hyponatraemia, MELD score ≥15 points, Child-Pugh B/C), there was no difference in SCre or eGFR with vs. without NSBBs (p = n.s. at 74/78 and 76/78 of analysed time points). However, multivariate analysis revealed that the presence of ascites (HR: 3.901, 95%CI: 1.352-11.251; p = .012) and pre-existing renal impairment (HR: 4.315, 95%CI: 1.054-17.672; p = .042) were independent risk factors for AKI. Importantly, NSBB use (HR: 0.319, 95%CI: 0.120-0.848; p = .022) was independently associated with improved TIPS-/transplant-free survival. CONCLUSIONS In our cohort of unselected, mostly compensated cirrhotic patients with GEVs, NSBB treatment was neither associated with worsening of kidney function nor with increased incidence of AKI. On the contrary, NSBB treatment improved TIPS-/transplant-free survival.
Collapse
Affiliation(s)
- Bernhard Scheiner
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Diego Parada-Rodriguez
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Theresa Bucsics
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Philipp Schwabl
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Mattias Mandorfer
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Nikolaus Pfisterer
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Florian Riedl
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Wolfgang Sieghart
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Arnulf Ferlitsch
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Michael Trauner
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Markus Peck-Radosavljevic
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| | - Thomas Reiberger
- a Department of Internal Medicine III , Division of Gastroenterology and Hepatology , Medical University of Vienna , Vienna , Austria.,b Vienna Hepatic Hemodynamic Laboratory , Medical University of Vienna , Vienna , Austria
| |
Collapse
|
|
44
|
Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol 2017; 67:399-411. [PMID: 28223101 DOI: 10.1016/j.jhep.2017.02.003] [Citation(s) in RCA: 181] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 02/04/2017] [Accepted: 02/06/2017] [Indexed: 02/06/2023]
Abstract
Portal hypertension (PH) leads to serious complications, such as bleeding from gastroesophageal varices, ascites and portosystemic encephalopathy in patients with chronic liver disease (CLD). Gold standard methods for assessing PH and its complications include the measurement of hepatic venous pressure gradient and endoscopy; however, these are invasive, expensive and not available at all centres. Therefore, non-invasive alternatives have been the subject of extensive investigation over the last 20years. The present review focuses on the role of ultrasound elastography - a novel group of non-invasive techniques used to measure stiffness in target organs. In the context of CLD these methods are used to identify the presence of PH, its severity, and the risk of PH-related complications. The rationale, accumulated evidence, advantages and limitations of liver and spleen stiffness measurements evaluated by different ultrasound elastography techniques in patients with advanced CLD is discussed. Recent data regarding the use of ultrasound elastography techniques in patients with non-cirrhotic forms of PH are also described.
Collapse
|
|
45
|
Non-invasive liver fibrosis assessment and HCV treatment initiation within a systematic screening program in HIV/HCV coinfected patients. Wien Klin Wochenschr 2017; 130:105-114. [PMID: 28744597 PMCID: PMC5816107 DOI: 10.1007/s00508-017-1231-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 06/26/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Hepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV). METHODS The FIB-4 was calculated in all HIV/HCV from 2014-2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of </≥1.45 (established cut-off for ruling out ADVFIB) and SIGFIB/ADVFIB were defined by liver stiffness >7.1 kPa/>9.5 kPa, respectively. RESULTS Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43). In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4 <1.45 underwent TE. Interestingly, 40% (23/57) and 18% (10/57) of these patients showed SIGFIB or even ADVFIB, respectively, and 78% (18/23) finally received interferon-free treatment. Overall, only 20% (42/210) of HIV/HCV received interferon-free treatment. CONCLUSION FIB-4 was not useful for ruling out SIGFIB/ADVFIB in our cohort of HIV/HCV. Treatment was initiated only in a small proportion (20%) of HIV/HCV during the first 2 years of interferon-free treatment availability, although the observed proportion of patients with SIGFIB (assessed by TE) was considerably higher (58%). Thus, it requires the ongoing combined efforts of both HIV and HCV specialists to increase treatment uptake rates in this special population.
Collapse
|
|
46
|
Short article: Noninvasive assessment of portal hypertension and detection of esophageal varices in cirrhosis: state-of-the-art. Eur J Gastroenterol Hepatol 2017; 29:531-534. [PMID: 28350741 DOI: 10.1097/meg.0000000000000830] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Portal hypertension (PHT) is a major consequence of any chronic liver disease and it is the main cause of complications in patients with cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for PHT assessment, together with its diagnosis and prognosis relevance. Even though hepatic vein pressure gradient measurement is a safe procedure, it is still considered an invasive technique and not widely available. There is thus a need for noninvasive methods that can predict the progression of PHT as well as the presence and the risk of complications related to esophageal varices. This review aimed to discuss the noninvasive markers used in the assessment of PHT and detection of high-risk esophageal varices in patients with liver cirrhosis. We focus on the main biomarkers, particularly those used in the routine assessment of chronic liver disease, and the physical methods that use tissue elastography as a diagnosis tool.
Collapse
|
|
47
|
Kim BK. Transient elastography can be integrated into routine clinical practice for the evaluation of portal hypertension? Clin Mol Hepatol 2017; 23:27-30. [PMID: 28349679 PMCID: PMC5381837 DOI: 10.3350/cmh.2017.0101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 02/20/2017] [Indexed: 12/15/2022] Open
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
| |
Collapse
|
|
48
|
You MW, Kim KW, Pyo J, Huh J, Kim HJ, Lee SJ, Park SH. A Meta-analysis for the Diagnostic Performance of Transient Elastography for Clinically Significant Portal Hypertension. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:59-68. [PMID: 27751595 DOI: 10.1016/j.ultrasmedbio.2016.07.025] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Revised: 07/18/2016] [Accepted: 07/31/2016] [Indexed: 06/06/2023]
Abstract
We aimed to evaluate the correlation between liver stiffness measurement using transient elastography (TE-LSM) and hepatic venous pressure gradient and the diagnostic performance of TE-LSM in assessing clinically significant portal hypertension through meta-analysis. Eleven studies were included from thorough literature research and selection processes. The summary correlation coefficient was 0.783 (95% confidence interval [CI], 0.737-0.823). Summary sensitivity, specificity and area under the hierarchical summary receiver operating characteristic curve (AUC) were 87.5% (95% CI, 75.8-93.9%), 85.3 % (95% CI, 76.9-90.9%) and 0.9, respectively. The subgroup with low cut-off values of 13.6-18 kPa had better summary estimates (sensitivity 91.2%, specificity 81.3% and partial AUC 0.921) than the subgroup with high cut-off values of 21-25 kPa (sensitivity 71.2%, specificity 90.9% and partial AUC 0.769). In summary, TE-LSM correlated well with hepatic venous pressure gradient and represented good diagnostic performance in diagnosing clinically significant portal hypertension. For use as a sensitive screening tool, we propose using low cut-off values of 13.6-18 kPa in TE-LSM.
Collapse
Affiliation(s)
- Myung-Won You
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Junhee Pyo
- WHO Collaborating Center for Pharmaceutical Policy and Regulation, Department of Pharmaceutical Science, Utrecht University, Netherlands
| | - Jimi Huh
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
49
|
Mandorfer M, Reiberger T. Beta blockers and cirrhosis, 2016. Dig Liver Dis 2017; 49:3-10. [PMID: 27717792 DOI: 10.1016/j.dld.2016.09.013] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Revised: 09/09/2016] [Accepted: 09/19/2016] [Indexed: 12/11/2022]
Abstract
To date, non-selective beta blockers (NSBBs) are a cornerstone in the treatment of portal hypertension. During the last years, our understanding of the potential benefits of early initiation of NSBB treatment, their effects beyond the prevention of variceal bleeding (i.e., their non-hemodyamic effects), as well as potential detrimental effects in patients with advanced disease has continuously evolved. In addition, we have learned that not all NSBBs are equal. Due to its additional anti-α1-adrenergic activity, carvedilol has been shown to be more potent in decreasing portal pressure, but might lead to more pronounced decreases in systemic arterial pressure, when compared to conventional NSBBs. It might be particularly beneficial in 'early' portal hypertension, when potential detrimental effects on systemic hemodynamics are less critical. In contrast, there is increasing evidence that the use of carvedilol or high NSBB doses should be carefully scrutinized in patients with severe or refractory ascites. Our review summarizes the current knowledge on the use of NSBBs for preventing variceal bleeding and other decompensating events and provides guidance for their safe use in hemodynamically 'vulnerable' patient populations. Finally, we also highlight areas for further research.
Collapse
Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Austria.
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Austria
| |
Collapse
|
|
50
|
Piecha F, Peccerella T, Bruckner T, Seitz HK, Rausch V, Mueller S. Arterial pressure suffices to increase liver stiffness. Am J Physiol Gastrointest Liver Physiol 2016; 311:G945-G953. [PMID: 27288426 DOI: 10.1152/ajpgi.00399.2015] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 06/01/2016] [Indexed: 01/31/2023]
Abstract
Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood.
Collapse
Affiliation(s)
- Felix Piecha
- Department of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Heidelberg, Germany; and
| | - Teresa Peccerella
- Department of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Heidelberg, Germany; and
| | - Tom Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Helmut-Karl Seitz
- Department of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Heidelberg, Germany; and
| | - Vanessa Rausch
- Department of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Heidelberg, Germany; and
| | - Sebastian Mueller
- Department of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Heidelberg, Germany; and
| |
Collapse
|