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Reddy S, Agrawal S, Reddy H, Kumar S, Dhondge RH, Acharya S, Kothari M, Khan M, Javvaji CK. Assessing the Utility of the Aspartate Aminotransferase to Platelet Ratio Index (APRI) as a Noninvasive Indicator for Liver Cirrhosis. Cureus 2024; 16:e59680. [PMID: 38836137 PMCID: PMC11148697 DOI: 10.7759/cureus.59680] [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: 04/25/2024] [Accepted: 05/05/2024] [Indexed: 06/06/2024] Open
Abstract
Background Of liver-related disorders, cirrhosis is currently the leading cause of death and has become a significant global public health concern. Aspartate aminotransferase to platelet ratio index (APRI), a newer prognostic modality, is a very effective noninvasive diagnostic for identifying advanced liver fibrosis. Methods A prospective observational study was conducted among individuals with liver disease, 100 cases and 100 controls for two years. All the sociodemographic details, clinical features of the patients, and clinical findings such as prothrombin time (PT), liver function tests, kidney function tests, and total blood count were recorded using a pretested semi-structured questionnaire. Results According to our survey results, 48% of the participants were between the ages of 40 and 60. Regarding aPTT (activated partial thromboplastin time) and liver function test characteristics (serum glutamic-oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase (SGPT)), we showed a substantial difference between the patients and controls. Regarding the APRI distribution, we also found a statistically significant variation between the research groups. When we compared the validity of APRI scores in diagnosing cirrhosis, we discovered that the ideal cutoff value of APRI was determined to be 3.99, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33%, 86%, 70%, and 56%, respectively. The area under the receiver operating characteristic (ROC) curve for APRI in detecting cirrhosis was also 0.693. Conclusion Thus, our study results conclude that APRI is a crucial noninvasive prognostic tool that can be utilized to prognostize liver cirrhosis.
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Affiliation(s)
- Siva Reddy
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sachin Agrawal
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Harshitha Reddy
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunil Kumar
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Rushikesh H Dhondge
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sourya Acharya
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Manjeet Kothari
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Maimoona Khan
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Chaitanya Kumar Javvaji
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Baumann-Durchschein F, Fürst S, Hammer HF. Practical application of breath tests in disorders of gut–brain interaction. Curr Opin Pharmacol 2022; 65:102244. [DOI: 10.1016/j.coph.2022.102244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 04/13/2022] [Accepted: 04/25/2022] [Indexed: 12/13/2022]
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Ollivier-Hourmand I, Repesse Y, Nahon P, Chaffaut C, Dao T, Nguyen TTN, Marcellin P, Roulot D, De Ledinghen V, Pol S, Guyader D, Archambeaud I, Zoulim F, Oberti F, Tran A, Bronowicki JP, D'Alteroche L, Ouzan D, Peron JM, Zarski JP, Bourliere M, Larrey D, Louvet A, Cales P, Abergel A, Mathurin P, Mallat A, Blanc JF, Nguyen-Khac E, Riachi G, Alric L, Serfaty L, Antonini T, Moreno C, Attali P, Thabut D, Pilette C, Grange JD, Silvain C, Carbonell N, Bernard-Chabert B, Goria O, Wartelle C, Moirand R, Christidis C, Perlemuter G, Ozenne V, Henrion J, Hillaire S, Di Martino V, Amiot X, Sutton A, Barget N, Chevret S, Ganne-Carrie N. ABO blood group does not influence Child-Pugh A cirrhosis outcome: An observational study from CIRRAL and ANRS CO12 CIRVIR cohorts. Liver Int 2022; 42:1386-1400. [PMID: 35025128 DOI: 10.1111/liv.15159] [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: 02/27/2021] [Revised: 12/13/2021] [Accepted: 01/03/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS We used two prospective cohorts of Child-Pugh A cirrhosis due to either alcohol or viral hepatitis. Primary end point was the cumulated incidence of 'Decompensation' at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin >45 μmol/L. Secondary end points were the cumulated incidences of (1) 'Disease Progression' including a « decompensation» or « the occurrence of one or more parameters » among: prothrombin time (PT) <45%, albumin <28 g/L, Child-Pugh worsening (B or C vs A or B, C vs B), hepatorenal syndrome, and hepato-pulmonary syndrome, (2) other events such as non-malignant portal vein thrombosis (nmPVT), and (3) overall survival. RESULTS Patients (n = 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (P = .27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (P = .26). Cumulated incidence of nmPVT was 2.7% in Non-O group and 2.8% in group O (P = .05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (P = 1). CONCLUSION Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients. Clinicals trial number NCT03342170.
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Affiliation(s)
| | - Yohann Repesse
- Hematology Laboratory, University Hospital, Caen, France
| | - Pierre Nahon
- AP-HP, Hôpital Avicenne, Bobigny, France
- University Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 « Functional Genomics of Solid Tumors », Centre de Recherche des Cordeliers, Université de Paris, Paris, France
| | - Cendrine Chaffaut
- SBIM, APHP, Hôpital Saint-Louis, Inserm, UMR-1153, ECSTRA Team, Paris, France
| | - Thông Dao
- Department of Hepatogastroenterology, University Hospital, Caen, France
| | | | | | - Dominique Roulot
- AP-HP, Hôpital Avicenne, Bobigny, France
- University Sorbonne Paris Nord, Bobigny, France
| | - Victor De Ledinghen
- Hepatology Unit, University Hospital Haut Levêque, CHU Bordeaux, Pessac, France
| | - Stanislas Pol
- AP- HP, Hôpital Cochin, Departement d'Hepatologie et INSERM U1016, Université Paris Descartes, Paris, France
| | | | | | - Fabien Zoulim
- Hôpital Hôtel Dieu, Service d'Hepatologie, Lyon, France
| | | | - Albert Tran
- CHU de Nice, Service d'Hepatologie, et INSERM U1065, Universite de Nice-Sophia-Antipolis, Nice, France
| | | | | | - Denis Ouzan
- Institut Arnaud Tzanck, Service d'Hepatologie, St Laurent du Var, France
| | - Jean-Marie Peron
- Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, France
| | | | - Marc Bourliere
- Hôpital Saint Joseph, Service d'Hepatologie, Marseille, France
| | | | | | - Paul Cales
- Liver Unit, University Hospital, Angers, France
| | - Armand Abergel
- Hôpital Hôtel Dieu, Service d'Hepatologie, Clermont-Ferrand, France
| | | | - Ariane Mallat
- AP-HP, Hôpital Henri Mondor, Service d'Hepatologie, Creteil, France
| | | | | | - Ghassan Riachi
- Liver Unit, University Hospital Charles-Nicolle, Rouen, France
| | - Laurent Alric
- CHU Toulouse, Service de Medecine Interne-Pôle Digestif UMR 152, Toulouse, France
| | - Lawrence Serfaty
- AP-HP, Hôpital Saint-Antoine, Service d'Hepatologie, Paris, France
| | | | - Christophe Moreno
- Liver Unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Attali
- AP-HP, CHU Kremlin-Bicêtre, Service d'Hepatologie, Le Kremlin-Bicêtre, France
| | - Dominique Thabut
- AP-HP, Hôpital La Pitié Salpétrière, Service d'Hepatologie, Paris, France
| | | | | | | | | | | | - Odile Goria
- Liver Unit, University Hospital Charles-Nicolle, Rouen, France
| | - Claire Wartelle
- Hôpital d'Aix-En-Provence, Service d'Hepatologie, Aix-En-Provence, France
| | - Romain Moirand
- University of Rennes, INSERM, INRA, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Rennes, France
| | | | | | | | - Jean Henrion
- Liver Unit, University Hospital, Haine Saint-Paul, Belgium
| | | | | | - Xavier Amiot
- AP-HP, Hôpital Tenon, Service d'Hepatologie, Paris, France
| | - Angela Sutton
- AP-HP, Hôpital Avicenne, Bobigny, France
- Inserm, UMR-1138 « Functional Genomics of Solid Tumors », Centre de Recherche des Cordeliers, Université de Paris, Paris, France
| | - Nathalie Barget
- AP-HP, Hôpital Avicenne, Bobigny, France
- Inserm, UMR-1138 « Functional Genomics of Solid Tumors », Centre de Recherche des Cordeliers, Université de Paris, Paris, France
| | - Sylvie Chevret
- SBIM, APHP, Hôpital Saint-Louis, Inserm, UMR-1153, ECSTRA Team, Paris, France
| | - Nathalie Ganne-Carrie
- AP-HP, Hôpital Avicenne, Bobigny, France
- University Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 « Functional Genomics of Solid Tumors », Centre de Recherche des Cordeliers, Université de Paris, Paris, France
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Renninger CH, Jaeblon T, Slobogean GP, O'Toole RV, O'Hara NN. Patients With Cirrhosis Who Have a Model for End-stage Liver Disease Sodium Score of 8 or Greater Are at Increased Risk of Poor Outcomes in Operatively Treated Tibia Fractures. Orthopedics 2022; 45:79-85. [PMID: 35021031 DOI: 10.3928/01477447-20220105-01] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The purpose of this study was to compare 30-day readmission rates for cirrhotic and non-cirrhotic patients after tibia fracture fixation by retrospectively identifying all surgically managed tibial plateau, tibial shaft, and pilon fractures from 2010 through 2018 in the National Surgical Quality Improvement Program database (N=14,028). The primary outcome measure was 30-day readmission rates. Secondary outcome measures included 30-day rates of reoperation, length of stay, pulmonary embolism, deep venous thrombosis, and wound complications, including deep or superficial infection. Cirrhotic patients (n=665) and non-cirrhotic patients (n=13,363) were identified using the aspartate aminotransferase to platelet ratio index test. Cirrhotic patients were more likely to have preoperative ascites, renal failure, bleeding disorders, and preoperative transfusions. No differences were reported between the two groups in readmission rate or any of the secondary outcome measures, except that cirrhotic patients' length of stay was longer by 0.5 day. Stratification of the cirrhotic cohort demonstrated that a Model for End-stage Liver Disease sodium (MELD-Na) score of 8 or greater was associated with a 4.1-fold increase in the rate of readmission (5.9% vs 1.5%; P<.01). No other differences were identified based on MELD-Na score stratification. Patients with advanced cirrhosis (MELD-Na score ≥8) have an increased risk of 30-day readmission after tibia fracture surgery. Cirrhosis associated with a lower MELD-Na score might not significantly increase the risk of 30-day complications in patients with tibia fractures. [Orthopedics. 2022;45(2):79-85.].
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Taher MY, El-Hadidi A, El-Shendidi A, Sedky A. Soluble CD163 for Prediction of High-Risk Esophageal Varices and Variceal Hemorrhage in Patients with Liver Cirrhosis. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2022; 29:82-95. [PMID: 35497666 PMCID: PMC8995632 DOI: 10.1159/000516913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 04/22/2021] [Indexed: 02/18/2025]
Abstract
INTRODUCTION Activation of hepatic macrophages in liver disease is pathogenically related to portal hypertension (PH). Soluble CD163 (sCD163) is shed in blood by activated macrophages and may predict PH progression noninvasively. This study was designed to investigate the relation of serum sCD163 to the grade and bleeding risk of esophageal varices (EV) and its role for prediction of variceal hemorrhage (VH). METHODS The study included cirrhotic patients divided into 3 groups: patients who presented with acute upper gastrointestinal bleeding (UGIB) proved to originate from EV on endoscopy, patients without any history of UGIB but who revealed EV on surveillance endoscopy, and patients without endoscopic evidence of varices. Variceal grade and risk signs and bleeding stigmata were noted simultaneously with measurement of serum sCD163 concentration. RESULTS Serum sCD163 concentration showed a significant increase in cirrhotic patients compared to healthy subjects (p < 0.001) with a stepwise increase among the group without varices, nonbleeder group, and bleeder group sequentially. Serum sCD163 levels correlated positively with the variceal grade and risk signs in both the bleeder and nonbleeder groups (p = 0.002, p < 0.001 and p = 0.004, p < 0.001, respectively). Serum sCD163 at a cutoff value of 3.6 mg/L performed significantly for prediction of EV presence (AUC = 0.888). Serum sCD163 at a cutoff value >4 mg/L significantly predicted large-size and high-risk EV (AUC = 0.910 and AUC = 0.939, respectively) and the index bleed risk (AUC = 0.977). Serum sCD163 at a cutoff value >4.05 mg/L modestly discriminated bleeding EV from those that had never bled (AUC = 0.811). CONCLUSIONS Serum sCD163 levels accurately predicted high-grade and high-risk EV and could help plan for primary prophylaxis. However, it modestly identified VH occurrence, and endoscopy would be required to make a definitive diagnosis.
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Affiliation(s)
- Mohamed Yousri Taher
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Abeer El-Hadidi
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Assem El-Shendidi
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed Sedky
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Keller J, Hammer HF, Afolabi PR, Benninga M, Borrelli O, Dominguez‐Munoz E, Dumitrascu D, Goetze O, Haas SL, Hauser B, Pohl D, Salvatore S, Sonyi M, Thapar N, Verbeke K, Fox MR. European guideline on indications, performance and clinical impact of 13 C-breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC. United European Gastroenterol J 2021; 9:598-625. [PMID: 34128346 PMCID: PMC8259225 DOI: 10.1002/ueg2.12099] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 04/06/2021] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION 13 C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers. METHODS This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of 13 C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed. RESULTS The guideline gives an overview over general methodology of 13 C-breath testing and provides recommendations for the use of 13 C-breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of 13 C-breath testing are summarized briefly. The recommendations specifically detail when and how individual 13 C-breath tests should be performed including examples for well-established test protocols, patient preparation, and reporting of test results. CONCLUSION This clinical practice guideline should improve pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, this guideline identifies areas of future clinical research involving the use of 13 C-breath tests.
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Affiliation(s)
- Jutta Keller
- Department of Internal MedicineIsraelitic HospitalAcademic Hospital University of HamburgHamburgGermany
| | - Heinz F. Hammer
- Department of Internal MedicineDivision of Gastroenterology and HepatologyMedical University of GrazGrazAustria
| | - Paul R. Afolabi
- NIHR Southampton Biomedical Research CentreUniversity Hospital Southampton NHS Foundation Trust and University of SouthamptonSouthamptonUK
| | - Marc Benninga
- Department of Pediatric Gastroenterology, Hepatology and NutritionEmma Children's HospitalAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - Osvaldo Borrelli
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
| | - Enrique Dominguez‐Munoz
- Department of Gastroenterology and HepatologyUniversity Hospital of Santiago de CompostelaSantiagoSpain
| | | | - Oliver Goetze
- Department of Medicine IIDivision of HepatologyUniversity Hospital WürzburgWürzburgGermany
| | - Stephan L. Haas
- Department of Upper GI DiseasesKarolinska University HospitalStockholmSweden
| | - Bruno Hauser
- Department of Paediatric Gastroenterology, Hepatology and NutritionKidZ Health Castle UZ BrusselsBrusselsBelgium
| | - Daniel Pohl
- Division of Gastroenterology and HepatologyUniversity Hospital ZürichZürichSwitzerland
| | - Silvia Salvatore
- Pediatric DepartmentHospital "F. Del Ponte"University of InsubriaVareseItaly
| | - Marc Sonyi
- Department of Internal MedicineDivision of Gastroenterology and HepatologyMedical University of GrazGrazAustria
- Clinic for General Medicine, Gastroenterology, and Infectious DiseasesAugustinerinnen HospitalCologneGermany
| | - Nikhil Thapar
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
- Department of Gastroenterology, Hepatology and Liver TransplantationQueensland Children's HospitalBrisbaneAustralia
| | - Kristin Verbeke
- Translational Research Center for Gastrointestinal DisordersKU LeuvenLeuvenBelgium
| | - Mark R. Fox
- Division of Gastroenterology and HepatologyUniversity Hospital ZürichZürichSwitzerland
- Digestive Function: Basel, Laboratory and Clinic for Motility Disorders and Functional Gastrointestinal DiseasesCentre for Integrative GastroenterologyKlinik ArlesheimArlesheimSwitzerland
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Møller S, la Cour Sibbesen E, Madsen JL, Bendtsen F. Indocyanine green retention test in cirrhosis and portal hypertension: Accuracy and relation to severity of disease. J Gastroenterol Hepatol 2019; 34:1093-1099. [PMID: 30221390 DOI: 10.1111/jgh.14470] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 08/16/2018] [Accepted: 09/04/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Patients with cirrhosis and portal hypertension often develop complications relating to hepatic excretory dysfunction. The standard measurement of the hepatic excretion is the constant infusion indocyanine green clearance (ICGCI ) technique. The ICG 15-min retention test (ICG-r15) is faster, more patient friendly, and cheaper. The aims were to compare the ICG-r15 test with the standard method, to assess relations to patient characteristics and survival, and to assess the ICG-r15 level in healthy control subjects. METHODS This study included 68 patients with cirrhosis and portal hypertension (Child class A/B/C:17/37/14). All patients underwent a full liver vein catheterization and hemodynamic evaluation with determination of ICG-r15 and ICGCI as the reference in a subset of 38 patients. Sixteen healthy control subjects were included for compiling a reference interval. RESULTS The ICG-r15 was increased in the cirrhotic patients with increasing values in parallel with liver dysfunction (15/41/58%) in Child class A/B/C compared with 7% in the controls (P < 0.001). ICG-r15 correlated highly significantly with the ICGCI (r = -0.96, P < 0.0001) and in a multivariate regression analysis with hepatic venous pressure gradient, markers of liver dysfunction and hyperdynamic circulation (P < 0.05-0.005). In the control group, normal reference values ranged from 0% to 13%. In addition, ICG-r15 was significantly related to mortality in the patient group (P = 0.02). CONCLUSIONS Indocyanine green-r15 reflects portal hypertension, the degree of hepatic failure, and survival and may replace the standard ICGCI . A more elaborated reference interval needs to be compiled, and the prognostic value of ICG-r15 should be validated.
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Affiliation(s)
- Søren Møller
- Center of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Else la Cour Sibbesen
- Center of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jan Lysgård Madsen
- Center of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division 360, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Hvidovre, Denmark
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Characteristics of Liver Disease in 100 Individuals With Joubert Syndrome Prospectively Evaluated at a Single Center. J Pediatr Gastroenterol Nutr 2018; 66:428-435. [PMID: 29112083 PMCID: PMC5825259 DOI: 10.1097/mpg.0000000000001816] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Joubert Syndrome (JS) is a rare, inherited, ciliopathy defined by cerebellar and brainstem malformations and is variably associated with liver, kidney, and ocular dysfunction. This study characterizes the hepatic findings in JS and identifies factors associated with probable portal hypertension. METHODS Hundred individuals with JS were prospectively evaluated at the National Institutes of Health Clinical Center. Laboratory tests, imaging, and DNA sequencing were performed. Patients were stratified based on the spleen length/patient height ratio as a marker of splenomegaly, used as a surrogate for probable portal hypertension. RESULTS Forty-three patients (43%) had liver involvement based on elevated liver enzymes and/or liver hyperechogenicity and/or splenomegaly. None of the patients had macroscopic liver cysts or bile duct dilatation. Based on the spleen length/patient height ratio, 13 patients were stratified into a probable portal hypertension group. We observed significant elevations in alkaline phosphatase (269 vs 169 U/L, P ≤ 0.001), alanine aminotransferase (92 vs 42 U/L, P = 0.004), aspartate aminotransferase (77 vs 40 U/L, P = 0.002), and gamma-glutamyl transferase (226 vs 51 U/L, P ≤ 0.001) in the probable portal hypertension group. Platelets were lower in the probable portal hypertension cohort (229 vs 299 × 10 cells/μL, P = 0.008), whereas synthetic function was intact in both groups. Probable portal hypertension was also more prevalent in patients with kidney disease (P = 0.001) and colobomas (P = 0.02), as well as mutations in the TMEM67 gene (P = 0.001). CONCLUSIONS In JS, probable portal hypertension is associated with abnormal hepatic enzymes, as well as presence of kidney disease, coloboma, and/or mutation in TMEM67. These findings may allow early identification of JS patients who have or are more likely to develop liver disease.
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Aubé C, Bazeries P, Lebigot J, Cartier V, Boursier J. Liver fibrosis, cirrhosis, and cirrhosis-related nodules: Imaging diagnosis and surveillance. Diagn Interv Imaging 2017; 98:455-468. [PMID: 28461073 DOI: 10.1016/j.diii.2017.03.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/09/2017] [Accepted: 03/09/2017] [Indexed: 02/06/2023]
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Yim SY, Lee JH, Ahn H, Kim SU, Kim SG, Kim YS, Kim JH, Choe WH, Kim TY, Jung YK, Suh SJ, Suk KT, An H, Yim HJ, Seo YS, Um SH. Subclinical Ascites Does Not Affect the Long-term Prognosis in Hepatitis B Virus-related Cirrhosis Patients Receiving Antivirals. J Clin Gastroenterol 2016; 50:676-685. [PMID: 27203430 DOI: 10.1097/mcg.0000000000000529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS This study evaluated the clinical significance of subclinical ascites in patients with hepatitis B virus-related cirrhosis treated with lamivudine (LMV) or entecavir (ETV). METHODS This multicenter retrospective study involved 8 hospitals. Patients were classified by degree of ascites: (1) no ascites (no ascites on imaging, no diuretics), (2) subclinical ascites (small amount of ascites on imaging, no diuretics), and (3) clinical ascites (moderate to severe ascites or diuretics). RESULTS Out of 501 patients, 336 (68%), 51 (10%), and 114 (23%) patients were classified as no-ascites, subclinical ascites, and clinical ascites, respectively. In all, 100 (20%) and 401 (80%) were treated with LMV and ETV, respectively. Over 58±24 months of follow-up, 105 patients (21%) developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma did not differ between LMV-treated and ETV-treated patients (P=0.61); it was higher in the clinical-ascites group than the no-ascites (P=0.054) and subclinical-ascites (P=0.03) groups, but it was comparable between the latter 2 (P=0.225). Forty-five patients (9%) died during follow-up. Survival was significantly shorter in the clinical-ascites group than the other 2 (both P<0.005), but it was comparable between no-ascites and subclinical-ascites groups (P=0.444). Multivariate analysis showed that mortality was significantly associated with prothrombin time [hazard ratio (HR)=2.42; 95% confidence interval (CI), 1.59-3.70], serum albumin (HR=0.54; 95% CI, 0.29-0.99), and presence of clinical ascites (HR=3.58; 95% CI, 1.54-8.30). CONCLUSIONS Subclinical ascites did not affect prognosis in patients with hepatitis B virus-related cirrhosis receiving antiviral treatment.
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Affiliation(s)
- Sun Young Yim
- Departments of *Internal Medicine **Biostatistics, Korea University College of Medicine †Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine ‡Department of Internal Medicine, Yonsei University College of Medicine ∥Department of Internal Medicine, Konkuk University College of Medicine, Seoul §Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon ¶Institue of Medical Science, Hanyang University College of Medicine, Guri #Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
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11
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Jain P, Tripathi BK, Gupta B, Bhandari B, Jalan D. Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis. J Clin Diagn Res 2015; 9:OC22-4. [PMID: 26672800 DOI: 10.7860/jcdr/2015/13944.6814] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 08/19/2015] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. AIM To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. MATERIALS AND METHODS Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (10(9)/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. RESULTS APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. CONCLUSION APRI could identify cirrhosis with high degree of accuracy in the studied patients.
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Affiliation(s)
- Princi Jain
- Ex Resident, Department of Medicine, VMMC & SJH , New Delhi, India
| | - B K Tripathi
- Professor, Department of Medicine, VMMC & SJH , New Delhi, India
| | - B Gupta
- Ex Professor and Head, Department of Medicine, VMMC & SJH , New Delhi, India
| | - Bharti Bhandari
- Assistant Professor, Department of Physiology, AIIMS , Jodhpur, India
| | - Divesh Jalan
- Assistant Professor, Department of Orthopaedics, AIIMS , Jodhpur, India
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12
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Levesque E, Martin E, Dudau D, Lim C, Dhonneur G, Azoulay D. Current use and perspective of indocyanine green clearance in liver diseases. Anaesth Crit Care Pain Med 2015; 35:49-57. [PMID: 26477363 DOI: 10.1016/j.accpm.2015.06.006] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 06/12/2015] [Indexed: 02/06/2023]
Abstract
Indocyanine green (ICG) is a water-soluble anionic compound that binds to plasma proteins after intravenous administration. It is selectively taken up at the first pass by hepatocytes and excreted unchanged into the bile. With the development of ICG elimination measurement by spectrophotometry, the ICG retention test has become a safe, rapid, reproducible, inexpensive and noninvasive tool for the assessment of liver function. Clinical evidence suggests that the ICG retention test can enable the establishment of tailored management strategies by providing prognostic information. In particular, this method has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and for the assessment of liver function in patients undergoing liver surgery. Since recent technology enables ICG-PDR to be measured noninvasively at the bedside, this parameter is an attractive addition to liver function and regional haemodynamic monitoring. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required.
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Affiliation(s)
- Eric Levesque
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France.
| | - Eléonore Martin
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Daniela Dudau
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Chetana Lim
- AP-HP, Hôpital Henri-Mondor, Service de Chirurgie Digestive, Hépatobiliaire, Pancréatique et Transplantation Hépatique, 94000 Créteil, France
| | - Gilles Dhonneur
- AP-HP, Hôpital Henri-Mondor, Service d'Anesthésie et des Réanimations Chirurgicales, 94000 Créteil, France
| | - Daniel Azoulay
- AP-HP, Hôpital Henri-Mondor, Service de Chirurgie Digestive, Hépatobiliaire, Pancréatique et Transplantation Hépatique, 94000 Créteil, France
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Goossens N, Nakagawa S, Hoshida Y. Molecular prognostic prediction in liver cirrhosis. World J Gastroenterol 2015; 21:10262-10273. [PMID: 26420954 PMCID: PMC4579874 DOI: 10.3748/wjg.v21.i36.10262] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Revised: 06/12/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction, and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature, and discuss critical issues to successfully define, evaluate, and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab test-based fibrosis assessment methods. However, recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care, and eventually achieve “precision medicine”.
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Lignon G, Boursier J, Delumeau S, Michalak-Provost S, Lebigot J, Oberti F, Aubé C. Screening for significant chronic liver disease by using three simple ultrasound parameters. Eur J Radiol 2015; 84:1466-1472. [DOI: 10.1016/j.ejrad.2015.05.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 04/25/2015] [Accepted: 05/09/2015] [Indexed: 12/17/2022]
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Abstract
PURPOSE OF REVIEW It is our opinion that there is an unmet need in hepatology for a minimally or noninvasive test of liver function and physiology. Quantitative liver function tests define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high-affinity hepatic transporters exhibit high 'first-pass' hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. RECENT FINDINGS We highlight one quantitative liver function test, the dual cholate test, and introduce the concept of a disease severity index linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. SUMMARY It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.
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Aubé C. Imaging modalities for the diagnosis of hepatic fibrosis and cirrhosis. Clin Res Hepatol Gastroenterol 2015; 39:38-44. [PMID: 25037179 DOI: 10.1016/j.clinre.2014.06.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 06/08/2014] [Indexed: 02/09/2023]
Abstract
Non-invasive methods for liver fibrosis diagnosis are now commonly used as first-intention tests for liver fibrosis diagnosis in chronic liver diseases. Even morphological parameters provided by ultrasound is now challenged by blood fibrosis tests and transient elastography, in experienced hands, it performed well and in certain situations, imaging can still be useful to detect patients with fibrosis. In parallel, to ultrasound and Doppler imaging, various methodologies have been explored. Some of them remain confined to clinical research for the moment, as perfusion, MR diffusion-weighted imaging, intravoxel incoherent motion or acoustic structure quantification; others have already taken a place in clinical practice. Regarding fast growing of new technology some methods may become available for daily practice in the near future. Ultrasound tools or automated quantification of different physical parameters of imaging data could provide an opportunity for early diagnosis of liver diseases; MRI techniques could lead to the development of a "global" liver examination.
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Affiliation(s)
- Christophe Aubé
- Département de radiologie, et laboratoire HIFIH, LUNAM université, université d'Angers, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex, France.
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17
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Crossan C, Tsochatzis EA, Longworth L, Gurusamy K, Davidson B, Rodríguez-Perálvarez M, Mantzoukis K, O'Brien J, Thalassinos E, Papastergiou V, Burroughs A. Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation. Health Technol Assess 2015; 19:1-vi. [PMID: 25633908 PMCID: PMC4781028 DOI: 10.3310/hta19090] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001561. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Catriona Crossan
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Louise Longworth
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | | | | | - Manuel Rodríguez-Perálvarez
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Konstantinos Mantzoukis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Julia O'Brien
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Evangelos Thalassinos
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Vassilios Papastergiou
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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Abstract
INTRODUCTION Assessing the formation and regression of fibrosis in chronic liver disease (CLD) is important. Current methods of assessment employed in clinical practice are inadequate. We present a review of the utility of non-invasive biomarkers of liver fibrosis. SOURCES OF DATA Published material on MEDLINE. AREAS OF AGREEMENT Liver biopsy is an imperfect 'gold standard'. Biomarkers are excellent at detecting significant fibrosis across different aetiologies of CLD. There is growing evidence that they also predict clinical outcomes. AREAS OF CONTROVERSY Non-invasive biomarkers can be used in clinical practice to screen for significant fibrosis, but the utility of liver biopsy is retained in answering specific questions. Biomarkers cannot be used robustly in clinical trials as doubts remain over their ability to detect small changes in fibrosis, inflammation and what influences them. AREAS TIMELY FOR DEVELOPING RESEARCH Community screening and algorithms are being developed with biomarkers to more effectively direct resources. Novel imaging techniques have huge potential advantages, particularly in secondary care for risk stratification.
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Affiliation(s)
- Robert Scott
- National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit (NDDBRU), Nottingham University Hospitals NHS Trust and University of Nottingham, E Floor, West Block QMC, Queen's Medical Centre, Nottingham NG7 2UH, UK
| | - Indra Neil Guha
- National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit (NDDBRU), Nottingham University Hospitals NHS Trust and University of Nottingham, E Floor, West Block QMC, Queen's Medical Centre, Nottingham NG7 2UH, UK
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Malinowski M, Jara M, Lüttgert K, Orr J, Lock JF, Schott E, Stockmann M. Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test. Dig Dis Sci 2014; 59:2983-91. [PMID: 24993690 DOI: 10.1007/s10620-014-3250-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 06/06/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. AIM We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. METHODS We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. RESULTS LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. CONCLUSIONS LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.
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Affiliation(s)
- Maciej Malinowski
- Department of General, Visceral and Transplantation Surgery, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany,
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Verma V, Sarin SK, Sharma P, Kumar A. Correlation of aspartate aminotransferase/platelet ratio index with hepatic venous pressure gradient in cirrhosis. United European Gastroenterol J 2014; 2:226-31. [PMID: 25360306 DOI: 10.1177/2050640614527084] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 02/06/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Hepatic venous pressure gradient (HVPG) is a prognostic marker in cirrhosis, but is invasive. There is a need to validate a noninvasive marker to measure portal hypertension. Aspartate aminotransferase/platelet ratio index (APRI) is proposed as a good noninvasive estimator of hepatic fibrosis. Whether APRI could be used as noninvasive tool to measure portal hypertension has not been studied. AIM To correlate APRI with HVPG in patients with cirrhosis and to determine the diagnostic usefulness of the APRI in detection of high portal pressure. METHODS APRI and HVPG were measured in consecutive patients of cirrhosis aged 18-75 years, with serum bilirubin <5 mg/dl, Child-Turcotte-Pugh (CTP) score ≤12, and without evidence of acute-on-chronic liver failure or flare. RESULTS This study included 74 patients (median age 47 years, range 20-70 years; 57 males, (77%). The aetiology of cirrhosis was: viral 33 (45%), alcohol 10 (14%), and cryptogenic and others 31 (42%). The median HVPG was 16 mmHg (range 2-28 mmHg). The median APRI was 1.19 (range 0.17-7.92). There was significant correlation between HVPG and APRI (Spearman's rho 0.365; p = 0.001). The ROC curve to study the performance of APRI for predicting high portal pressure (HVPG >12 mmHg) had area under curve 0.716 (95% CI 0.574-0.858). An APRI of ≥1.09 had a sensitivity 66%, specificity 73%, positive predictive value 85%, negative predictive value 47%, and diagnostic accuracy 68% for predicting HVPG >12 mmHg. CONCLUSIONS APRI correlates fairly with HVPG in patients of cirrhosis. An APRI score of ≥1.09 seems to have an acceptable accuracy for prediction of high portal pressure. APRI is a fair, bedside, cost-effective parameter for diagnosis of high portal pressure in patients with cirrhosis.
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Affiliation(s)
- Vipin Verma
- Maulana Azad Medical College, New Delhi, India
| | - Shiv Kumar Sarin
- Institute of Liver and Biliary Sciences, New Delhi, India ; GB Pant Hospital, New Delhi, India
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21
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Ji D, Shao Q, Han P, Li F, Li B, Zang H, Niu X, Li Z, Xin S, Chen G. The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations. PLoS One 2014; 9:e105183. [PMID: 25122123 PMCID: PMC4133303 DOI: 10.1371/journal.pone.0105183] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 07/17/2014] [Indexed: 12/30/2022] Open
Abstract
Objective To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients. Methods A total of 38,464 “real-life” Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM). Results LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m2, female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001). Conclusions The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.
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Affiliation(s)
- Dong Ji
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Qing Shao
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Ping Han
- Tumor Radiotherapy Center, 302 Military Hospital of China, Beijing, China
| | - Fan Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Bing Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Hong Zang
- Liver Failure Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Xiaoxia Niu
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Zhongbin Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Shaojie Xin
- Liver Failure Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
- * E-mail: (SJX); (GFC)
| | - Guofeng Chen
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
- * E-mail: (SJX); (GFC)
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22
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Zoller B, Spanaus K, Gerster R, Fasshauer M, Stehberger PA, Klinzing S, Vergopoulos A, von Eckardstein A, Béchir M. ICG-liver test versus new biomarkers as prognostic markers for prolonged length of stay in critically ill patients - a prospective study of accuracy for prediction of length of stay in the ICU. Ann Intensive Care 2014; 4:19. [PMID: 25045579 PMCID: PMC4100565 DOI: 10.1186/s13613-014-0019-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 05/22/2014] [Indexed: 12/05/2022] Open
Abstract
Background Prognostic abilities of medical parameters, which are scoring systems, measurements and biomarkers, are important for stratifying critically ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established clinical tool for the assessment of liver perfusion and function. Copeptin, MR-proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and pro-ADM to predict prolonged length of stay (pLOS) in the ICU. Methods This study was conducted as a prospective single center study including 110 consecutively admitted ICU patients. Primary endpoint was prolonged length of stay (pLOS) in the ICU, defined as more than three days of stay there. Results ROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR-proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU. Conclusions The prediction of pLOS in the ICU might be better by means of ICG-PDR than with the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more need for research to evaluate whether ICG-PDR is an overall prognostic marker for pLOS. Trial registration (ClinicalTrials.gov number, NCT01126554).
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Affiliation(s)
- Bernhard Zoller
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland
| | - Katharina Spanaus
- Institute of Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland
| | - Rahel Gerster
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland
| | - Mario Fasshauer
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland
| | - Paul A Stehberger
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland
| | - Stephanie Klinzing
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland
| | - Athanasios Vergopoulos
- Institute of Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland
| | - Arnold von Eckardstein
- Institute of Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland
| | - Markus Béchir
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland ; Swiss Paraplegic Center, Nottwil, Switzerland
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Pijls KE, de Vries H, Nikkessen S, Bast A, Wodzig WKWH, Koek GH. Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited. Liver Int 2014; 34:487-94. [PMID: 24428683 DOI: 10.1111/liv.12451] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 12/15/2013] [Indexed: 12/17/2022]
Abstract
As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.
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Affiliation(s)
- Kirsten E Pijls
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
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Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C. J Gastroenterol 2014; 49:527-37. [PMID: 23681425 DOI: 10.1007/s00535-013-0819-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Accepted: 04/15/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology. METHODS 650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis. RESULTS The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic. CONCLUSION A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.
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Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, Kamath PS, Talwalkar JA. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11:1573-84.e1-2; quiz e88-9. [PMID: 23954643 PMCID: PMC3900882 DOI: 10.1016/j.cgh.2013.07.034] [Citation(s) in RCA: 232] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 07/25/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver stiffness measurement (LSM), using elastography, can independently predict outcomes of patients with chronic liver diseases (CLDs). However, there is much variation in reporting and consistency of findings. We performed a systematic review and meta-analysis to evaluate the association between LSM and outcomes of patients with CLDs. METHODS We performed a systematic review of the literature, through February 2013, for studies that followed up patients with CLDs prospectively for at least 6 months and reported the association between baseline LSM and subsequent development of decompensated cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CIs) were estimated using the random effects model. RESULTS Our final analysis included 17 studies, reporting on 7058 patients with CLDs. Baseline LSM was associated significantly with risk of hepatic decompensation (6 studies; RR, 1.07; 95% CI, 1.03-1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05-1.18), death (5 studies; RR, 1.22; 95% CI, 1.05-1.43), or a composite of these outcomes (7 studies; RR, 1.32; 95% CI, 1.16-1.51). We observed considerable heterogeneity among studies-primarily in the magnitude of effect, rather than the direction of effect. This heterogeneity could not be explained by variations in study locations, etiologies and stages of CLD, techniques to measure liver stiffness, adjustment for covariates, or method of imputing relationship in the meta-analysis. CONCLUSIONS Based on a meta-analysis of cohort studies, the degree of liver stiffness is associated with risk of decompensated cirrhosis, HCC, and death in patients with CLDs. LSM therefore might be used in risk stratification.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
| | - Larissa L. Fujii
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Zhen Wang
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota
| | - Sumeet K. Asrani
- Division of Hepatology, Baylor University Medical Center, Dallas, Texas
| | - Richard L. Ehman
- Department of Diagnostic Radiology, Mayo Clinic, Rochester, Minnesota
| | - Patrick S. Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jayant A. Talwalkar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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Afolabi P, Wright M, Wootton SA, Jackson AA. 13C-aminopyrine demethylation is decreased in cirrhotic patients with normal biochemical markers. ISOTOPES IN ENVIRONMENTAL AND HEALTH STUDIES 2013; 49:346-356. [PMID: 23799253 DOI: 10.1080/10256016.2013.803098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
This study determined the rates of (13)C-aminopyrine metabolism in patients with varying degrees of liver cirrhosis as defined by clinical scores. Twenty-five cirrhotic patients and 18 healthy subjects underwent a (13)C-aminopyrine breath test. The cumulative per cent dose recovery (cPDR) of (13)C on breath expressed as a percentage of the administered dose at 2 h was significantly lower in cirrhotic patients than in healthy subjects (median: 1.7% versus 9.0%; p<.0001). Significant inverse associations between cPDR at 2 h and the model for end-stage liver disease score, Child-Pugh score, international normalised ratio and bilirubin (all p<.05), but not alanine aminotransferase or alkaline phosphatase were observed in the cirrhotic patients. Taking each biochemical marker independently, cirrhotic patients with normal biochemistry had a significantly lower cPDR at 2 h than healthy subjects (all p<.05). Differences in (13)C-aminopyrine metabolism were evident in cirrhotic patients with less severe disease and may mark hepatic dysfunction when conventional biochemical markers appear unchanged.
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Affiliation(s)
- Paul Afolabi
- a National Institute for Health Research Biomedical Research Centre (Nutrition), Southampton Centre for Biomedical Research, Southampton General Hospital , Southampton , UK
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Boursier J, Zarski JP, de Ledinghen V, Rousselet MC, Sturm N, Lebail B, Fouchard-Hubert I, Gallois Y, Oberti F, Bertrais S, Calès P. Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology 2013; 57:1182-91. [PMID: 22899556 DOI: 10.1002/hep.25993] [Citation(s) in RCA: 485] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Accepted: 06/17/2012] [Indexed: 12/12/2022]
Abstract
UNLABELLED Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10< IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and "poorly reliable" (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P < 10(-3) ). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P < 10(-3) ), 74.3% were reliable, and 16.6% were very reliable. CONCLUSION The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013).
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Affiliation(s)
- Jérôme Boursier
- Liver-Gastroenterology Department, University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4038, LUNAM University, Angers, France.
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201Tl Heart-Liver Radioactivity Uptake Ratio and Prediction of Decompensation in Patients With Cirrhosis. Clin Nucl Med 2013; 38:169-74. [DOI: 10.1097/rlu.0b013e31827087e3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Afolabi P, Wright M, Wootton SA, Jackson AA. Clinical utility of 13C-liver-function breath tests for assessment of hepatic function. Dig Dis Sci 2013; 58:33-41. [PMID: 22899241 DOI: 10.1007/s10620-012-2340-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Accepted: 07/25/2012] [Indexed: 12/16/2022]
Abstract
13C-Liver-function breath tests have been used in clinical diagnostics and, to a limited extent, to investigate hepatic function. From a practical perspective, tests such as the 13C-aminopyrine and 13C-methacetin breath tests are simple to administer, safe, and relatively inexpensive to perform. Surprisingly, they have not entered the mainstream of clinical practice, because they are perceived to lack the specificity and adequate precision needed to give accurate results in real time. The dynamic nature of 13C-liver-function breath tests, their possible versatility in terms of assessing a range of different liver functions, and the ease with which they can be repeated to follow relative changes in liver function with time, all imply the potential for wider clinical application. Therefore, there is a need for these tests to be critically evaluated and their potential clinical application be tested systematically against defined objectives. We describe refinements in the methodology of the tests and propose several situations in which currently reliable methods for assessment of liver function do not exist and where 13C-liver-function breath tests might be of use. We propose that use has been constrained by practical methodological considerations which could be addressed to offer tests better suited to routine application in the out-patient or community setting.
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Affiliation(s)
- P Afolabi
- NIHR Biomedical Research Unit (Nutrition, Diet, and Lifestyle), Southampton General Hospital, Southampton, SO16 6YD, UK.
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Modak AS. An Update on 13C-Breath Tests: The Transition to Acceptability into Clinical Practice. VOLATILE BIOMARKERS 2013:244-262. [DOI: 10.1016/b978-0-44-462613-4.00014-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Sheron N, Moore M, Ansett S, Parsons C, Bateman A. Developing a 'traffic light' test with potential for rational early diagnosis of liver fibrosis and cirrhosis in the community. Br J Gen Pract 2012; 62:e616-24. [PMID: 22947582 PMCID: PMC3426600 DOI: 10.3399/bjgp12x654588] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 01/04/2012] [Accepted: 04/12/2012] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver disease develops silently and presents late, with often fatal complications. AIM To develop a 'traffic light' test for liver disease suitable for community use that could enhance assessment of liver risk and allow rational referral of more severe disease to specialist care. DESIGN AND SETTING Two cohorts from Southampton University Hospital Trust Liver Unit: model development and a validation cohort to evaluate prognosis. METHOD A total of 1038 consecutive liver patients (inpatient and outpatient) (development n = 397, validation n = 641) for whom the relevant blood tests had been performed, were followed for a mean of 46 months (range 13-89 months). Blood tests for: hyaluronic acid (HA), procollagen-3 N-terminal peptide (P3NP), and platelet count were combined in a diagnostic algorithm to stage liver disease. RESULTS A simple clinical rule combined: HA, P3NP, and platelet count into a 'traffic light' algorithm, grading the results red--high risk, amber--intermediate risk, and green--low risk. In the validation cohort, no green subjects died or developed varices or ascites (n = 202); in the amber group, 9/267 (3.3%) died, 0/267 developed varices, and 2/267 (0.7%) developed ascites; in the red group, 24/172 died (14%), 24/172 (14%) developed varices, and 20/172 developed (11.6%) ascites. Survival was reduced in red (P<0.001) and amber (P<0.012) groups compared with green. CONCLUSION A simple blood test triages liver disease into three prognostic groups; used in the community, it could enhance the management of risk factors in primary care and rationalise secondary care referrals, including the many patients with fatty liver and relatively minor elevations in alanine transaminase.
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Affiliation(s)
- Nick Sheron
- Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton.
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Theile D, Haefeli WE, Seitz HK, Millonig G, Weiss J, Mueller S. Association of liver stiffness with hepatic expression of pharmacokinetically important genes in alcoholic liver disease. Alcohol Clin Exp Res 2012; 37 Suppl 1:E17-22. [PMID: 22827451 DOI: 10.1111/j.1530-0277.2012.01901.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Accepted: 05/17/2012] [Indexed: 12/23/2022]
Abstract
BACKGROUND Enhanced drug elimination in alcoholics remains largely indefinable. In contrast, the reduced elimination of drugs in patients with advanced alcoholic liver disease (ALD) is normally owing to hepatic end-stage disease such as cirrhosis. We here study the mRNA expression of various hepatic drug metabolizing enzymes and transporters in association with liver stiffness (LS) being a novel noninvasive parameter for the assessment of cirrhosis to unravel the dynamic relationship between ALD and determinants of pharmacokinetics such as drug metabolizing enzymes and transporters. METHODS We quantified mRNA expression levels of various cytochrome P-450 isoenzymes (CYPs) and drug transporters in 26 liver specimens of chronic alcoholics and 5 controls by quantitative polymerase chain reaction. In addition, liver histology, clinical data, and LS evaluated by transient elastography (Fibroscan) were obtained. RESULTS Eighteen patients had a normal or moderate LS < 8 kPa (69.2%), while in the remaining 8 patients (30.7%) advanced F3 or F4 fibrosis could be established with an LS > 8 kPa. Overall, CYP3A4, CYP2E1, and solute carrier organic anion transporter 1B1 (SLCO1B1) were negatively correlated with increasing LS. CYPs and drug transporters tended to be up-regulated in alcoholics without advanced fibrosis (LS < 8.0 kPa) compared to healthy controls supporting data of boosted drug elimination in alcoholics without advanced ALD. However, in alcoholics with severely increased LS (>8 kPa), expression levels of CYP2E1, SLC22A2, and SLCO1B1 were significantly lower. CONCLUSIONS In conclusion, CYPs and drug transporters seem to be induced in chronic alcoholics without irreversible liver damage but decline in case of manifest cirrhosis. Our study also suggests that noninvasive measurements of LS could be useful for pharmacokinetic predictions and individualized pharmacotherapy.
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Affiliation(s)
- Dirk Theile
- Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany
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Boursier J, Rousselet MC, Aubé C, Calès P. Liver fibrosis in patients with non-alcoholic fatty liver disease: diagnostic options in clinical practice. ACTA ACUST UNITED AC 2012; 6:381-94. [DOI: 10.1517/17530059.2012.691878] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Rychik J, Veldtman G, Rand E, Russo P, Rome JJ, Krok K, Goldberg DJ, Cahill AM, Wells RG. The precarious state of the liver after a Fontan operation: summary of a multidisciplinary symposium. Pediatr Cardiol 2012; 33:1001-12. [PMID: 22534759 PMCID: PMC3442163 DOI: 10.1007/s00246-012-0315-7] [Citation(s) in RCA: 230] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2012] [Accepted: 03/31/2012] [Indexed: 02/07/2023]
Abstract
As the cohort of survivors with the single-ventricle type of congenital heart disease grows, it becomes increasingly evident that the state of chronically elevated venous pressure and decreased cardiac output inherent in the Fontan circulation provides the substrate for a progressive decline in functional status. One organ at great risk is the liver. Wedged between two capillary beds, with the pulmonary venous bed downstream, which typically has no pulsatile energy added in the absence of a functional right ventricle, and the splanchnic bed upstream, which may have compromised inflow due to inherent cardiac output restriction characteristic of the Fontan circulation, the liver exists in a precarious state. This review summarizes a consensus view achieved at a multidisciplinary symposium held at The Children's Hospital of Philadelphia in June 2011. The discussion includes current knowledge concerning the hemodynamic foundations of liver problems, the diagnostic tools available, the unique histopathology of the liver after the Fontan operation, and proposed mechanisms for hepatic fibrosis at the cellular level. At the completion of the symposium, a consensus recommendation was made by the authors' group to pursue a new prospective protocol for clinical evaluation of the liver for all patients in our practice 10 years after the Fontan operation.
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Affiliation(s)
- Jack Rychik
- Division of Cardiology, Single Ventricle Survivorship Program, The Cardiac Center at Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
| | - Gruschen Veldtman
- Department of Congenital Heart Disease, Southampton University Hospital, Southampton, UK
| | - Elizabeth Rand
- Division of Gastroenterology, The Children’s Hospital of Philadelphia, Philadelphia, PA USA ,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Pierre Russo
- Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA USA ,Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Jonathan J. Rome
- Division of Cardiology, Single Ventricle Survivorship Program, The Cardiac Center at the Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104 USA ,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Karen Krok
- Division of Gastroenterology, Hospital of The University of Pennsylvania, Philadelphia, PA USA ,Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - David J. Goldberg
- Division of Cardiology, Single Ventricle Survivorship Program, The Cardiac Center at the Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104 USA ,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Anne Marie Cahill
- Division of Interventional Radiology, The Children’s Hospital of Philadelphia, Philadelphia, PA USA ,Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Rebecca G. Wells
- Division of Gastroenterology, Hospital of The University of Pennsylvania, Philadelphia, PA USA ,Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
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Magnetic Resonance Elastography and Biomarkers to Assess Fibrosis From Recurrent Hepatitis C in Liver Transplant Recipients. Transplantation 2011; 92:581-6. [DOI: 10.1097/tp.0b013e31822805fa] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Afolabi P, Wright M, Wootton S, Jackson AA. A comparison of the reproducibility of the parameters of the ¹³C-aminopyrine breath test for the assessment of hepatic function. ISOTOPES IN ENVIRONMENTAL AND HEALTH STUDIES 2011; 47:390-399. [PMID: 21745035 DOI: 10.1080/10256016.2011.595791] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
This study determined the within-subject and between-subject variability of different ways of expressing the results of the (13)C-aminopyrine breath test ((13)C-ABT) and the effect of shortening the test duration. The (13)C-ABT was conducted on three separate occasions in 10 healthy volunteers and on a single occasion in 22 patients with established liver cirrhosis. The within-subject variability of cumulative percentage dose recovered (cPDR), using measured CO(2) production rate (VCO(2)), in the reference group over three trials was 15% over 120 min. Higher within-subject variability in cPDR would have been evident if the test was terminated at either 30 or 60 min. Substitution of predicted VCO(2) to calculate cPDR yielded comparable values at all time points. Significant differences between cirrhotics and reference group were evident after just 10 min using PDR/h, cPDR or enrichment (all P<0.05). The ABT demonstrates clinically acceptable reproducibility. Shortening of the duration may make the test more acceptable clinically, but it is associated with increasing imprecision.
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Affiliation(s)
- Paul Afolabi
- Southampton NIHR Biomedical Research Unit in Nutrition, Diet & Lifestyle, Southampton General Hospital, Southampton, SO16 6YD, UK.
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Irwin RJ, Irwin TC. A principled approach to setting optimal diagnostic thresholds: where ROC and indifference curves meet. Eur J Intern Med 2011; 22:230-4. [PMID: 21570638 DOI: 10.1016/j.ejim.2010.12.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Revised: 12/16/2010] [Accepted: 12/20/2010] [Indexed: 11/23/2022]
Abstract
Making clinical decisions on the basis of diagnostic tests is an essential feature of medical practice and the choice of the decision threshold is therefore crucial. A test's optimal diagnostic threshold is the threshold that maximizes expected utility. It is given by the product of the prior odds of a disease and a measure of the importance of the diagnostic test's sensitivity relative to its specificity. Choosing this threshold is the same as choosing the point on the Receiver Operating Characteristic (ROC) curve whose slope equals this product. We contend that a test's likelihood ratio is the canonical decision variable and contrast diagnostic thresholds based on likelihood ratio with two popular rules of thumb for choosing a threshold. The two rules are appealing because they have clear graphical interpretations, but they yield optimal thresholds only in special cases. The optimal rule can be given similar appeal by presenting indifference curves, each of which shows a set of equally good combinations of sensitivity and specificity. The indifference curve is tangent to the ROC curve at the optimal threshold. Whereas ROC curves show what is feasible, indifference curves show what is desirable. Together they show what should be chosen.
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Affiliation(s)
- R John Irwin
- Department of Psychology, The University of Auckland, New Zealand.
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