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López-Sánchez M, Bautista-Santos A, Milke-García MDP, Allende-López A, Moreno-Alcántar R, Morán S. Nutritional Status and Incidence of Hepatocellular Carcinoma in Patients with Compensated Liver Cirrhosis. Arch Med Res 2025; 56:103127. [PMID: 39591900 DOI: 10.1016/j.arcmed.2024.103127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 10/08/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Malnutrition in patients with liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) has been associated with adverse outcomes. However, there is little information on the incidence of HCC during the compensated phase of LC in relation to the nutritional status. AIM To evaluate the association between the incidence of HCC in compensated LC and their nutritional status. METHODS Patients with compensated liver cirrhosis with no previous history of ascites, hepatic encephalopathy, or variceal bleeding attending the Gastroenterology outpatient service at Centro Medico Nacional Siglo XXI were included in a prospective cohort. Clinical and nutritional parameters were collected, including the Royal Free Hospital Subjective Global Assessment (RFH-SGA) as an indicator of protein-calorie malnutrition and the triceps skinfold thickness, which classified patients as having normal subcutaneous adipose tissue (SAT), above average SAT, and below average SAT. Follow-up was censored at the time of HCC diagnosis or LC decompensation. RESULTS About 31/187 (16.0%) and 22/187 (11.8%) patients were categorized as having above- or below-average SAT at baseline, respectively. 10/187 patients (5.3%) developed HCC during the compensated phase of LC at a median of 22 months (IQR: 10.0-36.75). A higher risk of HCC was observed in subjects below average SAT (HR: 4.064, CI 95%: 1.012-16.317, p = 0.048). After adjusting the Cox models for age and α-fetoprotein at baseline, the statistical significance of the association between SAT and HCC was not modified. CONCLUSION These results suggest that decreased SAT may precede the diagnosis of HCC in compensated LC.
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Affiliation(s)
- Marlene López-Sánchez
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Aleida Bautista-Santos
- Gastroenterology Service, Instituto Mexicano del Seguro Social Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - María Del Pilar Milke-García
- Hemato-Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Aldo Allende-López
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Rosalba Moreno-Alcántar
- Gastroenterology Service, Instituto Mexicano del Seguro Social Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Segundo Morán
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Liu C, Cao Z, Yan H, Wong YJ, Xie Q, Hirooka M, Enomoto H, Kim TH, Hanafy AS, Liu Y, Huang Y, Li X, Kang N, Koizumi Y, Hiasa Y, Nishimura T, Iijima H, Jung YK, Yim HJ, Guo Y, Zhang L, Ma J, Kumar M, Jindal A, Teh KB, Sarin SK, Qi X. A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study. Am J Gastroenterol 2022; 117:1605-1613. [PMID: 35973168 PMCID: PMC9531993 DOI: 10.14309/ajg.0000000000001873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 04/12/2022] [Indexed: 02/05/2023]
Abstract
INTRODUCTION In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD. METHODS Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285). RESULTS In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83-0.94) and 0.83 (95% CI: 0.73-0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at -6 and -4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively ( P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80-0.90). DISCUSSION The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.
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Affiliation(s)
- Chuan Liu
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Zhujun Cao
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
| | - Huadong Yan
- Department of Infectious Disease, Shulan Hospital, Hangzhou, China;
| | - Yu Jun Wong
- Department of Gastroenterology & Hepatology, Changi General Hospital, SingHealth, Singapore;
- Duke-NUS Medical School, Singapore;
| | - Qing Xie
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
| | - Tae Hyung Kim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Amr Shaaban Hanafy
- Division of Gastroenterology, Hepatology and Endoscopy, Internal Medicine, Zagazig University Faculty of Medicine, Egypt
| | - Yanna Liu
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Yifei Huang
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Xiaoguo Li
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Ning Kang
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan;
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan;
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Ying Guo
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Linpeng Zhang
- Department of Interventional Radiology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Jianzhong Ma
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Kok Ban Teh
- Department of Gastroenterology & Hepatology, Changi General Hospital, SingHealth, Singapore;
- Duke-NUS Medical School, Singapore;
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Xiaolong Qi
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
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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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Abstract
BACKGROUND/AIMS In patients with acute-on-chronic liver failure (ACLF), type 1 hepatorenal syndrome (HRS) is a critical organ failure complication that resulted in rapid mortality. There are no efficient parameters to predict HRS in hepatitis B virus (HBV)-related ACLF. To assess HBV-ACLF risk factors and evaluate the association between mean arterial pressures (MAP), HRS and survival in patients with HBV-ACLF. METHODS A total of 420 ACLF patients were screened from June 2015 to June 2016, and 57 HBV-ACLF patients were included in the study. Clinical data and MAP measurements of these patients were collected. Multivariate analyses, Cox proportional hazards regression and receiver operator characteristic (ROC) curves were used to analyze. RESULTS In a 30-day study period, 43 (75.44%) patients survived. Patients in the HRS group were older and had higher Model for End-Stage Liver Disease (MELD) scores than patients in the non-HRS group. A MAP drop of ≥9.5 mmHg was an independent predictor of HRS with a sensitivity and specificity of 92.86 and 69.77%, respectively. The baseline MELD score was also an independent risk factor of HRS. MAP drop (OR, 1.582; P = 0.000), prothrombin time, HRS, MELD and FIB were independent prognostic factors for 30-day mortality. The area under the ROC curve of MAP drop was 0.808 (P = 0.001). CONCLUSION A decrease in MAP was a valuable predictor of HRS in patients with HBV-related ACLF. MAP drop ≥9.5 mmHg may be useful for predicting patient prognosis and exploring new treatment measures in patients with HBV-related ACLF.
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Wan S, Lei Y, Li M, Wu B. A prognostic model for hepatocellular carcinoma patients based on signature ferroptosis-related genes. Hepatol Int 2021; 16:112-124. [PMID: 34449009 DOI: 10.1007/s12072-021-10248-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/08/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Considering the increase in the number of HCC patients, it is critical to predict the survival of patients. Although ferroptosis is closely related to HCC progression, predicting the survival of HCC patients through ferroptosis-related genes is challenging. METHODS RNA-seq and clinical data of HCC in the TCGA database were analyzed to establish a prognostic model, and ICGC and GSE14520 data were used for validation. Risk score was constructed with 5 genes identified by univariate and LASSO Cox regression analysis. Risk score, TNM stage and cirrhosis were incorporated to construct a nomogram through univariate and multivariate Cox regression analysis. RESULTS Five genes identified from 70 ferroptosis-related DEGs were used to construct a gene signature that predicts survival of HCC patients in the TCGA cohort. PCA and heatmap showed clear differences between patients in different score groups. Next, risk score, TNM stage and cirrhosis were combined in a nomogram for overall survival prediction. Survival analysis indicated that the overall survival of the low-risk group was significantly higher than that of the high-risk group. The data from the GSE14520 cohort confirmed satisfactory nomogram performance. Furthermore, KEGG and GO functional enrichment analyses indicated that the difference in overall survival between risk groups was closely related to immune-related pathways. Further analyses implied that an immune-suppressive tumor microenvironment might contribute to the difference in the prognosis between risk groups. CONCLUSION The nomogram based on ferroptosis-related genes showed good performance for predicting the prognosis of HCC patients. The model may provide a reference for the evaluation of HCC patients by targeting ferroptosis.
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Affiliation(s)
- Sizhe Wan
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.,Guangdong Provincial Key Laboratory of Liver Disease Research, 600 Tianhe Road, Guangzhou, 510630, China
| | - Yiming Lei
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.,Guangdong Provincial Key Laboratory of Liver Disease Research, 600 Tianhe Road, Guangzhou, 510630, China
| | - Mingkai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.,Guangdong Provincial Key Laboratory of Liver Disease Research, 600 Tianhe Road, Guangzhou, 510630, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China. .,Guangdong Provincial Key Laboratory of Liver Disease Research, 600 Tianhe Road, Guangzhou, 510630, China.
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Calzadilla-Bertot L, Vilar-Gomez E, Wong VWS, Romero-Gomez M, Aller-de la Fuente R, Wong GLH, Castellanos M, Eslam M, Desai AP, Jeffrey GP, George J, Chalasani N, Adams LA. ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver-Related Cirrhosis. Hepatology 2021; 73:2238-2250. [PMID: 32978796 DOI: 10.1002/hep.31576] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 08/28/2020] [Accepted: 09/07/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is an increasingly important cause of liver cirrhosis and subsequent complications. We retrospectively developed and validated a model to predict hepatic decompensation in patients with NAFLD and cirrhosis and compared this with currently available models. APPROACH AND RESULTS Baseline variables from an international cohort of 299 patients with biopsy-proven NAFLD with compensated cirrhosis were examined to construct a model using competing risk multivariate regression and Akaike/Bayesian information criteria. Validation was performed in 244 patients with biopsy-proven NAFLD cirrhosis from the United States. Prognostic accuracy was compared with the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and albumin-bilirubin (ALBI)-FIB-4 score using time-dependent area under the curve (tAUC) analysis. During a median follow-up of 5.6 years (range 2.4-14.1) and 5.4 years (range 1.5-13.8), hepatic decompensation occurred in 81 and 132 patients in the derivation and validation cohorts, respectively. In the derivation cohort, independent predictors of hepatic decompensation (Aspartate aminotransferase/alanine aminotransferase ratio, Bilirubin, International normalized ratio, type 2 Diabetes, and Esophageal varices) were combined into the ABIDE model. Patients with a score ≥4.1 compared with those with a score <4.1 had a higher risk of decompensation (subhazard ratio, 6.7; 95% confidence interval [CI], 4.0-11.2; P < 0.001), a greater 5-year cumulative incidence (37% vs. 6%, P < 0.001), and shorter mean duration to decompensation (3.8 vs 6.7 years, P < 0.001). The accuracy of the ABIDE model at 5 years was good in the derivation (tAUC, 0.80; 95% CI, 0.73-0.84) and validation cohorts (0.78; 95% CI, 0.74-0.81) and was significantly more accurate than the NFS (0.72), FIB-4 (0.74), MELD (0.69), CTP (0.72), and ALBI-FIB-4 (0.73) (all P < 0.001). CONCLUSIONS In patients with NAFLD and compensated cirrhosis, ABIDE, a predictive model of routine clinical measures, predicts future hepatic decompensation.
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Affiliation(s)
- Luis Calzadilla-Bertot
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
- Unit for the Clinical Management of Digestive Diseases, Centro para la Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Virgen del Rocio University Hospital, University of Seville, Seville, Spain
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases, Centro para la Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Virgen del Rocio University Hospital, University of Seville, Seville, Spain
| | - Rocio Aller-de la Fuente
- Department of Digestive Disease, Institute of Endocrinology and Nutrition, University of Valladolid, Valladolid, Spain
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Marlen Castellanos
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Archita P Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Gary P Jeffrey
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Leon A Adams
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
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D'Amico G, Perricone G, Morabito A, Latteri F, Filì D, Affronti A, Pietrosi G, Maida M, Rizzo GEM, Bronte F, Petridis I, Bavetta MG, Volpes R, Malizia G, Luca A. Model for end stage liver disease for prediction of mortality in people with cirrhosis. Cochrane Database Syst Rev 2021. [DOI: 10.1002/14651858.cd013849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
| | - Giovanni Perricone
- S.C. Epatologia e Gastroenterologia; Azienda Socio-Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda; Milan Italy
| | - Alberto Morabito
- Istituto di Statistica Medica e Biometria; Universita di Milano; Milano Italy
| | | | | | | | | | - Marcello Maida
- Gastroenterology and Endoscopy Unit; S Elia - Raimondi Hospital - Caltanissetta; Caltanissetta Italy
| | | | | | | | | | | | | | - Angelo Luca
- Hepatology; CEO, IRCCS-ISMETT; Palermo Italy
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10
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Castellanos Fernández MI, Cepeda Mullo ME, la Rosa Hernández D, Vega Sánchez H, González Fabian L, Gish RG, Torres González AL, Dorta Guridi Z. Autoimmune Hepatitis in Cuban Patients: A Retrospective Analysis of Clinical and Histological Profiles, Treatments, and Outcomes. CURRENT THERAPEUTIC RESEARCH 2020; 93:100594. [PMID: 32922567 PMCID: PMC7476064 DOI: 10.1016/j.curtheres.2020.100594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 07/03/2020] [Indexed: 10/26/2022]
Abstract
BACKGROUND Population-based studies on the clinical course and prognosis of autoimmune hepatitis (AIH) from Caribbean countries are limited. OBJECTIVE The aim of this study was to provide information regarding the clinical and laboratory findings, histological profile, treatments, and outcomes of patients with AIH with long-term follow-up in a tertiary referral center. METHODS A retrospective study was performed at the National Institute of Gastroenterology in Havana, Cuba, by enrolling 82 patients with a well-documented, long-term clinical course of AIH. Clinical and laboratory findings, histological profiles, treatments, and outcomes were analyzed. RESULTS At diagnosis, 73 (89%) patients had AIH type 1, 84.1% were women, and their median age was 46.5 years (range, 17-79 years). The median follow-up period was 84 months (interquartile range, 12-276 months). Clinical onset was mild or subclinical in 72% of patients and asymptomatic in 12.2%. At diagnosis, the Hennes's median score was 6 (range, 3-8). Complications were seen in 44 (53.6%) patients, 42 (51.2%) with liver-related complications and 9 (10.9%) without liver-related complications. Cirrhosis was present at diagnosis in 32 (39%) patients. Cirrhosis was subsequently diagnosed in the other 28 patients who were not cirrhotic at diagnosis, over a median follow-up of 12 (IQR, 2-84) months. During follow-up, 6 patients died (7.3%). Cumulative survival at 5 and 10 years was 98.4% and 89%, respectively. A complete biochemical response was achieved in 79% of patients in a mean (SD) of 11.7 (11.6) months. Side effects due to treatment were reported in 76 (92.7%) patients, and no pretreatment factors were found to predict treatment response. CONCLUSIONS These Cuban patients with AIH had acceptable disease remission rate and a prompt treatment response. Although most patients had advanced-stage liver disease at diagnosis or developed during follow-up, the cumulative survival rate was high when patients were receiving and complying with treatment.
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Affiliation(s)
| | | | | | - Hector Vega Sánchez
- Department of Immunology, National Institute of Gastroenterology, Havana, Cuba
| | | | - Robert G. Gish
- Las Vegas, Nevada Hepatitis B Foundation, University of Nevada, Las Vegas, Las Vegas, Nevada
| | | | - Zaily Dorta Guridi
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
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11
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Tapper EB, Aberasturi D, Zhao Z, Hsu CY, Parkih ND. Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis. Aliment Pharmacol Ther 2020; 51:1397-1405. [PMID: 32363684 PMCID: PMC7266029 DOI: 10.1111/apt.15749] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/03/2020] [Accepted: 04/03/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatic encephalopathy is a devastating complication of cirrhosis. AIM To describe the outcomes after developing hepatic encephalopathy among contemporary, aging patients. METHODS We examined data for a 20% random sample of United States Medicare enrolees with cirrhosis and Part D prescription coverage from 2008 to 2014. Among 49 164 persons with hepatic encephalopathy, we evaluated the associations with transplant-free survival using Cox proportional hazard models with time-varying covariates (hazard ratios, HR) and incidence rate ratios (IRR) for healthcare utilisation measured in hospital-days and 30-day readmissions per person-year. We validated our findings in an external cohort of 2184 privately insured patients with complete laboratory values. RESULTS Hepatic encephalopathy was associated with median survivals of 0.95 and 2.5 years for those ≥65 or <65 years old and 1.1 versus 3.9 years for those with and without ascites. Non-alcoholic fatty-liver disease posed the highest adjusted risk of death among aetiologies, HR 1.07 95% CI (1.02, 1.12). Both gastroenterology consultation and rifaximin utilisation were associated with lower mortality, respective adjusted-HR 0.73 95% CI (0.67, 0.80) and 0.40 95% CI (0.39, 0.42). Thirty-day readmissions were fewer for patients seen by gastroenterologists (0.71 95% CI [0.57-0.88]) and taking rifaximin (0.18 95% CI [0.08-0.40]). Lactulose alone was associated with fewer hospital-days, IRR 0.31 95% CI (0.30-0.32), than rifaximin alone, 0.49 95% CI (0.45-0.53), but the optimal therapy combination was lactulose/rifaximin, IRR 0.28 95% CI (0.27-0.30). These findings were validated in the privately insured cohort adjusting for model for endstage liver disease-sodium score and serum albumin. CONCLUSIONS Hepatic encephalopathy remains morbid and associated with poor outcomes among contemporary patients. Gastroenterology consultation and combination lactulose-rifaximin are both associated with improved outcomes. These data inform the development of care coordination efforts for subjects with cirrhosis.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor
| | | | - Zhe Zhao
- Department of Biostatistics, University of Michigan
| | - Chia-Yang Hsu
- Division of Gastroenterology and Hepatology, University of Michigan
| | - Neehar D. Parkih
- Division of Gastroenterology and Hepatology, University of Michigan
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12
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Tapper EB, Henderson JB, Parikh ND, Ioannou GN, Lok AS. Incidence of and Risk Factors for Hepatic Encephalopathy in a Population-Based Cohort of Americans With Cirrhosis. Hepatol Commun 2019; 3:1510-1519. [PMID: 31701074 PMCID: PMC6824059 DOI: 10.1002/hep4.1425] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022] Open
Abstract
Hepatic encephalopathy (HE) is a devastating complication of cirrhosis. Data are limited regarding the incidence of and risk factors for HE among contemporary patients in the context of the shifting epidemiology of cirrhosis. We examined a 20% random sample of U.S. Medicare enrollees with cirrhosis and Part D prescription coverage from 2008 to 2014. We modelled incident HE using demographic, clinical, and pharmacologic data. Risk factors for HE were evaluated, including demographics/socioeconomics, cirrhosis etiology, severity of liver disease, and pharmacotherapy, along with gastroenterology consultation, as time-varying covariates. Among 166,192 Medicare enrollees with cirrhosis followed for 5.25 (interquartile range [IQR], 2.00-7.00) years, the overall incidence of HE was 11.6 per 100 patient-years. The cohort's median age was 65 years (IQR, 57-72), 31% had alcohol-related cirrhosis, and 49% had likely nonalcoholic fatty liver disease cirrhosis. The two strongest associations with HE were alcohol-related cirrhosis (adjusted hazard ratio [AHR], 1.44; 95% confidence interval [CI], 1.40, 1.47, relative to nonalcoholic nonviral cirrhosis) and the presence of portal hypertension (AHR, 3.42; 95% CI, 3.34, 3.50). Adjusting for confounders, benzodiazepines (AHR, 1.24; 95% CI, 1.21, 1.27), gamma aminobutyric acid (GABA)ergics (AHR, 1.17; 95% CI, 1.14, 1.21), opioids (AHR, 1.24; 95% CI, 1.21, 1.27), and proton pump inhibitors (PPIs) (AHR, 1.41; 95% CI, 1.38, 1.45) were all associated with incident HE. Only benzodiazepines, however, were associated with the risk of hospitalization with HE (incidence-rate ratio, 1.23; 95% CI, 1.20, 1.26). Conclusion: Novel data regarding the risk of HE for contemporary patients with cirrhosis are provided. The incidence of HE in an older population of Americans with cirrhosis is high, particularly among those with alcohol-related cirrhosis and portal hypertension. Several medication classes, namely PPIs, opiates, GABAergics, and benzodiazepines, represent potentially modifiable risk factors for HE.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
- Gastroenterology SectionVA Ann Arbor Healthcare SystemAnn ArborMI
| | - James B. Henderson
- Center for Statistical Consultation and ResearchUniversity of MichiganAnn ArborMI
| | - Neehar D. Parikh
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
- Gastroenterology SectionVA Ann Arbor Healthcare SystemAnn ArborMI
| | - George N. Ioannou
- Division of GastroenterologyDepartment of MedicineVeterans Affairs Puget Sound Healthcare System and University of WashingtonSeattleWA
| | - Anna S. Lok
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMI
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13
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Elfayoumy KN, Berengy MS, Emran T. Insulin/high-density lipoprotein cholesterol ratio: A newly-discovered predictor of esophageal varices in patients with hepatitis C virus-related cirrhosis in the absence of diabetes mellitus. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:155-162. [PMID: 30541737 DOI: 10.5152/tjg.2018.18237] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND/AIMS Insulin resistance (IR) is closely linked with chronic hepatitis C virus (HCV) and its complications, particularly hepatic fibrosis. The aim of the present study was to investigate some biochemical markers that are potentially related to IR as predictors of esophageal varices (EV) in patients with compensated HCV cirrhosis who do not have diabetes or metabolic syndrome. MATERIALS AND METHODS One hundred subjects without diabetes with compensated HCV-related cirrhosis who did not fulfill the diagnostic criteria of metabolic syndrome were subjected to clinical, laboratory, ultrasonographic, and endoscopic assessments. RESULTS EV were evident in 73 patients with lower platelet counts and high-density lipoprotein cholesterol (HDL-C) levels. On the contrary, the fasting values of both insulin and glucose, the homeostatic model assessment for insulin resistance (HOMA-IR) score, and the bipolar diameter of the spleen of patients with EV were higher than those of other patients who were varices-free. Multivariate analysis confirmed insulin/HDL-C ratio (P=0.01) and HOMA-IR score (P=0.039) as predictors for the presence of varices. The best cut-off values above which the risk of the latter occurrence increased were 0.147 (sensitivity 89%) and 2.24 (sensitivity 72.6%) for both predictors, respectively. CONCLUSION The present study recorded two valid predictors of HCV-related EV: HOMA-IR score and insulin/HDL-C ratio. The latter is more sensitive and is likely more convenient in the case of individuals without diabetes. The validity of two IR-related predictors in the absence of metabolic syndrome confirmed the suggestion that the mechanism of IR-related HCV is different from that of the traditional metabolic syndrome.
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Affiliation(s)
- Khaled Nagy Elfayoumy
- Department of Internal Medicine, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
| | - Mahmoud Saad Berengy
- Department of Internal Medicine, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
| | - Tarek Emran
- Department Clinical Pathology, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
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14
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Tapper EB. Predicting Overt Hepatic Encephalopathy for the Population With Cirrhosis. Hepatology 2019; 70:403-409. [PMID: 30703852 PMCID: PMC6597301 DOI: 10.1002/hep.30533] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Accepted: 01/25/2019] [Indexed: 12/20/2022]
Abstract
Hepatic encephalopathy (HE) is associated with poor quality of life, sharply increased mortality, repeated hospitalizations, falls, and motor vehicle accidents. HE manifests with a dynamic spectrum of severity. Overt HE is clinically obvious disorientation, even coma. Although multiple strategies are available to characterize early-stage HE, data are limited that validate these methods in predicting overt HE, many are impractical in clinical practice, and test cutoffs relevant to the average patient clinicians manage are lacking. To accurately and efficiently classify the risk of overt HE in the population with cirrhosis, novel strategies may be needed. Herein, we review the potential competing strategies for the prediction of overt HE. Conclusion: We propose refining diagnostic cutoffs for tests that are designed to define early HE, using overt HE as a gold standard and expanding prediction tools by using measures of components from the risk pathway for HE.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor
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15
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Nilsson E, Anderson H, Sargenti K, Lindgren S, Prytz H. Clinical course and mortality by etiology of liver cirrhosis in Sweden: a population based, long-term follow-up study of 1317 patients. Aliment Pharmacol Ther 2019; 49:1421-1430. [PMID: 30957910 DOI: 10.1111/apt.15255] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/21/2019] [Accepted: 03/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy. AIM To compare the clinical course, patterns of survival and causes of death by etiology during long-term follow-up in a large population-based cohort of patients with incident cirrhosis. METHODS We used population-based medical registries for a cohort study of patients with liver cirrhosis diagnosed January 2001 to December 2010, in the Scania region of Sweden. Medical records were reviewed. Patients were classified according to etiology and clinical parameters were registered. Patients were followed until December 2017. RESULTS The cohort comprised 1317 patients, 631 were decompensated at diagnosis and 387 decompensated during follow-up. The cumulative 10-year incidence of decompensation, with death and transplantation as competing risks, was 89% in alcoholic cirrhosis, 58% in hepatitis C and 75% in cryptogenic cirrhosis. The lowest 10-year transplantation-free survival rates were found in cryptogenic cirrhosis (11%), alcohol-related cirrhosis (18%) and alcohol combined with hepatitis C (12%). Autoimmune hepatitis cirrhosis showed the best 10-year survival (53%) and hepatitis C, non-alcoholic steatohepatitis, primary biliary cholangitis, and primary sclerosing cholangitis and other causes averaged 30%. Decompensation at diagnosis was an important predictor for death in all etiologies apart from alcoholic cirrhosis. 991 patients died and 91 were transplanted. CONCLUSION Our results show that the clinical course and survival in cirrhosis differ considerably by both etiology and state at diagnosis.
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Affiliation(s)
- Emma Nilsson
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Gastroenterology Clinic, Skåne University Hospital, Lund University, Lund, Sweden
| | - Harald Anderson
- Department of Clinical Sciences, Cancer Epidemiology, Lund University, Lund, Sweden
| | - Konstantina Sargenti
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Gastroenterology Clinic, Skåne University Hospital, Lund University, Lund, Sweden
| | - Stefan Lindgren
- Gastroenterology Clinic, Skåne University Hospital, Lund University, Lund, Sweden
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Hanne Prytz
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Gastroenterology Clinic, Skåne University Hospital, Lund University, Lund, Sweden
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16
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D’Amico G, Perricone G. Prediction of Decompensation in Patients with Compensated Cirrhosis: Does Etiology Matter? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00473-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
PURPOSE OF REVIEW We sought to review the contemporary epidemiology of cirrhosis, focusing on the relative burden of the most common chronic liver diseases. RECENT FINDINGS The key findings in the review highlight the increasing prevalence and impact of alcohol-related liver disease, particularly among young people, and the epidemic of nonalcoholic fatty liver commensurate with rising rates of obesity. We also contrast recent advances in the care of persons with hepatitis C with the lamentable rise in new infections associated with intravenous drug use. Finally, we highlight the impact of both conventional complications of cirrhosis (namely hepatic encephalopathy) but also the host of patient-reported outcomes adversely impacted by the symptoms of cirrhosis. Cirrhosis is associated with an expanding footprint in contemporary public health. In order to improve global outcomes, we must not only focus on the identifying and treating persons with viral hepatitis but also preventing the rise of alcohol-related liver disease and nonalcoholic fatty liver disease while attending to the urgent patient-centered needs posed by the symptoms of cirrhosis.
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Affiliation(s)
- Jad A Baki
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA. .,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
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18
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Shalaby H, El-Meghawry ES, Al-Azhary S, Elfayoumy KN, Zeid ESA. Portal hypertensive colopathy in Egyptian cirrhotic patients: an endoscopic study. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_42_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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19
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Mensa FJ, Lovell S, Pilot-Matias T, Liu W. Glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection. Future Microbiol 2018; 14:89-110. [PMID: 30499343 DOI: 10.2217/fmb-2018-0233] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
In recent years, management of chronic hepatitis C virus (HCV) infection has been revolutionized by the availability of oral direct-acting antivirals (DAAs), which have significantly better efficacy and safety profiles than interferon-containing regimens. Simple, short-duration DAA therapies will facilitate expansion of HCV treatment to nonspecialist providers, which will be vital to achieve the WHO target of eliminating chronic HCV as a major public health threat by 2030. Coformulated glecaprevir/pibrentasvir is the only 8-week, pan-genotypic, 2-DAA regimen recommended by international guidelines as a first-line regimen in treatment-naive, noncirrhotic HCV genotype 1-6 patients. This review provides a comprehensive summary of the pharmacodynamic and pharmacokinetic parameters, efficacy, safety and place in the HCV treatment paradigm for glecaprevir/pibrentasvir.
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Affiliation(s)
- Federico J Mensa
- Department of Clinical Development Infectious Diseases, AbbVie Inc., North Chicago, IL 60064, USA
| | - Sandra Lovell
- Department of Statistics, AbbVie Inc., North Chicago, IL 60064, USA
| | - Tami Pilot-Matias
- Department of Clinical Virology, AbbVie Inc., North Chicago, IL 60064, USA
| | - Wei Liu
- Department of Pharmacokinetics, AbbVie Inc., North Chicago, IL 60064, USA
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20
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Tapper EB, Parikh ND, Sengupta N, Mellinger J, Ratz D, Lok ASF, Su GL. A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis. Hepatology 2018; 68:1498-1507. [PMID: 29091289 DOI: 10.1002/hep.29628] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 09/18/2017] [Accepted: 10/30/2017] [Indexed: 12/25/2022]
Abstract
UNLABELLED Over 40% of patients with cirrhosis will develop hepatic encephalopathy (HE). HE is associated with decreased survival, falls, motor vehicle accidents, and frequent hospitalization. Accordingly, we aimed to develop a tool to risk-stratify patients for HE development. We studied a population-based cohort of all patients with cirrhosis without baseline HE (n = 1,979) from the Veterans Administration from Michigan, Indiana, and Ohio (January 1, 2005-December 31, 2010) using demographic, clinical, laboratory, and pharmacy data. The primary outcome was the development of HE. Risk scores were constructed with both baseline and longitudinal data (annually updated parameters) and validated using bootstrapping. The cohort had a mean age of 58.0 ± 8.3 years, 36% had hepatitis C, and 17% had ascites. Opiates, benzodiazepines, statins, and nonselective beta-blockers were taken at baseline by 24%, 13%, 17%, and 12%, respectively. Overall, 863 (43.7%) developed HE within 5 years. In multivariable models, risk factors (hazard ratio, 95% confidence interval) for HE included higher bilirubin (1.07, 1.05-1.09) and nonselective beta-blocker use (1.34, 1.09-1.64), while higher albumin (0.54, 0.48-0.59) and statin use (0.80, 0.65-0.98) were protective. Other clinical factors, including opiate and benzodiazepine use, were not predictive. The areas under the receiver operating characteristics curve for HE using the four significant variables in baseline and longitudinal models were 0.68 (0.66-0.70) and 0.73 (0.71-0.75), respectively. Model effects were validated and converted into a risk score. A score ≤0 in our longitudinal model assigns a 6% 1-year probability of HE, while a score >20 assigns a 38% 1-year risk. CONCLUSION Patients with cirrhosis can be stratified by a simple risk score for HE that accounts for changing clinical data; our data also highlight a role for statins in reducing cirrhosis complications including HE. (Hepatology 2017).
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
| | - Neil Sengupta
- Section of Gastroenterology, University of Chicago, Chicago, IL
| | | | - David Ratz
- VA Center for Clinical Management Research, Ann Arbor, MI
| | - Anna S-F Lok
- Division of Gastroenterology and Hepatology, University of Michigan
| | - Grace L Su
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
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Mazzarelli C, Prentice WM, Heneghan MA, Belli LS, Agarwal K, Cannon MD. Palliative care in end-stage liver disease: Time to do better? Liver Transpl 2018; 24:961-968. [PMID: 29729119 DOI: 10.1002/lt.25193] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 03/28/2018] [Accepted: 04/08/2018] [Indexed: 12/12/2022]
Abstract
Optimal involvement of palliative care (PC) services in the management of patients with decompensated cirrhosis and end-stage liver disease (ESLD) is limited. This may result from both ignorance and the failure to recognize the spectrum and unpredictability of the underlying liver condition. Palliative care is a branch of medicine that focuses on quality of life (QoL) by optimizing symptom management and providing psychosocial, spiritual, and practical support for both patients and their caregivers. Historically, palliative care has been underutilized for patients with decompensated liver disease. This review provides an evidence-based analysis of the benefits of the integration of palliative care into the management of patients with ESLD. Liver Transplantation 24 961-968 2018 AASLD.
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Affiliation(s)
- Chiara Mazzarelli
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.,Hepatology and Gastroenterology Unit, ASST Ospedale Niguarda, Milan, Italy
| | - Wendy M Prentice
- Cicely Saunders Institute, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Luca S Belli
- Hepatology and Gastroenterology Unit, ASST Ospedale Niguarda, Milan, Italy
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Mary D Cannon
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
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22
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Cacciola I, Filomia R, Alibrandi A, Franzè MS, Caccamo G, Maimone S, Saitta C, Saffioti F, Squadrito G, Raimondo G. Hypergammaglobulinemia is a strong predictor of disease progression, hepatocellular carcinoma, and death in patients with compensated cirrhosis. Liver Int 2018; 38:1220-1229. [PMID: 29194934 DOI: 10.1111/liv.13649] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Accepted: 11/19/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long-lasting follow-up. METHODS Two hundred and seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63 years, range 34-81) were analysed. All patients were followed up for a median time of 96 months (range 21-144) through periodically performed clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic examinations. RESULTS During the follow-up, 97 individuals (36%) were clinically stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%) progressed towards C-P class B/C without developing cancer. One hundred and thirty-one patients (48%) died or underwent liver transplantation. Multivariate regression analysis showed that clinical stability was significantly associated with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8 gr/dL (P = .01). HCC development was significantly associated with younger age (P = .01) and serum gamma globulin values ≥1.8 gr/dL (P < .001). C-P score progression was associated with oesophageal varices (P < .001), lower serum albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P = .02). Death was associated with younger age (P < .001) and hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan-Meier's survival test confirmed that gammaglobulinemia ≥1.8 g/dL was a significant predictor of death (P < .02, and P < .01 respectively). CONCLUSIONS Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk of disease progression, HCC development and death.
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Affiliation(s)
- Irene Cacciola
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Roberto Filomia
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Angela Alibrandi
- Department of Economics, Unit of Statistical and Mathematical Sciences, University of Messina, Messina, Italy
| | - Maria Stella Franzè
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Gaia Caccamo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Carlo Saitta
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Francesca Saffioti
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giovanni Squadrito
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
- Department of Human Pathology, University of Messina, Messina, Italy
| | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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23
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Chen S, Peng Z, Wei M, Liu W, Dai Z, Wang H, Mei J, Cheong M, Zhang H, Kuang M. Sorafenib versus Transarterial chemoembolization for advanced-stage hepatocellular carcinoma: a cost-effectiveness analysis. BMC Cancer 2018; 18:392. [PMID: 29621988 PMCID: PMC5887167 DOI: 10.1186/s12885-018-4308-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Accepted: 03/26/2018] [Indexed: 12/14/2022] Open
Abstract
Background Sorafenib and transarterial chemoembolization (TACE) might both provide survival benefit for advanced hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. We aimed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC. Methods A Markov model was constructed in a hypothetical cohort of patients aged 60 years with advanced HCC and Child-Pugh A/B cirrhosis over a 2-year time frame. Three strategies (full or dose-adjusted sorafenib and TACE) were compared in two cost settings: China and the USA. Transition probabilities, utility and costs were extracted from systematic review of 27 articles. Sensitivity analysis and Monte Carlo analysis were conducted. Results Full and dose-adjusted sorafenib respectively produced 0.435 and 0.482 quality-adjusted life years (QALYs) while TACE produced 0.375 QALYs. The incremental cost-effectiveness ratio (ICER) of full-dose sorafenib versus TACE was $101,028.83/QALY in China whereas full-dose sorafenib is a dominant strategy (ICER of -$1,014,507.20/ QALY) compared with TACE in the USA. Compared to full-dose sorafenib, dose-adjusted sorafenib was the dominant strategy with the negative ICERs in both China (−$132,238.94/QALY) and the USA (−$230,058.09/QALY). However, dose-adjusted sorafenib is not available currently, so full-dose sorafenib should be compared with TACE. As the acceptability curves shown, full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries. Specifically, full-dose sorafenib was the cost-effective treatment compared with TACE if a WTP was set above $21,670 in the USA, whereas in China, TACE could be more favorable than full-dose sorafenib if a WTP was set below $10,473. Conclusions Dose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients. However, when confining the comparisons between full-dose sorafenib and TACE, full-dose sorafenib was cost-effective for these patients, under the accepted thresholds of WTP. Electronic supplementary material The online version of this article (10.1186/s12885-018-4308-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shuling Chen
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhenwei Peng
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.,Clinical Research Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Mengchao Wei
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Weifeng Liu
- Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Zihao Dai
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Haibo Wang
- Clinical Research Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Jie Mei
- Clinical Research Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Mingfong Cheong
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Hanmei Zhang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Ming Kuang
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. .,Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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24
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D'Amico G, Morabito A, D'Amico M, Pasta L, Malizia G, Rebora P, Valsecchi MG. Clinical states of cirrhosis and competing risks. J Hepatol 2018; 68:563-576. [PMID: 29111320 DOI: 10.1016/j.jhep.2017.10.020] [Citation(s) in RCA: 360] [Impact Index Per Article: 51.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Revised: 09/26/2017] [Accepted: 10/24/2017] [Indexed: 12/12/2022]
Abstract
The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of these disease states prompted the concept of clinical states of cirrhosis. A multistate approach has been considered to describe the clinical course of the disease. Such an approach requires the assessment of the probabilities of different outcomes in each state, which compete with each other to occur first and mark the transition towards a different state. This requires the use of competing risks analysis, since the traditional Kaplan-Meier analysis should only be used in two-state settings. Accounting for competing risks also has implications for prognosis and treatment efficacy research. The aim of this review is to summarise relevant clinical states and to show examples of competing risks analysis in multistate models of cirrhosis.
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Affiliation(s)
- Gennaro D'Amico
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy.
| | | | - Mario D'Amico
- Radiology Department, Università di Palermo, Palermo, Italy
| | - Linda Pasta
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy
| | - Giuseppe Malizia
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy
| | - Paola Rebora
- Dipartimento di Medicina e Chirurgia Università di Milano-Bicocca, Milano, Italy
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25
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Wong JCT, Chan HLY, Tse YK, Yip TCF, Wong VWS, Wong GLH. Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis. Aliment Pharmacol Ther 2017; 46:1001-1010. [PMID: 28940673 DOI: 10.1111/apt.14341] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 06/27/2017] [Accepted: 09/05/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND Decompensated liver disease due to portal hypertension leads to significant morbidity and mortality. Statins can modulate intrahepatic vascular tone, but the clinical significance remains uncertain. AIM To determine the effects of statin use on the risk of liver decompensation and death among patients with chronic viral hepatitis. METHODS We conducted a population wide cohort study using a hospital based database from the Hong Kong Hospital Authority. Adults with chronic viral hepatitis without prior liver decompensation were identified from 2000 to 2012 by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes. Statin use was defined as a cumulative defined daily dose of >28. Landmark analysis was used to overcome immortal time bias. Propensity score weighting was further performed to minimise baseline confounders. Primary outcome was a composite of portal hypertension related liver decompensation events, with adjustment for death as a competing risk. RESULTS A total of 69 184 patients with chronic viral hepatitis (2053 statin users and 67 131 statin non-users) were identified for the 2-year landmark analysis. After propensity score weighting of 23 baseline covariates, statin use was associated with a significant reduction in composite liver decompensation events (HR: 0.55; 95% CI: 0.36-0.83; P = .005), ascites (HR: 0.57; 95% CI: 0.36-0.92; P = .02), and a dose-dependent decrease in death (HR: 0.87; 95% CI: 0.76-0.99; P = .035) relative to no statin use. CONCLUSIONS Patients with chronic viral hepatitis who used statins have a reduced risk of liver decompensation and death compared to non-users in this propensity score weighted landmark analysis.
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Affiliation(s)
- J C-T Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - H L-Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Y-K Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - T C-F Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - V W-S Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - G L-H Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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26
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Voican CS, Louvet A, Trabut JB, Njiké-Nakseu M, Dharancy S, Sanchez A, Corouge M, Lamouri K, Lebrun A, Balian A, Prévot S, Lachgar M, Maitre S, Agostini H, Mathurin P, Perlemuter G, Naveau S. Transient elastography alone and in combination with FibroTest ® for the diagnosis of hepatic fibrosis in alcoholic liver disease. Liver Int 2017; 37:1697-1705. [PMID: 28387018 DOI: 10.1111/liv.13440] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 03/26/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The reliability of transient elastography (TE) to assess liver fibrosis is insufficiently validated in alcoholic liver disease (ALD). We aimed to validate the diagnostic utility of TE for liver fibrosis in patients with excessive alcohol consumption and evaluate whether Fibrotest® adds diagnostic value relative to or in combination with TE. METHODS We conducted a multicentre prospective study on a total of 217 heavy drinkers with high serum aminotransferase levels. Patients underwent liver biopsy, TE, Fibrotest® , PGAA, APRI, FIB-4 and FORNS. The overall diagnostic performance was evaluated by the area under the receiver operating characteristic (AUROC) curves and Obuchowski measures. RESULTS TE values correlated with fibrosis stage (r=.73; P<.0001) and steatosis stage (r=.19; P<.01). Patients with alcoholic hepatitis had higher TE values than those without alcoholic hepatitis (P<.0001). In an multivariate analysis, fibrosis stage and the presence of alcoholic hepatitis were the only parameters that correlated with liver stiffness. For the diagnosis of advanced fibrosis (F≥3), the AUROC curves were 0.90, 0.85, 0.83, 0.91 and 0.90 for TE, Fibrotest® , PGAA and associations TE-Fibrotest® , TE-PGAA respectively. For the diagnosis of cirrhosis, the AUROC curves were 0.93, 0.88, 0.89, 0.94 and 0.95 respectively. The Obuchowski measures for the diagnosis of fibrosis were 0.94, 0.92, 0.91, 0.95 and 0.94 respectively. The performance of TE was not significantly different than those of Fibrotest® , PGAA and combinations TE-Fibrotest® , TE-PGAA. CONCLUSIONS TE has excellent diagnostic value for liver fibrosis in alcoholic liver disease. The combined use of TE-Fibrotest® or TE-PGAA does not improve the performance of TE.
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Affiliation(s)
- Cosmin Sebastian Voican
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France.,INSERM, U996, Labex Lermit, IPSIT, Clamart, France.,Faculté de médecine Paris-Sud, Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Kremlin-Bicêtre, France
| | - Alexandre Louvet
- Service des Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Lille, France.,Unité INSERM U995 Lille, Lille, France
| | - Jean-Baptiste Trabut
- AP-HP, Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hépatologie et d'Addictologie, Paris, France
| | - Micheline Njiké-Nakseu
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France
| | - Sébastien Dharancy
- Service des Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Lille, France.,Unité INSERM U995 Lille, Lille, France
| | - Andrea Sanchez
- APHP, Groupe Hospitalier Cochin Saint-Vincent de Paul, Service d'Anatomo-pathologie, Paris, France
| | - Marion Corouge
- AP-HP, Département d'Hépatologie, Groupe Hospitalier Cochin Saint-Vincent de Paul, Paris, France
| | - Karima Lamouri
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France
| | - Amandine Lebrun
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France.,Faculté de médecine Paris-Sud, Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Kremlin-Bicêtre, France
| | - Axel Balian
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France
| | - Sophie Prévot
- Faculté de médecine Paris-Sud, Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Kremlin-Bicêtre, France.,AP-HP, Service d'Anatomie pathologique, Hôpital Antoine Béclère, Clamart, France
| | - Mounia Lachgar
- AP-HP, Service de Biochimie-Hormonologie, Hôpital Antoine Béclère, Clamart, France
| | - Sophie Maitre
- AP-HP, Service de Radiologie, Hôpital Antoine Béclère, Clamart, France
| | - Hélène Agostini
- AP-HP, Unité de recherche clinique Paris-Sud, Hôpital Bicêtre, Kremlin-Bicêtre, France
| | - Philippe Mathurin
- Service des Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Lille, France.,Unité INSERM U995 Lille, Lille, France
| | - Gabriel Perlemuter
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France.,INSERM, U996, Labex Lermit, IPSIT, Clamart, France.,Faculté de médecine Paris-Sud, Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Kremlin-Bicêtre, France
| | - Sylvie Naveau
- AP-HP, Service d'hépato-gastroentérologie et nutrition, Hôpital Antoine Béclère, Clamart, France.,INSERM, U996, Labex Lermit, IPSIT, Clamart, France.,Faculté de médecine Paris-Sud, Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Kremlin-Bicêtre, France
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27
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Dimitrova M, Pavlov K, Mitov K, Genov J, Petrova GI. Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria. Front Med (Lausanne) 2017; 4:125. [PMID: 28824914 PMCID: PMC5545579 DOI: 10.3389/fmed.2017.00125] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 07/17/2017] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014). METHODS It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing. RESULTS 76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score. CONCLUSION HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.
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Affiliation(s)
| | - Kaloyan Pavlov
- University Hospital "Queen Joanna-ISUL", Sofia, Bulgaria
| | | | - Jordan Genov
- University Hospital "Queen Joanna-ISUL", Sofia, Bulgaria
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28
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New concepts on the clinical course and stratification of compensated and decompensated cirrhosis. Hepatol Int 2017; 12:34-43. [DOI: 10.1007/s12072-017-9808-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 06/08/2017] [Indexed: 12/14/2022]
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29
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Nowicki TK, Markiet K, Szurowska E. Diagnostic Imaging of Hepatocellular Carcinoma - A Pictorial Essay. Curr Med Imaging 2017; 13:140-153. [PMID: 28553196 PMCID: PMC5427776 DOI: 10.2174/1573405612666160720123748] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Revised: 07/12/2016] [Accepted: 07/13/2016] [Indexed: 12/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which develops mostly in the setting of chronic liver disease. European Association for the Study of the Liver (EASL) and European Organization for Research and Treatment of Cancer (EORTC) prepared guidelines for screening, follow-up and diagnosis of HCC to facilitate decision making and optimize both diagnostic and therapeutic protocols. The review briefly describes etiology, epidemiology and histopathology of HCC and presents EASL-EORTC guidelines for surveillance and diagnosis of HCC. Target population and screening algorithm is presented in the surveillance section. Ultrasound imaging of HCC and the role of contrast enhanced ultrasound are described as well as the value of laboratory tests in screening. Further, radiological features of HCC in multiphase CT and dynamic contrast enhanced MRI and diagnostic criteria are presented. Additionally, the advantages of advanced techniques in MRI such as diffusion weighed imaging and the use of hepatocyte-specific contrast agents are discussed. Lastly, the EASL-EORTC guidelines are compared with the guidelines of the American Association for the Study of Liver Diseases and the Japan Society of Hepatology. Also LI-RADS and the Barcelona Clinic Liver Cancer classification are mentioned. In the near future, due to the ongoing advances in imaging a revision of the guidelines may be expected.
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Affiliation(s)
- Tomasz K. Nowicki
- 2 Department of Radiology, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdansk, Poland
| | - Karolina Markiet
- 2 Department of Radiology, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdansk, Poland
| | - Edyta Szurowska
- 2 Department of Radiology, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdansk, Poland
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30
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Rinaldi L, Nascimbeni F, Giordano M, Masetti C, Guerrera B, Amelia A, Fascione MC, Ballestri S, Romagnoli D, Zampino R, Nevola R, Baldelli E, Iuliano N, Rosato V, Lonardo A, Adinolfi LE. Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis. World J Gastroenterol 2017; 23:1458-1468. [PMID: 28293093 PMCID: PMC5330831 DOI: 10.3748/wjg.v23.i8.1458] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 11/21/2016] [Accepted: 01/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis. METHODS A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression. RESULTS At the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A. CONCLUSION Undiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.
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Kim KA. [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 67:123-6. [PMID: 26996180 DOI: 10.4166/kjg.2016.67.3.123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment.
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Affiliation(s)
- Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
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Atla PR, Sheikh MY, Gill F, Kundu R, Choudhury J. Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis. Ann Gastroenterol 2016; 29:515-520. [PMID: 27708520 PMCID: PMC5049561 DOI: 10.20524/aog.2016.0072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Accepted: 06/23/2016] [Indexed: 12/23/2022] Open
Abstract
Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.
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Affiliation(s)
- Pradeep R Atla
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Muhammad Y Sheikh
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Firdose Gill
- Department of Medicine, Kaiser Permanente Fresno Medical Center (Firdose Gill), Fresno, California, USA
| | - Rabindra Kundu
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Jayanta Choudhury
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
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Maor Y, Malnick SDH, Melzer E, Leshno M. Treatment of Chronic Hepatitis C in the Aged - Does It Impact Life Expectancy? A Decision Analysis. PLoS One 2016; 11:e0157832. [PMID: 27410963 PMCID: PMC4943667 DOI: 10.1371/journal.pone.0157832] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 06/04/2016] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND AND AIMS Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naïve patients with HCV as a function of patient's age and fibrosis stage. METHODS We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. RESULTS Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. CONCLUSIONS There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis.
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Affiliation(s)
- Yaakov Maor
- Institute of Gastroenterology and Hepatology, Kaplan Medical Center, Rehovot, Israel
| | - Stephen D. H. Malnick
- Institute of Gastroenterology and Hepatology, Kaplan Medical Center, Rehovot, Israel
- Department of Internal Medicine C, Kaplan Medical Center, Rehovot, Israel
| | - Ehud Melzer
- Institute of Gastroenterology and Hepatology, Kaplan Medical Center, Rehovot, Israel
| | - Moshe Leshno
- Faculty of Management and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Di Marco V, Calvaruso V, Ferraro D, Bavetta MG, Cabibbo G, Conte E, Cammà C, Grimaudo S, Pipitone RM, Simone F, Peralta S, Arini A, Craxì A. Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension. Gastroenterology 2016; 151:130-139.e2. [PMID: 27039970 DOI: 10.1053/j.gastro.2016.03.036] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Revised: 02/22/2016] [Accepted: 03/15/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Clearance of hepatitis C virus (HCV) via antiviral treatment changes the course of liver disease. We evaluated the benefit of sustained virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and with (stage 2) esophageal varices (EV). METHODS We performed a prospective cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1 and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June 2001 through December 2009 at the University of Palermo, Italy and followed for a median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to identify variables associated with appearance or progression of EVs, development of hepatocellular carcinoma (HCC), liver decompensation, and overall survival. RESULTS In the intention-to-treat analysis, 67 patients with stage 1 disease (30.7%) and 41 patients with stage 2 disease (18.1%) achieved an SVR (P = .003). Patients with stage 1 disease and an SVR were less likely to develop EVs than stage 1 patients without an SVR (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11-0.48; P < .001). However, SVR did not affect whether patients with stage 2 disease developed further EVs (HR, 1.58; 95% CI, 0.33-1.03; P = .07, by log-rank test). An SVR was associated with lower risk for HCC (HR, 0.25; 95% CI, 0.12-0.55; P < .001). Patients with stage 2 disease, regardless of SVR, were at greater risk than patients with stage 1 disease for liver decompensation (HR, 2.82; 95% CI, 1.73-4.59; P < .001) or death (HR, 1.77; 95% CI, 1.12-2.80; P = .015). A lower proportion of patients with stage 1 disease and an SVR died from HCC (2.9%), compared with those without an SVR (11.9%) (P = .03) or developed liver decompensation (none vs 7.1% without an SVR; P = .009). A lower proportion of patients with stage 2 disease and an SVR died from causes secondary to HCC (2.0%) compared with those without an SVR (18.4%) (P = .003). Death from causes secondary to liver decompensation did not differ significantly between patients with stage 2 disease with or without an SVR (12.1% vs 25.4%; P = .15). CONCLUSIONS In a prospective study of 444 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death, regardless of whether the patients had EVs.
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Affiliation(s)
- Vito Di Marco
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy.
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Donatella Ferraro
- Sezione di Microbiologia, Dipartimento di Scienze per la Promozione della Salute e Materno-Infantile G. D'Alessandro, University of Palermo, Italy
| | - Maria Grazia Bavetta
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Giuseppe Cabibbo
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Elisabetta Conte
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Stefania Grimaudo
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Rosaria Maria Pipitone
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Fabio Simone
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Sergio Peralta
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Andrea Arini
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy
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D'Ambrosio R, Colombo M. Should surveillance for liver cancer be modified in hepatitis C patients after treatment-related cirrhosis regression? Liver Int 2016; 36:783-90. [PMID: 26936383 DOI: 10.1111/liv.13106] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 02/24/2016] [Indexed: 02/13/2023]
Abstract
Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long-standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non-viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well-compensated liver disease who in fact were interferon able. This may not be the case for most real-life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no-return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non-invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non-viraemic patients, and this prompts to follow international societies' recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.
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Affiliation(s)
- Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan, Italy
| | - Massimo Colombo
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan, Italy
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Choi JW, Lee JS, Paik WH, Song TJ, Kim JW, Bae WK, Kim KA, Kim JG. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C. Clin Mol Hepatol 2016; 22:168-71. [PMID: 27044768 PMCID: PMC4825169 DOI: 10.3350/cmh.2016.22.1.168] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 09/17/2014] [Accepted: 10/21/2014] [Indexed: 12/18/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.
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Affiliation(s)
- Jong Wook Choi
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - June Sung Lee
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Tae Jun Song
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Jung Wook Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Won Ki Bae
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Jung Gon Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2016; 22:76-139. [PMID: 27044763 PMCID: PMC4825161 DOI: 10.3350/cmh.2016.22.1.76] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 02/22/2016] [Indexed: 12/11/2022] Open
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Calzadilla-Bertot L, Vilar-Gomez E, Torres-Gonzalez A, Socias-Lopez M, Diago M, Adams LA, Romero-Gomez M. Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis. Dig Liver Dis 2016; 48:283-90. [PMID: 26797261 DOI: 10.1016/j.dld.2015.12.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/30/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Glucose metabolism abnormalities frequently coexist with liver cirrhosis; however, the impact of these on liver-related outcomes has not been fully investigated. AIMS We examined the influence of glucose abnormalities on overall mortality and liver-related complications in cirrhotic patients. METHODS A prospective cohort of 250 subjects with compensated hepatitis C virus-related cirrhosis and without known diabetes underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks. RESULTS At baseline, 67 (27%) had type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (sHR: 2.2, 95% CI: 1.04-4.6, P=0.04) and hepatic decompensation events (sHR: 1.9, 95% CI: 1.05-3.3, P=0.03) were significantly higher in diabetic patients. Subjects with a HOMA-IR >5 showed higher rates of mortality (sHR: 2.2, 95% CI: 1.03-4.8, P=0.04). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (sHR: 1.7, 95% CI: 1.04-2.9, P=0.03). Overall, 2h-plasma glucose was the most robust predictor of overall mortality (sHR: 2.5, 95% CI: 1.03-6, P=0.04) and decompensation (sHR: 2.7, 95% CI: 1.4-5.5, P<0.01). CONCLUSIONS In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival and increased risk of hepatic decompensation.
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Affiliation(s)
| | - Eduardo Vilar-Gomez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba; Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain.
| | - Ana Torres-Gonzalez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Maray Socias-Lopez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Moises Diago
- Liver Unit, Department of Gastroenterology, Valencia University General Hospital, Valencia, Spain
| | - Leon A Adams
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain
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Bruno S, Boccaccio V, Russo ML, Maisonneuve P. Is the benefit of treating patients with cirrhosis proven? Liver Int 2016; 36 Suppl 1:21-7. [PMID: 26725893 DOI: 10.1111/liv.13013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 11/02/2015] [Indexed: 01/16/2023]
Abstract
Hepatitis C virus (HCV)-related cirrhosis is an extremely heterogeneous pathological condition with a wide spectrum of clinical manifestations, ranging from pre-clinical to compensated and decompensated stages, each of which is characterized by a different clinical outcome. To measure the benefit of a sustained virological response (SVR) with interferon (IFN)-based therapy, several studies have been performed in patients with compensated disease, while only a few have been performed in decompensated disease. Nevertheless, these studies have certain methodological weaknesses that may limit the accuracy of results. Access to new, more effective and safe direct acting antivirals (DAAs) has significantly changed these outcomes, with SVR rates that were not seen previously, making antiviral treatment available to patients with end-stage liver disease. However, the clinical benefit of treating patients with late stage disease is still poorly understood and must be investigated. The existence of a point of no return beyond which a SVR is not beneficial has not yet been determined. All of these issues are discussed in this review.
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Affiliation(s)
- Savino Bruno
- Department of Internal Medicine, Humanitas University Medicine, Rozzano, Italy.,Department of Internal Medicine, Humanitas Research Hospital, Rozzano, Italy
| | - Vincenzo Boccaccio
- Department of Internal Medicine, Humanitas Research Hospital, Rozzano, Italy
| | - Maria Luisa Russo
- Department of Internal Medicine, Humanitas Research Hospital, Rozzano, Italy
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
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Wu X, Li J, Wang C, Zhang G, Zheng N, Wang X. Application of Different Imaging Methods in the Early Diagnosis of Primary Hepatic Carcinoma. Gastroenterol Res Pract 2015; 2016:8763205. [PMID: 26819614 PMCID: PMC4706941 DOI: 10.1155/2016/8763205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 07/30/2015] [Accepted: 08/02/2015] [Indexed: 12/13/2022] Open
Abstract
Primary hepatic carcinoma (PHC) is the one of the most common tumors and the common cause of cancer death in the world. Detecting PHC in its early stage by imaging methods may greatly increase survival rates of patients. Ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography are common imaging methods in the diagnosis of PHC. In this paper, the application of different imaging methods in diagnosing the primary hepatic carcinoma will be discussed.
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Affiliation(s)
- Xin'ai Wu
- Inner Mongolia Medical University, Hohhot 010050, China
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
| | - Jianbo Li
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
| | - Cheng Wang
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
| | - Guojian Zhang
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
| | - Na Zheng
- Inner Mongolia Medical University, Hohhot 010050, China
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
| | - Xuemei Wang
- Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot 010050, China
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Boursier J, Ducancelle A, Vergniol J, Veillon P, Moal V, Dufour C, Bronowicki JP, Larrey D, Hézode C, Zoulim F, Fontaine H, Canva V, Poynard T, Allam S, De Lédinghen V. The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients. J Viral Hepat 2015. [PMID: 26216230 DOI: 10.1111/jvh.12433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.
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Affiliation(s)
- J Boursier
- Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.,HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
| | - A Ducancelle
- HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Virology Department, CHU d'Angers, Angers, France
| | - J Vergniol
- Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France
| | - P Veillon
- Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.,HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Virology Department, CHU d'Angers, Angers, France
| | - V Moal
- HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Biochemistry Department, CHU d'Angers, Angers, France
| | - C Dufour
- Inserm UMR-S1136, Université Pierre-et-Marie-Curie Paris 6, Paris, France
| | - J-P Bronowicki
- Department of Hepatology and Gastroenterology, CHU de Nancy, Université de Lorraine, Inserm U954, Vandoeuvre-lès-Nancy, France
| | - D Larrey
- Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France
| | - C Hézode
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - F Zoulim
- Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France
| | - H Fontaine
- Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, Inserm U1016, Paris, France
| | - V Canva
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France
| | - T Poynard
- Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France
| | - S Allam
- Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France
| | - V De Lédinghen
- Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.,INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
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Lee YJ, Lee JM, Lee JS, Lee HY, Park BH, Kim YH, Han JK, Choi BI. Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology 2015; 275:97-109. [PMID: 25559230 DOI: 10.1148/radiol.14140690] [Citation(s) in RCA: 380] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE To perform a systematic review and meta-analysis of the diagnostic performance of computed tomography (CT) and magnetic resonance (MR) imaging as noninvasive modalities for evaluating hepatocellular carcinoma (HCC) in patients with chronic liver disease. MATERIALS AND METHODS A search of the MEDLINE, EMBASE, and Cochrane Library databases was performed to identify studies providing per-patient or per-lesion diagnostic accuracies of multidetector CT and MR imaging for HCCs in patients with chronic liver disease. Studies published from January 2000 to December 2012 that used a reference standard based on histopathologic findings and/or findings at follow-up were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model with further exploration with meta-regression and subgroup analyses. RESULTS Forty studies (six on multidetector CT, 22 on MR imaging, and 12 on both CT and MR imaging) were included. The studies evaluated a total of 1135 patients with multidetector CT and 2489 patients with MR imaging. The overall per-patient sensitivity of MR imaging was 88% (95% confidence interval [CI]: 83%, 92%), with a specificity of 94% (95% CI: 85%, 98%). The overall per-lesion sensitivity of MR imaging was higher than that of multidetector CT when the paired data of the 11 available studies were pooled (80% vs 68%, P = .0023). Gadoxetic acid-enhanced MR imaging showed significantly higher per-lesion sensitivity than MR imaging performed with other contrast agents (87% vs 74%, P = .03). Per-lesion sensitivity was significantly lower for HCCs smaller than 1 cm than that for HCCs 1 cm or larger (P < .001 for CT, P = .02 for MR imaging) and for those in explanted livers (P = .04 for CT, P < .001 for MR imaging). CONCLUSION MR imaging showed higher per-lesion sensitivity than multidetector CT and should be the preferred imaging modality for the diagnosis of HCCs in patients with chronic liver disease.
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Affiliation(s)
- Yoon Jin Lee
- From the Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si, Korea (Y.J.L., Y.H.K.); Department of Radiology, Institute of Radiation Medicine, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Korea (J.M.L., J.K.H., B.I.C.); Biostatistical Consulting Unit, Soonchunhyang University Medical Center, Seoul, Korea (J.S.L.); and Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Korea (H.Y.L., B.H.P.)
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Vorobioff JD, Groszmann RJ. Prevention of portal hypertension: from variceal development to clinical decompensation. Hepatology 2015; 61:375-81. [PMID: 24913395 PMCID: PMC4545530 DOI: 10.1002/hep.27249] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 05/31/2014] [Indexed: 12/12/2022]
Abstract
Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastroesophageal varices-related events at different frameworks, including prophylactic, emergency, or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding, and prevent bleeding recurrence, respectively. The objective of preprimary prophylaxis (PPP) is to avoid variceal development, and therefore it necessarily deals with patients with cirrhosis at earlier stages of the disease. At these earlier stages, nonselective beta-blockers (NSBBs) have been ineffective in preventing the development of varices and other complications of PH. Therefore, treatment should not rely on NSBB. It is possible that, at these earlier stages, etiological treatment of liver disease itself could prevent progression of PH. This review will focus mainly on early treatment of PH, because, if successful, it may translate into histological-hemodynamic improvements, avoiding not only variceal development, but also other PH-related complications, such as ascites and portosystemic encephalopathy. Moreover, the advent of new therapies may allow not only the prevention of the complications of PH, but also the chance of a substantial degree of regression in the cirrhotic process, with the possible prevention of hepatocellular carcinoma (HCC).
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Mankal PK, Abed J, Aristy JD, Munot K, Suneja U, Engelson ES, Kotler DP. Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2014; 41:177-82. [PMID: 25320839 DOI: 10.3109/00952990.2014.964358] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). METHODS Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. RESULTS 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. CONCLUSIONS While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.
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Pol S, Corouge M. Treatment of hepatitis C: perspectives. Med Mal Infect 2014; 44:449-54. [PMID: 25174659 DOI: 10.1016/j.medmal.2014.07.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 07/15/2014] [Accepted: 07/22/2014] [Indexed: 12/20/2022]
Abstract
The treatment of hepatitis C virus (HCV) infection has significantly improved in the last 2 decades. The association of pegylated interferon alfa and ribavirin (PR) has allowed a sustained virologic response (SVR) for nearly 15 years i.e. a viral cure of the infection for 45% of genotype 1-, 65% of genotype 4-, 70% of genotype 3- and around 85% of genotype 2-infected patients. A better understanding of the HCV life cycle has led to the development of direct-acting antiviral drugs (DAAs) targeted against viral proteins (NS3/4A protease, NS5B polymerase with nucleotide and non-nucleotide inhibitors, NS5A viral replication complex). The combination of first-generation protease inhibitors with PR demonstrated a high antiviral effectiveness (75% of SVR but restricted to genotypes 1) with substantial adverse effects for the first-generation protease inhibitors, which obtained market approval in 2011 (telaprevir and boceprevir), recommendations for use in HCV monoinfected patients in 2012, and in HCV/HIV coinfected in 2013. Then, the combination of second-generation protease inhibitors with PR increased SVR rates from 75 to 90%, while reducing treatment duration, adverse effects, and the number of pills. The next step will be using an interferon and ribavirin-free combination of DAAs; it should become the standard of care in 2015. These excellent results in "easy-to-treat" patients and in small populations in the first studies were confirmed in phase III studies and in "difficult-to-treat" patients (treatment-- especially protease inhibitors--previously treated patients, cirrhotic patients, liver and renal transplant patients, HIV coinfected patients, and multi-drug treated patients, at increased risk of drug interaction). The high antiviral potency of these new combinations has changed the definition of "difficult-to-treat patients". These unique achievements in drug history make any previous publication on hepatitis C treatment obsolete.
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Affiliation(s)
- S Pol
- Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1016, Institut Cochin, Paris, France.
| | - M Corouge
- Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1016, Institut Cochin, Paris, France
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Gomez EV, Bertot LC, Rodriguez YS, Gonzalez AT, Perez YM, Garcia AY. The natural history of HCV-related cirrhosis and its temporal progression across the different clinical stages. Hepatol Int 2014. [DOI: 10.1007/s12072-014-9565-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Samonakis DN, Koulentaki M, Coucoutsi C, Augoustaki A, Baritaki C, Digenakis E, Papiamonis N, Fragaki M, Matrella E, Tzardi M, Kouroumalis EA. Clinical outcomes of compensated and decompensated cirrhosis: A long term study. World J Hepatol 2014; 6:504-512. [PMID: 25068002 PMCID: PMC4110542 DOI: 10.4254/wjh.v6.i7.504] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 03/21/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study these characteristics and prognostic patterns in a Greek patient population.
METHODS: We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period. We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma (HCC) occurrence and ultimately patient survival.
RESULTS: Five hundreds and twenty-two patients with median age 67 (range, 29-91) years and average follow up 9 years-10 mo (range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus (HCV, 41%) followed by alcohol (31%). The median survival time in compensated cirrhotics was 115 mo (95%CI: 95-133), whereas in decompensated patients was 55 mo (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV patients). Hepatitis B virus (HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression.
CONCLUSION: Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time.
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Yang CH, Chiu YC, Chen CH, Chen CH, Tsai MC, Chuah SK, Lee CH, Hu TH, Hung CH. Diabetes mellitus is associated with gastroesophageal variceal bleeding in cirrhotic patients. Kaohsiung J Med Sci 2014; 30:515-20. [PMID: 25438683 DOI: 10.1016/j.kjms.2014.06.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/04/2014] [Accepted: 04/29/2014] [Indexed: 12/21/2022] Open
Abstract
Diabetes mellitus (DM) has been reported to increase the risk of complications of liver cirrhosis of any etiology and subsequent survival. However, the impact of DM on the development of gastroesophageal variceal bleeding (GEVB) remains unclear. We aimed to elucidate whether DM is an independent risk factor for GEVB among cirrhotic patients. A total of 146 consecutive patients with liver cirrhosis (Child-Pugh Class A, n = 75; Class B, n = 40; and Class C, n = 31) were prospectively enrolled. Data on clinical and biochemical characteristics and history of ascites, GEVB, hepatic encephalopathy, and spontaneous bacterial peritonitis were retrospectively reviewed. Of these 146 patients, 37 (25%) had DM. Patients with DM had significantly higher ratio of Child-Pugh Class B/C (p = 0.043), renal insufficiency (p = 0.002), and history of GEVB (p = 0.006) compared with non-DM patients. GEVB was associated with Child-Pugh Class B/C (p = 0.001), ascites (p = 0.002), hepatic encephalopathy (p = 0.023), and low platelet counts (p < 0.001). Based on stepwise multiple logistic regression analysis, Child-Pugh class B/C [odds ratio (OR) = 4.90, p = 0.003] and DM (OR = 2.99, p = 0.022) were identified as independent predictors of GEVB. In the subgroup analysis, DM significantly correlated with GEVB in patients with Child-Pugh Class A (p = 0.042), but not in patients with Child-Pugh Class B/C (p = 0.128). DM is independently associated with GEVB in cirrhotic patients, especially in those with Child-Pugh Class A.
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Affiliation(s)
- Chun-Hsun Yang
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Yi-Chun Chiu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chih-Hung Chen
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chih-Hsiung Lee
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
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Hézode C, Fontaine H, Dorival C, Zoulim F, Larrey D, Canva V, De Ledinghen V, Poynard T, Samuel D, Bourliere M, Alric L, Raabe JJ, Zarski JP, Marcellin P, Riachi G, Bernard PH, Loustaud-Ratti V, Chazouilleres O, Abergel A, Guyader D, Metivier S, Tran A, Di Martino V, Causse X, Dao T, Lucidarme D, Portal I, Cacoub P, Gournay J, Grando-Lemaire V, Hillon P, Attali P, Fontanges T, Rosa I, Petrov-Sanchez V, Barthe Y, Pawlotsky JM, Pol S, Carrat F, Bronowicki JP. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. Gastroenterology 2014; 147:132-142.e4. [PMID: 24704719 DOI: 10.1053/j.gastro.2014.03.051] [Citation(s) in RCA: 201] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 03/20/2014] [Accepted: 03/31/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.
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Affiliation(s)
- Christophe Hézode
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - Helene Fontaine
- Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France
| | - Celine Dorival
- INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France
| | - Fabien Zoulim
- Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France
| | - Dominique Larrey
- Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France
| | - Valerie Canva
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France
| | - Victor De Ledinghen
- Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | - Thierry Poynard
- Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France
| | - Marc Bourliere
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, UMR-152, Toulouse III University, Toulouse, France
| | - Jean-Jacques Raabe
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France
| | - Jean-Pierre Zarski
- Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France
| | - Patrick Marcellin
- Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France
| | - Ghassan Riachi
- Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France
| | - Pierre-Henri Bernard
- Service d'Hépatologie et Gastroentérologie, Hôpital Saint-André, Bordeaux, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | - Veronique Loustaud-Ratti
- Department of Hepatology and Gastroenterology, CHU Dupuytren, Université de Limoges, UMR INSERM U1092, Limoges, France
| | | | - Armand Abergel
- Department of Hepatology and Gastroenterology, CHU Estaing, Université d'Auvergne, UMR 6284, Clermont-Ferrand, France
| | - Dominique Guyader
- Service des Maladies du Foie, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France
| | - Sophie Metivier
- Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France
| | - Albert Tran
- Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France
| | - Vincent Di Martino
- Service d'Hépatologie, CHU Jean Minjoz, Université de Franche Comté, Besançon, France
| | - Xavier Causse
- Department of Hepatology and Gastroenterology and Digestive Oncology, CHR La Source, Orléans, France
| | - Thong Dao
- Department of Hepatology and Gastroenterology, CHU, INSERM U1075, Caen, France
| | - Damien Lucidarme
- Department of Hepatology and Gastroenterology, Groupe Hospitalier de l'Institut Catholique Lillois, Faculté Libre de Médecine, Lille, France
| | - Isabelle Portal
- Department of Hepatology and Gastroenterology, Hôpital de la Conception, Marseille, France
| | - Patrice Cacoub
- Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM, UMR-S959, CNRS, UMR 7211, Paris, France
| | - Jerome Gournay
- Department of Hepatology and Gastroenterology, Hôpital Hôtel-Dieu, Nantes, France
| | - Veronique Grando-Lemaire
- Department of Hepatology and Gastroenterology, Hôpital Jean Verdier, AP-HP, Université Paris 13, Bondy, France
| | - Patrick Hillon
- Department of Hepatology and Gastroenterology, CHU de Dijon, Université de Bourgogne, Dijon, France
| | - Pierre Attali
- Department of Hepatology and Gastroenterology, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
| | - Thierry Fontanges
- Department of Hepatology and Gastroenterology, Hôpital P Oudot, Bourgoin-Jallieu, France
| | - Isabelle Rosa
- Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France
| | - Ventzislava Petrov-Sanchez
- Unit for Basic and Clinical Research on Viral Hepatitis, French National Agency for Research on AIDS and Viral Hepatitis, Paris, France
| | - Yoann Barthe
- INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - Stanislas Pol
- Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France
| | - Fabrice Carrat
- INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France; Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Jean-Pierre Bronowicki
- Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France.
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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