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Amaris NR, Marenco-Flores A, Barba R, Rubio-Cruz D, Medina-Morales E, Goyes D, Saberi B, Patwardhan V, Bonder A. Acute Liver Failure Etiology Determines Long-Term Outcomes in Patients Undergoing Liver Transplantation: An Analysis of the UNOS Database. J Clin Med 2024; 13:6642. [PMID: 39597786 PMCID: PMC11594988 DOI: 10.3390/jcm13226642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
Background: Acute liver failure (ALF) involves rapid liver injury, often leading to multi-organ failure. Liver transplantation (LT) has improved survival rates, with U.S. rates reaching 92%. This study analyzes UNOS data (2002-2020) to evaluate long-term survival and identify risk factors affecting waitlist and post-LT outcomes in ALF patients. Methods: A retrospective analysis was performed on adult ALF patients waitlisted for LT (Status 1/1A). ALF etiologies, including viral infections, drug-induced liver injury (DILI), acetaminophen (APAP) overdose, autoimmune hepatitis (AIH), Wilson disease (WD), and unknown causes, were assessed with patient and donor characteristics. Kaplan-Meier and Cox regression analyses identified predictors of patient and graft survival. Sensitivity analysis confirmed the model's robustness. Results: We identified 2759 ALF patients. APAP (HR 1.7; p < 0.001) and unknown etiology (HR 1.3; p = 0.037) were linked to higher waitlist removal risk, while WD (HR 0.36; p < 0.001) increased LT probability. Among 2014 LT recipients, WD showed improved survival (HR 0.53; p = 0.002). Black/African American race (HR 1.47; p < 0.001), diabetes (HR 1.81; p < 0.001), and encephalopathy (HR 1.27; p < 0.001) predicted higher mortality. AIH had the lowest 1- and 10-year survival (83% and 62%), while APAP had the lowest 5-year survival (76%). WD had the highest graft survival at 1, 5, and 10 years (93%, 88%, and 80%). Conclusions: ALF etiology significantly affects survival outcomes. AIH and APAP are associated with worse survival, while WD shows favorable outcomes. Tailored post-LT management is essential to improve survival in ALF patients.
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Affiliation(s)
- Natalia Rojas Amaris
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Ana Marenco-Flores
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Romelia Barba
- Department of Internal Medicine, Texas Tech University System, Lubbock, TX 79430, USA
| | - Denisse Rubio-Cruz
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Esli Medina-Morales
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Daniela Goyes
- Division of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520, USA
| | - Behnam Saberi
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Vilas Patwardhan
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Alan Bonder
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Patel PV, Livingston S, Rakela JL, Stravitz RT, Reuben A, Bass NM, Tujios SR, Larson AM, Sussman NL, Rule JA, Durkalski-Mauldin VL, Lee WM, Ganger DR. Indeterminate etiology of acute liver failure in North America: Less common, still grave prognosis. Clin Transplant 2023; 37:e15128. [PMID: 37705387 PMCID: PMC11459373 DOI: 10.1111/ctr.15128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 08/22/2023] [Accepted: 09/03/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND-ALF). In this study, we summarize findings from patients with IND-ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND-ALF. METHODS Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21-day transplant-free survival (TFS). RESULTS Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true-IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%). CONCLUSION We illustrate the poor prognoses that true-IND-ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases.
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Affiliation(s)
- Parita V Patel
- Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Sherry Livingston
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jorge L Rakela
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - R Todd Stravitz
- Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Adrian Reuben
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Nathan M Bass
- Department of Medicine, University of California, San Francisco, California, USA
| | - Shannan R Tujios
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Anne M Larson
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Norman L Sussman
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Jody A Rule
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | | | - William M Lee
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Daniel R Ganger
- Department of Medicine, Northwestern University, Chicago, Illinois, USA
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3
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Vento S, Cainelli F. Acute liver failure in low-income and middle-income countries. Lancet Gastroenterol Hepatol 2023; 8:1035-1045. [PMID: 37837969 DOI: 10.1016/s2468-1253(23)00142-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/28/2023] [Accepted: 05/03/2023] [Indexed: 10/16/2023]
Abstract
Acute liver failure is a rare condition involving the rapid development, progression, and worsening of liver dysfunction, characterised by coagulopathy and encephalopathy, and has a high mortality unless liver transplantation is performed. Population-based studies are scarce, and most published data are from high-income countries, where the main cause of acute liver failure is paracetamol overdose. This Review provides an overview of the scanty literature on acute liver failure in low-income and middle-income countries, where patients are often admitted to primary care hospitals and viral hepatitis (especially hepatitis E), tropical infections (eg, dengue), traditional medicines, and drugs (especially anti-tuberculosis drugs) have an important role. We discuss incidence, cause, occurrence in children and pregnant women, prognostic factors and scores, treatment, and mortality. To conclude, we advocate for international collaboration, the establishment of central registries for the condition, and better diagnostics.
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Affiliation(s)
- Sandro Vento
- Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia.
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4
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Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis. Infection 2022:10.1007/s15010-022-01945-1. [DOI: 10.1007/s15010-022-01945-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
Abstract
Purpose
Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt.
Methodology
Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson’s disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A–E viruses, cytomegalovirus, Epstein–Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus.
Results
A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease.
Conclusion
This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.
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Abstract
Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.
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Affiliation(s)
- Shannan Tujios
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - R. Todd Stravitz
- Section of Hepatology, Department of Internal Medicine, Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, Virginia
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
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6
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Patterson J, Hussey HS, Silal S, Goddard L, Setshedi M, Spearman W, Hussey GD, Kagina BM, Muloiwa R. Systematic review of the global epidemiology of viral-induced acute liver failure. BMJ Open 2020; 10:e037473. [PMID: 32690747 PMCID: PMC7375632 DOI: 10.1136/bmjopen-2020-037473] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention. PARTICIPANTS This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review. RESULTS This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries. CONCLUSIONS Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure. REGISTRATION PROSPERO registration number: CRD42017079730.
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Affiliation(s)
- Jenna Patterson
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Hannah Sophia Hussey
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Sheetal Silal
- Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Liz Goddard
- Department of Paediatrics, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
| | - Mashiko Setshedi
- Department of Medicine, Division of Gastroenterology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Wendy Spearman
- Department of Medicine, Division of Hepatology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Gregory D Hussey
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Benjamin M Kagina
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Rudzani Muloiwa
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
- Department of Pediatrics & Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
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Mendizabal M, Tagliafichi V, Rubinstein F, Rojas P, Marciano S, Yantorno S, Cejas N, Barrabino M, Anders M, Cairo F, Villamil F, Blazquez L, Zerega A, Ferretti S, Fernández D, Paredes S, Aballay Soteras G, Gaite L, Bisigniano L, Silva MO. Liver transplantation in adults with acute liver failure: Outcomes from the Argentinean Transplant Registry. Ann Hepatol 2020; 18:338-344. [PMID: 31053539 DOI: 10.1016/j.aohep.2018.11.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN).
| | - Viviana Tagliafichi
- Instituto Nacional Central Unico Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | | | - Paloma Rojas
- Liver Transplant Unit, Hospital El Cruce, Florencio Varela, Buenos Aires, Argentina
| | | | - Silvina Yantorno
- Hepatology and Liver Transplant Program, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - Nora Cejas
- Liver Transplant Program, Hospital Dr. Cosme Argerich, Buenos Aires, Argentina
| | - Martín Barrabino
- Liver Transplant Unit, Hospital Privado de Córdoba, Córdoba, Argentina
| | - Margarita Anders
- Hepatology and Liver Transplant Unit, Hospital Alemán, Buenos Aires, Argentina
| | - Fernando Cairo
- Liver Transplant Unit, Hospital El Cruce, Florencio Varela, Buenos Aires, Argentina; Liver Transplant Unit, Hospital Británico, Buenos Aires, Argentina
| | - Federico Villamil
- Liver Transplant Unit, Hospital El Cruce, Florencio Varela, Buenos Aires, Argentina; Liver Transplant Unit, Hospital Británico, Buenos Aires, Argentina
| | - Laura Blazquez
- Liver Transplant Program, Hospital Italiano de Mendoza, Mendoza, Argentina
| | - Alina Zerega
- Liver Transplant Unit, Sanatorio Allende, Córdoba, Argentina
| | | | - Diego Fernández
- Liver Transplant Program, Clínica Privada Pueyrredón, Mar del Plata, Buenos Aires, Argentina
| | - Sebastián Paredes
- Liver Transplant Program, Hospital de Alta Complejidad "Juan D. Perón", Formosa, Argentina
| | - Gabriel Aballay Soteras
- Liver Transplant Program, Hospital Dr. Cosme Argerich, Buenos Aires, Argentina; Liver Transplant Unit, Sanatorio Mitre, Buenos Aires, Argentina
| | - Luis Gaite
- Liver Transplant Program, Clinica de Nefrología, Urología y Enfermedades Cardiovasculares, Santa Fe, Argentina
| | - Liliana Bisigniano
- Instituto Nacional Central Unico Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Marcelo O Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN)
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8
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Di Lello FA, Blejer J, Alter A, Bartoli S, Vargas F, Ruiz R, Galli C, Blanco S, Gallego S, Fernández R, Martínez AP, Flichman DM. Hepatitis B surface antibodies seroprevalence among people born before and after implementation of universal HBV vaccination. Vaccine 2020; 38:2678-2682. [PMID: 32061386 DOI: 10.1016/j.vaccine.2020.02.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/22/2020] [Accepted: 02/05/2020] [Indexed: 12/16/2022]
Abstract
Universal vaccination is the most effective strategy to control hepatitis B virus (HBV) infection. In Argentina, vaccination against HBV was incorporated in year 2000 for newborns and in 2003 for 11 years old children. However, there is a paucity of data about protection levels against HBV infection. The aim of this work was to determine the prevalence of seroprotective anti-HBs antibodies (aHBs) in Argentina. Serum samples negative for HBsAg and anti-HBc from 132 children born after year 2000 and 762 blood donors, older than 18 years, from five centers across the country, were analyzed for aHBs. Titers ≥10 mIU/mL were observed in 74/132 children (56.1%) and 336/762 (44.1%) in blood donors. The median age for blood donors was 33.9 (23-43); from them, 210 (27.6%) were born after 1992 and, therefore, were catch-up by vaccine implementation at 11 years old age. Donors born in 1992 or before showed a significantly lower frequency of protection (32.2%) compared to donors born after 1992 (75.2%), p < 0.0001. In addition, significant differences were observed in the status of seroprotection between different participating centers (p = 0.024). Implementation of HBV vaccine in 2000 and 2003 implied an overall increase of the aHBs seroprotective rates, with a particularly adequate response in children vaccinated at 11 years old age. The observed results suggest that population born in 1992 or before is currently the most susceptible. Consequently, it would be advisable to become aware of the risk of transmission in this age group and to stress this population vaccination campaigns.
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Affiliation(s)
- Federico A Di Lello
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
| | - Jorgelina Blejer
- Fundación Hemocentro, Ciudad Autónoma de Buenos Aires, Argentina
| | - Adriana Alter
- Fundación Hemocentro, Ciudad Autónoma de Buenos Aires, Argentina
| | - Sonia Bartoli
- Centro Regional de Hemoterapia Jujuy, San Salvador de Jujuy, Jujuy, Argentina
| | - Fabiana Vargas
- Centro Regional de Hemoterapia de Mendoza, Mendoza, Mendoza, Argentina
| | - Rosángela Ruiz
- Hospital Regional Rio Grande, Rio Grande, Tierra del Fuego, Argentina
| | - Claudio Galli
- Hospital Regional Rio Grande, Rio Grande, Tierra del Fuego, Argentina
| | - Sebastián Blanco
- Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Córdoba, Argentina; Fundación Banco Central de Sangre, Córdoba, Córdoba, Argentina
| | - Sandra Gallego
- Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Córdoba, Argentina; Fundación Banco Central de Sangre, Córdoba, Córdoba, Argentina
| | | | - Alfredo P Martínez
- Sección Virología, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Ciudad Autónoma de Buenos Aires, Argentina
| | - Diego M Flichman
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida (INBIRS)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
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9
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Dellatore P, Mishra A, Rustgi V. Prognostic Models in Acute and Acute on Chronic Liver Failure. LIVER FAILURE 2020:91-107. [DOI: 10.1007/978-3-030-50983-5_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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10
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Vieira V, Pacheco L, Demetrio L, Balbi E, Bellinha T, Toledo R, Auler L, Halpern M, Pinto L, Guaraldi B, Victor L, Bigi J, Carius L, Roma J. Liver Transplantation for Acute Liver Failure due to Yellow Fever: A Case Report. Transplant Proc 2019; 51:1625-1628. [DOI: 10.1016/j.transproceed.2019.01.046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Song ATW, D'Albuquerque YLAC. [Not Available]. Clin Liver Dis (Hoboken) 2019; 13:S24-S27. [PMID: 31333825 PMCID: PMC6541045 DOI: 10.1002/cld.841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 11/07/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Alice Tung Wan Song
- Disciplina de Trasplante de Hígado y Órganos del Aparato Digestivo, Departamento de Gastroenterología, Hospital das Clinicas HCFMUSP, Facultad de MedicinaUniversidad de Sáo PauloSáo PauloBrasil,LIM‐37, Hospital das Clinicas HCFMUSP, Facultad de MedicinaUniversidad de Sáo PauloSao PauloBrasil
| | - y Luiz Augusto Carneiro D'Albuquerque
- Disciplina de Trasplante de Hígado y Órganos del Aparato Digestivo, Departamento de Gastroenterología, Hospital das Clinicas HCFMUSP, Facultad de MedicinaUniversidad de Sáo PauloSáo PauloBrasil,LIM‐37, Hospital das Clinicas HCFMUSP, Facultad de MedicinaUniversidad de Sáo PauloSao PauloBrasil
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12
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Song ATW, Carneiro D’Albuquerque LA. Acute Liver Failure Secondary to Yellow Fever: A Challenging Scenario. Clin Liver Dis (Hoboken) 2019; 13:58-61. [PMID: 31139357 PMCID: PMC6465781 DOI: 10.1002/cld.784] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 11/07/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Alice Tung Wan Song
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de GastroenterologiaHospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloSão PauloBrazil,LIM‐37, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloSão PauloBrazil
| | - Luiz Augusto Carneiro D’Albuquerque
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de GastroenterologiaHospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloSão PauloBrazil,LIM‐37, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloSão PauloBrazil
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13
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Mainardi V, Rando K, Valverde M, Olivari D, Castelli J, Rey G, Gerona S. Acute Liver Failure due to Wilson Disease: Eight Years of the National Liver Transplant Program in Uruguay. Ann Hepatol 2019; 18:187-192. [PMID: 31113589 DOI: 10.5604/01.3001.0012.7911] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 07/04/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Wilson's disease (WD) is an uncommon cause of acute liver failure (ALF). Our aim was to describe clinical features, diagnostic findings, treatments, and outcomes of patients with ALF due to WD. MATERIAL AND METHODS Retrospective medical record reviews of all patients with ALF due to WD in eight years in Uruguay. RESULTS WD was the cause of six (15%) of thirty-nine ALF cases. All patients were females, with a mean age of 18 years. Four patients presented with hyperacute liver failure and two with acute failure. Jaundice was the main complaint of all patients. Mean total bilirubin (TB), alkaline phosphatase (AP), AST, and ALT were 27.5 mg/dL, 45.5 lU/l, 156 IU/L, and 51 IU/L, respectively. Ceruloplasmin levels were low in four patients, urinary cooper was high in four, and two had Kayser-Fleischer rings. All patients had Coombs-negative hemolytic anemia, acute kidney injury, histochemical identifiable copper, and advanced fibrosis on liver histology. The average MELD score was 36. All patients were treated with d-penicillamine and listed for urgent liver transplantation (LT). Prometheus® was performed in one patient. Three patients died: two without LT and one after LT. Three patients survived: one without LT (New Wilson Index<11) and two with LT. The referral time to the program and the total time (referral plus waiting list time) were longer for non-survivors than for survivors (14 vs. 3 days and 23 vs. 8 respectively). CONCLUSION All cases had typical clinical, analytical and histopathology characteristics. Early referral was determinant of prognosis.
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Affiliation(s)
- Victoria Mainardi
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay.
| | - Karina Rando
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
| | - Marcelo Valverde
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
| | - Daniela Olivari
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
| | - Jorge Castelli
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
| | - Gabriela Rey
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
| | - Solange Gerona
- Hepatic Biliary and Pancreatic National Center - Teaching and Assistance Unit (UDA) and Bi-Intuitional Unit of Liver Transplantation, Military Hospital, Montevideo, Uruguay
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14
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Colaci CS, Mendizabal M, Bessone F. Idiosyncratic Drug-Induced Acute Liver Failure: A Challenging and Distressing Scenario. Curr Drug Saf 2019; 14:94-101. [PMID: 30767751 DOI: 10.2174/1574886314666190215115434] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 01/17/2019] [Accepted: 02/09/2019] [Indexed: 01/02/2023]
Abstract
BACKGROUND Idiosyncratic Drug Induced Liver Injury (DILI) is a rare adverse event to drugs that occasionally leads to severe liver damage, being one of the leading causes of Acute Liver Failure (ALF) in developed countries. DILI is largely a diagnosis of exclusion. DISCUSSION AND CONCLUSION Careful history of drug taking and ruling out other competing etiologies is mandatory given that DILI can present with an extremely variable phenotype. Several prognostic scores have been developed to promptly identify patients with potential risk of developing ALF. New biomarkers to diagnose and predict DILI evolution are under study and hopefully we will benefit from these novel tools in the near future.
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Affiliation(s)
- Carla Stefania Colaci
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Buenos Aires, Argentina
| | - Fernando Bessone
- Hospital Provincial del Centenario, University of Rosario School of Medicine, Rosario, Santa Fe, Argentina
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15
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Ganger DR, Rule J, Rakela J, Bass N, Reuben A, Stravitz RT, Sussman N, Larson AM, James L, Chiu C, Lee WM. Acute Liver Failure of Indeterminate Etiology: A Comprehensive Systematic Approach by An Expert Committee to Establish Causality. Am J Gastroenterol 2018; 113:1319. [PMID: 29946176 PMCID: PMC9252260 DOI: 10.1038/s41395-018-0160-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 05/15/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES In the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases. METHODS Specific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide liver biopsy and/or explant reports and to update serological findings not reported previously. RESULTS Nearly half (142, 46.9%) of the 303 IND-ALF cases could be reassigned to a single, defined etiology and rated as highly likely or probable; 11 additional cases, upon review, did not meet ALF criteria. Amongst reassigned etiologies, 45 were previously unrecognized APAP, 34 autoimmune hepatitis (AIH), 24 drug-induced liver injury (DILI), 13 various viral causes, 12 ischemia, and 14 miscellaneous other etiologies. The remaining 150, deemed true IND-ALF, represented just 5.5%. CONCLUSIONS The indeterminate etiology in ALF includes patients with a diagnosis that is discernible after closer examination. Revision of etiologic diagnoses of indeterminate cases using added testing and expert opinion is useful in understanding all aspects of ALF.
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Affiliation(s)
- Daniel R. Ganger
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jody Rule
- Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jorge Rakela
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Nathan Bass
- Department of Medicine, UCSF San Francisco, San Francisco, CA, USA
| | - A Reuben
- Medical University of South Carolina, Charleston, SC, USA
| | - RT Stravitz
- Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA
| | - Norman Sussman
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA
| | - Anne M. Larson
- Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA
| | - Laura James
- Section of Pediatric Pharmacology and Toxicology, Arkansas Children’s Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Charles Chiu
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA,UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA,Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA
| | - William M. Lee
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
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16
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Mendizabal M, Silva M. Acute liver failure: Do the EASL guidelines address the whole spectrum? J Hepatol 2018; 68:843. [PMID: 29133245 DOI: 10.1016/j.jhep.2017.08.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 08/11/2017] [Indexed: 01/07/2023]
Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina.
| | - Marcelo Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
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17
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Linecker M, Krones T, Berg T, Niemann CU, Steadman RH, Dutkowski P, Clavien PA, Busuttil RW, Truog RD, Petrowsky H. Potentially inappropriate liver transplantation in the era of the "sickest first" policy - A search for the upper limits. J Hepatol 2018; 68:798-813. [PMID: 29133246 DOI: 10.1016/j.jhep.2017.11.008] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/11/2017] [Accepted: 11/06/2017] [Indexed: 12/11/2022]
Abstract
Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for "equity", trying to save every patient, regardless of the overall utility; and "efficiency", rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose "absolute" and "relative" conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates.
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Affiliation(s)
- Michael Linecker
- Swiss HPB and Transplantation Center, University Hospital Zurich, Switzerland; Department of Surgery and Transplantation, University Hospital Zurich, Switzerland
| | - Tanja Krones
- Division of Clinical Ethics, University Hospital Zurich, Switzerland; Institute of Biomedical Ethics and History of Medicine, University of Zurich, Switzerland
| | - Thomas Berg
- Division of Hepatology, University of Leipzig, Germany
| | - Claus U Niemann
- Department of Anesthesiology, University of California, San Francisco, USA; Department of Surgery, University of California San Francisco, USA
| | - Randolph H Steadman
- Department of Anesthesiology and Perioperative Medicine, Ronald Reagan Medical Center, University of California Los Angeles, Los Angeles, USA
| | - Philipp Dutkowski
- Swiss HPB and Transplantation Center, University Hospital Zurich, Switzerland; Department of Surgery and Transplantation, University Hospital Zurich, Switzerland
| | - Pierre-Alain Clavien
- Swiss HPB and Transplantation Center, University Hospital Zurich, Switzerland; Department of Surgery and Transplantation, University Hospital Zurich, Switzerland
| | - Ronald W Busuttil
- Dumont-UCLA Transplant Center, Ronald Reagan Medical Center, University of California Los Angeles, USA
| | - Robert D Truog
- Center for Bioethics, Harvard Medical School, Boston, USA; Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, USA
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center, University Hospital Zurich, Switzerland; Department of Surgery and Transplantation, University Hospital Zurich, Switzerland.
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18
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Mainardi V, Rando K, Olivari D, Rey G, Castelli J, Grecco G, Leites A, Harguindeguy M, Gerona S. Mortality Analysis of Acute Liver Failure in Uruguay. Transplant Proc 2018; 50:465-471. [PMID: 29579829 DOI: 10.1016/j.transproceed.2017.12.037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 12/14/2017] [Accepted: 12/15/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Acute liver failure (ALF) is a syndrome with high mortality. OBJECTIVE Describe characteristics and outcomes of patients with ALF in Uruguay, and identify factors associated with mortality. METHODS A retrospective analysis of 33 patients with ALF was performed between 2009 and 2017. RESULTS The patients' median age was 43 years, and 64% were women. Average Model for End-Stage Liver Disease (MELD) score at admission was 33. The median referral time to the liver transplant (LT) center was 7 days. The most common etiologies were viral hepatitis (27%), indeterminate (21%), autoimmune (18%), and Wilson disease (15%). Overall mortality was 52% (71% of transplanted and 46% of nontransplanted patients). Dead patients had higher referral time (10 vs 4 days, P = .008), higher MELD scores at admission (37 vs 28) and highest achieved MELD scores (42 vs 29; P < .001), and higher encephalopathy grade III to IV (94% vs 25%, P < .001) than survivors. Patients without LT criteria (n = 4) had lower MELD score at admission (25 vs 34, P = .001) and highest achieved MELD score (27 vs 37, P = .008) compared with the others. Patients with LT criteria but contraindications (n = 7) had higher MELD scores at admission (38 vs 31, P = .02), highest achieved MELD scores (41 vs 34, P = .03), and longer referral time (10 days) than those without contraindications (3.5 days) or those without LT criteria (7.5 days, P = .02). Twenty-two patients were listed; LT was performed in 7, with a median time on waiting list of 6 days. CONCLUSIONS ALF in Uruguay has high mortality associated with delayed referral to the LT center, MELD score, and encephalopathy. The long waiting times to transplantation might influence mortality.
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Affiliation(s)
- V Mainardi
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay.
| | - K Rando
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - D Olivari
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - G Rey
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay
| | - J Castelli
- National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - G Grecco
- National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - A Leites
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - M Harguindeguy
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - S Gerona
- Hepatic Biliary and Pancreatic National Center-Teaching and Assistance Unit (UDA) from Uruguay University (UDELAR), Montevideo, Uruguay; National Liver Transplant Program, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
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19
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Haddad L, Marciano S, Cleres M, Zerega A, Piñero F, Orozco F, Braslavsky G, Mendizabal M, Gondolesi G, Gil O, Silva M, Mastai R, Imventarza O, Descalzi V, Gadano A. Characteristics of Liver Transplantation in Argentina: A Multicenter Study. Transplant Proc 2018; 50:478-484. [PMID: 29579832 DOI: 10.1016/j.transproceed.2017.11.072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 11/11/2017] [Indexed: 11/16/2022]
Abstract
INTRODUCTION There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS We believe the information contained in this article might be of value for reviewing current practices and developing local policies.
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Affiliation(s)
- L Haddad
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
| | - S Marciano
- Departamento de Investigación, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - M Cleres
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - A Zerega
- Unidad de Trasplante Hepático, Sanatorio Allende, Córdoba, Argentina
| | - F Piñero
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - F Orozco
- Unidad de Trasplante Hepático Hospital Alemán, Buenos Aires, Argentina
| | - G Braslavsky
- Unidad de Trasplante Hepático Hospital Dr. Cosme Argerich, Buenos Aires, Argentina
| | - M Mendizabal
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - G Gondolesi
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - O Gil
- Unidad de Trasplante Hepático, Sanatorio Allende, Córdoba, Argentina
| | - M Silva
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - R Mastai
- Unidad de Trasplante Hepático Hospital Alemán, Buenos Aires, Argentina
| | - O Imventarza
- Unidad de Trasplante Hepático Hospital Dr. Cosme Argerich, Buenos Aires, Argentina
| | - V Descalzi
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - A Gadano
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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20
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Mendizabal M, Silva MO. Developing multicenter consortia in liver disease in Latin America: Challenges and opportunities. Liver Transpl 2017; 23:1210-1215. [PMID: 28590520 DOI: 10.1002/lt.24793] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 05/26/2017] [Accepted: 05/31/2017] [Indexed: 12/12/2022]
Abstract
The development of consortia has been useful for exploring challenging scenarios and uncharted territories in liver disease treatments. Several consortia already developed in the United States and Europe have become key factors in patient care decision-making processes and medical education, and they have also impacted policy makers' decisions. In Latin America, the situation is different. As a result of a combination of different factors, our region has not been able to develop networking advantages in research and education in liver diseases. Thus far, most of the initial experiences focused on the development of collaborative groups established to investigate a particular topic, which were dissolved once the questions were answered. It is the aim of this review to describe those difficulties we confront in developing multicenter liver consortia in Latin America, to identify those challenges we face, and also to describe the opportunities we have for improvement. Liver Transplantation 23 1210-1215 2017 AASLD.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina.,Latin American Liver Research, on behalf of the Latin American Liver Research, Educational and Awareness Network, Pilar, Provincia de Buenos Aires, Argentina
| | - Marcelo O Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina.,Latin American Liver Research, on behalf of the Latin American Liver Research, Educational and Awareness Network, Pilar, Provincia de Buenos Aires, Argentina
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21
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Li YN, Ma H, Zhou L, Zhang J, Guo LP, Li SQ, Qian YQ, Wang BM. Autoimmune Hepatitis-related Cirrhosis: Clinical Features and Effectiveness of Immunosuppressive Treatment in Chinese Patients. Chin Med J (Engl) 2016; 129:2434-2440. [PMID: 27748335 PMCID: PMC5072255 DOI: 10.4103/0366-6999.191760] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background: The long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable. However, little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment. We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital. Methods: Patients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed. Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study. Among these patients, 87 presented with cirrhosis when initially diagnosed for AIH. Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis. Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed. Independent risk factors were assessed for predicting the prognosis of patients. The t-test and Cox regression statistical analysis were used. Results: In total, 96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy. The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients (84.4%), whereas 9/96 (9.4%) achieved incomplete response, and 6/96 (6.3%) occurred treatment failure. Compared to noncirrhotic patients, patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response (noncirrhosis 50/57 [87.7%] vs. cirrhosis 31/39 [79.5%], P = 0.275), incomplete remission (noncirrhosis 4/57 [7.0%] vs. cirrhosis 5/39 [12.8%], P = 0.338), and treatment failure (noncirrhosis 3/57 [5.3%] vs. cirrhosis 3/39 [7.7%], P = 0.629). Importantly, the remission rate was comparable (54/57 [94.7%] and 36/39 [92.3%], P = 0.629) for noncirrhotic and cirrhotic patients after immunosuppressive therapy. Compared to patients who maintained remission (n = 19) after drug withdrawal, patients who experienced relapse (n = 17) had significantly higher levels of serum immunoglobulin G at entry (15.0 ± 6.5 g/L vs. 22.3 ± 5.8 g/L, t = 2.814, P = 0.004). Moreover, cirrhosis at presentation significantly increased the risk of disease exacerbation (hazard ratio [HR]: 4.603; P = 0.002). The treatment of immunosuppressant (HR: 0.058; P = 0.005) and the level of aspartate aminotransferase at presentation (HR: 1.002; P = 0.017) also increased the risk of disease progression. Conclusions: The efficacy of initial immunosuppressive treatment in AIH patients with cirrhosis is comparable to that in those without cirrhosis. Cirrhotic patients not treated by immunosuppressants have poor long-term outcomes.
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Affiliation(s)
- Yan-Ni Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
| | - Huan Ma
- Department of Gastroenterology and Hepatology, Hebei Medical University Third Hospital, Hebei Medical University, Shijiazhuang, Heibei 050051, China
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
| | - Li-Ping Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
| | - Shu-Qian Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
| | - Yi-Qi Qian
- Department of Preventive Medicine, School of Public Health, Tianjin Medical University, Tianjin 300070, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300054, China
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22
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Tannuri ACA, Porta G, Kazue Miura I, Santos MM, Moreira DDAR, de Rezende NMA, Miyatani HT, Tannuri U. Pediatric acute liver failure in Brazil: Is living donor liver transplantation the best choice for treatment? Liver Transpl 2016; 22:1006-13. [PMID: 26946330 DOI: 10.1002/lt.24435] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 02/04/2016] [Accepted: 02/07/2016] [Indexed: 02/07/2023]
Abstract
Acute liver failure (ALF) in children is a life-threatening condition that often leads to urgent liver transplantation (LT). The aim of the present investigation was to describe the experience in Brazil in treating pediatric ALF, with an emphasis on the role of living donor liver transplantation (LDLT) in treating this condition. All children with ALF who fulfilled the criteria for an urgent LT were admitted to the intensive care unit. Patients were divided into 2 groups based on the moment of admission: before and after June 2007, when the LDLT program for ALF was started. Statistical analyses were performed to identify prognostic factors of patients with ALF. For the study, 115 children with ALF were admitted. All patients had some degree of encephalopathy. Among the patients, 26% of them required intracranial pressure monitoring (IPM), 12.8% of the patients required hemodialysis, and 79 patients underwent transplantation (50 deceased donors and 29 living donors) corresponding to 12.4% of all pediatric LTs. Only 9 children recovered without LT. The need for IPM and nonperformance of LT were related to a higher mortality. The mortality rate of patients who underwent LT was significantly lower than that of children with ALF who did not undergo a LT (48.1% versus 75%; P = 0.02). The incidences of primary nonfunction and mortality were statistically higher among deceased donor liver transplantations than LDLTs. Finally, it was verified that the overall survival rate of transplanted patients was increased after the introduction of LDLT (P = 0.02). In conclusion, ALF in children continues to be a severe and devastating condition, and a LT should be performed promptly. The introduction of LDLT could increase the survival rate of patients in Brazil. Liver Transplantation 22 1006-1013 2016 AASLD.
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Affiliation(s)
| | - Gilda Porta
- Liver Transplantation Unit, Children's Institute, University of São Paulo, São Paulo, Brazil
| | - Irene Kazue Miura
- Liver Transplantation Unit, Children's Institute, University of São Paulo, São Paulo, Brazil
| | - Maria Merces Santos
- Liver Transplantation Unit, Children's Institute, University of São Paulo, São Paulo, Brazil
| | | | | | - Helena Thie Miyatani
- Liver Transplantation Unit, Children's Institute, University of São Paulo, São Paulo, Brazil
| | - Uenis Tannuri
- Liver Transplantation Unit, Children's Institute, University of São Paulo, São Paulo, Brazil
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23
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McPhail MJW, Farne H, Senvar N, Wendon JA, Bernal W. Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis. Clin Gastroenterol Hepatol 2016; 14:516-525.e5; quiz e43-e45. [PMID: 26499930 DOI: 10.1016/j.cgh.2015.10.007] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 09/22/2015] [Accepted: 10/02/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Several prognostic factors are used to identify patients with acute liver failure (ALF) who require emergency liver transplantation. We performed a meta-analysis to determine the accuracy of King's College criteria (KCC) versus the model for end-stage liver disease (MELD) scores in predicting hospital mortality among patients with ALF. METHODS We performed a systematic search of the literature for articles published from 2001 through 2015 that compared the accuracy of the KCC with MELD scores in predicting hospital mortality in patients with ALF. We identified 23 studies (comprising 2153 patients) and assessed the quality of data, and then performed a meta-analysis of pooled sensitivity and specificity values, diagnostic odds ratios (DORs), and summary receiver operating characteristic curves. Subgroups analyzed included study quality, era, location (Europe vs non-Europe), and size; ALF etiology (acetaminophen-associated ALF [AALF] vs nonassociated [NAALF]); and whether or not the study included patients who underwent liver transplantation and if the study center was also a transplant center. RESULTS The DOR for the KCC was 5.3 (95% confidence interval [CI], 3.7-7.6; 57% heterogeneity) and the DOR for MELD score was 7.0 (95% CI, 5.1-9.7; 48% heterogeneity), so the MELD score and KCC are comparable in overall accuracy. The summary area under the receiver operating characteristic curve values was 0.76 for the KCC and 0.78 for MELD scores. The KCC identified patients with AALF who died with 58% sensitivity (95% CI, 51%-65%) and 89% specificity (95% CI, 85%-93%), whereas MELD scores identified patients with AALF who died with 80% sensitivity (95% CI, 74%-86%) and 53% specificity (95% CI, 47%-59%). The KCC predicted hospital mortality in patients with NAALF with 58% sensitivity (95% CI, 54%-63%) and 74% specificity (95% CI, 69%-78%), whereas MELD scores predicted hospital mortality in patients with NAALF with 76% sensitivity (95% CI, 72%-80%) and 73% specificity (95% CI, 69%-78%). In patients with AALF, the KCC's DOR was 10.4 (95% CI, 4.9-22.1) and the MELD score's DOR was 6.6 (95% CI, 2.1-20.2). In patients with NAALF, the KCC's DOR was 4.16 (95% CI, 2.34-7.40) and the MELD score's DOR was 8.42 (95% CI, 5.98-11.88). CONCLUSIONS Based on a meta-analysis of studies, the KCC more accurately predicts hospital mortality among patients with AALF, whereas MELD scores more accurately predict mortality among patients with NAALF. However, there is significant heterogeneity among studies and neither system is optimal for all patients. Given the importance of specificity in decision making for listing for emergency liver transplantation, MELD scores should not replace the KCC in predicting hospital mortality of patients with AALF, but could have a role for NAALF.
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Affiliation(s)
- Mark J W McPhail
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom; Department of Hepatology, St Mary's Hospital, Imperial College London, London, United Kingdom.
| | - Hugo Farne
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Naz Senvar
- Department of Hepatology, St Mary's Hospital, Imperial College London, London, United Kingdom
| | - Julia A Wendon
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
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24
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Nalpas B, Ichaï P, Jamot L, Carbonell N, Rudler M, Mathurin P, Durand F, Gerken G, Manns M, Trautwein C, Larrey D, Radenne S, Duvoux C, Leroy V, Bernuau J, Faivre J, Moniaux N, Bréchot C, Amouyal G, Amouyal P, Samuel D. A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases. PLoS One 2016; 11:e0150733. [PMID: 26983031 PMCID: PMC4794150 DOI: 10.1371/journal.pone.0150733] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 02/17/2016] [Indexed: 11/18/2022] Open
Abstract
Objective No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. Design double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. Results 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). Conclusion ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. Trial Registration ClinicalTrials.gov NCT01318525
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Affiliation(s)
- Bertrand Nalpas
- Inserm, Département de l’Information Scientifique et de la Communication, Paris, France
- * E-mail:
| | - Philippe Ichaï
- Centre Hépatobiliaire Paul Brousse and Inserm U 1193, Villejuif, France
- Hôpital Universitaire Paul Brousse, Villejuif, France
| | | | - Nicolas Carbonell
- Service Hépato-gastro-entérologie, Hôpital Saint Antoine, Paris, France
| | - Marika Rudler
- Service Hépatologie et de Gastroentérologie, Hôpital La Pitié Salpétrière, Paris, France
| | - Philippe Mathurin
- Service des maladies de l'appareil digestif, Hôpital Claude Huriez, Lille, France
| | | | - Guido Gerken
- Gastroenterology and Hepatology Unit, University of Essen, Essen, Germany
| | - Michael Manns
- Gastroenterology and Hepatology Unit, University of Hanover, Hanover, Germany
| | | | - Dominique Larrey
- Service Hépato-Gastro-Entérologie, Hôpital Saint-Eloi, Montpellier, France
| | - Sylvie Radenne
- Service Hépatologie et Gastro-Entérologie, Hôpital Croix-Rousse, Lyon, France
| | - Christophe Duvoux
- Service d'Hépato-Gastro-Entérologie, Hôpital Henri MondorCréteil, France
| | - Vincent Leroy
- Département d’Hépato-Gastroentérologie, Hôpital de Grenoble, Grenoble, France
| | | | - Jamila Faivre
- Centre Hépatobiliaire Paul Brousse and Inserm U 1193, Villejuif, France
- Hôpital Universitaire Paul Brousse, Villejuif, France
| | - Nicolas Moniaux
- Centre Hépatobiliaire Paul Brousse and Inserm U 1193, Villejuif, France
| | | | | | | | - Didier Samuel
- Centre Hépatobiliaire Paul Brousse and Inserm U 1193, Villejuif, France
- Hôpital Universitaire Paul Brousse, Villejuif, France
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25
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Bessone F, Hernandez N, Lucena MI, Andrade RJ. The Latin American DILI Registry Experience: A Successful Ongoing Collaborative Strategic Initiative. Int J Mol Sci 2016; 17:313. [PMID: 26938524 PMCID: PMC4813176 DOI: 10.3390/ijms17030313] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 02/17/2016] [Accepted: 02/19/2016] [Indexed: 02/07/2023] Open
Abstract
Drug induced liver injury (DILI) is a rare but well recognized serious adverse reaction. Pre-marketing studies may not detect liver injury, and DILI becomes very often apparent after the drug is launched to the market. Specific biomarkers for DILI prediction or diagnosis are not available. Toxic liver reactions present with a wide spectrum of phenotypes and severity, and our knowledge on the mechanisms underlying idiosyncratic reactions and individual susceptibility is still limited. To overcome these limitations, country-based registries and multicenter research networks have been created in Europe and North America. Reliable epidemiological data on DILI in Latin America (LA), a region with a large variety of ethnic groups, were however lacking. Fortunately, a LA network of DILI was set up in 2011, with the support of the Spanish DILI Registry from the University of Malaga. The primary aim of the Latin DILI Network (LATINDILIN) Registry was to prospectively identify bona fide DILI cases and to collect biological samples to study genetic biomarkers. Physicians involved in the project must complete a structured report form describing the DILI case presentation and follow-up which is submitted to a Coordinator Center in each country, where it is further assessed for completeness. During the last four years, several LA countries (Argentina, Uruguay, Chile, Mexico, Paraguay, Brazil, Ecuador, Peru, Venezuela and Colombia) have joined the network and committed with this project. At that point, to identify both our strengths and weaknesses was a very important issue. In this review, we will describe how the LATINDILI Registry was created. The aims and methods to achieve these objectives will be discussed in depth. Additionally, both the difficulties we have faced and the strategies to solve them will be also pinpointed. Finally, we will report on our preliminary results, and discuss ideas to expand and to keep running this network.
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Affiliation(s)
- Fernando Bessone
- Hospital Provincial del Centenario, University of Rosario School of Medicine, Urquiza 3101, 2000 Rosario, Argentina.
| | - Nelia Hernandez
- Hospital de Clínicas, Facultad de Medicina, UdelaR, Av Italia s/n, 11600 Montevideo, Uruguay.
| | - M Isabel Lucena
- Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Blvd. L Pasteur 32, 29071 Málaga, Spain.
| | - Raúl J Andrade
- Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Blvd. L Pasteur 32, 29071 Málaga, Spain.
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26
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Mendizabal M, Silva MO. Liver transplantation in acute liver failure: A challenging scenario. World J Gastroenterol 2016; 22:1523-1531. [PMID: 26819519 PMCID: PMC4721985 DOI: 10.3748/wjg.v22.i4.1523] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/14/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.
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27
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Fulminant presentation of autoimmune hepatitis: clinical features and early predictors of corticosteroid treatment failure. Eur J Gastroenterol Hepatol 2015; 27:644-8. [PMID: 25923939 DOI: 10.1097/meg.0000000000000353] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS Classical features of autoimmune hepatitis (AIH) may be altered during the abrupt onset of the disease. Corticosteroid therapy can be life-saving, but its use in the fulminant presentation of AIH (F-AIH) remains controversial. We aimed to assess the clinical features of patients with F-AIH and to describe the role of corticosteroids in this population. PATIENTS AND METHODS We retrospectively analyzed 154 adult patients with fulminant hepatic failure who were admitted to six liver transplantation (LT) programs. The AIH simplified criteria were used to identify patients with F-AIH. RESULTS We identified 40 (26%) patients with F-AIH. Compared with other etiologies, patients with F-AIH presented a longer interval from jaundice to encephalopathy (26 vs. 16 days, P=0.02) and a lower Model for End-Stage Liver Disease (MELD) score on admission (29 vs. 33, P=0.002). Overall, 25 (62%) patients with F-AIH underwent LT, eight (20%) patients survived, and seven (18%) died without LT. Seventeen patients received corticosteroids therapy, of whom seven (41%) survived without LT. Among the treated patients, higher MELD score and encephalopathy grade of 3 or more were associated significantly with corticosteroid failure. CONCLUSION Patients with F-AIH have a more indolent presentation compared with the non-F-AIH population. Altogether, only eight (20%) patients presenting with F-AIH survived without LT. A subset of patients with F-AIH and an initial MELD score less than 27 and low-grade hepatic encephalopathy might benefit from administration of corticosteroids.
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28
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Goldberg DS, Forde KA, Carbonari DM, Lewis JD, Leidl KBF, Reddy KR, Haynes K, Roy J, Sha D, Marks AR, Schneider JL, Strom BL, Corley DA, Lo Re V. Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology 2015; 148:1353-61.e3. [PMID: 25733099 PMCID: PMC4446162 DOI: 10.1053/j.gastro.2015.02.050] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Revised: 02/24/2015] [Accepted: 02/24/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Medications are a major cause of acute liver failure (ALF) in the United States, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated health care system that approximates a population-based cohort. METHODS We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) health care system between January 1, 2004, and December 31, 2010. We included all KPNC members age 18 years and older with 6 months or more of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. RESULTS Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 events (18.8%), antimicrobials in 2 events (6.3%), and miscellaneous medications in 6 events (18.8%). One patient with acetaminophen-induced ALF died (5.6%; 0.06 events/1,000,000 person-years) compared with 3 patients with non-acetaminophen-induced ALF (21.4%; 0.18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06-2.35) and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59-1.63), respectively. CONCLUSIONS Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.
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Affiliation(s)
- David S Goldberg
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Kimberly A Forde
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Dean M Carbonari
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - James D Lewis
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kimberly B F Leidl
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - K Rajender Reddy
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kevin Haynes
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; HealthCore, Inc, Wilmington, Delaware
| | - Jason Roy
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Daohang Sha
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Amy R Marks
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Jennifer L Schneider
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Brian L Strom
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Rutgers Biomedical and Health Sciences, Newark, New Jersey
| | - Douglas A Corley
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Vincent Lo Re
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Obed A, Stern S, Jarrad A, Lorf T. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients. World J Gastroenterol 2015; 21:4423-4426. [PMID: 25892898 PMCID: PMC4394109 DOI: 10.3748/wjg.v21.i14.4423] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/12/2015] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed.
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