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Ge J, Kim WR, Kwong AJ. Common definitions and variables are needed for the United States to join the conversation on acute-on-chronic liver failure. Am J Transplant 2024; 24:1755-1760. [PMID: 38977243 PMCID: PMC11439574 DOI: 10.1016/j.ajt.2024.06.021] [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: 02/10/2024] [Revised: 06/19/2024] [Accepted: 06/28/2024] [Indexed: 07/10/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a variably defined syndrome characterized by acute decompensation of cirrhosis with organ failures. At least 13 different definitions and diagnostic criteria for ACLF have been proposed, and there is increasing recognition that patients with ACLF may face disadvantages in the current United States liver allocation system. There is a need, therefore, for more standardized data collection and consensus to improve study design and outcome assessment in ACLF. In this article, we discuss the current landscape of transplantation for patients with ACLF, strategies to optimize organ utility, and data opportunities based on emerging technologies to facilitate improved data collection.
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Affiliation(s)
- Jin Ge
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California - San Francisco, San Francisco, California, USA
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Allison J Kwong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
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Orosz L, Sárvári KP, Dernovics Á, Rosztóczy A, Megyeri K. Pathogenesis and clinical features of severe hepatitis E virus infection. World J Virol 2024; 13:91580. [PMID: 38984076 PMCID: PMC11229844 DOI: 10.5501/wjv.v13.i2.91580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/08/2024] [Accepted: 04/15/2024] [Indexed: 06/24/2024] Open
Abstract
The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.
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Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Károly Péter Sárvári
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Áron Dernovics
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - András Rosztóczy
- Department of Internal Medicine, Division of Gastroenterology, University of Szeged, Szeged 6725, Csongrád-Csanád, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
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Fantilli A, López Villa SD, Zerega A, Di Cola G, López L, Wassaf Martínez M, Pisano MB, Ré VE. Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure. Virol J 2021; 18:245. [PMID: 34886883 PMCID: PMC8662871 DOI: 10.1186/s12985-021-01714-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023] Open
Abstract
Background The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.
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Affiliation(s)
- Anabella Fantilli
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina.
| | | | | | - Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Luis López
- Instituto Modelo de Cardiología, Córdoba, Argentina
| | | | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Viviana Elizabeth Ré
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
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Wang F, Sun W, Xiao Q, Liang C, Jiang S, Lian Y, Shao J, Tan S, Zheng S. Peripheral T lymphocytes predict the severity and prognosis in patients with HBV-related acute-on-chronic liver failure. Medicine (Baltimore) 2021; 100:e24075. [PMID: 33592861 PMCID: PMC7870253 DOI: 10.1097/md.0000000000024075] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome with high mortality. Biomarkers are urgently needed to predict the prognosis of HBV-ACLF. Recent evidence suggests a key role for immune system in the pathology of HBV-ACLF. Here, we analyzed the correlation between peripheral blood T lymphocytes and the severity and prognosis in HBV-ACLF patients. METHOD Sixty-six patients with HBV-ACLF received conventional medical treatments for 4 weeks. Twenty-five healthy subjects and 20 HBV patients were enrolled for comparison. We determined white blood cell count, lymphocytes, CD3+, CD4+ and CD8+ T cells, and CD4+CD25+ Treg cells in the blood of all subjects. Their associations with laboratory parameters before or after treatments were statistically analyzed. RESULT The results showed that compare normal subjects and chronic hepatitis B patients, HBV-ACLF patients had significantly increased white blood count, CD4+ T cells and decreased lymphocytes, CD3+ T cells, and Treg cells. Correlation analysis showed that white blood cell, lymphocytes, and peripheral T lymphocytes were correlated with prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores. After treatment, white blood cell, lymphocytes, and peripheral T lymphocytes were also correlated with PTA and MELD scores. Additionally, total bilirubin (TBIL), alanine aminotransferase (ALT), international standard ratio (INR), MELD, and white blood cell count were potential prognostic criteria for HBV-ACLF patients. CONCLUSION HBV-ACLF patients had depletion and dysfunction of immune system. Changes of peripheral T lymphocytes were closely related to the pathogenesis and prognosis of disease. Our results may contribute to predict the severity of HBV-ACLF, and provide a prognosis response to improve the treatment of HBV-ACLF.
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Affiliation(s)
- Feixia Wang
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weiwei Sun
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qian Xiao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chongfeng Liang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shulian Jiang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanan Lian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
| | - Shanzhong Tan
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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Tang C, Cao D, Wang L. The association between SNPs and hepatitis B virus related acute-on-chronic liver failure. INFECTION GENETICS AND EVOLUTION 2020; 86:104615. [PMID: 33152536 DOI: 10.1016/j.meegid.2020.104615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/24/2020] [Accepted: 10/29/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This study intended to investigate the association between ten single nucleotide polymorphisms (rs1143623, rs12692386, rs1799983, rs2297518, rs2910164, rs3129859, rs4251961, rs4846085, rs641738, rs873457) with susceptibility and prognosis of hepatitis B related acute-on-chronic liver failure (HBV-ACLF). METHODS This is a hospital-based case-control study included 274 patients with HBV-ACLF and 534 patients with chronic hepatitis B. The patients who were successfully followed were divided into the survival group and the death group according to the clinical outcome during the hospitalization and 90 days after discharge. The ten SNPs were genotyped in all subjects by using imLDR. Genotype, allele frequency, dominant model, recessive model and codominant model were constructed to investigate the association between single nucleotide polymorphisms with susceptibility and prognosis of HBV-ACLF. RESULTS The genotype distribution of rs1143623 was statistically different between the two groups (P = 0.04), but the allele frequency was not statistically significant (P = 0.44). GC and GG + CG genotypes at rs1143623 reduced the risk of HBV-ACLF. There were only two GG and GT genotypes in rs1799983 in our study, and the genotype and allele frequency were statistically different between the death group and the survival group (P = 0.027, P = 0.023). Patients with T allele may reduce the risk of death in patients with HBV-ACLF. The genotype and allele frequency of rs2297518 showed no significant difference. In dominant models, patients with GA + AA genotypes at rs2297518 had a reduced risk of death.
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Affiliation(s)
- Congchen Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Dan Cao
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Lichun Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
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Abstract
PURPOSE OF REVIEW Hospitalizations due to complications of cirrhosis continue to rise. Patients with chronic liver disease who suffer acute decompensation [acute-on-chronic liver failure (ACLF)] often require intensive care support and are at high risk for short-term mortality. Given the high mortality rate associated with this condition is incumbent on intensive care providers who care for this patient population to have a working knowledge of ACLF with its associated complications, management strategies and prognosis. RECENT FINDINGS Recognizing ACLF as a distinct clinical entity has gained international attention in recent years though a consensus does not exist. There has been progress on better defining this clinical entity and recent studies have begun to address the critical care needs of these patients. Additional studies are required to define the best care practices for patients with ACLF. SUMMARY ACLF is a condition occurring in patients with chronic liver disease which is commonly associated with a need for intensive care support and carries a high risk of short-term mortality. Intensive care specialists must be familiar with diagnosis and management of this condition.
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Liu X, Li C, Zhu J, Li W, Zhu Q. Dysregulation of FTX/miR-545 signaling pathway downregulates Tim-3 and is responsible for the abnormal activation of macrophage in cirrhosis. J Cell Biochem 2019; 120:2336-2346. [PMID: 30304545 DOI: 10.1002/jcb.27562] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 08/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Accumulating evidence has suggested the involvement of miR-545 and long noncoding RNA (lncRNA) FTX in a wide range of diseases. Therefore, this study aimed to investigate the molecular mechanism underlying the function of miR-545 and lncRNA FTX in hepatitis B virus (HBV)-related cirrhosis. METHOD The level of Tim-3, TLR-4, and endotoxin was detected in CD14+ , CD14 + CD16 + , and CD14 + CD16 - monocytes isolated from both patients with cirrhosis and healthy controls. ELISA assays were performed to detect the effect of Lipopolysaccharide (LPS) or FTX on the expression of tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), IL-1β, and Nuclear factor kB (NF-kB). In-silico analysis, luciferase assay, real-time polymerase chain reaction (PCR), and Western blot analysis were utilized to determine the regulatory relationship between miR-545 and Tim-3. RESULTS The levels of Tim-3, Tim-3 MIF and endotoxin were reduced in the CD14+ monocytes isolated from patients with cirrhosis. In addition, the level of Tim-3 was also decreased in the CD14 + CD16 - monocytes isolated from patients with cirrhosis, whereas the level of Tim-3 in CD14 + CD16 + monocytes showed no evident difference between healthy controls and patients with cirrhosis. Furthermore, TLR-4 was highly expressed in CD14 + CD16 + monocytes isolated from patients with cirrhosis, whereas Tim-3 was negatively regulated by endotoxin and the correlation coefficient was -0.5287. After the LPS stimulation, although the level of TNF-a, IL-6, IL-1β, and NF-kB was higher in both patients with cirrhosis and healthy controls, the effect of LPS in patients with cirrhosis was much more significant. In addition, the cirrhosis group showed a lower level of FTX and Tim-3, but a higher level of miR-545. Moreover, miR-545 directly bound to the 3'untranslated region (3'UTR) of Tim-3 and inhibited the luciferase activity of cells cotransfected with miR-545 mimics and wild-type 3'UTR of Tim-3. Furthermore, FTX downregulated the expression of miR-545, TNF-a, IL-6, IL-1β, and NF-kB, but upregulated the expression of Tim-3. CONCLUSION The results of this study confirmed the effect of FTX, miR-545, and Tim-3 on the expression of inflammatory cytokines, the lymphocyte/monocyte ratio, and the severity and prognosis of HBV-related cirrhosis.
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Affiliation(s)
- Xia Liu
- Department of Gastroenterology, Shandong Provincial Hospital Afflilated to Shandong University, Jinan, Shandong, China.,Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China
| | - Cong Li
- Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Zhu
- Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China
| | - Wenshuai Li
- Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Afflilated to Shandong University, Jinan, Shandong, China
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Satsangi S, Duseja A, Sachdeva M, Tomer S, Arora SK, Taneja S, Dhiman RK, Chawla YK. Monocyte human leukocyte antigen - Antigen D related, neutrophil oxidative burst and cytokine analysis in patients of decompensated cirrhosis with and without acute-on chronic liver failure. PLoS One 2018; 13:e0200644. [PMID: 30020985 PMCID: PMC6051623 DOI: 10.1371/journal.pone.0200644] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 06/30/2018] [Indexed: 12/13/2022] Open
Abstract
Background and aim Due to a dysregulated immune response, patients with acute-on-chronic liver failure (ACLF) have increased risk of infection and multi organ failure in comparison to compensated cirrhosis. The comparative data on the presence of ‘immune paresis’ in patients with ACLF and decompensated cirrhosis without ACLF is not available. Aim of the present study was to compare the immunological parameters in patients with decompensated cirrhosis with and without ACLF. Methodology In a prospective study, 76 patients with decompensated cirrhosis with (n = 38) and without (n = 38) ACLF and 10 healthy controls (HC) were evaluated for monocytic human leukocyte antigen–antigen D Related (HLA-DR) expression, mean density of HLA-DR expressed on the surface of these cells, neutrophil oxidative burst (NOB) capacity and serum levels of cytokines (IL-1, IL-6, IL-8, IL10, IL-12, and TNF-α). Results Patients of decompensated cirrhosis with and without ACLF demonstrated significantly lower mean percentage of monocytes expressing HLA-DR and quantitative increase in the NOB after stimulation with PMA when compared to HC. However there was no difference in mean percentage of monocytes with HLA-DR expression (43.61±26.56% vs. 43.10±20.98%) (p = 0.91), mean density of HLA-DR expression on the surface (30.34±29.32 vs. 41.71±52.13) (p = 0.42) and quantitative increase in NOB after stimulation with PMA (16.55±11.91 vs. 17.24±16.18) (p = 0.47) amongst patients with decompensated cirrhosis with and without ACLF. Patients with ACLF had significantly higher pro-inflammatory and anti-inflammatory cytokines in comparison to patients with decompensated cirrhosis without ACLF. Conclusion Patients with decompensated cirrhosis demonstrate a component of immune-paresis, however there is similar impairment in HLA–DR expression and NOB capacity in patients with and without ACLF. Both inflammatory and anti-inflammatory cytokines are increased in patients with ACLF in comparison to patients with decompensated cirrhosis without ACLF.
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Affiliation(s)
- Sandeep Satsangi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
- * E-mail:
| | - Meenakshi Sachdeva
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shallu Tomer
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil K. Arora
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Bajaj JS, Reddy RK, Tandon P, Wong F, Kamath PS, Biggins SW, Garcia-Tsao G, Fallon M, Maliakkal B, Lai J, Vargas HE, Subramanian RM, Thuluvath P, Thacker LR, OʼLeary JG. Prediction of Fungal Infection Development and Their Impact on Survival Using the NACSELD Cohort. Am J Gastroenterol 2018; 113:556-563. [PMID: 29257141 DOI: 10.1038/ajg.2017.471] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 11/02/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Bacterial infections are associated with negative outcomes in cirrhosis but fungal infections are being increasingly recognized. The objective of this study is to define risk factors for fungal infection development and impact on 30-day survival. METHODS In a large, multi-center cirrhotic inpatient cohort, demographics, cirrhosis details, intensive care unit (ICU), organ failures/acute-on-chronic liver failure (ACLF), and 30-day survival were compared between patients without infections and with bacterial infections alone, with those with fungal infections. Variables associated with fungal infection development were determined using multi-variable regression. Ordinal variables (0=no infection, 1=community-acquired bacterial infection, 2=nosocomial bacterial, and 3=fungal infection) were input into a 30-day survival model. RESULTS A total of 2,743 patients (1,691 no infection, 918 bacterial, and 134 fungal infections) were included. Patients with fungal infection, all of which were nosocomial, were more likely to be admitted with bacterial infections, on spontaneous bacterial peritonitis prophylaxis, and have diabetes and advanced cirrhosis. Bacterial infection types did not predict risk for fungal infections. Multi-variable analysis showed male gender to be protective, whereas diabetes, longer stay, ICU admission, acute kidney injury (AKI), and admission bacterial infection were associated with fungal infection development (area under the curve (AUC)=0.82). Fungal infections were associated with significantly higher ACLF, inpatient stay, ICU admission, and worse 30-day survival. The case fatality rate was 30% with most fungal infections but >50% for fungemia and fungal peritonitis. On a multi-variable analysis, age, AKI, model for end-stage liver disease, ICU admission, and ordinal infection variables impaired survival (P<0.0001, AUC=0.83). CONCLUSIONS Fungal infections are associated with a poor 30-day survival in hospitalized cirrhotic patients compared with uninfected patients, and those with bacterial infections. Patients with diabetes, AKI, and those with an admission bacterial infection form a high-risk subgroup.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | | | | | | | | | - Scott W Biggins
- University of Colorado, Denver, Colorado, USA.,University of Washington, Seattle, Washington, USA
| | | | - Michael Fallon
- University of Texas, Houston, Texas, USA.,University of Arizona, Phoenix, Arizona, USA
| | - Benedict Maliakkal
- University of Rochester, Rochester, New York, USA.,University of Tennessee, Memphis, Tennessee, USA
| | - Jennifer Lai
- University of California, San Francisco, California, USA
| | | | | | | | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Jacqueline G OʼLeary
- Baylor University Medical Center, Dallas, Texas, USA.,Dallas VA Medical Center, Dallas, Texas, USA
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A novel dynamic model for predicting outcome in patients with hepatitis B virus related acute-on-chronic liver failure. Oncotarget 2017; 8:108970-108980. [PMID: 29312583 PMCID: PMC5752496 DOI: 10.18632/oncotarget.22447] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 10/27/2017] [Indexed: 12/11/2022] Open
Abstract
Aim It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients. Methods 305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC). Results The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001). Conclusion The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.
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11
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Zheng YX, Zhong X, Li YJ, Fan XG. Performance of scoring systems to predict mortality of patients with acute-on-chronic liver failure: A systematic review and meta-analysis. J Gastroenterol Hepatol 2017; 32:1668-1678. [PMID: 28303605 DOI: 10.1111/jgh.13786] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 03/03/2017] [Accepted: 03/13/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Acute-on-chronic liver failure (ACLF) has characteristic feature of multisystem organ failure, rapid progression, and low early transplant-free survival. We performed a meta-analysis to determine the accuracy of five scoring systems in predicting mortality of ACLF patients. METHODS A systematic database search was performed, and retrieved articles were graded according to methodological quality. Collated data was meta-analyzed by hierarchical summarized receiver operating characteristic model and bivariate model to evaluate the diagnostic accuracy of scoring systems. RESULTS Of 4223 studies identified, 26 studies involving 4732 ACLF patients were included. The model of end-stage liver disease (MELD) score was found to have largest the area under summarized receiver operating characteristic (AUROC) (0.82) compared with other estimated scoring systems, especially for 3-month mortality. MELD serum sodium (MELD-Na) score showed homologous high accuracy, with the AUROC was 0.81. However, meta-analyses of 16 studies showed that Child-Pugh-Turcotte score had least AUROC (0.71). Sequential organ failure assessment (SOFA) score presented moderately lower diagnostic accuracy, with AUROC being 0.73. Moreover, chronic liver failure-SOFA score presented excellent accuracy of prognostication with highest diagnostic odds ratios. CONCLUSION This review demonstrated that MELD had moderate diagnostic accuracy to predict mortality of ACLF patients. Considering the expectative diagnostic value, chronic liver failure-SOFA could be regarded as a promising replacement of MELD. To improve the predictive power of scoring systems, multicenter prospective studies of large sample sizes with long-term follow-up are needed.
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Affiliation(s)
- Yi-Xiang Zheng
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Zhong
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
| | - Ya-Jun Li
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
| | - Xue-Gong Fan
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
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12
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Olson JC. Acute-on-chronic and Decompensated Chronic Liver Failure: Definitions, Epidemiology, and Prognostication. Crit Care Clin 2017; 32:301-9. [PMID: 27339672 DOI: 10.1016/j.ccc.2016.02.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure.
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Affiliation(s)
- Jody C Olson
- Hepatology and Critical Care Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 1023, Kansas City, KS 66160, USA.
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13
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Tornai T, Vitalis Z, Sipeki N, Dinya T, Tornai D, Antal-Szalmas P, Karanyi Z, Tornai I, Papp M. Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection. Liver Int 2016; 36:1628-1638. [PMID: 27031405 DOI: 10.1111/liv.13133] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 03/29/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Innate immune system dysfunction is common in advanced cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and macrophages express the scavenger receptor CD163, which is regulated by inflammatory mediators. Cleavage of the receptor leads to the formation of soluble (s)CD163 that represents an anti-inflammatory response. We aimed to study the clinical importance of sCD163 in cirrhosis. METHODS Sera of 378 patients were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute decompensation (AD)]. A 5-year follow-up observational study was conducted to assess the possible association between sCD163 level and poor disease outcomes. RESULTS sCD163 level was associated with disease severity, but not with the presence of varices or prior variceal bleeding. In outpatients, sCD163 level did not predict the development of disease-specific complications or the long-term mortality. In patients with AD episode, sCD163 level was significantly higher compared to outpatients but only in the presence of bacterial infection (INF) (AD-INF:4586, AD-NON-INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001, respectively). sCD163 level gradually increased according to severity of infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was associated with increased mortality rate (42% vs. 17%, P < 0.001) and was identified as an independent predictor of 28-day mortality (hazard ratio:2.96, 95% confidence intervals:1.27-6.95) in multivariate Cox-regression model comprising aetiology, co-morbidity, model for end-stage liver disease score and leucocyte count as covariates. CONCLUSIONS High sCD163 level is useful to identify patients with high-risk of death during an AD episode complicated by bacterial infection. This finding serves as an additional hint towards the significance of anti-inflammatory response during bacterial infection.
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Affiliation(s)
- Tamas Tornai
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Nora Sipeki
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamas Dinya
- Institute of Surgery, University of Debrecen, Debrecen, Hungary
| | - David Tornai
- Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsolt Karanyi
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Istvan Tornai
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
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14
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Zhang J, Gao S, Duan Z, Hu KQ. Overview on acute-on-chronic liver failure. Front Med 2016; 10:1-17. [PMID: 26976617 DOI: 10.1007/s11684-016-0439-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Accepted: 01/28/2016] [Indexed: 12/11/2022]
Abstract
Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.
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Affiliation(s)
- Jing Zhang
- Department of Hepatitis C and Drug Induced Liver Injury, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Shan Gao
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Zhongping Duan
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China.
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine, Medical Center, Orange, CA, 92868, USA.
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15
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Asrani SK, Simonetto DA, Kamath PS. Acute-on-Chronic Liver Failure. Clin Gastroenterol Hepatol 2015; 13:2128-39. [PMID: 26188138 PMCID: PMC4625547 DOI: 10.1016/j.cgh.2015.07.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 06/30/2015] [Accepted: 07/09/2015] [Indexed: 12/18/2022]
Abstract
Over the past 2 decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF thus is characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short-term mortality. Multiple organ failure and an increased risk for mortality are key to the diagnosis of ACLF. The prevalence of ACLF ranges from 24% to 40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using the following 4-part model: predisposing event, injury caused by a precipitating event, response to injury, and organ failure. Although several mathematic scores have been proposed for identifying outcomes with ACLF, it is as yet unclear whether these organ failure scores are truly prognostic or only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation before onset of irreversible multiple organ failure.
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Affiliation(s)
- Sumeet K Asrani
- Division of Hepatology, Baylor University Medical Center, Dallas, Texas
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Patrick S Kamath
- Division of Hepatology, Baylor University Medical Center, Dallas, Texas; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
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16
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Sun FK, Wang K. Application of glucocorticoids in liver failure. Shijie Huaren Xiaohua Zazhi 2015; 23:4611-4616. [DOI: 10.11569/wcjd.v23.i29.4611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The pathogenesis of liver failure is complicated. Currently, there is a lack of effective measures for the treatment of liver failure. Immune-mediated liver injury plays an important role in the early pathogenesis of liver failure. As an immune and inflammatory inhibitor, glucocorticoids can be considered one of the methods for the treatment of liver failure. However, the application of steroids in the treatment of liver failure in current clinical practice is controversial. This paper summarizes the progress in glucocorticoid use for the treatment of liver failure in recent years. Besides, the focus of controversy on glucocorticoids for treatment of liver failure is also discussed.
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17
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Mikolasevic I, Milic S, Radic M, Orlic L, Bagic Z, Stimac D. Clinical profile, natural history, and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Wien Klin Wochenschr 2015; 127:283-9. [PMID: 25821053 DOI: 10.1007/s00508-015-0707-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Accepted: 01/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection culminating in the end-organ dysfunction. Its main features are reversibility and high short-term mortality due to multiorgan failure (MOF). We aimed to analyze the clinical, laboratory, and etiological predictors of mortality and outcome in patients with ACLF. METHODS We evaluated 1215 patients with chronic liver disease; 90 patients met the criteria for ACLF. RESULTS The most common cause of underlying chronic liver disease was alcohol, and the most common acute insult (AI) in those patients was superadded alcoholic hepatitis. In all, 50% of all patients died within 30 days (71.1 % within the first 14 days after admission). MOF was the cause of death in 70 % of cases. On multivariate analysis, high serum potassium, serum creatinine higher than 90 µmol/L, and C-reactive protein > 30 mg/L were found to be independent baseline predictors of mortality. APACHE II (Acute Physiology and Chronic Health Evaluation II) score was the best predictor of short-term mortality (area under the curve (AUC), 0.878). MOF was a valuable predictor of mortality (AUC, 0.923); 33 of 35 patients who had MOF at admission died. Presence of positive systemic inflammatory response syndrome criteria at admission was also correlated with in-hospital mortality (AUC, 0.742). CONCLUSION ACLF is a serious condition with high short-term mortality. Because ACLF is reversible, it is necessary to identify at-risk patients as soon as possible to treat acute events in a timely manner.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, Division of Internal Medicine, University Hospital Rijeka, Krešimirova 42, Rijeka, Croatia,
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18
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Siba Y, Obiokoye K, Ferstenberg R, Robilotti J, Culpepper-Morgan J. Case report of acute-on-chronic liver failure secondary to diffuse large B-cell lymphoma. World J Gastroenterol 2014; 20:16774-16778. [PMID: 25469050 PMCID: PMC4248225 DOI: 10.3748/wjg.v20.i44.16774] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2014] [Revised: 08/04/2014] [Accepted: 09/30/2014] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure is a rare presentation of hematologic malignancy. Acute on chronic liver failure (ACLF) is a newly recognized clinical entity that describes acute hepatic decompensation in persons with preexisting liver disease. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin’s lymphoma (NHL) with increasing incidence in older males, females and blacks. However, it has not yet been reported, to present with acute liver failure in patients with preexisting chronic liver disease due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection. We describe a case of ACLF as the presenting manifestation of DLBCL in an elderly black man with HIV/HCV co-infection and prior Hodgkin’s disease in remission for three years. The rapidly fatal outcome of this disease is highlighted as is the distinction of ACLF from decompensated cirrhosis. Due to the increased prevalence of HIV/HCV co-infection in the African American 1945 to 1965 birth cohort and the fact that both are risk factors for chronic liver disease and NHL we postulate that the incidence of NHL presenting as ACLF may increase.
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Abstract
The Model for End-Stage Liver Disease (MELD) has been the single best predictor of outcome of the progression of cirrhosis. Acute-on-chronic liver failure (ACLF) has been proposed as an alternative path in the natural history of cirrhosis. ACLF occurs in patients with chronic liver disease and is characterized by a precipitating event, resulting in acute deterioration in liver function, multiorgan system failure, and high short-term mortality. In this review, the natural course of patients with ACLF, especially as it relates to management of cirrhotic patients on the transplant waiting list, and its impact on liver transplantation outcomes are defined.
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20
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Rong YH, Wan ZH, Song H, Li YL, Zhu B, Zang H, Zhao Y, Liu HL, Zhang AM, Xiao L, Xin SJ, You SL. Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+natural killer-like T cells in patients with chronic hepatitis B. ACTA ACUST UNITED AC 2014; 83:76-81. [PMID: 24397461 DOI: 10.1111/tan.12278] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 11/26/2013] [Accepted: 12/02/2013] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+ natural killer like T (NKT-like) cells in chronic hepatitis B (CHB) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 CHB patients and 60 healthy controls. Tim-3+CD14+ cells and Tim-3+CD3+CD16/CD56+ cells were analyzed by flow cytometry. Results showed that expression of Tim-3 was significantly increased on both the monocytes and NKT-like cells in CHB patients than in controls (P = 0.002 and P < 0.001, respectively). Tim-3 levels on monocytes and NKT-like cells were further upregulated in patients with acute-on-chronic liver failure (ACLF). In addition, we assessed the correlation of Tim-3 expression with levels of alanine aminotransferase (ALT) and tumor necrosis factor alpha (TNF-α). Data revealed that Tim-3 expression on both monocytes and NKT-like cells was positively correlated with level of ALT (r = 0.59, P < 0.001, and r = 0.60, P < 0.001, respectively), whereas Tim-3 expression on NKT-like cells was negatively correlated with serum level of TNF-α (r = -0.54, P < 0.001) in CHB patients. Our results suggest that Tim-3 may play important roles in the pathogenesis of CHB.
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Affiliation(s)
- Y-H Rong
- Medical School of Chinese PLA, Beijing, China; Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China
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21
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Kumar A, Saraswat VA. Hepatitis E and Acute-on-Chronic Liver Failure. J Clin Exp Hepatol 2013; 3:225-30. [PMID: 25755504 PMCID: PMC3940130 DOI: 10.1016/j.jceh.2013.08.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2013] [Accepted: 08/26/2013] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials.
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Key Words
- ACLF, acute-on-chronic liver failure
- APASL, Asia–Pacific Association for the Study of Liver
- AVH, acute viral hepatitis
- CHB, chronic hepatitis B
- HAV, hepatitis A virus
- HBV, hepatitis B virus
- HEV, hepatitis E virus
- HEV-ACLF, HEV-related ACLF
- ICU, intensive care unit
- INR, international normalized ratio
- MELD, model for end-stage liver disease
- acute-on-chronic liver failure
- cirrhosis
- hepatitis E virus
- liver failure
- ribavirin
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Affiliation(s)
- Ashish Kumar
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110 060, India,Address for correspondence: Ashish Kumar, Associate Professor & Consultant Hepatologist, Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110 060, India. Tel.: +91 9312792573.
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India
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Association of Toll-like receptor 3 polymorphisms with chronic hepatitis B and hepatitis B-related acute-on-chronic liver failure. Inflammation 2013; 36:413-8. [PMID: 23076446 DOI: 10.1007/s10753-012-9560-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and is responsible for recognizing viral pathogens. It has been reported that the TLR3 C1234T polymorphism is associated with various diseases. The aim of this study was to investigate whether TLR3 polymorphisms were correlated with susceptibility to chronic HBV infection. Two polymorphisms in the TLR3 gene, A952T and C1234T, were tested by direct sequencing in 452 chronic hepatitis B (CHB) patients and 462 healthy controls. Data showed that subjects carrying 1234CT genotype and TT genotype had 1.42-fold and 2.31-fold increased risk of chronic HBV infection compared to those with CC genotype (95 % confidence interval [CI] = 1.08-1.86, p = 0.012; 95 % CI = 1.34-3.96, p = 0.002, respectively). Further analysis revealed that the prevalence of 1234CT genotype and T allele was significantly increased in CHB patients with acute-on-chronic liver failure (ACLF) than those without ACLF (odds ratio [OR] = 1.55, p = 0.030; OR = 1.43, p = 0.040, respectively). These results indicate that TLR3 C1234T polymorphism could be a risk factor for the development of chronic HBV infection, especially the CHB-related ACLF.
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