|
1
|
Alemnew Ayal M, Admasu Dessie Y, Eshetie Nega M, Tsegaw Negash W, Mulat Berihun S. Treatment outcomes of chronic liver disease and associated factors among patients treated at hospitals in Bahir Dar city, north-west Ethiopia. BMC Gastroenterol 2025; 25:141. [PMID: 40050738 PMCID: PMC11883907 DOI: 10.1186/s12876-025-03719-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 02/20/2025] [Indexed: 03/10/2025] Open
Abstract
BACKGROUND Chronic liver disease is an on-going loss of liver structure and functions that lasts for at least six months. About 1.5 billion population suffered with this devastating disease worldwide. OBJECTIVES The aim of this study is to assess the treatment outcome and associated factors in patients with chronic liver disease at Bahir Dar, North West Ethiopia. METHOD A retrospective cross sectional study was conducted in both governmental and private hospitals of Bahir Dar city from January to August 2024. All patients with liver disease for at least six months and treated for their specific causes and/or complications were included. Descriptive statistics was employed to explain socio-demographic and relevant clinical characteristics. Binary logistic regression was employed to determine associated factors with poor treatment outcome. Texts, tables and charts used to present statistically and/or clinically significant results. A p-value of < 0.05 was considered statistically significant. RESULT A total of 213 medical records of chronic liver disease patients were reviewed. Most of the study participants (72.8%) were male and resided in rural area (63.8%). Viral hepatitis was the most frequent (60.0%) etiology followed by parasitic (23.0%) and alcohol misuse (11.5%). The percentage of patients with chronic liver disease who experienced poor treatment outcomes was 39.0% and 54.2% were not taking medications specifically tailored to their condition. Stages of chronic liver disease (AOR = 2.68; 95%CI: 1.50-4.76, p = 0.001), carcinoma status (AOR = 2.68; 95%CI: 1.07-6.68, p = 0.035) and treatment duration (AOR = 0.38; 95%CI: 0.15-0.98, p = 0.045) were independent predictors for poor treatment outcome. CONCLUSION The overall treatment outcome of chronic liver disease in our study was inadequate. Decompensated stages of cirrhosis, cellular carcinoma and shorter treatment duration were significant factors of treatment failure. Timely initiation of appropriate therapy is warranted to improve the treatment outcome of chronic liver disease patients.
Collapse
Affiliation(s)
- Melese Alemnew Ayal
- Department of clinical pharmacy, Bahir Dar Health Science College, Po.Box 684, Bahir Dar, Ethiopia.
| | - Yeshiwas Admasu Dessie
- Department of clinical pharmacy, GAMBY medical and business college, Bahir Dar, Ethiopia
| | | | | | | |
Collapse
|
|
2
|
Hudson D, Valentin Cortez FJ, León IHDD, Malhi G, Rivas A, Afzaal T, Rad MR, Diaz LA, Khan MQ, Arab JP. Advancements in MELD Score and Its Impact on Hepatology. Semin Liver Dis 2024. [PMID: 39515784 DOI: 10.1055/a-2464-9543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-Stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article will highlight the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation. LAY SUMMARY: Organ donation is crucial for the management of patients unwell with liver disease, but organs must be allocated fairly and equitably. One method used for this is the Model for End-Stage Liver Disease (MELD) score, which helps objectively decide which patient is a candidate for liver transplant. Over time, the MELD score has been refined to better reflect patients' needs. For example, the latest version, MELD 3.0, now considers factors like nutrition and gender. This should ensure that more patients, especially females, are candidates and receive appropriate access to liver transplantation. However, not every country uses the MELD score. Some countries have created their own scoring systems based on local research. This review will explain where the MELD score came from, how it has changed, the current characteristics of the MELD 3.0 score, and what the future might hold for organ allocation in liver transplants.
Collapse
Affiliation(s)
- David Hudson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | | | - Ivonne Hurtado Díaz de León
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Gurpreet Malhi
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Angelica Rivas
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Tamoor Afzaal
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Mahsa Rahmany Rad
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology and Hepatology, MASLD Research Center, University of California San Diego, San Diego, California
| | - Mohammad Qasim Khan
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| |
Collapse
|
|
3
|
Khanam A, Kottilil S. Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management. Front Med (Lausanne) 2021; 8:752875. [PMID: 34820395 PMCID: PMC8606418 DOI: 10.3389/fmed.2021.752875] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 10/07/2021] [Indexed: 12/21/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.
Collapse
Affiliation(s)
- Arshi Khanam
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
| |
Collapse
|
|
4
|
Sun L, Wen S, Li Q, Lai X, Chen R, Zhang Z, Li D, Sun S. L-theanine relieves acute alcoholic liver injury by regulating the TNF-α/NF-κB signaling pathway in C57BL/6J mice. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
|
|
5
|
Abstract
Alcoholic liver diseases (ALD) are a wide spectrum of liver diseases caused by excessive alcohol consumption, from steatosis to cirrhosis. The pathogenesis of ALD is insufficiently understood, but mainly involves oxidative stress, inflammation, bacterial translocation, cell death, and impaired regeneration. Despite numerous attempts to improve patient prognosis, the treatment of advanced ALD is still based on abstinence, brief exposure to corticosteroids, or liver transplantation. However, poor response to corticosteroids and the shortage of liver donors leaves patients helpless towards the end stages. Advances in basic research have contributed to a better understanding of ALD pathophysiology, which offers new options for treatment. In recent years, several therapies related to liver regeneration have been tested with promising prospects, including molecule-induced liver regeneration, stem cell transplantation, and full-function 3D artificial liver assembly. This review discusses mechanisms underlying ALD that can be considered therapeutic targets for regeneration-based treatments.
Collapse
Affiliation(s)
- Yi Lv
- Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China
| | - Kwok Fai So
- Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China
| | - Jia Xiao
- Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China.,Institute of Clinical Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| |
Collapse
|
|
6
|
Hyun J, Sun Z, Ahmadi AR, Bangru S, Chembazhi UV, Du K, Chen T, Tsukamoto H, Rusyn I, Kalsotra A, Diehl AM. Epithelial splicing regulatory protein 2-mediated alternative splicing reprograms hepatocytes in severe alcoholic hepatitis. J Clin Invest 2020; 130:2129-2145. [PMID: 31945016 PMCID: PMC7108908 DOI: 10.1172/jci132691] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 01/14/2020] [Indexed: 12/21/2022] Open
Abstract
Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality is known to correlate with hepatic accumulation of immature liver cells, why this occurs and how it causes death are unclear. Here, we demonstrate that expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA-splicing factor that maintains the nonproliferative, mature phenotype of adult hepatocytes, was suppressed in both human SAH and various mouse models of SAH in parallel with the severity of alcohol consumption and liver damage. Inflammatory cytokines released by excessive alcohol ingestion reprogrammed adult hepatocytes into proliferative, fetal-like cells by suppressing ESRP2. Sustained loss of ESRP2 permitted reemergence of a fetal RNA-splicing program that attenuates the Hippo signaling pathway and thus allows fetal transcriptional regulators to accumulate in adult liver. We further showed that depleting ESRP2 in mice exacerbated alcohol-induced steatohepatitis, enabling surviving hepatocytes to shed adult hepatocyte functions and become more regenerative, but threatening overall survival by populating the liver with functionally immature hepatocytes. Our findings revealed a mechanism that explains why liver failure develops in patients with the clinical syndrome of SAH, suggesting that recovery from SAH might be improved by limiting adult-to-fetal reprogramming in hepatocytes.
Collapse
Affiliation(s)
- Jeongeun Hyun
- Department of Medicine, Duke University Health System, Durham, North Carolina, USA
- Regeneration Next, Duke University School of Medicine, Durham, North Carolina, USA
- Institute of Tissue Regeneration Engineering (ITREN) and College of Science and Technology, Dankook University, Cheonan, South Korea
| | - Zhaoli Sun
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ali Reza Ahmadi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sushant Bangru
- Department of Biochemistry, School of Molecular and Cellular Biology, and
- Cancer Center at Illinois, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
| | - Ullas V. Chembazhi
- Department of Biochemistry, School of Molecular and Cellular Biology, and
| | - Kuo Du
- Department of Medicine, Duke University Health System, Durham, North Carolina, USA
| | - Tianyi Chen
- Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
| | - Hidekazu Tsukamoto
- Southern California Research Center for ALPD and Cirrhosis and Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, USA
- Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Ivan Rusyn
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, USA
| | - Auinash Kalsotra
- Department of Biochemistry, School of Molecular and Cellular Biology, and
- Cancer Center at Illinois, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
| | - Anna Mae Diehl
- Department of Medicine, Duke University Health System, Durham, North Carolina, USA
| |
Collapse
|
|
7
|
Point shear wave elastography predicts fibrosis severity and steatohepatitis in alcohol-related liver disease. Hepatol Int 2019; 14:270-280. [PMID: 31858403 DOI: 10.1007/s12072-019-10009-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 12/03/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Point shear wave elastography (pSWE) is a convenient noninvasive tool for assessing liver fibrosis in chronic liver disease. However, there is little information on the correlation between pSWE and the histological findings of alcohol-related liver disease (ALD). Thus, we investigated the diagnostic performance of pSWE in discriminating the fibrosis stage of patients with ALD. METHODS A total of 251 Korean patients with ALD were prospectively enrolled. The diagnostic performance of pSWE was evaluated on the basis of histological fibrosis severity according to Kleiner/Brunt et al.'s criteria and the Laennec classification. RESULTS Median liver stiffness on pSWE significantly increased as liver fibrosis stage increased (p < 0.001). Liver stiffness measurement proved to be an excellent diagnostic indicator in the evaluation of a ≥ F2 stage (area under the receiver operating characteristics curve [AUROC] 0.93; cutoff > 1.46 m/s), ≥ F3 stage (AUROC 0.90; cutoff > 1.47 m/s), and F4 stage (AUROC 0.91; cutoff > 1.66 m/s). Compared with noninvasive serum fibrosis tests, pSWE had the highest AUROC for predicting ≥ F2, ≥ F3, and = F4 stages and the highest Obuchowski index (0.931 ± 0.007; all p < 0.001). The AUROC for discriminating steatohepatitis from simple steatosis was 0.93 (> 1.49 m/s) and the AUROC for discriminating cirrhosis with steatohepatitis from cirrhosis without steatohepatitis was 0.92 (> 2.52 m/s). CONCLUSION pSWE not only gives an accurate indication of liver fibrosis stage in ALD, but also can allow patients with severe alcoholic steatohepatitis to begin corticosteroid treatment without exposing them to the risks of liver biopsy. CLINICAL TRIAL REGISTRATION Clincialtrials.gov Identifier NCT01943318.
Collapse
|
|
8
|
Maras JS, Das S, Sharma S, Sukriti S, Kumar J, Vyas AK, Kumar D, Bhat A, Yadav G, Choudhary MC, Sharma S, Kumar G, Bihari C, Trehanpati N, Maiwall R, Sarin SK. Iron-Overload triggers ADAM-17 mediated inflammation in Severe Alcoholic Hepatitis. Sci Rep 2018; 8:10264. [PMID: 29980709 PMCID: PMC6035223 DOI: 10.1038/s41598-018-28483-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 06/21/2018] [Indexed: 02/07/2023] Open
Abstract
Severe alcoholic hepatitis (SAH) is associated with iron accumulation in hepatocytes/macrophages. This possibly correlates with inflammation and stress but the exact mechanism still remains obscure. To understand the role of iron and the mechanisms of systemic iron-overload, a transcriptomic study of liver and Peripheral Blood -Mononuclear-Cells (PBMCs) was undertaken in SAH patients, with and without hepatic iron-overload. Our results show that iron-overload in hepatocytes/macrophages is due to an increased expression of iron-loading receptors and CD163 signaling cascade. Increase in labile iron pool induces expression of iron-loading, oxidative-stress and inflammatory genes along with expression of CD163 and ADAM17. Increased liver iron correlated with circulatory iron, TNF-α, macrophage activation (sCD163) and peroxide-stress in CD163+macrophages in patients who were iron-overloaded and died. Circulatory TNF-α and sCD163 levels were associated with poor outcome. Temporal iron/Fenton stress induced in healthy monocyte-derived-macrophage (MDM)/Tohoku-Hospital-Pediatrics-1(THP1) cells showed higher expression of iron-regulatory, inflammatory and oxidative-stress genes. These genes could be suppressed by iron-chelation. These results suggest that iron mediates inflammation through ADAM17 induction, resulting in macrophage activation and increased shedding of TNF-α and sCD163. These events could be inhibited with iron chelation or with ADAM17-blockade, postulating a therapeutic strategy for SAH patients with iron overload.
Collapse
Affiliation(s)
- Jaswinder Singh Maras
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Sukanta Das
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Sachin Sharma
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Sukriti Sukriti
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Jitendra Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ashish Kumar Vyas
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Dhananjay Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Adil Bhat
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Gaurav Yadav
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manish Chandra Choudhary
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Shvetank Sharma
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Guresh Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Shiv Kumar Sarin
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, 110070, India. .,Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| |
Collapse
|
|
9
|
Maras JS, Das S, Sharma S, Shasthry SM, Colsch B, Junot C, Moreau R, Sarin SK. Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome. Hepatol Commun 2018; 2:628-643. [PMID: 29881815 PMCID: PMC5983217 DOI: 10.1002/hep4.1176] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 02/27/2018] [Accepted: 03/02/2018] [Indexed: 12/20/2022] Open
Abstract
Severe alcoholic hepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra‐high performance liquid chromatography and high‐resolution mass spectrometry. Patients were categorized as responders (Rs, n = 52) and nonresponders (NRs, n = 8) at day 7 according to the Lille score. Multivariate projection analysis identified metabolites in the discovery cohort (n = 60) and assessed these in a validation cohort of 80 patients (60 Rs, 20 NRs). A total of 212 features were annotated by using metabolomic/biochemical/spectral databases for metabolite identification. After a stringent selection procedure, a total of nine urinary metabolites linked to mitochondrial functions significantly discriminated nonresponders, most importantly by increased acetyl‐L‐carnitine (12‐fold), octanoylcarnitine (4‐fold), decanoylcarnitine (4‐fold), and alpha‐ketoglutaric acid (2‐fold) levels. Additionally, urinary acetyl‐L‐carnitine and 3‐hydroxysebasic acid discriminated nonsurvivors (P < 0.01). These urinary metabolites significantly correlated to severity indices and mortality (r > 0.3; P < 0.01) and were associated with nonresponse (odds ratio >3.0; P < 0.001). In the validation cohort, baseline urinary acetyl‐L‐carnitine documented an area under the receiver operating curve of 0.96 (0.85‐0.99) for nonresponse prediction and a hazard ratio of 3.5 (1.5‐8.3) for the prediction of mortality in patients with SAH. Acetyl‐L‐carnitine at a level of >2,500 ng/mL reliably segregated survivors from nonsurvivors (P < 0.01, log‐rank test) in our study cohort. Conclusion: Urinary metabolome signatures related to mitochondrial functions can predict pretherapy steroid response and disease outcome in patients with SAH. (Hepatology Communications 2018;2:628‐643)
Collapse
Affiliation(s)
- Jaswinder Singh Maras
- Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India
| | - Sukanta Das
- Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India
| | - Shvetank Sharma
- Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India
| | - Saggere M Shasthry
- Department of Hepatology Institute of Liver and Biliary Sciences New Delhi India
| | - Benoit Colsch
- Service de Pharmacologie et Immunoanalyse, Laboratoire d'Etude du Métabolisme des Médicaments, DRF/Institut Joliot, CEA-Saclay, MetaboHUB Université Paris-Saclay Gif-sur-Yvette France
| | - Christophe Junot
- Service de Pharmacologie et Immunoanalyse, Laboratoire d'Etude du Métabolisme des Médicaments, DRF/Institut Joliot, CEA-Saclay, MetaboHUB Université Paris-Saclay Gif-sur-Yvette France
| | - Richard Moreau
- Department of Hepatology Institute of Liver and Biliary Sciences New Delhi India.,INSERM, Université Paris Diderot, Centre de Recherche sur l'Inflammation Paris France.,Département Hospitalo-Universitaire UNITY, Service d'Hépatologie, Hôpital Beaujon Assistance Publique-Hôpitaux de Paris Clichy France.,Laboratoire d'Excellence Inflamex COMUE Sorbonne Paris Cité Paris France
| | - Shiv Kumar Sarin
- Department of Hepatology Institute of Liver and Biliary Sciences New Delhi India
| |
Collapse
|
|
10
|
Abstract
Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.
Collapse
Affiliation(s)
- Benjamin L. Woolbright
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Hartmut Jaeschke
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA
| |
Collapse
|
|
11
|
Mou HY, Nie HM, Hu XY. Gutuo Jiejiu decoction improves survival of patients with severe alcoholic hepatitis: A retrospective cohort study. World J Gastroenterol 2017; 23:2957-2963. [PMID: 28522913 PMCID: PMC5413790 DOI: 10.3748/wjg.v23.i16.2957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/13/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH).
METHODS We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed.
RESULTS One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients’ baseline characteristics (P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group (P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant (P < 0.05). No significant differences in complications and adverse effects were found between the two groups.
CONCLUSION Gutuo Jiejiu decoction could improve the survival rates and clinical parameters of liver injury in patients with SAH, and may represent a new option for treating SAH.
Collapse
|
|
12
|
Kim SH, Kim BG, Kim W, Oh S, Kim HY, Jung YJ, Jeong JB, Kim JW, Lee KL. Characterization of gastrointestinal hemorrhage and prediction of mortality in Asian patients with alcoholic hepatitis. J Gastroenterol Hepatol 2016; 31:814-21. [PMID: 26513408 DOI: 10.1111/jgh.13220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 10/14/2015] [Accepted: 10/15/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Gastrointestinal bleeding (GIB) often accompanies alcoholic hepatitis (AH). The study aimed to investigate clinical characteristics of GIB in AH patients and to identify risk factors for mortality in AH patients with GIB. METHODS Data from 329 patients hospitalized with AH in a single center during 1999-2014 were retrospectively analyzed. Patients with AH were dichotomized into GIB and non-GIB groups. The GIB group was further divided into portal hypertensive bleeding (PHB) and non-PHB groups. Clinical characteristics and survival outcomes were compared between the groups. Risk factors for mortality were analyzed using Cox regression. RESULTS Among the 329 AH patients, 132 experienced GIB at admission or during hospitalization. The most common cause of GIB was an esophageal varix. The GIB group had worse survival outcomes than the non-GIB group (log-rank test, P = 0.034). The PHB group had worse survival outcomes than the non-PHB group (log-rank test, P = 0.001). On multivariate analysis, alcohol consumption, ascites, encephalopathy, infection, Maddrey's discriminant function, and the model for end-stage liver disease (MELD) score independently predicted mortality in the entire AH cohort. The MELD score (hazard ratio, 1.085; 95% confidence interval, 1.052-1.120; P < 0.001) and PHB (hazard ratio, 2.162; 95% confidence interval, 1.021-4.577; P = 0.044) were significant prognosticators for patients with AH and GIB. CONCLUSIONS The presence of PHB and a higher MELD score adversely affected survival in AH patients with GIB. Accordingly, prompt endoscopic examination for exploring the etiologies of GIB may alert physicians to predict the risk of death in AH patients with GIB.
Collapse
Affiliation(s)
- Su Hwan Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sohee Oh
- Department of Biostatistics, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yong Jin Jung
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ji Bong Jeong
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| |
Collapse
|
|
13
|
Ezquer F, Bruna F, Calligaris S, Conget P, Ezquer M. Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease. World J Gastroenterol 2016; 22:24-36. [PMID: 26755858 PMCID: PMC4698489 DOI: 10.3748/wjg.v22.i1.24] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 08/06/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic alcohol consumption is a major cause of liver disease. The term alcoholic liver disease (ALD) refers to a spectrum of mild to severe disorders including steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. With limited therapeutic options, stem cell therapy offers significant potential for these patients. In this article, we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), based on their potential to differentiate into hepatocytes, their immunomodulatory properties, their potential to promote residual hepatocyte regeneration, and their capacity to inhibit hepatic stellate cells. The perfect match between ALD pathogenesis and MSC therapeutic mechanisms, together with encouraging, available preclinical data, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression.
Collapse
|
|
14
|
Méndez-Sánchez N, Vítek L, Aguilar-Olivos NE, Uribe M. Bilirubin as a Biomarker in Liver Disease. BIOMARKERS IN DISEASE: METHODS, DISCOVERIES AND APPLICATIONS 2016:1-25. [DOI: 10.1007/978-94-007-7742-2_25-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
|
|
15
|
|