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Rutledge SM, Soper ER, Ma N, Pejaver V, Friedman SL, Branch AD, Kenny EE, Belbin GM, Abul-Husn NS. Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries. Clin Gastroenterol Hepatol 2023; 21:2578-2587.e11. [PMID: 36610497 DOI: 10.1016/j.cgh.2022.12.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 11/23/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND & AIMS Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record-linked biobank in New York City. METHODS This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. RESULTS Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). CONCLUSIONS Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.
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Affiliation(s)
- Stephanie M Rutledge
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Emily R Soper
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ning Ma
- Division of Liver Medicine, Icahn School of Medicine Mount Sinai, New York, New York
| | - Vikas Pejaver
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Scott L Friedman
- Division of Liver Medicine, Icahn School of Medicine Mount Sinai, New York, New York
| | - Andrea D Branch
- Division of Liver Medicine, Icahn School of Medicine Mount Sinai, New York, New York
| | - Eimear E Kenny
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Gillian M Belbin
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York; Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Noura S Abul-Husn
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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Plants-based medicine implication in the evolution of chronic liver diseases. Biomed Pharmacother 2023; 158:114207. [PMID: 36916432 DOI: 10.1016/j.biopha.2022.114207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/29/2022] [Accepted: 12/30/2022] [Indexed: 01/05/2023] Open
Abstract
Hepatic disorders are considered major health problems, due to their high incidence, increased risk of chronicling or death and the costs involved in therapies. A large number of patients with chronic liver diseases use herbal medicines and dietary supplements in parallel with allopathic treatment. The current review provides a thorough analysis of the studies conducted on the most important species of medicinal plants used in this disease, bioactive compounds and on the activity of herbal medicines in the evolution of chronic liver diseases. However, a negative aspect is that there is frequently a lack of comprehensive data on the progression of the illness and the living standards of patients who are affected when evaluating the effects of these phytocomponents on the evolution of chronic liver disease, the patients' health, and their quality of life. It is essential to take this impairment into account when evaluating the long-term effects of herbal treatments on the health of individuals who suffer from liver illness. Bioactive phytocomponents may be a suitable source for the development of novel medications due to the correlation between traditional uses and medical advances. Additional high-quality preclinical examinations utilizing cutting-edge approaches are needed to assess safety and effectiveness and to detect, categorize, and standardize the active substances and their formulations for the most suitable therapeutic management of liver illnesses.
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Obeid JS, Khalifa A, Xavier B, Bou-Daher H, Rockey DC. An AI Approach for Identifying Patients With Cirrhosis. J Clin Gastroenterol 2023; 57:82-88. [PMID: 34238846 PMCID: PMC8741865 DOI: 10.1097/mcg.0000000000001586] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 06/05/2021] [Indexed: 02/05/2023]
Abstract
GOAL The goal of this study was to evaluate an artificial intelligence approach, namely deep learning, on clinical text in electronic health records (EHRs) to identify patients with cirrhosis. BACKGROUND AND AIMS Accurate identification of cirrhosis in EHR is important for epidemiological, health services, and outcomes research. Currently, such efforts depend on International Classification of Diseases (ICD) codes, with limited success. MATERIALS AND METHODS We trained several machine learning models using discharge summaries from patients with known cirrhosis from a patient registry and random controls without cirrhosis or its complications based on ICD codes. Models were validated on patients for whom discharge summaries were manually reviewed and used as the gold standard test set. We tested Naive Bayes and Random Forest as baseline models and a deep learning model using word embedding and a convolutional neural network (CNN). RESULTS The training set included 446 cirrhosis patients and 689 controls, while the gold standard test set included 139 cirrhosis patients and 152 controls. Among the machine learning models, the CNN achieved the highest area under the receiver operating characteristic curve (0.993), with a precision of 0.965 and recall of 0.978, compared with 0.879 and 0.981 for the Naive Bayes and Random Forest, respectively (precision 0.787 and 0.958, and recalls 0.878 and 0.827). The precision by ICD codes for cirrhosis was 0.883 and recall was 0.978. CONCLUSIONS A CNN model trained on discharge summaries identified cirrhosis patients with high precision and recall. This approach for phenotyping cirrhosis in the EHR may provide a more accurate assessment of disease burden in a variety of studies.
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Affiliation(s)
- Jihad S. Obeid
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Ali Khalifa
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Brandon Xavier
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Halim Bou-Daher
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Don C. Rockey
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
- Medical University of South Carolina Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
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Smith M, Vaughan Sarrazin M, Wang X, Nordby P, Yu M, DeLonay AJ, Jaffery J. Risk from delayed or missed care and non-COVID-19 outcomes for older patients with chronic conditions during the pandemic. J Am Geriatr Soc 2022; 70:1314-1324. [PMID: 35211958 PMCID: PMC9106879 DOI: 10.1111/jgs.17722] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 01/14/2022] [Accepted: 02/06/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND During the COVID-19 pandemic, patients with chronic illnesses avoided regular medical care, raising concerns about long-term complications. Our objective was to identify a population of older patients with chronic conditions who may be at risk from delayed or missed care (DMC) and follow their non-COVID outcomes during the pandemic. METHODS We used a retrospective matched cohort design using Medicare claims and electronic health records at a large health system with community and academic clinics. Participants included 14,406 patients over 65 years old with two or more chronic conditions who had 1 year of baseline data and up to 9 months of postpandemic follow-up from March 1, 2019 to December 31, 2020; and 14,406 matched comparison patients from 1 year prior. Risk from DMC was defined by 13 indicators, including chronic conditions, frailty, disability affecting the use of telehealth, recent unplanned acute care, prior missed outpatient care, and social determinants of health. Outcomes included mortality, inpatient events, Medicare payments, and primary care and specialty care visits (in-person and telehealth). RESULTS A total of 25% of patients had four or more indicators for risk from DMC. Per 1000 patients annually, those with four or more indicators had increased mortality of 19 patients (95% confidence interval, 4 to 32) and decreased utilization, including unplanned events (-496 events, -611 to -381) and primary care visits (-1578 visits, -1793 to -1401). CONCLUSIONS Older patients who had four or more indicators for risk from DMC had higher mortality and steep declines in inpatient and outpatient utilization during the pandemic.
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Affiliation(s)
- Maureen Smith
- Department of Population Health SciencesUniversity of Wisconsin – Madison School of Medicine and Public HealthMadisonWisconsinUSA
- Department of Family Medicine and Community HealthUniversity of Wisconsin – Madison School of Medicine and Public HealthMadisonWisconsinUSA
- Health Innovation ProgramUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Mary Vaughan Sarrazin
- Department of Internal Medicine, College of MedicineUniversity of IowaIowa CityIowaUSA
| | - Xinyi Wang
- Health Innovation ProgramUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Peter Nordby
- Health Innovation ProgramUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Menggang Yu
- Department of Biostatistics and Medical InformaticsUniversity of Wisconsin – Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Allie J. DeLonay
- Health Innovation ProgramUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Jonathan Jaffery
- Office of Population HealthUW HealthMadisonWisconsinUSA
- Department of MedicineUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
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Bressler SS, Bruden D, Nolen LD, Bruce MG, Towshend-Bulson L, Spradling P, McMahon BJ. Mortality among Alaska Native Adults with Confirmed Hepatitis C Virus Infection Compared with the General Population in Alaska, 1995-2016. Can J Gastroenterol Hepatol 2022; 2022:2573545. [PMID: 35178364 PMCID: PMC8847038 DOI: 10.1155/2022/2573545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 01/06/2022] [Accepted: 01/07/2022] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. METHODS This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. RESULTS The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. CONCLUSIONS Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States.
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Affiliation(s)
- Sara S. Bressler
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Dana Bruden
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Leisha D. Nolen
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Michael G. Bruce
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
| | - Lisa Towshend-Bulson
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - Philip Spradling
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
| | - Brian J. McMahon
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK, USA
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
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Kposowa AJ, Breault K. Disability Status, Unemployment, and Alcohol-Related Liver Disease (ALD) Mortality: A Large Sample Individual Level Longitudinal Study. Subst Abuse Rehabil 2021; 12:81-88. [PMID: 34703353 PMCID: PMC8541791 DOI: 10.2147/sar.s334851] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/05/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose Unlike previous research, we evaluate disability within expanded employment status factors and stratify gender, race and ethnicity in alcohol-related liver disease (ALD) mortality in a large sample individual level longitudinal study. Materials and Methods The National Longitudinal Mortality Study (NLMS) was used covering the period 1990–2011. Statistical analysis involved the use of proportional hazards regression on a sample of almost 1.4 million people aged 18 and older, of whom 2638 died of ALD by the end of the follow-up period. Results With expanded employment status factors, disability (HR=3.76 [95%] CI 3.22, 4.39), unemployment (HR=1.90, CI 1.56, 2.31), and those not otherwise in the labor force (HR=2.31, CI 2.08, 2.56) were strongly related to ALD mortality compared to the employed. When stratified, gender, race, and ethnicity were not important modifiers in the relationships between disability, unemployment, those not in the labor force and subsequent ALD mortality. Consistent with other studies, males, minority status, living in a highly urban area, renting as opposed to owning a home, lower educational attainment, marital statuses other than marriage, low income, and age were related to ALD mortality. Conclusion In addition to unemployment which has been previously studied in a large longitudinal sample, disabled people who were unable to work and those not looking for work had a higher risk of ALD mortality. Alcohol consumption, abuse and morbidity in these populations are of considerable clinical concern.
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Affiliation(s)
| | - Kevin Breault
- Department of Sociology and Anthropology, Middle Tennessee State University, Murfreesboro, TN, USA
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Sheu MJ, Liang FW, Lin CY, Lu TH. Changes in liver-related mortality by etiology and sequelae: underlying versus multiple causes of death. Popul Health Metr 2021; 19:22. [PMID: 33926463 PMCID: PMC8082829 DOI: 10.1186/s12963-021-00249-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/31/2021] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data. METHODS We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality. RESULT Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65-74 years. CONCLUSION The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.
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Affiliation(s)
- Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
- Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Fu-Wen Liang
- Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yih Lin
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
| | - Tsung-Hsueh Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Gao E, Hercun J, Heller T, Vilarinho S. Undiagnosed liver diseases. Transl Gastroenterol Hepatol 2021; 6:28. [PMID: 33824932 DOI: 10.21037/tgh.2020.04.04] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
The landscape of chronic liver disease has drastically changed over the past 20 years, largely due to advances in antiviral therapy and the rise of metabolic syndrome and associated non-alcoholic fatty liver disease (NAFLD). Despite advances in the diagnosis and treatment of a variety of liver diseases, the burden of chronic liver disease is increasing worldwide. The first step to addressing any disease is accurate diagnosis. Here, we discuss liver diseases that remain undiagnosed, either because they are difficult to diagnose or due to hepatic manifestations of an unrecognized systemic disease. Additionally, their underlying etiology may remain unknown or they represent previously uncharacterized and therefore novel liver diseases. Our goal is to provide a framework for approaching undiagnosed liver diseases which elude standard hepatic diagnostic work-up and whose patterns of disease are often overlooked.
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Affiliation(s)
- Emily Gao
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Julian Hercun
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Theo Heller
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Sílvia Vilarinho
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.,Department of Pathology, Yale School of Medicine, New Haven, CT, USA
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Silva JM, Silva MJ, Calinas F, Nogueira PJ. Burden of Liver Cirrhosis in Portugal between 2010 and 2017. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 28:153-161. [PMID: 34056037 PMCID: PMC8138255 DOI: 10.1159/000510729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/26/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Liver cirrhosis is a prevalent disease in Portugal. Recent changes in alcohol consumption, as well as the wide use of direct-acting antivirals for hepatitis C since 2015, may be contributing to changes in the national burden of liver cirrhosis in the last few years. OBJECTIVES We aim to characterize the burden of cirrhosis in Portugal between 2010 and 2017. PATIENTS AND METHODS We analyzed all hospital admission episodes due to cirrhosis in Portugal Mainland between 2010 and 2017, registered in the national Diagnosis-Related Group database, according to etiology of cirrhosis. We also analyzed data on mortality and potential years of life lost from liver cirrhosis and chronic liver disease, retrieved from Statistics Portugal (National Institute for Statistics). RESULTS Between 2010 and 2017, a total of 51,438 admissions for liver cirrhosis occurred in Portugal. The annual number of admissions decreased (p = 0.044) during the analyzed period. The most frequent cause of cirrhosis was alcoholic liver disease, present in 78.9% of all admissions (n = 40,595), followed by chronic hepatitis C virus infection, present in 11.3% (n = 5,823). A male predominance was identified in the admissions for every analyzed cause of cirrhosis. Annual admissions for alcoholic cirrhosis remained stable (p = 0.075) during the 8-year period. The same stable tendency was observed in the number of admissions for cirrhosis caused by hepatitis C virus (p = 0.861) and alcohol plus hepatitis C virus infection (p = 0.082), although these admissions for hepatitis C-related cirrhosis increased until 2014-2015 and steadily decreased thereafter. Annual deaths due to liver cirrhosis and chronic liver disease decreased from 1,357 in 2010 to 1,038 in 2017 (p = 0.002). The number of potential years of life lost decreased as well in the period (p = 0.001). CONCLUSION The burden of cirrhosis, evaluated by hospital admissions, mortality, and potential years of life lost, decreased in Portugal between 2010 and 2017.
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Affiliation(s)
| | - Mário Jorge Silva
- Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Filipe Calinas
- Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Paulo Jorge Nogueira
- Instituto de Medicina Preventiva e Saúde Pública, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Public Health Research Centre, NOVA National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), NOVA National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal
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Banait S, Badole SM, Jain J, Thorat A. Risk factors for chronic liver disease in population of Central India: a case-control study from rural India. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00077-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Abstract
Background
Chronic liver disease (CLD) is one of the leading causes of morbidity and mortality in today’s world. Common risk factors for CLD are alcohol, chronic hepatitis B, chronic hepatitis C, non-alcoholic steatohepatitis (NASH), malnutrition, toxins, and some tropical infections. This case-control study was carried out to determine the risk factors of domestic CLD in a resource-constrained setting in central rural India. A hospital-based matched case-control study was carried out among eligible CLD cases from November 2015 to October 2017. A total of 200 cases and 200 age- and gender-matched community controls were selected using consecutive sampling from tertiary care hospitals from central rural India. Information on socio-demographic, etiological was collected through using a pretested structured questionnaire after obtaining informed written consent. Univariate and multivariate analyses were carried out to find the risk factors associated with CLD.
Results
The median age of study participant was 58.5 years among the cases. There were 75% male and remaining 25% were female in each case and control group. On multivariate analysis, we found less education, poor socioeconomic status, diabetes mellitus, increased body mass index (BMI), alcohol consumption, and tobacco chewing were significant risk factors for CLD in comparison to controls. However, amount of alcohol, smoking, and occupation were not found to be statistically significant association with CLD.
Conclusions
The findings showed that in patients with CLD when compared to controls, high alcohol intake, diabetes mellitus, tobacco chewing, central obesity, low education, and low-income group are significant risk factors in our rural population. An initiative needs to be taken to reduce alcohol, and tobacco chewing habits at various levels through awareness campaigns, strict control, and legislation to limit further abuse. Control of blood glucose and reduction of obesity may be important in preventing CLD in our rural community.
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A Comprehensive Analysis of Liver Transplantation Outcomes Among Ethnic Minorities in the United States. J Clin Gastroenterol 2020; 54:263-270. [PMID: 31169758 DOI: 10.1097/mcg.0000000000001236] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
GOALS The aim of this study was to perform a comprehensive assessment of liver transplant (LT) outcomes among US adults with a specific focus on understanding race/ethnicity-specific disparities. BACKGROUND Despite improvements in the liver allocation and LT-related care, disparities in LT outcomes persist. STUDY Using data from the 2005 to 2016 United Networks for Organ Sharing LT registry, we evaluated waitlist survival, probability of receiving LT, and post-LT survival among US adults stratified by race/ethnicity and liver disease etiology. Kaplan-Meier methods evaluated unadjusted waitlist and post-LT outcomes, and multivariate regression models evaluated adjusted waitlist and post-LT outcomes. RESULTS Among 88,542 listed for LT patients (41.3% hepatitis C virus, 25.3% alcoholic liver disease, 22.3% nonalcoholic steatohepatitis, 11.1% hepatitis C virus/alcoholic liver disease), significant race/ethnicity-specific disparities were observed. Compared with non-Hispanic whites, Hispanics had a significantly lower risk of waitlist death [hazard ratio (HR)=0.84, 95% confidence interval (CI): 0.79-0.90, P<0.001]. Compared with non-Hispanic whites, significantly lower likelihood of receiving LT was observed in African Americans (HR=0.94, 95% CI: 0.91-0.98, P<0.001), Hispanics (HR=0.70, 95% CI: 0.68-0.73, P<0.001) and Asians (HR=0.74, 95% CI: 0.69-0.80, P<0.001). Compared with non-Hispanic whites, African Americans had a significantly higher risk of 5-year post-LT death (HR=1.31, 95% CI: 1.23-1.39, P<0.001). CONCLUSION Among US adults awaiting LT, significant race/ethnicity-specific disparities in LT outcomes were observed. Despite evaluating an era after implementation of the Model for End-Stage Liver Disease, ethnic minorities continue to demonstrate a lower probability of receiving LT, and significantly higher risk of death post-LT in African Americans.
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Mera J, Joshi K, Thornton K, Box T, Scott J, Sedillo M, Deming P, David C, Essex W, Manch R, Kohli A. Retrospective Study Demonstrating High Rates of Sustained Virologic Response After Treatment With Direct-Acting Antivirals Among American Indian/Alaskan Natives. Open Forum Infect Dis 2019; 6:ofz128. [PMID: 31289725 PMCID: PMC6610205 DOI: 10.1093/ofid/ofz128] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 07/03/2019] [Indexed: 12/29/2022] Open
Abstract
Background Treatment for chronic hepatitis C virus (HCV) has rapidly evolved to simple, well-tolerated, all-oral regimens of direct-acting antivirals (DAAs). There are few data on the epidemiology of HCV in American Indians/Alaska Natives (AI/ANs), a population disproportionately affected by HCV. Methods In this retrospective cohort study, all HCV-infected AI/AN patients treated with DAA therapies between January 1, 2014, and February 24, 2016, in specialty clinics or by primary care clinicians participating in Extension for Community Healthcare Outcomes (ECHO) were included. Demographic, clinical, and virologic data on all patients treated for HCV from pretreatment through sustained virologic response at 12 weeks (SVR12) were collected. Results Two hundred eighty patients were included; 71.1% of patients (n = 199) were infected with genotype 1 (GT1), 18.2% (n = 51) with GT2, and 10.7% with (n = 30) GT3. At baseline, 26.1% (n = 73) patients had cirrhosis and 22.6% (n = 56) had active substance use disorder; eighty-eight percent (n = 232) of patients achieved SVR12. Among the 165 GT1 patients treated with sofosbuvir (SOF)/ledipasvir for 8, 12, and 24 weeks, SVR12 was achieved by 91.5% (n = 54), 92.2% (n = 71), and 100% (n = 13), respectively. Among GT2 patients, 87.2% (n = 34) and 71.4% (n = 5) treated with 12 and 16 weeks of SOF/ribavirin (RBV) achieved SVR12, respectively. Among GT3 patients, 100% (n = 2) and 83.3% (n = 20) treated with 12 and 24 weeks of SOF/RBV achieved SVR12, respectively. SVR12 rates remained high among patients with active substance use disorder. Conclusions DAA therapies are highly efficacious in HCV-infected AI/ANs. SVR12 rates remained high among patients with active substance use disorder. More steps must be taken to increase access to treatment for this underserved, vulnerable population.
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Affiliation(s)
- Jorge Mera
- Division of Infectious Diseases, Cherokee Nation W.W. Hastings Hospital, Tahlequah, Oklahoma
| | - Kartik Joshi
- Division of Hepatology, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.,Institute for Liver Health, Chandler, Arizona
| | - Karla Thornton
- Division of Infectious Diseases, Project ECHO, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, New Mexico
| | - Terry Box
- Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, Utah
| | - John Scott
- Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington
| | - Miranda Sedillo
- Division of Infectious Diseases, Project ECHO, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, New Mexico
| | - Paulina Deming
- Division of Infectious Diseases, Project ECHO, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, New Mexico
| | - Crystal David
- Division of Infectious Diseases, Cherokee Nation W.W. Hastings Hospital, Tahlequah, Oklahoma
| | - Whitney Essex
- Division of Infectious Diseases, Cherokee Nation W.W. Hastings Hospital, Tahlequah, Oklahoma
| | - Richard Manch
- Division of Hepatology, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.,Institute for Liver Health, Chandler, Arizona
| | - Anita Kohli
- Institute for Liver Health, Chandler, Arizona.,Division of Infectious Disease, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
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13
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Abstract
The term blood-bile barrier (BBlB) refers to the physical structure within a hepatic lobule that compartmentalizes and hence segregates sinusoidal blood from canalicular bile. Thus, this barrier provides physiological protection in the liver, shielding the hepatocytes from bile toxicity and restricting the mixing of blood and bile. BBlB is primarily composed of tight junctions; however, adherens junction, desmosomes, gap junctions, and hepatocyte bile transporters also contribute to the barrier function of the BBlB. Recent findings also suggest that disruption of BBlB is associated with major hepatic diseases characterized by cholestasis and aberrations in BBlB thus may be a hallmark of many chronic liver diseases. Several molecular signaling pathways have now been shown to play a role in regulating the structure and function and eventually contribute to regulation of the BBlB function within the liver. In this review, we will discuss the structure and function of the BBlB, summarize the methods to assess the integrity and function of BBlB, discuss the role of BBlB in liver pathophysiology, and finally, discuss the mechanisms of BBlB regulation. Collectively, this review will demonstrate the significance of the BBlB in both liver homeostasis and hepatic dysfunction.
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Affiliation(s)
- Tirthadipa Pradhan-Sundd
- *Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- †Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Satdarshan Pal Monga
- *Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- †Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- ‡Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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14
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Maithani M, Raturi R, Gupta V, Bansal P. Assessment of compliance level of ICH guidelines for organic volatile impurities in common ayurvedic hepatic formulations. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2019; 16:/j/jcim.ahead-of-print/jcim-2018-0159/jcim-2018-0159.xml. [PMID: 30870142 DOI: 10.1515/jcim-2018-0159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 10/07/2018] [Indexed: 11/15/2022]
Abstract
Background Herbal medicines have been used in the treatment of liver diseases for a long time. In recent years, the use of herbal medicines for protection from other strong antibiotics as well as drugs that can damage the liver during their metabolism in liver and for treatment of liver diseases has increased all over the world. It is important to mention that a number of organic solvents are used at different stages of extraction/formulation development for these traditional preparations in industries/pharmacies. In addition, some of these solvents possess established carcinogenic properties and may enter the formulation as residual solvents. Hence as per ICH guidelines it is mandatory to keep the level of these solvents up to permissible limits. There has been a lot of hue and cry that ayurvedic formulations available in the market are not properly standardized for their quality due to lack of stringent regulations and standards from regulatory authorities. Therefore the aim of present work was to assess the compliance of ICH guidelines for level of organic volatile impurities in common marketed ayurvedic hepatic formulations. Methods In this study, 25 ayurvedic herbal formulations available as OTC product have been assessed for presence of residual solvents using gas chromatography with flame ionization detector. Results This study on 25 fast moving hepatic formulations in the market reflects that no residual solvents were detected in any of the formulations however if present were within prescribed permissible limits of ICH guidelines. The data was also subjected to statistical analysis (F-test and t-test at 95% confidence level). Conclusions Results indicate the safety of these hepatic formulations with respect to residual solvents. In addition presents a simple, linear, specific, accurate, precise and rugged gas chromatographic method for estimation of residual solvents.
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Affiliation(s)
- M Maithani
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - R Raturi
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - V Gupta
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - P Bansal
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
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15
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MELD is the only predictor of short-term mortality in cirrhotic patients with C. difficile infection. Dig Liver Dis 2019; 51:275-280. [PMID: 30172651 DOI: 10.1016/j.dld.2018.07.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 07/09/2018] [Accepted: 07/25/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is the most common nosocomial infection in the US and cirrhotic patients with CDI have increased risk for poor outcome. AIM The aim of this study is to evaluate the impact of CDI on short-term mortality in patients with cirrhosis and identify predictors of mortality in these patients. METHODS We retrospectively identified patients at Montefiore Medical Center from 2010 to 2014 with cirrhosis, diarrhea and a C. difficile toxin assay. Demographics, co-morbidities, medications, laboratory data and outcomes were recorded. RESULTS Of 701 patients with cirrhosis who had a CDI assay, 183 were CDI+ and 518 CDI-. Patients with CDI were older, had more frequent CKD on hemodialysis and heart failure, were less frequently on rifaximin and lactulose and had increased glucocorticoid exposure. 30-day mortality was higher in patients with CDI (23.0% vs 16.6%, p < 0.05) compared to those without. Univariate predictors of 30-day mortality included WBC, corticosteroid use, AST, ALT, MELD, albumin, HBV and HCV infection; however, via multivariate analysis, only MELD (HR: 1.04 ± 0.02, p < 0.05) remained significant. CONCLUSION Patients with cirrhosis and CDI are at greater risk of 30-day mortality than those without CDI and the only multivariate predictor of mortality is MELD. These patients should have their disease severity triaged based upon MELD score.
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16
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de Mello CL, da Conceição TMA, Dal Pont T, Peruzzolo CC, Lúcio MN, Paulin E. The Benefits of Neuromuscular Electrical Stimulation in the Muscular and Functional Capacity of Patients With Liver Cirrhosis: Protocol for a Randomized Clinical Trial. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2018; 11:1179552218811834. [PMID: 30505152 PMCID: PMC6256309 DOI: 10.1177/1179552218811834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 10/02/2018] [Indexed: 11/16/2022]
Abstract
Cirrhosis causes systemic and metabolic changes that culminate in various complications, such as compromised pulmonary function, ascites, hepatic encephalopathy, weight loss, and muscle weakness with significant physical function limitations. Our aim is to evaluate the effects of training with neuromuscular electrical stimulation (NMES) on the muscular and functional capacity of patients with cirrhosis classified as Child-Pugh B and C. A total of 72 patients diagnosed with cirrhosis will be recruited and randomized to perform an NMES protocol for 50 minutes, 3 times a week, for 4 weeks. The evaluations will be performed at the beginning and after 12 sessions, and patients will be submitted to a pulmonary function test, an ultrasound evaluation of the rectus femoris, an evaluation of peripheral muscle strength, a submaximal exercise capacity test associated with an evaluation of peripheral tissue oxygenation, a quality of life evaluation, and orientation about monitoring daily physical activities. The evaluators and patients will be blinded to the allocation of the groups. Training Group will be treated with the following parameters: frequency of 50 Hz, pulse width of 400 μs, rise and fall times of 2 s, and on:off 1:1; Sham Group: 5 Hz, 100 μs, on:off 1:3. The data will be analyzed using the principles of the intention to treat. This study provides health professionals with information on the benefits of this intervention. In this way, we believe that the results of this study could stimulate the use of NMES as a way of rehabilitating patients with more severe cirrhosis, with the objective of improving these patients' functional independence.
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Affiliation(s)
| | | | - Tarcila Dal Pont
- Universidade do Estado de Santa Catarina (UDESC), Florianópolis, Brazil
| | | | | | - Elaine Paulin
- Universidade do Estado de Santa Catarina (UDESC), Florianópolis, Brazil.,Universidade de São Paulo, São Paulo, Brazil.,Centro de Ciências da Saúde e do Esporte-CEFID, Laboratório de Fisioterapia Respiratória-LAFIR, Universidade do Estado de Santa Catarina (UDESC), Florianópolis, Brazil
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17
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Pradhan-Sundd T, Vats R, Russell JM, Singh S, Michael AA, Molina L, Kakar S, Cornuet P, Poddar M, Watkins SC, Nejak-Bowen KN, Monga SP, Sundd P. Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver Injury in Mice. Gastroenterology 2018; 155:1218-1232.e24. [PMID: 29964040 PMCID: PMC6174089 DOI: 10.1053/j.gastro.2018.06.048] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 05/09/2018] [Accepted: 06/24/2018] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS Liver fibrosis, hepatocellular necrosis, inflammation, and proliferation of liver progenitor cells are features of chronic liver injury. Mouse models have been used to study the end-stage pathophysiology of chronic liver injury. However, little is known about differences in the mechanisms of liver injury among different mouse models because of our inability to visualize the progression of liver injury in vivo in mice. We developed a method to visualize bile transport and blood-bile barrier (BBlB) integrity in live mice. METHODS C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE) diet or a diet containing 0.1% 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) for up to 4 weeks to induce chronic liver injury. We used quantitative liver intravital microscopy (qLIM) for real-time assessment of bile transport and BBlB integrity in the intact livers of the live mice fed the CDE, DDC, or chow (control) diets. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, real-time polymerase chain reaction, and immunoblots. RESULTS Mice with liver injury induced by a CDE or a DDC diet had breaches in the BBlB and impaired bile secretion, observed by qLIM compared with control mice. Impaired bile secretion was associated with reduced expression of several tight-junction proteins (claudins 3, 5, and 7) and bile transporters (NTCP, OATP1, BSEP, ABCG5, and ABCG8). A prolonged (2-week) CDE, but not DDC, diet led to re-expression of tight junction proteins and bile transporters, concomitant with the reestablishment of BBlB integrity and bile secretion. CONCLUSIONS We used qLIM to study chronic liver injury, induced by a choline-deficient or DDC diet, in mice. Progression of chronic liver injury was accompanied by loss of bile transporters and tight junction proteins.
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Affiliation(s)
| | - Ravi Vats
- Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Jacqueline M Russell
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Sucha Singh
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | | | - Laura Molina
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Shelly Kakar
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Pamela Cornuet
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Minakshi Poddar
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Simon C Watkins
- Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Kari N Nejak-Bowen
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA,Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Satdarshan P. Monga
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA,Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA,Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA,Corresponding authors: ,
| | - Prithu Sundd
- Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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18
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Tomedi LE, Roeber J, Landen M. Alcohol Consumption and Chronic Liver Disease Mortality in New Mexico and the United States, 1999-2013. Public Health Rep 2018; 133:287-293. [PMID: 29664698 PMCID: PMC5958395 DOI: 10.1177/0033354918766890] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE Current chronic liver disease (CLD) mortality surveillance methods may not adequately capture data on all causes of CLD mortality. The objective of this study was to calculate and compare CLD death rates in New Mexico and the United States by using both an expanded definition of CLD and estimates of the fractional impact of alcohol on CLD deaths. METHODS We defined CLD mortality as deaths due to alcoholic liver disease, cirrhosis, viral hepatitis, and other liver conditions. We estimated alcohol-attributable CLD deaths by using national and state alcohol-attributable fractions from the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact application. We classified causes of CLD death as being alcohol-attributable, non-alcohol-attributable, or hepatitis C. We calculated average annual age-adjusted CLD death rates during five 3-year periods from 1999 through 2013, and we stratified those rates by sex, age, and race/ethnicity. RESULTS By cause of death, CLD death rates were highest for alcohol-attributable CLD. By sex and race/ethnicity, CLD death rates per 100 000 population increased from 1999-2001 to 2011-2013 among American Indian men in New Mexico (67.4-90.6) and the United States (38.9-49.4), American Indian women in New Mexico (48.4-63.0) and the United States (27.5-39.5), Hispanic men in New Mexico (48.6-52.0), Hispanic women in New Mexico (16.9-24.0) and the United States (12.8-13.1), non-Hispanic white men in New Mexico (17.4-21.3) and the United States (15.9-18.4), and non-Hispanic white women in New Mexico (9.7-11.6) and the United States (7.6-9.7). CLD death rates decreased among Hispanic men in the United States (30.5-27.4). CONCLUSIONS An expanded CLD definition and alcohol-attributable fractions can be used to create comprehensive data on CLD mortality. When stratified by CLD cause and demographic characteristics, these data may help states and jurisdictions improve CLD prevention programs.
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Affiliation(s)
- Laura E. Tomedi
- Epidemiology and Response Division, New Mexico Department of Health, Santa Fe, NM, USA
| | - Jim Roeber
- Epidemiology and Response Division, New Mexico Department of Health, Santa Fe, NM, USA
| | - Michael Landen
- Epidemiology and Response Division, New Mexico Department of Health, Santa Fe, NM, USA
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19
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Duan X, Meng Q, Wang C, Liu Z, Sun H, Huo X, Sun P, Ma X, Peng J, Liu K. Effects of calycosin against high-fat diet-induced nonalcoholic fatty liver disease in mice. J Gastroenterol Hepatol 2018; 33:533-542. [PMID: 28699662 DOI: 10.1111/jgh.13884] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 07/03/2017] [Accepted: 07/10/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Nonalcoholic fatty liver disease (NAFLD) has become a major health concern worldwide. The present study was designed to investigate the effects of calycosin against high-fat diet (HFD)-induced NAFLD in mice. METHODS C57BL/6 J male mice were fed with HFD to induce NAFLD model and treated with or without calycosin for 12 weeks. The levels of ALT, AST, insulin, and adiponectin were measured using biochemical methods. Hemotoxylin and eosin staining and Oil Red O staining were used to determine the liver histopathology changes and measure the degree of lipid accumulation respectively. Glucose tolerance tests and insulin tolerance tests were performed followed by quantitative insulin sensitivity check index determination. Western blot and quantitative real-time polymerase chain reaction were used to explore the potential mechanism involved in the beneficial effects of calycosin. RESULTS Calycosin effectively decreased the levels of ALT and AST, increased the levels of adiponectin and insulin. Hemotoxylin and eosin staining indicated calycosin treatment remarkably improved liver injury. Oil Red O staining indicated calycosin treatment remarkably improved lipid accumulation. Quantitative insulin sensitivity check index in HFD fed mice was significantly lower than in the standard chow fed mice. Further, calycosin suppressed phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, sterol-regulatory element binding protein 1c, and FASN involved in gluconeogenesis and triglyceride synthesis. Calycosin increased glycogen synthase kinase 3 beta, glucose transporter 4, and phosphorylated insulin receptor substrates 1 and 2 expressions involved in glucose metabolism. The aforementioned beneficial effects of calycosin against HFD-induced NAFLD may be attributed to farnesoid X receptor activation. CONCLUSION Calycosin could produce the favorable effects against HFD-induced NAFLD in mice.
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Affiliation(s)
- Xingping Duan
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Department of Pharmacy, Maternal and Child Health Care Hospital of Zigong, Zigong, Sichuan, China
| | - Qiang Meng
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Changyuan Wang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Zhihao Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Huijun Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Xiaokui Huo
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Pengyuan Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Xiaodong Ma
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Jinyong Peng
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
| | - Kexin Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
- Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, China
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20
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Khan A, Pan JH, Cho S, Lee S, Kim YJ, Park YH. Investigation of the Hepatoprotective Effect of Prunus mume Sieb. et Zucc Extract in a Mouse Model of Alcoholic Liver Injury Through High-Resolution Metabolomics. J Med Food 2017. [PMID: 28650205 DOI: 10.1089/jmf.2016.3874] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
This study aimed to identify the changes in the metabolomics profile of liver damage caused by alcohol consumption and verify the beneficial effect of Prunus mume Sieb. et Zucc extract (PME) in protection of alcohol-induced injury by attenuating the level of identified metabolites. Mice were treated with PME and saline or untreated once daily for 5 days, followed by alcohol injection. The plasma samples were analyzed using liquid chromatography-mass spectrometry-based high-resolution metabolomics followed by a multivariate statistical analysis using MetaboAnalyst 3.0 to obtain significantly expressed metabolites, using a false discovery rate threshold of q = 0.05. Metabolites were annotated using Metlin database and mapped through Kyoto Encyclopedia of Genes and Genomes (KEGG). Among 4999 total features, 101 features were significant among alcohol- and PME-treated mice groups. All the samples cluster showed a clear separation in the heat map, and the scores plot of orthogonal partial least squares-discriminant analysis (OPLS-DA) model discriminated the three groups. Phosphatidylcholine, Saikosaponin BK1, Ganoderiol I, and N-2-[4-(3,3-dimethylallyloxy) phenyl] ethylcinnamide were among the significant compounds with a low intensity in alcohol group compared to PME group, suggesting that these compounds have a relation in the development of PME's protective effect. The study confirms the hepatoprotective, antioxidant, and anti-inflammatory effects of PME against alcohol-induced liver steatosis, inflammation, and apoptosis.
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Affiliation(s)
- Adnan Khan
- 1 Metabolomics Laboratory, College of Pharmacy, Korea University , Sejong, Korea
| | - Jeong Hoon Pan
- 2 Department of Food and Biotechnology, Korea University , Sejong, Korea
| | - Seongha Cho
- 1 Metabolomics Laboratory, College of Pharmacy, Korea University , Sejong, Korea
| | - Sojung Lee
- 2 Department of Food and Biotechnology, Korea University , Sejong, Korea
| | - Young Jun Kim
- 2 Department of Food and Biotechnology, Korea University , Sejong, Korea
| | - Youngja H Park
- 1 Metabolomics Laboratory, College of Pharmacy, Korea University , Sejong, Korea
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21
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Ge J, Roberts JP, Lai JC. Race/ethnicity is associated with ABO-nonidentical liver transplantation in the United States. Clin Transplant 2017; 31. [PMID: 28517242 DOI: 10.1111/ctr.13011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2017] [Indexed: 12/17/2022]
Abstract
United Network for Organ Sharing (UNOS) policies allow for ABO-nonidentical liver transplantation (LT) in candidates with Model for End-Stage Liver Disease (MELD) scores greater than 30. Previous studies showed ABO-nonidentical LT resulted in an 18% and 55% net gain in livers for B and AB candidates. These results suggested that the current liver ABO allocation policies may need refinement. There are, however, strong associations between ABO blood groups and race/ethnicity. We hypothesized that race/ethnicity is associated with ABO-nonidentical LT and that this is primarily influenced by recipient ABO status. We examined non-status 1 adult candidates registered between July 1, 2013, and December 31, 2015. There were 27 835 candidates (70% non-Hispanic White, 15% Hispanic, 9% Black, 4% Asian, 1% Other/Multiracial). A total of 11 369 underwent deceased donor LT: 93% ABO identical, 6% ABO compatible, and 1% ABO incompatible. Black and Asian race/ethnicity were associated with increased likelihoods of ABO-nonidentical LT. Adjustment for disease etiology, listing MELD, transplant center volume, and UNOS region did not alter this association. Stepwise inclusion of recipient ABO status did eliminate this significant association of race/ethnicity with ABO-nonidentical LT. Blacks and Asians may be advantaged by ABO-nonidentical LT, and we suspect that changes to the existing policies may disproportionately impact these groups.
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Affiliation(s)
- Jin Ge
- Department of Medicine, University of California-San Francisco, San Francisco, CA, USA
| | - John P Roberts
- Division of Transplant Surgery, Department of Surgery, University of California-San Francisco, San Francisco, CA, USA
| | - Jennifer C Lai
- Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA
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22
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Campos S, Silva N, Carvalho A. A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study. Ann Hepatol 2017; 16:285-290. [PMID: 28233751 DOI: 10.5604/16652681.1231588] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. MATERIAL AND METHODS We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. RESULTS We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. CONCLUSION Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.
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Affiliation(s)
- Sara Campos
- Gastroenterology department, Centro Hospitalar e Universitário de Coimbra (CHUC)
| | - Nuno Silva
- Internal Medicine department, Centro Hospitalar e Universitário de Coimbra
| | - Armando Carvalho
- Internal Medicine department, Centro Hospitalar e Universitário de Coimbra (CHUC)
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Landaverde C, Wells J, Hamner R, Goldstein JL. Dual therapy of grazoprevir and elbasvir for the treatment of hepatitis C infection. Expert Rev Gastroenterol Hepatol 2016; 10:419-29. [PMID: 26818134 DOI: 10.1586/17474124.2016.1147346] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The impact of chronic hepatitis C (HCV) worldwide is expected to increase as the population infected with HCV ages and more undiagnosed individuals are identified and linked to care through nation-wide initiatives. The development of interferon-free regimens involving the use of direct-acting antiviral agents, which disrupt key steps in viral replication, has revolutionized the treatment of chronic HCV infection. However, there remains a great medical need for HCV therapy that is of shorter duration, all-oral, with a high barrier to resistance, and highly effective for all patient populations including those with end-stage renal disease (ESRD) and cirrhosis. Grazoprevir, an HCV NS3/4A protease inhibitor and elbasvir, an NS5A inhibitor, have broad in vitro activity against most HCV genotypes and retain in vitro activity against many clinically relevant resistance-associated variants. The once daily regimen is well-tolerated and highly efficacious across wide-ranging patient populations including those with ESRD on hemodialysis.
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Affiliation(s)
- Carmen Landaverde
- a Metabolic Liver Disease Program , Texas Liver Institute , Austin , TX , USA.,b University of Texas Health Sciences Center San Antonio (UTHSCSA) , San Antonio , TX , USA.,c Dell Medical School , UT Austin , Austin , TX , USA
| | - Jennifer Wells
- b University of Texas Health Sciences Center San Antonio (UTHSCSA) , San Antonio , TX , USA.,c Dell Medical School , UT Austin , Austin , TX , USA.,d Regenerative Liver and Neoplasia , Texas Liver Institute , Austin , TX , USA
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Goyal A, Chatterjee K, Shah N, Singh S. Is cirrhosis associated with lower odds of ischemic stroke: A nationwide analysis? World J Hepatol 2016; 8:1564-1568. [PMID: 28050237 PMCID: PMC5165270 DOI: 10.4254/wjh.v8.i35.1564] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Revised: 10/01/2016] [Accepted: 11/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the association between cirrhosis and ischemic stroke in a large nationally representative sample. METHODS A retrospective cross-sectional study of all hospitalized patients during 2012 and 2013 in the United States was performed using the National Inpatient Sample database. Hospitalizations with acute stroke, cirrhosis and other risk factors were identified using ICD-9-CM codes. RESULTS There were a total of 72082638 hospitalizations in the United States during the years 2012 and 2013. After excluding hospitalizations with missing demographic variables, that there were a total of 1175210 (1.6%) out of these were for acute ischemic stroke. Cirrhosis was present among 5605 (0.4%) cases of ischemic stroke. Mean age among the cirrhotic and non-cirrhotic groups with ischemic stroke were 66.4 and 70.5 years, respectively. Prevalence of risk factors among the two groups was also calculated. After adjusting for various known risk factors the odds of having an ischemic stroke (OR = 0.28, P < 0.001) were 72% lower in cirrhotics compared to non-cirrhotics. CONCLUSION Our study suggests that in a large, nationally representative sample of the United States population, cirrhosis is associated with a lower likelihood of stroke.
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Affiliation(s)
- Abhinav Goyal
- Abhinav Goyal, Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA 19141, United States
| | - Kshitij Chatterjee
- Abhinav Goyal, Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA 19141, United States
| | - Nishi Shah
- Abhinav Goyal, Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA 19141, United States
| | - Shailender Singh
- Abhinav Goyal, Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA 19141, United States
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Atla PR, Sheikh MY, Gill F, Kundu R, Choudhury J. Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis. Ann Gastroenterol 2016; 29:515-520. [PMID: 27708520 PMCID: PMC5049561 DOI: 10.20524/aog.2016.0072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Accepted: 06/23/2016] [Indexed: 12/23/2022] Open
Abstract
Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.
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Affiliation(s)
- Pradeep R Atla
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Muhammad Y Sheikh
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Firdose Gill
- Department of Medicine, Kaiser Permanente Fresno Medical Center (Firdose Gill), Fresno, California, USA
| | - Rabindra Kundu
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Jayanta Choudhury
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
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Guimaraes AR, Siqueira L, Uppal R, Alford J, Fuchs BC, Yamada S, Tanabe K, Chung RT, Lauwers G, Chew ML, Boland GW, Sahani DV, Vangel M, Hahn PF, Caravan P. T2 relaxation time is related to liver fibrosis severity. Quant Imaging Med Surg 2016; 6:103-14. [PMID: 27190762 DOI: 10.21037/qims.2016.03.02] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. METHODS This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multi-slice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. RESULTS (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (~2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). CONCLUSIONS The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.
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Affiliation(s)
- Alexander R Guimaraes
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Luiz Siqueira
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Ritika Uppal
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Jamu Alford
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Bryan C Fuchs
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Suguru Yamada
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Kenneth Tanabe
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Raymond T Chung
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Gregory Lauwers
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Michael L Chew
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Giles W Boland
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Duhyant V Sahani
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Mark Vangel
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Peter F Hahn
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Peter Caravan
- 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA
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Jacobs-Wingo JL, Espey DK, Groom AV, Phillips LE, Haverkamp DS, Stanley SL. Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999-2009. Am J Public Health 2016; 106:906-14. [PMID: 26890168 PMCID: PMC4985112 DOI: 10.2105/ajph.2015.303033] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2015] [Indexed: 01/13/2023]
Abstract
OBJECTIVES To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. METHODS We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999-2009 and compared those with corresponding urban White and rural AI/AN death rates. RESULTS The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. CONCLUSIONS Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities.
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Affiliation(s)
- Jasmine L Jacobs-Wingo
- Jasmine L. Jacobs-Wingo, at the time of the study, was with the Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA. David K. Espey is with the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. Amy V. Groom is with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Leslie E. Phillips, at the time of the study, was with the Urban Indian Health Institute, Seattle, WA. Donald S. Haverkamp is with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. At the time of study, Sandte L. Stanley was with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
| | - David K Espey
- Jasmine L. Jacobs-Wingo, at the time of the study, was with the Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA. David K. Espey is with the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. Amy V. Groom is with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Leslie E. Phillips, at the time of the study, was with the Urban Indian Health Institute, Seattle, WA. Donald S. Haverkamp is with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. At the time of study, Sandte L. Stanley was with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
| | - Amy V Groom
- Jasmine L. Jacobs-Wingo, at the time of the study, was with the Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA. David K. Espey is with the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. Amy V. Groom is with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Leslie E. Phillips, at the time of the study, was with the Urban Indian Health Institute, Seattle, WA. Donald S. Haverkamp is with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. At the time of study, Sandte L. Stanley was with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
| | - Leslie E Phillips
- Jasmine L. Jacobs-Wingo, at the time of the study, was with the Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA. David K. Espey is with the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. Amy V. Groom is with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Leslie E. Phillips, at the time of the study, was with the Urban Indian Health Institute, Seattle, WA. Donald S. Haverkamp is with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. At the time of study, Sandte L. Stanley was with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
| | - Donald S Haverkamp
- Jasmine L. Jacobs-Wingo, at the time of the study, was with the Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA. David K. Espey is with the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. Amy V. Groom is with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Leslie E. Phillips, at the time of the study, was with the Urban Indian Health Institute, Seattle, WA. Donald S. Haverkamp is with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. At the time of study, Sandte L. Stanley was with the Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
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Uhanova J, Minuk G, Lopez Ficher F, Chandok N. Nonalcoholic Fatty Liver Disease in Canadian First Nations and Non-First Nations Patients. Can J Gastroenterol Hepatol 2016; 2016:6420408. [PMID: 27446857 PMCID: PMC4904639 DOI: 10.1155/2016/6420408] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 02/25/2016] [Indexed: 02/06/2023] Open
Abstract
Background. Features of nonalcoholic fatty liver disease (NAFLD) have yet to be described in the Canadian First Nations (FN) population. The aim of this study was to compare the prevalence, severity, and outcome of NAFLD in FN versus non-FN patients at an urban, tertiary care centre. Methods. Adults with NAFLD and no additional liver disease were identified in a prospectively derived database at the University of Manitoba. Demographic, clinical, laboratory, imaging, and histologic data were analyzed. Results. 482 subjects fulfilled diagnostic criteria for NAFLD, including 33 (7%) FN. Aside from rural residence, diabetes and cholestasis being more common in FN patients, the ages, gender distributions, clinical and radiologic features, and liver enzyme/function test results were similar in the two cohorts. Noninvasive tests of fibrosis (APRI and NAFLD fibrosis scores) were also similar in the two cohorts. There were no significant differences in liver enzyme or function tests in either cohort after approximately three years of follow-up. Conclusion. Compared to the prevalence of FN persons in the general population of this study site (10-15%), FN patients were underrepresented in this NAFLD population. The severity and progression of liver disease in FN patients appear to be similar to those in non-FN patients.
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Affiliation(s)
- Julia Uhanova
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, 804D-715 McDermot Avenue, Winnipeg, MB, Canada R3E 3P4
| | - Gerald Minuk
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, 804D-715 McDermot Avenue, Winnipeg, MB, Canada R3E 3P4
| | - Federico Lopez Ficher
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, 804D-715 McDermot Avenue, Winnipeg, MB, Canada R3E 3P4
| | - Natasha Chandok
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, 804D-715 McDermot Avenue, Winnipeg, MB, Canada R3E 3P4
- Division of Gastroenterology, University of Western Ontario, Room ALL-107, 339 Windermere Road, London, ON, Canada N6A 5A5
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Johnson SL, Palta M, Bartels CM, Thorpe CT, Weiss JM, Smith MA. Examining systemic steroid Use in older inflammatory bowel disease patients using hurdle models: a cohort study. BMC Pharmacol Toxicol 2015; 16:34. [PMID: 26643112 PMCID: PMC4672478 DOI: 10.1186/s40360-015-0034-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 11/18/2015] [Indexed: 01/15/2023] Open
Abstract
Background Interpreting clinical guideline adherence and the appropriateness of medication regimens requires consideration of individual patient and caregiver factors. Factors leading to initiation of a medication may differ from those determining continued use. We believe this is the case for systemic steroid therapy in inflammatory bowel disease (IBD), resulting in a need to apply methods that separately consider factors associated with initiation and duration of therapy. To evaluate the relationship between patient characteristics and the frequency and duration of incident steroid use we apply a 2-part hurdle model to Medicare data. We do so in older patients with tumor necrosis factor antagonist (anti-TNFs) contraindications, as they are of special interest for compliance with Medicare-adopted, quality metrics calling for anti-TNFs and nonbiologic immune therapies to reduce steroid utilization. Many older patients have contraindications to anti-TNFs. However, nonbiologics cause adverse events that are concerning in older adults, limiting their use in this population and increasing reliance on systemic steroids. Methods We used a national Medicare sample for 2006–2009 including patients with 12 months or greater of Parts A and B and 6 months or greater of Part D coverage, IBD confirmed with at least 2 claims for ICD-9CM 555.xx or 556.xx, anti-TNF contraindications and without contraindications to nonbiologic agents. We applied a negative binomial-logit hurdle model to examine patient characteristics associated with systemic steroid utilization. Results Among the 1,216 IBD patients without baseline steroid use, 21 % used systemic steroids. Odds of receiving systemic steroids were greater in those younger, rural, and those receiving other agents. Available patient characteristics failed to predict longer steroid treatment duration. Conclusions Our study identified differences in predictors of frequency and duration of medication use and suggests the utility of two-part models to examine drug utilization patterns. Applying such a model to Medicare data, we determined that despite medical consensus that systemic steroid use should be minimized, its use was substantial. Findings indicate anticipated difficulties in implementing recently adopted quality measures to avoid systemic steroids.
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Affiliation(s)
- Sophia L Johnson
- Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Room 01-218, Baltimore, MD, 21201, USA.
| | - Mari Palta
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut Street, 53726 608-263-2520, Madison, Wisconsin, USA. .,Department of Biostatistics & Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
| | - Christie M Bartels
- Department of Medicine, Rheumatology Division, University of Wisconsin School of Medicine and Public Health, 800 Highland Avenue, 608-263-3457, Madison, Wisconsin, USA.
| | - Carolyn T Thorpe
- Center for Health Equity Research and Promotion, Veterans Affairs Pittsburgh Medical Center, 3501 Terrace Street, 412-624-7794, Pittsburgh, Pennsylvania, USA. .,Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
| | - Jennifer M Weiss
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Room 4230, 608-263-1995, Madison, Wisconsin, USA.
| | - Maureen A Smith
- Department of Biostatistics & Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. .,Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. .,Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
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Hong M, Li S, Tan HY, Wang N, Tsao SW, Feng Y. Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects. Int J Mol Sci 2015; 16:28705-28745. [PMID: 26633388 PMCID: PMC4691073 DOI: 10.3390/ijms161226126] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 11/25/2015] [Accepted: 11/25/2015] [Indexed: 02/07/2023] Open
Abstract
Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.
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Affiliation(s)
- Ming Hong
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Hor Yue Tan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Sai-Wah Tsao
- Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Silva MJ, Rosa MV, Nogueira PJ, Calinas F. Ten years of hospital admissions for liver cirrhosis in Portugal. Eur J Gastroenterol Hepatol 2015; 27:1320-1326. [PMID: 26275086 DOI: 10.1097/meg.0000000000000449] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND AND AIMS More data on epidemiology of liver diseases in Europe are needed. We aimed to characterize hospital admissions for liver cirrhosis in Portugal during the past decade. PATIENTS AND METHODS We analyzed all hospital admissions for cirrhosis in Portugal Mainland between 2003 and 2012 registered in the national Diagnosis-Related Group database. Cirrhosis was classified according to etiology considering alcohol, hepatitis B, and hepatitis C. RESULTS Between 2003 and 2012, there were 63,910 admissions for cirrhosis in Portugal Mainland; 74.4% involved male patients. Etiologies of admitted cirrhosis were as follows: 76.0% alcoholic, 1.1% hepatitis B, 1.4% hepatitis B plus alcohol, 3.6% hepatitis C, and 4.0% hepatitis C plus alcohol. There was a significant decline (P<0.001) in admissions for alcoholic cirrhosis, whereas hospitalizations for cirrhosis caused by hepatitis C or hepatitis C plus alcohol increased by almost 50% (P<0.001). Patients admitted with alcoholic plus hepatitis B or C cirrhosis were significantly younger than those with either alcoholic or viral cirrhosis (53.1 vs. 59.4 years, respectively, P<0.001). Hospitalization rates for cirrhosis were 124.4/100,000 in men and 32.6/100,000 in women. Hepatocellular carcinoma and fluid retention were more common in viral cirrhosis, whereas encephalopathy and variceal bleeding were more frequent in alcoholic cirrhosis. Hepatorenal syndrome was the strongest predictor of mortality among cirrhosis complications (odds ratio 12.97; 95% confidence interval 11.95-14.09). In-hospital mortality was 15.2%. CONCLUSION Despite the decline in admissions for alcoholic cirrhosis and the increase in those related to hepatitis C, the observed burden of hospitalized liver cirrhosis in Portugal was essentially attributable to alcoholic liver disease.
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Affiliation(s)
- Mário J Silva
- aGastroenterology Department, Central Lisbon Hospital Centre bNOVA Medical School cDirectorate of Analysis and Information, Directorate-General of Health dInstitute for Preventive Medicine and Public Health, Faculty of Medicine, University of Lisbon, Portugal
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Ursic-Bedoya J, Faure S, Donnadieu-Rigole H, Pageaux GP. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues. World J Gastroenterol 2015; 21:10994-11002. [PMID: 26494956 PMCID: PMC4607899 DOI: 10.3748/wjg.v21.i39.10994] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/10/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a “self-inflicted” condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient’s commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates.
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Feld JJ, Kato GJ, Koh C, Shields T, Hildesheim M, Kleiner DE, Taylor JG, Sandler NG, Douek D, Haynes-Williams V, Nichols JS, Hoofnagle JH, Liang TJ, Gladwin MT, Heller T. Liver injury is associated with mortality in sickle cell disease. Aliment Pharmacol Ther 2015; 42:912-21. [PMID: 26235444 PMCID: PMC6478018 DOI: 10.1111/apt.13347] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 06/25/2015] [Accepted: 07/15/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems. AIM To report the long-term consequences of liver dysfunction in SCD. METHODS A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression. RESULTS Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension. CONCLUSIONS Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.
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Affiliation(s)
- Jordan J. Feld
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH),Toronto Centre for Liver Disease, Sandra Rotman Center for Global Health, University of Toronto
| | - Gregory J. Kato
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH),Vascular Medicine Institute, University of Pittsburgh Medical Center
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - Tammy Shields
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Mariana Hildesheim
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health (NIH)
| | - James G Taylor
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Netanya G. Sandler
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
| | - Daniel Douek
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
| | - Vanessa Haynes-Williams
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - James S. Nichols
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Jay H. Hoofnagle
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - Mark T. Gladwin
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH),Vascular Medicine Institute, University of Pittsburgh Medical Center
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
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Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T. BIOMED RESEARCH INTERNATIONAL 2015; 2015:387653. [PMID: 26421287 PMCID: PMC4569760 DOI: 10.1155/2015/387653] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 10/15/2014] [Accepted: 10/18/2014] [Indexed: 01/02/2023]
Abstract
Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.
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Abstract
BACKGROUND AND AIMS Liver cirrhosis is an important public health concern in the United States and a significant source of morbidity and mortality. However, the epidemiology of cirrhosis is incompletely understood. The aims of this study were to estimate the prevalence of cirrhosis in the general US population, determine characteristics of affected Americans with a focus on health disparities, and calculate excess mortality attributable to cirrhosis. METHODS National Health And Nutrition Examination Survey data conducted between 1999 and 2010 were used to estimate cirrhosis prevalence and factors associated with cirrhosis. The National Center for Health Statistics-linked death certificate data from the National Death Index were linked to the National Health And Nutrition Examination Survey database for the years 1999 to 2004, and attributable mortality was calculated using propensity score adjustment. Cirrhosis was ascertained by aspartate aminotransferase-to-platelet ratio of >2 and abnormal liver function tests. RESULTS The prevalence of cirrhosis in the United States was approximately 0.27%, corresponding to 633,323 adults. Sixty-nine percent reported that they were unaware of having liver disease. The prevalence was higher in non-Hispanic blacks and Mexican Americans, those living below the poverty level, and those with less than a 12th grade education. Diabetes, alcohol abuse, hepatitis C and B, male sex, and older age were all independently associated with cirrhosis, with a population attributable fraction of 53.5% from viral hepatitis (mostly hepatitis C), diabetes, and alcohol abuse. Mortality was 26.4% per 2-year interval in cirrhosis compared with 8.4% in propensity-matched controls. CONCLUSIONS The prevalence of cirrhosis is higher than previously estimated. Many cases may be undiagnosed, and more than half are potentially preventable by controlling diabetes, alcohol abuse, and viral hepatitis. Public health efforts are needed to reduce this disease burden, particularly among racial/ethnic minorities and individuals at lower socioeconomic status.
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Ly KN, Speers S, Klevens RM, Barry V, Vogt TM. Measuring chronic liver disease mortality using an expanded cause of death definition and medical records in Connecticut, 2004. Hepatol Res 2015; 45:960-968. [PMID: 25319958 PMCID: PMC11005817 DOI: 10.1111/hepr.12437] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 10/08/2014] [Accepted: 10/12/2014] [Indexed: 02/08/2023]
Abstract
AIM Chronic liver disease (CLD) is a leading cause of death and is defined based on a specific set of underlying cause-of-death codes on death certificates. This conventional approach to measuring CLD mortality underestimates the true mortality burden because it does not consider certain CLD conditions like viral hepatitis and hepatocellular carcinoma. We measured how much the conventional CLD mortality case definition will underestimate CLD mortality and described the distribution of CLD etiologies in Connecticut. METHODS We used 2004 Connecticut death certificates to estimate CLD mortality two ways. One way used the conventional definition and the other used an expanded definition that included more conditions suggestive of CLD. We compared the number of deaths identified using this expanded definition with the number identified using the conventional definition. Medical records were reviewed to confirm CLD deaths. RESULTS Connecticut had 29 314 registered deaths in 2004. Of these, 282 (1.0%) were CLD deaths identified by the conventional CLD definition while 616 (2.1%) were CLD deaths defined by the expanded definition. Medical record review confirmed that most deaths identified by the expanded definition were CLD-related (550/616); this suggested a 15.8 deaths/100 000 population mortality rate. Among deaths for which hepatitis B, hepatitis C and alcoholic liver disease were identified during medical record review, only 8.6%, 45.4% and 36.5%, respectively, had that specific cause-of-death code cited on the death certificate. CONCLUSION An expanded CLD mortality case definition that incorporates multiple causes of death and additional CLD-related conditions will better estimate CLD mortality.
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Affiliation(s)
- Kathleen N. Ly
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Suzanne Speers
- Connecticut Department of Public Health, Hartford, Connecticut, USA
| | - R. Monina Klevens
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Vaughn Barry
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Tara M. Vogt
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
- Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Noh HM, Ahn EM, Yun JM, Cho BL, Paek YJ. Angelica keiskei Koidzumi extracts improve some markers of liver function in habitual alcohol drinkers: a randomized double-blind clinical trial. J Med Food 2015; 18:166-72. [PMID: 25531033 DOI: 10.1089/jmf.2014.3222] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Alcohol induces oxidative stress and inflammatory response, which can lead to hepatitis and cirrhosis. Previous studies reported that the extracts of Angelica keiskei Koidzumi (AKE) have antioxidant and anti-inflammatory properties, suggesting that AKE could improve abnormalities associated with alcoholic liver disease. In this study, the effectiveness of AKE supplementation was assessed in 82 habitual alcohol drinkers (male: more than 14 units per week, female: more than 7 units per week) with abnormal liver biochemistry in a placebo-controlled, randomized double-blind trial over 12 weeks. Among the subjects, 65% (n=43) were heavy drinkers consuming more than 35 units per week. Among heavy drinkers, gamma-glutamyl transferase levels of 19 subjects per AKE-treated group were significantly decreased (21.16±37.63, P=.016) with significant differences observed compared to the 24 subjects per placebo group (P=.046). However, no significant differences were observed in aspartate aminotransferase and alanine aminotransferase levels between the AKE- and placebo-treated groups. These results suggest that AKE supplementation might improve liver function in heavy drinkers.
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Affiliation(s)
- Hye-Mi Noh
- 1 Department of Family Medicine, Hallym University College of Medicine , Anyang, Korea
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Lee SJ, Uhm JS, Kim JY, Pak HN, Lee MH, Joung B. The safety and efficacy of vitamin K antagonist in patients with atrial fibrillation and liver cirrhosis. Int J Cardiol 2015; 180:185-91. [DOI: 10.1016/j.ijcard.2014.11.183] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 10/14/2014] [Accepted: 11/23/2014] [Indexed: 01/15/2023]
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Abstract
This study aimed to analyze trends in the 10 leading causes of death in Korea from 1983 to 2012. Death rates were derived from the Korean Statistics Information Service database and age-adjusted to the 2010 population. Joinpoint regression analysis was used to identify the points when statistically significant changes occurred in the trends. Between 1983 and 2012, the age-standardized death rate (ASR) from all causes decreased by 61.6% for men and 51.2% for women. ASRs from malignant neoplasms, diabetes mellitus, and transport accidents increased initially before decreasing. ASRs from hypertensive diseases, heart diseases, cerebrovascular diseases and diseases of the liver showed favorable trends (ASR % change: -94.4%, -53.8%, -76.0%, and -78.9% for men, and -77.1%, -36.5%, -67.8%, and -79.9% for women, respectively). ASRs from pneumonia decreased until the mid-1990s and thereafter increased. ASRs from intentional self-harm increased persistently since around 1990 (ASR % change: 122.0% for men and 217.4% for women). In conclusion, death rates from all causes in Korea decreased significantly in the last three decades except in the late 1990s. Despite the great strides made in the overall mortality, temporal trends varied widely by cause. Mortality trends for malignant neoplasms, diabetes mellitus, pneumonia and intentional self-harm were unfavorable.
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Affiliation(s)
- Daroh Lim
- Center for Health Industry Information and Statistics, Bureau of Health Industry Policy, Korea Health Industry Development Institute, Cheongju, Korea
| | - Mina Ha
- Department of Health Infrastructure Development, Bureau of Health Technology R&D Planning and Budget Management, Korea Health Industry Development Institute, Cheongju, Korea
- Department of Preventive Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Inmyung Song
- Department of Pharmaceutical Industry, Bureau of Health Industry Promotion, Korea Health Industry Development Institute, Cheongju, Korea
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Suryaprasad A, Byrd KK, Redd JT, Perdue DG, Manos MM, McMahon BJ. Mortality caused by chronic liver disease among American Indians and Alaska Natives in the United States, 1999-2009. Am J Public Health 2014; 104 Suppl 3:S350-8. [PMID: 24754616 DOI: 10.2105/ajph.2013.301645] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES We compared chronic liver disease (CLD) mortality from 1999 to 2009 between American Indians and Alaska Natives (AI/ANs) and Whites in the United States after improving CLD case ascertainment and AI/AN race classification. METHODS We defined CLD deaths and causes by comprehensive death certificate-based diagnostic codes. To improve race classification, we linked US mortality data to Indian Health Service enrollment records, and we restricted analyses to Contract Health Service Delivery Areas and to non-Hispanic populations. We calculated CLD death rates (per 100,000) in 6 geographic regions. We then described trends using linear modeling. RESULTS CLD mortality increased from 1999 to 2009 in AI/AN persons and Whites. Overall, the CLD death rate ratio (RR) of AI/AN individuals to Whites was 3.7 and varied by region. The RR was higher in women (4.7), those aged 25 to 44 years (7.4), persons residing in the Northern Plains (6.4), and persons dying of cirrhosis (4.0) versus hepatocellular carcinoma (2.5), particularly those aged 25 to 44 years (7.7). CONCLUSIONS AI/AN persons had greater CLD mortality, particularly from premature cirrhosis, than Whites, with variable mortality by region. Comprehensive prevention and care strategies are urgently needed to stem the CLD epidemic among AI/AN individuals.
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Affiliation(s)
- Anil Suryaprasad
- Anil Suryaprasad and Kathy K. Byrd are with the Division of Viral Hepatitis; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Centers for Disease Control and Prevention (CDC); US Department of Health and Human Services; Atlanta, GA. John T. Redd is with the Santa Fe Public Health Service Indian Hospital, Indian Health Service, US Department of Health and Human Services, Santa Fe, NM. David G. Perdue is with the American Indian Cancer Foundation and Minnesota Gastroenterology PA, Minneapolis. M. Michele Manos is with the Kaiser Permanente Division of Research, Oakland, CA. Brian J. McMahon is with the Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AL
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Landen M, Roeber J, Naimi T, Nielsen L, Sewell M. Alcohol-attributable mortality among American Indians and Alaska Natives in the United States, 1999-2009. Am J Public Health 2014; 104 Suppl 3:S343-9. [PMID: 24754661 DOI: 10.2105/ajph.2013.301648] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
OBJECTIVES We describe the relative burden of alcohol-attributable death among American Indians/Alaska Natives (AI/ANs) in the United States. METHODS National Death Index records were linked with Indian Health Service (IHS) registration records to identify AI/AN deaths misclassified as non-AI/AN. We calculated age-adjusted alcohol-attributable death rates from 1999 to 2009 for AI/AN and White persons by sex, age, geographic region, and leading causes; individuals of Hispanic origin were excluded. RESULTS AI/AN persons had a substantially higher rate of alcohol-attributable death than Whites from 2005 to 2009 in IHS Contract Health Service Delivery Area counties (rate ratio = 3.3). The Northern Plains had the highest rate of AI/AN deaths (123.8/100,000), and the East had the lowest (48.9/100,000). For acute causes, the largest relative risks for AI/AN persons compared with Whites were for hypothermia (14.2) and alcohol poisoning (7.6). For chronic causes, the largest relative risks were for alcoholic psychosis (5.0) and alcoholic liver disease (4.9). CONCLUSIONS Proven strategies that reduce alcohol consumption and make the environment safer for excessive drinkers should be further implemented in AI/AN communities.
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Affiliation(s)
- Michael Landen
- Michael Landen and Jim Roeber are with the Epidemiology and Response Division, New Mexico Department of Health, Santa Fe. Tim Naimi is with the Section of Internal Medicine, Boston Medical Center, MA. Larry Nielsen is with the National Association for Public Health Statistics and Information Systems, Silver Spring, MD. Mack Sewell is with the Wyoming Department of Workforce Services, Cheyenne
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Apica BS, Ocama P, Seremba E, Opio KC, Kagimu MM. Decompensated cirrhosis-related admissions in a large urban hospital in Uganda: prevalence, clinical and laboratory features and implications for planning patient management. Afr Health Sci 2013; 13:927-32. [PMID: 24940314 PMCID: PMC4056489 DOI: 10.4314/ahs.v13i4.10] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Cirrhosis-related complications are a major cause of morbidity and mortality in areas where its risk factors are endemic. OBJECTIVE We determined the prevalence of decompensated cirrhosis among patients on the gastroenterology service of Mulago Hospital and described the clinical and laboratory features of these patients. METHODS All patients admitted to the unit were assessed and their diagnosis documented. Patients with cirrhosis had clinical features of decompensation recorded. History of alcohol consumption was taken and testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) performed. RESULTS Between September 2010 and January 2011, we enrolled 482 patients. The majority (53.7%) were male, overall median age 38 years. Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients, 47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%) patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%). CONCLUSION Cirrhosis is common in Mulago hospital presenting mainly with ascites and variceal bleeding. Aside from controlling causes of liver diseases, especially alcohol and hepatitis B virus infection, in the interim it is necessary to manage complications in patients who already have cirrhosis.
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Affiliation(s)
- B S Apica
- Department of Medicine, Mulago Hospital, Makerere University College of Health Sciences, Kampala, Uganda
| | - P Ocama
- Department of Medicine, Mulago Hospital, Makerere University College of Health Sciences, Kampala, Uganda
| | - E Seremba
- Department of Medicine, Mulago Hospital, Makerere University College of Health Sciences, Kampala, Uganda
| | - K C Opio
- Department of Medicine, Mulago Hospital, Makerere University College of Health Sciences, Kampala, Uganda
| | - M M Kagimu
- Department of Medicine, Mulago Hospital, Makerere University College of Health Sciences, Kampala, Uganda
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Stahre MA, Toomey TL, Erickson DJ, Forster JL, Okuyemi KS, Ahluwalia JS. The Effects of a Tobacco Intervention on Binge Drinking Among African American Light Smokers. J Addict Dis 2013; 32:377-86. [DOI: 10.1080/10550887.2013.849972] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Rates and risk factors for hepatitis B reactivation in a cohort of persons in the inactive phase of chronic hepatitis B-Alaska, 2001-2010. J Clin Virol 2013; 58:396-400. [PMID: 24001884 DOI: 10.1016/j.jcv.2013.08.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Revised: 08/06/2013] [Accepted: 08/08/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons. OBJECTIVES Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska. STUDY DESIGN A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA<2000 IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA≥2000 IU/mL and ALT≥40 IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation. RESULTS A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR)=2.41; 95% Confidence Interval (CI): 1.17-4.96), HBV DNA≥1000 IU/mL at study entry (HR=7.61; 95% CI: 2.81-20.6), and HBV genotype B (HR=6.08; 95% CI: 1.32-28.0). CONCLUSIONS The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA≥1000 IU/mL need to be followed-up more frequently.
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Asrani SK, Larson JJ, Yawn B, Therneau TM, Kim WR. Underestimation of liver-related mortality in the United States. Gastroenterology 2013; 145:375-82.e1-2. [PMID: 23583430 PMCID: PMC3890240 DOI: 10.1053/j.gastro.2013.04.005] [Citation(s) in RCA: 239] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 03/29/2013] [Accepted: 04/03/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS According to the National Center for Health Statistics (NCHS), chronic liver disease and cirrhosis is the 12(th) leading cause of death in the United States. However, this single descriptor might not adequately enumerate all deaths from liver disease. The aim of our study was to update data on liver mortality in the United States. METHODS Mortality data were obtained from the Rochester Epidemiology Project (1999-2008) and the National Death Registry (1979-2008). Liver-specific mortality values were calculated. In contrast to the narrow NCHS definition, updated liver-related causes of death included other specific liver diagnoses (eg, hepatorenal syndrome), viral hepatitis, and hepatobiliary cancers. RESULTS The Rochester Epidemiology Project database contained information on 261 liver-related deaths, with an age- and sex-adjusted death rate of 27.0/100,000 persons (95% confidence interval: 23.7-30.3). Of these, only 71 deaths (27.2%) would have been captured by the NCHS definition. Of cases for which viral hepatitis or hepatobiliary cancer was the cause of death, 96.9% and 94.3% had liver-related immediate causes of death, respectively. In analysis of data from the National Death registry (2008), use of the updated definition increased liver mortality by >2-fold (from 11.7 to 25.7 deaths/100,000, respectively). Using NCHS definitions, liver-related deaths decreased from 18.9/100,000 in 1979 to 11.7/100,000 in 2008-a reduction of 38%. However, using the updated estimate, liver-related deaths were essentially unchanged from 1979 (25.8/100,000) to 2008 (25.7/100,000). Mortality burden was systematically underestimated among non-whites and persons of Hispanic ethnicity. CONCLUSIONS Based on analyses of the Rochester Epidemiology Project and National Death databases, liver-related mortality has been underestimated during the past 2 decades in the United States.
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Affiliation(s)
- Sumeet K Asrani
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
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Orrskog S, Medin E, Tsolova S, Semenza JC. Causal inference regarding infectious aetiology of chronic conditions: a systematic review. PLoS One 2013; 8:e68861. [PMID: 23935899 PMCID: PMC3723854 DOI: 10.1371/journal.pone.0068861] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 05/31/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. METHODS AND FINDINGS We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤ 3) and when applying the three different criteria of evidence the strength of the causality was weak. CONCLUSIONS Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.
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Affiliation(s)
| | - Emma Medin
- Heron Evidence Development AB, Stockholm, Sweden
- Karolinska Institutet, Stockholm, Sweden
| | - Svetla Tsolova
- European Centres for Disease Prevention and Control, Stockholm, Sweden
| | - Jan C. Semenza
- European Centres for Disease Prevention and Control, Stockholm, Sweden
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Tempalski B, Pouget ER, Cleland CM, Brady JE, Cooper HLF, Hall HI, Lansky A, West BS, Friedman SR. Trends in the population prevalence of people who inject drugs in US metropolitan areas 1992-2007. PLoS One 2013; 8:e64789. [PMID: 23755143 PMCID: PMC3673953 DOI: 10.1371/journal.pone.0064789] [Citation(s) in RCA: 115] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Accepted: 04/17/2013] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND People who inject drugs (PWID) have increased risk of morbidity and mortality. We update and present estimates and trends of the prevalence of current PWID and PWID subpopulations in 96 US metropolitan statistical areas (MSAs) for 1992-2007. Current estimates of PWID and PWID subpopulations will help target services and help to understand long-term health trends among PWID populations. METHODOLOGY We calculated the number of PWID in the US annually from 1992-2007 and apportioned estimates to MSAs using multiplier methods. We used four types of data indicating drug injection to allocate national annual totals to MSAs, creating four distinct series of component estimates of PWID in each MSA and year. The four component estimates are averaged to create the best estimate of PWID for each MSA and year. We estimated PWID prevalence rates for three subpopulations defined by gender, age, and race/ethnicity. We evaluated trends using multi-level polynomial models. RESULTS PWID per 10,000 persons aged 15-64 years varied across MSAs from 31 to 345 in 1992 (median 104.4) to 34 to 324 in 2007 (median 91.5). Trend analysis indicates that this rate declined during the early period and then was relatively stable in 2002-2007. Overall prevalence rates for non-Hispanic black PWID increased in 2005 as compared to other racial/ethnic groups. Hispanic prevalence, in contrast, declined across time. Importantly, results show a worrisome trend in young PWID prevalence since HAART was initiated--the mean prevalence was 90 to 100 per 10,000 youth in 1992-1996, but increased to >120 PWID per 10,000 youth in 2006-2007. CONCLUSIONS Overall, PWID rates remained constant since 2002, but increased for two subpopulations: non-Hispanic black PWID and young PWID. Estimates of PWID are important for planning and evaluating public health programs to reduce harm among PWID and for understanding related trends in social and health outcomes.
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Affiliation(s)
- Barbara Tempalski
- Institute for AIDS Research, National Development and Research Institutes, Inc.-NDRI, New York, New York, United States of America.
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Czaja AJ. Autoimmune hepatitis in diverse ethnic populations and geographical regions. Expert Rev Gastroenterol Hepatol 2013; 7:365-85. [PMID: 23639095 DOI: 10.1586/egh.13.21] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Autoimmune hepatitis has diverse clinical phenotypes and outcomes in ethnic groups within a country and between countries, and these differences may reflect genetic predispositions, indigenous etiological agents, pharmacogenomic mechanisms and socioeconomic reasons. In the USA, African-American patients have cirrhosis more commonly, treatment failure more frequently and higher mortality than white American patients. Survival is poorest in Asian-American patients. Autoimmune hepatitis in other countries is frequently associated with genetic predispositions that may favor susceptibility to indigenous etiological agents. Cholestatic features influence treatment response; acute-on-chronic liver disease increases mortality and socioeconomic and cultural factors affect prognosis. Ethnic-based deviations from classical phenotypes and the frequency of late-stage disease can complicate the diagnosis and management of autoimmune hepatitis in non-white populations.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Hepatitis C virus in American Indian/Alaskan Native and Aboriginal peoples of North America. Viruses 2013; 4:3912-31. [PMID: 23342378 PMCID: PMC3528296 DOI: 10.3390/v4123912] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Liver diseases, such as hepatitis C virus (HCV), are “broken spirit” diseases. The prevalence of HCV infection for American Indian/Alaskan Native (AI/AN) in the United States and Canadian Aboriginals varies; nonetheless, incidence rates of newly diagnosed HCV infection are typically higher relative to non-indigenous people. For AI/AN and Aboriginal peoples risk factors for the diagnosis of HCV can reflect that of the general population: predominately male, a history of injection drug use, in midlife years, with a connection with urban centers. However, the face of the indigenous HCV infected individual is becoming increasingly female and younger compared to non-indigenous counterparts. Epidemiology studies indicate that more effective clearance of acute HCV infection can occur for select Aboriginal populations, a phenomenon which may be linked to unique immune characteristics. For individuals progressing to chronic HCV infection treatment outcomes are comparable to other racial cohorts. Disease progression, however, is propelled by elevated rates of co-morbidities including type 2 diabetes and alcohol use, along with human immunodeficiency virus (HIV) co-infection relative to non-indigenous patients. Historical and personal trauma has a major role in the participation of high risk behaviors and associated diseases. Although emerging treatments provide hope, combating HCV related morbidity and mortality will require interventions that address the etiology of broken spirit diseases.
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Barclay SM, Jeffres MN, Nguyen K, Nguyen T. Evaluation of Pharmacologic Prophylaxis for Venous Thromboembolism in Patients with Chronic Liver Disease. Pharmacotherapy 2013; 33:375-82. [DOI: 10.1002/phar.1218] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | | | - KimChi Nguyen
- College of Pharmacy; Roseman University of Health Sciences; Henderson; Nevada
| | - Tamdan Nguyen
- College of Pharmacy; Roseman University of Health Sciences; Henderson; Nevada
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