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Danpanichkul P, Pang Y, Diaz LA, Arab JP, Hwang SY, Dejvajara D, Suresh V, Suenghataiphorn T, Wannaphut C, Suparan K, Wijarnpreecha K, Kim H, Kim D, Singal AG, Yang JD. Young Adults and Alcohol-Associated Liver Cancer: Incidence and Death from 2000 to 2021. Cancers (Basel) 2025; 17:609. [PMID: 40002204 PMCID: PMC11853673 DOI: 10.3390/cancers17040609] [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: 12/17/2024] [Revised: 01/25/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES The incidence and mortality of early-onset cancers have been rising in recent decades. While epidemiological studies have examined various types of cancer, updated global data on alcohol-attributable primary liver cancer (PLC) in young adults remains limited. METHODS This study utilized data from the Global Burden of Disease (GBD) study spanning 2000 to 2021 to evaluate the age-standardized incidence, mortality, and corresponding rates of alcohol-attributable PLC among young adults aged 15-49 years. RESULTS In 2021, there were 8290 incidence cases and 6590 deaths from alcohol-attributable PLC in young adults. The age-standardized incidence rate has increased in Europe (annual percent change [APC]: 0.44%, 95%CI 0.35 to 0.54%), Southeast Asia (APC: 0.40%, 95% CI 0.37 to 0.44%), and the Western Pacific region (APC: 0.65%, 95% CI 0.44 to 0.86%). In 2021, alcohol-attributable PLC in young adults represented 11% (+2% from 2000) of incident cases and 11% of (+2% from 2000) deaths among all PLC in young adults. About half of the countries showed an increase in the age-standardized incidence rate of alcohol-attributable PLC among young adults between 2000 and 2021. CONCLUSIONS The incidence rate of alcohol-attributable liver cancer in young adults has shifted significantly over the past two decades, with notable increases in Europe and the Asia-Pacific region. This trend underscores the need for global strategies to address the rising prevalence of alcohol use disorder and alcohol-associated liver disease and their impact on young adults.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79409, USA
| | - Yanfang Pang
- Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533099, China
- National Immunological Laboratory of Traditional Chinese Medicine, Baise 533000, China
- Center for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533099, China
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Luis Antonio Diaz
- Metabolic-Dysfunction Associated Steatotic Liver Disease Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA 92037, USA
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago 8320165, Chile
- Observatorio Multicéntrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile
| | - Juan Pablo Arab
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
| | - Soo Young Hwang
- Department of Internal Medicine, University of Maryland Medical Center, Midtown Campus, Baltimore, MD 21201, USA
| | | | - Varshini Suresh
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79409, USA
| | | | - Chalothorn Wannaphut
- Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
| | - Kanokphong Suparan
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, AZ 85004, USA
- BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA
| | - Hyunseok Kim
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94063, USA
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Chen Q, Huang S, Peng J, Wang P, Shi X, Luo R, Xu H, Zhang W, Shi L, Peng Y, Yuan F, Tang X. The Burden of Hepatitis B and C in Asia, 1990-2019: An Update Analysis From the Global Burden of Disease Study 2019. Liver Int 2025; 45:e70004. [PMID: 39840788 DOI: 10.1111/liv.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 12/11/2024] [Accepted: 01/10/2025] [Indexed: 01/23/2025]
Abstract
AIM This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors. RESULT A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50-54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI. CONCLUSION Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.
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Affiliation(s)
- Qi Chen
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Shu Huang
- Department of Gastroenterology, Lianshui County People' Hospital, Huaian, China
- Department of Gastroenterology, Lianshui People' Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian, China
| | - Jieyu Peng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Ping Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Xiaomin Shi
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Rui Luo
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Huan Xu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Wei Zhang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Lei Shi
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Yan Peng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Fangfang Yuan
- Department of Intensive Care Unit, The 3rd Xiangya Hospital, Central South University, Changsha, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
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Chen JS, Levintow SN, Tran HV, Sibley AL, Blackburn NA, Sripaipan T, Hutton HE, Go VF, Chander G. Prevalence of hepatitis coinfection and substance use among antiretroviral therapy clinic clients with hazardous alcohol use in Vietnam. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0003744. [PMID: 39636896 PMCID: PMC11620398 DOI: 10.1371/journal.pgph.0003744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 09/29/2024] [Indexed: 12/07/2024]
Abstract
The confluence of injection drug use (IDU), alcohol consumption, and viral hepatitis increases morbidity among persons living with HIV (PWH). We present a secondary analysis of a randomized controlled trial of alcohol reduction interventions in Thai Nguyen, Vietnam conducted between 2016-2018. We assessed hepatitis B (HBV) and hepatitis C (HCV) coinfection among PWH reporting hazardous alcohol consumption and examined differences in IDU and alcohol use by coinfection status. Participants were ≥18 years old, living with HIV, and reported hazardous alcohol consumption per the WHO Alcohol Use Disorders Identification Test Consumption (AUDIT-C; score ≥4 for men, score ≥3 for women). At enrollment, participants were tested for hepatitis coinfection with HBV surface antigen tests and rapid serological HCV tests. Demographic information, IDU, and recent alcohol consumption were assessed via behavioral survey and 30-day timeline follow back. Fishers Exact and Kruskal-Wallis tests were used for statistical testing. Hepatitis coinfection was common among the 440 enrolled PWH: HCV: n = 355 (81%); HBV: n = 5 (1%); HBV and HCV: n = 37 (8%). Only 10% (n = 43) of participants had no hepatitis coinfection. Among those who tested positive for HBV, 36% had previously been diagnosed with HBV; among those who tested seropositive for HCV, 18% had previously received an HCV diagnosis. History of IDU was higher among those with hepatitis coinfection (HBV or HCV coinfection: 88%; HBV and HCV coinfections: 97%) than those without hepatitis coinfection (7%; p<0.01). Median days of alcohol consumption in the last 30 days was higher among those with coinfection (HBV or HCV coinfection: 20 (Interquartile Range (IQR): 10-30); HBV and HCV coinfections: 22 (IQR: 13-28) than those without hepatitis coinfection (10; IQR: 6-21; p<0.01). The syndemic conditions of HIV, hepatitis, IDU, and alcohol use are deeply entangled and challenging to parse out. Integrated health services are warranted to reduce the risk of liver-related morbidity.
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Affiliation(s)
- Jane S. Chen
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Sara N. Levintow
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Ha V. Tran
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Adams L. Sibley
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Natalie A. Blackburn
- RTI International, Research Triangle Park, North Carolina, United States of America
| | - Teerada Sripaipan
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Heidi E. Hutton
- Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Vivian F. Go
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Geetanjali Chander
- Division of General Internal Medicine, University of Washington, Seattle, Washington, United States of America
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Ratshisusu L, Simani OE, Blackard JT, Selabe SG. The Impact of Drugs and Substance Abuse on Viral Pathogenesis-A South African Perspective. Viruses 2024; 16:971. [PMID: 38932263 PMCID: PMC11209167 DOI: 10.3390/v16060971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.
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Affiliation(s)
- Lufuno Ratshisusu
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (O.E.S.); (J.T.B.); (S.G.S.)
| | - Omphile E. Simani
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (O.E.S.); (J.T.B.); (S.G.S.)
| | - Jason T. Blackard
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (O.E.S.); (J.T.B.); (S.G.S.)
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA
| | - Selokela G. Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (O.E.S.); (J.T.B.); (S.G.S.)
- National Health Laboratory Service, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa
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Andaloro S, Mancuso F, Miele L, Addolorato G, Gasbarrini A, Ponziani FR. Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease. Nutrients 2024; 16:613. [PMID: 38474740 DOI: 10.3390/nu16050613] [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: 01/16/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 03/14/2024] Open
Abstract
Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.
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Affiliation(s)
- Silvia Andaloro
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Fabrizio Mancuso
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Miele
- Department of Abdominal, Endocrine and Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Liver Transplant Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Addolorato
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Alcohol Related Disease Unit, Columbus-Gemelli Hospital, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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Mahoney BJ, Morford KL, Biegacki ET, Tetrault JM. Hepatitis C virus and integrated care for substance use disorders. Clin Liver Dis (Hoboken) 2024; 23:e0241. [PMID: 38952692 PMCID: PMC11216679 DOI: 10.1097/cld.0000000000000241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 04/24/2024] [Indexed: 07/03/2024] Open
Affiliation(s)
| | - Kenneth L. Morford
- APT Foundation, Central Medical Unit, New Haven, Connecticut, USA
- Program in Addiction Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Emma T. Biegacki
- Program in Addiction Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Jeanette M. Tetrault
- APT Foundation, Central Medical Unit, New Haven, Connecticut, USA
- Program in Addiction Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
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Yoladı FB, Burmaoğlu E, Palabıyık ŞS. Experimental In Vivo Toxicity Models for Alcohol Toxicity. Eurasian J Med 2023; 55:82-90. [PMID: 39109811 PMCID: PMC11075036 DOI: 10.5152/eurasianjmed.2023.23345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 12/26/2023] [Indexed: 08/11/2024] Open
Abstract
Alcohol consumption poses a significant risk for the development of chronic illnesses, one of the leading causes of "preventable" disease and death worldwide. Harmful consumption of alcohol is thought to result in approximately 2.5-3 million deaths each year, the majority of which are caused by alcohol-related liver diseases. Hepatocellular carcinoma, cirrhosis, fibrosis, steatosis, and steatohepatitis are among the liver illnesses caused by alcohol. The mechanisms behind human diseases are often mimicked and understood through the use of animal models. Rodents are the ideal animals to study alcohol-related liver diseases. In these experimental models using rodents, the ethanol ratio, method of administration, and diet to be applied vary. Within the scope of this review, it is aimed at providing information about the experimental models used today for alcohol toxicity and the advantages and disadvantages of these models.
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Affiliation(s)
- Fatma Betül Yoladı
- Department of Pharmaceutical Toxicology, Atatürk University Faculty of Pharmacy, Erzurum, Turkey
- Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Ankara, Turkey
| | | | - Şaziye Sezin Palabıyık
- Department of Pharmaceutical Toxicology, Atatürk University Faculty of Pharmacy, Erzurum, Turkey
- Clinical Research, Development and Design Application and Research Center, Atatürk University, Erzurum, Turkey
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Jiang X, Song HJ, Chang CY, Wilson DL, Lo-Ciganic WH, Park H. Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C. Med Care 2023; 61:505-513. [PMID: 37223993 PMCID: PMC10330248 DOI: 10.1097/mlr.0000000000001870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
OBJECTIVE The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). SUBJECTS This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. METHODS Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. RESULTS Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). CONCLUSIONS Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.
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Affiliation(s)
- Xinyi Jiang
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Hyun Jin Song
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Ching-Yuan Chang
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Debbie L. Wilson
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
| | - Wei-Hsuan Lo-Ciganic
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
- Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL
| | - Haesuk Park
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
- Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL
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Shi B, Qian J, Miao H, Zhang S, Hu Y, Liu P, Xu L. Mulberroside A ameliorates CCl4-induced liver fibrosis in mice via inhibiting pro-inflammatory response. Food Sci Nutr 2023; 11:3433-3441. [PMID: 37324833 PMCID: PMC10261818 DOI: 10.1002/fsn3.3333] [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: 11/23/2022] [Revised: 03/07/2023] [Accepted: 03/10/2023] [Indexed: 04/03/2023] Open
Abstract
Liver fibrosis is caused by a variety of pathogenic factors. It is mainly characterized by chronic liver damage mediated by the imbalance between extracellular matrix synthesis and degradation. If the injury factor cannot be removed for a long time, fibrosis will progress to cirrhosis or even cancer. The development of liver fibrosis is a very complex process which is related to the activation of hepatic stellate cells (HSCs), oxidative stress, and cytokines produced by immune cells. At present, screening of substances with anti-inflammatory activity from natural plant extracts has become a new research focus in the prevention and treatment of liver fibrosis. Mulberry twig is a commonly used traditional Chinese medicine. Pharmacological studies have shown that mulberry twig has anti-inflammatory and antioxidant activities. Thus, it is likely that Mulberry twig contains active substances with liver protection functions. The present study aimed to explore the effect of Mulberroside A (MulA), the main active ingredient from Mulberry twig, on acute liver injury induced by CCl4 in mice. MulA treatment could significantly alleviate the CCl4-induced liver injury, as evidenced by histological analysis and Masson staining. However, we observed that MulA inhibited the expressions of collagen I and α-SMA in livers of CCl4-treated mice but did not directly inhibit the proliferation and activation of HSCs. Finally, we analyzed the anti-inflammatory effect of MulA and demonstrated that it could markedly inhibit the pro-inflammatory cytokines release in liver tissues and in cultured macrophages, thereby alleviating liver fibrosis. Our findings suggest MulA as a potential therapeutic candidate for liver injury and inflammatory diseases.
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Affiliation(s)
- Baozhang Shi
- Department of General SurgeryHaishu Branch of Ningbo First HospitalNingboChina
| | - Jinqiang Qian
- Department of GeriatricsTianjin Medical University General HospitalTianjinChina
| | - Hongyue Miao
- Department of Hepatobiliary and Pancreatic SurgeryHaishu Branch of Ningbo First HospitalNingboChina
| | - Shuo Zhang
- Department of Breast SurgeryThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
| | - Yue Hu
- Department of Hepatobiliary and Pancreatic SurgeryHaishu Branch of Ningbo First HospitalNingboChina
| | - Puqing Liu
- Department of Pharmacy, The Second School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Liping Xu
- Department of General SurgeryHaishu Branch of Ningbo First HospitalNingboChina
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Chang W, Cai L, Chen T, Ni W, Xie Z, Yang C, Liao J. Current Helicobacter pylori Infection Is Associated with Early Liver Injury: A Cross-Sectional Study in the General Population. Am J Trop Med Hyg 2023; 108:684-692. [PMID: 36878209 PMCID: PMC10076991 DOI: 10.4269/ajtmh.22-0340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 12/05/2022] [Indexed: 03/08/2023] Open
Abstract
Early prevention of liver injury by controlling risk factors deserves concern because of the heavy liver disease burden. Helicobacter pylori (HP) infection affects half of the world's population and the relationship between it and early liver damage is unclear. This study focuses on assessing the correlation between them in the general population to provide clues to prevent liver disease. A total of 12,931 individuals underwent liver function and imaging tests as well as 13C/14C-urea breath tests. Results showed that the detection rate of HP was 35.9%, and the HP-positive group had a higher rate of liver injury (47.0% versus 44.5%, P = 0.007). Specifically, Fibrosis-4 (FIB-4) and alpha-fetoprotein levels in the HP-positive group were higher whereas the serum albumin level was lower. HP infection would raise the percentage of elevated aspartate aminotransferase (AST; 2.5% versus 1.7%, P = 0.006), elevated FIB-4 (20.2% versus 17.9%, P = 0.002), and abnormal liver imaging (31.0% versus 29.3%, P = 0.048). Most of these results remained stable after covariate adjustment but, for liver injury and liver imaging, the conclusions only held in young people (ORliver injury, odds ratio of liver injury, 1.127, P = 0.040; ORAST, 1.33, P = 0.034; ORFIB-4, 1.145, P = 0.032; ORimaging, 1.149, P = 0.043). Overall, HP infection might be associated with early liver injury, particularly in youth, suggesting that people with early liver injury should pay more attention to HP infection to prevent the occurrence of severe liver diseases.
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Affiliation(s)
- Wenling Chang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Lin Cai
- Department of Gastroenterology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
- Non-Communicable Diseases Research Center, West China-Peking Union Medical College C. C. Chen Institute of Health, Sichuan University, Chengdu, China
| | - Tingting Chen
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Weigui Ni
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Zhihao Xie
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Chunxia Yang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
- Non-Communicable Diseases Research Center, West China-Peking Union Medical College C. C. Chen Institute of Health, Sichuan University, Chengdu, China
| | - Juan Liao
- Department of Gastroenterology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
- Non-Communicable Diseases Research Center, West China-Peking Union Medical College C. C. Chen Institute of Health, Sichuan University, Chengdu, China
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11
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Gómez-Medina C, Melo L, Martí-Aguado D, Bataller R. Subclinical versus advanced forms of alcohol-related liver disease: Need for early detection. Clin Mol Hepatol 2023; 29:1-15. [PMID: 35430784 PMCID: PMC9845676 DOI: 10.3350/cmh.2022.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/11/2022] [Indexed: 02/02/2023] Open
Abstract
Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.
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Affiliation(s)
- Concepción Gómez-Medina
- Division of Gastroenterology and Hepatology, Medical Department, Clinic University Hospital of Valencia, Valencia, Spain
| | - Luma Melo
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David Martí-Aguado
- Division of Gastroenterology and Hepatology, Medical Department, Clinic University Hospital of Valencia, Valencia, Spain
| | - Ramón Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA,Corresponding author : Ramón Bataller Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, 200 Lothrop Street, BSTW Suite 1116, Pittsburgh, PA 15213, USA Tel: +1-412-383-4241, Fax: +1-412-648-4055, E-mail:
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12
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Zhu L, Li HD, Xu JJ, Li JJ, Cheng M, Meng XM, Huang C, Li J. Advancements in the Alcohol-Associated Liver Disease Model. Biomolecules 2022; 12:biom12081035. [PMID: 36008929 PMCID: PMC9406170 DOI: 10.3390/biom12081035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/22/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is an intricate disease that results in a broad spectrum of liver damage. The presentation of ALD can include simple steatosis, steatohepatitis, liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). Effective prevention and treatment strategies are urgently required for ALD patients. In previous decades, numerous rodent models were established to investigate the mechanisms of alcohol-associated liver disease and explore therapeutic targets. This review provides a summary of the latest developments in rodent models, including those that involve EtOH administration, which will help us to understand the characteristics and causes of ALD at different stages. In addition, we discuss the pathogenesis of ALD and summarize the existing in vitro models. We analyse the pros and cons of these models and their translational relevance and summarize the insights that have been gained regarding the mechanisms of alcoholic liver injury.
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Affiliation(s)
| | | | | | | | | | - Xiao-Ming Meng
- Correspondence: (X.-M.M.); (C.H.); (J.L.); Tel.: +86-551-65161001 (J.L.); Fax: +86-551-65161001 (J.L.)
| | - Cheng Huang
- Correspondence: (X.-M.M.); (C.H.); (J.L.); Tel.: +86-551-65161001 (J.L.); Fax: +86-551-65161001 (J.L.)
| | - Jun Li
- Correspondence: (X.-M.M.); (C.H.); (J.L.); Tel.: +86-551-65161001 (J.L.); Fax: +86-551-65161001 (J.L.)
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13
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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14
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AshaRani PV, Karuvetil MZ, Brian TYW, Satghare P, Roystonn K, Peizhi W, Cetty L, Zainuldin NA, Subramaniam M. Prevalence and Correlates of Physical Comorbidities in Alcohol Use Disorder (AUD): a Pilot Study in Treatment-Seeking Population. Int J Ment Health Addict 2022; 21:1-18. [PMID: 35095353 PMCID: PMC8783789 DOI: 10.1007/s11469-021-00734-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/07/2021] [Indexed: 12/17/2022] Open
Abstract
This study aimed to understand the prevalence of physical comorbidities, undiagnosed and inadequately controlled chronic physical conditions and correlates of high cholesterol, hypertension and liver enzyme abnormalities in those with alcohol use disorder (AUD). Participants (n = 101) with AUD were recruited from a tertiary care centre through convenient sampling. The prevalence of physical and psychiatric comorbidities in the sample was 83.17% and 51.49%, respectively. Around 53.47% had two or more chronic physical conditions (multimorbidity). Hypertension (44.55%), asthma (23.76%), high cholesterol (22.77%) and liver enzyme abnormalities (21.78%) were the top four physical comorbidities. The prevalence of undiagnosed and inadequately controlled chronic physical conditions was 61.4% and 32.7%, respectively. Gender, education and body mass index (BMI) were associated with hyperlipidaemia while age and education were associated with hypertension. Higher waist-hip ratio was associated with liver enzyme abnormalities. Routine clinical care must include regular screening and follow-up of the risk groups to monitor their physical and mental health.
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Affiliation(s)
- P. V. AshaRani
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Mohamed Zakir Karuvetil
- National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Tan Yeow Wee Brian
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Pratika Satghare
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Kumarasan Roystonn
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Wang Peizhi
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Laxman Cetty
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Noor Azizah Zainuldin
- National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
| | - Mythily Subramaniam
- Research Division, Institute of Mental Health, 10 Buangkok View, Singapore, 539747 Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549 Singapore
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15
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Park H, Jiang X, Song HJ, Lo Re V, Childs-Kean LM, Lo-Ciganic WH, Cook RL, Nelson DR. The Impact of Direct-Acting Antiviral Therapy on End-Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders. Hepatology 2021; 74:566-581. [PMID: 33544904 PMCID: PMC8339171 DOI: 10.1002/hep.31732] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 12/22/2020] [Accepted: 01/19/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.
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Affiliation(s)
- Haesuk Park
- Pharmaceutical Outcomes and PolicyCollege of PharmacyUniversity of FloridaGainesvilleFL
| | - Xinyi Jiang
- Pharmaceutical Outcomes and PolicyCollege of PharmacyUniversity of FloridaGainesvilleFL
| | - Hyun Jin Song
- Pharmaceutical Outcomes and PolicyCollege of PharmacyUniversity of FloridaGainesvilleFL
| | - Vincent Lo Re
- Division of Infectious DiseasesDepartment of Medicine and Center for Clinical Epidemiology and BiostatisticsDepartment of Biostatistics, Epidemiology, and InformaticsPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA
| | - Lindsey M Childs-Kean
- Pharmacotherapy and Translational ResearchCollege of PharmacyUniversity of FloridaGainesvilleFL
| | - Wei-Hsuan Lo-Ciganic
- Pharmaceutical Outcomes and PolicyCollege of PharmacyUniversity of FloridaGainesvilleFL
| | - Robert L Cook
- Department of MedicineUniversity of FloridaGainesvilleFL
| | - David R Nelson
- Department of MedicineUniversity of FloridaGainesvilleFL
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16
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Ordak M, Nasierowski T, Muszynska E, Bujalska-Zadrozny M. Psychoactive Substances Taken with Mephedrone and HCV Infection. J Clin Med 2021; 10:jcm10153218. [PMID: 34362002 PMCID: PMC8348849 DOI: 10.3390/jcm10153218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/16/2021] [Accepted: 07/21/2021] [Indexed: 11/24/2022] Open
Abstract
Background: In recent years, the observed frequency of hospitalization of patients taking mephedrone with other psychoactive substances has increased. There are no data in the literature on the effect of mephedrone use on liver function in patients, including the frequency of HCV infection. We have analysed the impact of taking mephedrone together with other psychoactive substances on the incidence of HCV infection. We have also analysed the effect of taking mephedrone with heroin, alcohol, and benzodiazepines on liver enzyme levels. Methods: The study included patients taking mephedrone with: alcohol (n = 115), heroin (n = 85) and benzodiazepines (n = 130) hospitalized in 2010–2018. The control group consisted of patients addicted to alcohol (n = 180), heroin (n = 221) and benzodiazepines (n = 152). Clinical data and laboratory findings were collected from medical records. Results: Taking mephedrone together with benzodiazepines is a statistically significant predictor of HCV infection in this group of patients, OR (8.44); 95% CI 5.63–12.64; p < 0.001). A statistically significant interaction of the group with HCV infection was observed, i.e., for the level of alanine transaminase (p < 0.001) and aspartate transaminase (p < 0.001). Increased levels of liver enzymes in each of the studied groups was characteristic in patients with HCV infection (p < 0.001). Taking additional mephedrone by this group of patients did not increase the level of liver enzymes. Conclusion: HCV infection is a statistically significant factor affecting the increase in liver enzymes levels in the group of patients taking mephedrone.
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Affiliation(s)
- Michal Ordak
- Department of Pharmacodynamics, Centre for Preclinical, Research and Technology (CePT), Medical University of Warsaw, 02-091 Warsaw, Poland;
- Correspondence:
| | - Tadeusz Nasierowski
- Department of Psychiatry, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Elzbieta Muszynska
- Department of Medical Biology, Medical University of Bialystok, 15-089 Bialystok, Poland;
| | - Magdalena Bujalska-Zadrozny
- Department of Pharmacodynamics, Centre for Preclinical, Research and Technology (CePT), Medical University of Warsaw, 02-091 Warsaw, Poland;
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17
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Pravdivtseva MS, Shevelev OB, Yanshole VV, Moshkin MP, Koptyug IV, Akulov AE. In Vitro 1H NMR Metabolic Profiles of Liver, Brain, and Serum in Rats After Chronic Consumption of Alcohol. APPLIED MAGNETIC RESONANCE 2021; 52:661-675. [DOI: 10.1007/s00723-021-01338-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 04/05/2021] [Accepted: 04/16/2021] [Indexed: 01/06/2025]
Abstract
AbstractThe impact of alcohol on the body can be investigated with NMR spectroscopy in vitro, which can detect a wide range of metabolites but preparing samples includes tissue biopsy. Blood sampling is less invasive, but blood metabolic content might not reflect the changes occurring in other tissues. Thus, this study aimed to investigate the liver, brain, and serum metabolism and evaluate the link between tissues and serum metabolic content. Two experimental groups with ten outbred rats each were provided intragastrically with water (control group) and 50% ethanol solution (alcohol group) for 28 days. 1H NMR spectroscopy in vitro was performed on the brain cortex, liver, and serum samples. Student’s t test with Holm–Bonferroni correction was used to investigate significant differences between groups. Partial least-squares discriminant analysis (PLS-DA) and two-way ANOVA were performed to compare liver and serum, brain and serum. In all, 38, 37, and 21 metabolites were identified in the liver, brain, and serum samples, respectively. Significant differences for three metabolites were found in the liver (alanine, proline, and glutathione, p < 0.002) and four in serum (lactate, betaine, acetate, and formic acid, p < 0.002) were detected between the control and alcohol groups. The contents of glucose, betaine, and isoleucine were correlated (r > 0.65) between serum and liver samples. PLS-DA determined separation between all tissues (p < 0.001) and between control and alcohol groups only for liver and serum (p < 0.001). Alcohol had a more substantial effect on liver and serum metabolism than on the brain.
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18
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Mari PC, Gulati R, Fragassi P. Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2021; 12:45-53. [PMID: 33994820 PMCID: PMC8112853 DOI: 10.2147/ahmt.s263864] [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: 12/17/2020] [Accepted: 04/21/2021] [Indexed: 12/09/2022]
Abstract
The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.
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Affiliation(s)
- Paula Chaves Mari
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Reema Gulati
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Philip Fragassi
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
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19
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Subramaniyan V, Chakravarthi S, Jegasothy R, Seng WY, Fuloria NK, Fuloria S, Hazarika I, Das A. Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy. Toxicol Rep 2021; 8:376-385. [PMID: 33680863 PMCID: PMC7910406 DOI: 10.1016/j.toxrep.2021.02.010] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 02/11/2021] [Accepted: 02/12/2021] [Indexed: 12/13/2022] Open
Abstract
One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.
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Key Words
- ALD, alcohol associated liver disease
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Alcohol
- CD14, cluster of differentiation14
- CHD, congenital heart disease
- ECM, extracellualr matrix
- FASD, fetal alcohol spectrum disorders
- FDA, food and drug administration
- GGTP, gamma-glutamyl transpeptidase
- GSH, Glutathione
- H2O2, hydrogen peroxide
- HCV, chronic hepatitis C
- HSC, hepatic stellate cells
- IGR, intrauterine growth retardation
- IL, interleukin
- Immune modulation
- JECH, Japan Environment and Children's Study
- Liver pathogenesis
- MDF, maddrey’s discriminant function
- NA, nutritional assessment
- NAC, N-acetylcysteine
- NADPH, Nicotinamide adenine dinucleotide phosphate
- OLT, Orthotopic liver transplantation
- Pregnancy
- ROS, reactive oxygen species
- TLR4, toll-like receptor 4
- TNF, Tumor necrosis factor
- Targeted therapy
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Affiliation(s)
- Vetriselvan Subramaniyan
- Department of Pharmacology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Srikumar Chakravarthi
- Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Ravindran Jegasothy
- Department of Obstetrics and Gynecology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Wu Yuan Seng
- Department of Biochemistry, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia
| | - Neeraj Kumar Fuloria
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy AIMST University, Jalan Bedong-Semeling, 08100, Malaysia
| | - Shivkanya Fuloria
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy AIMST University, Jalan Bedong-Semeling, 08100, Malaysia
| | - Iswar Hazarika
- Department of Pharmacology, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, 781017, India
| | - Anju Das
- Department of Pharmacology, Royal School of Pharmacy, Royal Global University, Guwahati, 781035, India
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20
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Roesch-Dietlen F, González-Santes M, Sánchez-Maza Y, Díaz-Roesch F, Cano-Contreras A, Amieva-Balmori M, García-Zermeño K, Salgado-Vergara L, Remes-Troche J, Ortigoza-Gutiérrez S. Influence of socioeconomic and cultural factors in the etiology of cirrhosis of the liver. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021. [DOI: 10.1016/j.rgmxen.2020.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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21
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Osna NA, Bhatia R, Thompson C, Batra SK, Kumar S, Cho Y, Szabo G, Molina PE, Weinman SA, Ganesan M, Kharbanda KK. Role of non-Genetic Risk Factors in Exacerbating Alcohol-related organ damage. Alcohol 2020; 87:63-72. [PMID: 32497558 PMCID: PMC7483997 DOI: 10.1016/j.alcohol.2020.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 02/08/2023]
Abstract
This review provides a summary of the symposium titled "Role of Non-Genetic Risk Factors in Exacerbating Alcohol-Related Organ Damage", which was held at the 42nd Annual Meeting of the Research Society on Alcoholism. The goals of the symposium were to provide newer insights into the role of non-genetic factors, including specific external factors, notably infectious agents or lifestyle factors, that synergistically act to exacerbate alcohol pathogenicity to generate more dramatic downstream biological defects. This summary of the symposium will benefit junior/senior basic scientists and clinicians currently investigating/treating alcohol-induced organ pathology, as well as undergraduate, graduate, and post-graduate students and fellows.
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Affiliation(s)
- Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Rakesh Bhatia
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States
| | - Christopher Thompson
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States
| | - Surinder K Batra
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States
| | - Sushil Kumar
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States
| | - Yeonhee Cho
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Patricia E Molina
- Department of Physiology, LSUHSC-New Orleans, New Orleans, LA, United States
| | - Steven A Weinman
- Department of Internal Medicine and the Liver Center, University of Kansas Medical Center, Kansas City, KS, United States
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States; Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States.
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22
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Llamosas-Falcón L, Shield KD, Gelovany M, Manthey J, Rehm J. Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection - a systematic review. SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY 2020; 15:45. [PMID: 32605584 PMCID: PMC7325038 DOI: 10.1186/s13011-020-00287-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 06/23/2020] [Indexed: 02/08/2023]
Abstract
Liver cirrhosis and other chronic liver diseases are usually compartmentalized into separate categories based on etiology (e.g., due to alcohol, virus infection, etc.), but it is important to study the intersection of, and possible interactions between, risk factors. The aim of this study is to summarize evidence on the association between alcohol use disorders (AUDs) and decompensated liver cirrhosis and other complications in patients with chronic Hepatitis C virus (HCV) infection. A systematic search of epidemiological studies was conducted using Ovid Medline databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Relative Risk estimates were combined using random-effects meta-analyses. The proportion of cases with liver disease progression that could be avoided if no person with a chronic HCV infection had an AUD was estimated using an attributable fraction methodology. A total of 11 studies fulfilled the inclusion criteria, providing data from 286,641 people with chronic HCV infections, of whom 63,931 (22.3%) qualified as having an AUD. Using decompensated liver cirrhosis as the outcome for the main meta-analysis (n = 7 unique studies), an AUD diagnosis was associated with a 3.3-fold risk for progression of liver disease among people with a chronic HCV infection (95% Confidence Interval (CI): 1.8–4.8). In terms of population-attributable fractions, slightly less than 4 out of 10 decompensated liver cirrhosis cases were attributable to an AUD: 35.2% (95% CI: 16.2–47.1%). For a secondary analyses, all outcomes related to liver disease progression were pooled (i.e., liver deaths or cirrhosis in addition to decompensated liver cirrhosis), which yielded a similar overall effect (n = 13 estimates; OR = 3.7; 95% CI: 2.2–5.3) and a similar attributable fraction (39.3%; 95% CI: 21.9–50.4%). In conclusion, AUDs were frequent in people with chronic HCV infections and contributed to worsening the course of liver disease. Alcohol use and AUDs should be assessed in patients who have liver disease of any etiology, and interventions should be implemented to achieve abstinence or to reduce consumption to the greatest possible extent.
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Affiliation(s)
- Laura Llamosas-Falcón
- Preventive Medicine and Public Health, Preventive Medicine, Universitary Hospital "12 de Octubre", Avda de Córdoba s/n 28041, Madrid, Spain.,Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada
| | - Kevin D Shield
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada.,Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, M5T 1P8, Canada
| | - Maya Gelovany
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada
| | - Jakob Manthey
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246, Hamburg, Germany.,Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada. .,Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, M5T 1P8, Canada. .,Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany. .,Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5T 2S1, Canada. .,Faculty of Medicine, Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada. .,Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, Ontario, M5T 1R8, Canada. .,Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Trubetskaya str., 8, b. 2, Moscow, Russian Federation, 119992.
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23
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Dysregulation in Plasma ω3 Fatty Acids Concentration and Serum Zinc in Heavy Alcohol-Drinking HCV Patients. Adv Virol 2020; 2020:7835875. [PMID: 32565809 PMCID: PMC7301182 DOI: 10.1155/2020/7835875] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 04/30/2020] [Indexed: 12/20/2022] Open
Abstract
Alcohol use disorder (AUD) patients comorbid with hepatitis C virus (HCV) infection (HCV + AUD) could have progressively severe clinical sequels of liver injury and inflammation. Serum zinc and several polyunsaturated fatty acids (PUFAs) get dysregulated in AUD as well as HCV. However, the extent of dysregulation of PUFAs and zinc deficiency and their interaction in HCV + AUD as a comorbid pathology has not been studied. We examined the role of dysregulation of FAs and low zinc in HCV + AUD patients. 138 male and female participants aged 21-67 years were grouped as HCV-only (Gr. 1; n = 13), HCV + AUD (Gr. 2; n = 25), AUD without liver injury (Gr. 3; n = 37), AUD with liver injury (Gr. 4; n = 51), and healthy volunteers (Gr. 5 or HV; n = 12). Drinking history, individual demographic measures, fasting fatty acids, liver function, and zinc were measured and analyzed. HCV + AUD patients showed the highest ALT level compared to the rest of the groups. Serum zinc concentrations were the lowest, and the proinflammatory shift was the highest (characterized by ω6 : ω3 ratio) in the HCV + AUD patients. Total ω3, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) were the lowest in HCV + AUD patients. Total ω3, α-linoleic acid (α-LA) along with covariable number of drinking days past 90 days (NDD90), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) independently showed significant association with low zinc in the HCV + AUD patients. Heavy drinking pattern showed that NDD90 has a significant mediating role in the representation of the relationship between candidate ω3 PUFAs and zinc uniquely in the HCV + AUD patients. Low serum zinc showed a distinctively stronger association with total and candidate ω3s in the HCV + AUD patients compared to the patients with HCV or AUD alone, supporting dual mechanism involved in the exacerbation of the proinflammatory response in this comorbid cohort. This trial is registered with NCT#00001673.
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24
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Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH). Ann Hepatol 2020; 18:518-535. [PMID: 31053546 DOI: 10.1016/j.aohep.2019.04.005] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 03/06/2019] [Indexed: 02/04/2023]
Abstract
Alcohol-related liver disease (ALD) is a major cause of advanced chronic liver disease in Latin-America, although data on prevalence is limited. Public health policies aimed at reducing the alarming prevalence of alcohol use disorder in Latin-America should be implemented. ALD comprises a clinical-pathological spectrum that ranges from steatosis, steatohepatitis to advanced forms such as alcoholic hepatitis (AH), cirrhosis and hepatocellular carcinoma. Besides genetic factors, the amount of alcohol consumption is the most important risk factor for the development of ALD. Continuous consumption of more than 3 standard drinks per day in men and more than 2 drinks per day in women increases the risk of developing liver disease. The pathogenesis of ALD is only partially understood and recent translational studies have identified novel therapeutic targets. Early forms of ALD are often missed and most clinical attention is focused on AH, which is defined as an abrupt onset of jaundice and liver-related complications. In patients with potential confounding factors, a transjugular biopsy is recommended. The standard therapy for AH (i.e. prednisolone) has not evolved in the last decades yet promising new therapies (i.e. G-CSF, N-acetylcysteine) have been recently proposed. In both patients with early and severe ALD, prolonged abstinence is the most efficient therapeutic measure to decrease long-term morbidity and mortality. A multidisciplinary team including alcohol addiction specialists is recommended to manage patients with ALD. Liver transplantation should be considered in the management of patients with end-stage ALD that do not recover despite abstinence. In selected cases, increasing number of centers are proposing early transplantation for patients with severe AH not responding to medical therapy.
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25
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Roesch-Dietlen F, González-Santes M, Sánchez-Maza YJ, Díaz-Roesch F, Cano-Contreras AD, Amieva-Balmori M, García-Zermeño KR, Salgado-Vergara L, Remes-Troche JM, Ortigoza-Gutiérrez S. Influence of socioeconomic and cultural factors in the etiology of cirrhosis of the liver. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020; 86:28-35. [PMID: 32345507 DOI: 10.1016/j.rgmx.2020.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 01/28/2020] [Accepted: 01/29/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Cirrhosis of the liver is a serious public health problem worldwide, with regional variations determined by cultural factors and economic development. AIM To know the characteristics of the social, cultural, and economic factors of the patients with cirrhosis of the liver in Veracruz. MATERIALS AND METHODS A multicenter, retrolective, relational research study was conducted on patients with cirrhosis of the liver at five healthcare institutions in Veracruz. The variables analyzed were etiology, age, sex, civil status, educational level, occupation, and income. Descriptive and inferential statistics were utilized, and statistical significance was set at a P<.05. The Windows IBM-SPSS version 25.0 program was employed. RESULTS A total of 182 case records of patients with cirrhosis of the liver were included. The etiologic factors were chronic alcohol consumption (47.8%), viral disease (28.5%), nonalcoholic fatty liver disease (NAFLD) (8.79%), autoimmune liver disease (4.4%), cholestasis (1.64%), and cryptogenic liver disease (8.8%). Mean patient age was 66.14±13.91, with a predominance of men (58.79%). In comparing the socioeconomic and cultural factors related to etiology, secondary and tertiary education and singleness were statistically significant in male alcoholics (P<.05), viral diseases and NAFLD were significantly associated with women with no income (P<.05), cryptogenic liver disease was significantly associated with women (P<.05), and cholestasis and autoimmune liver disease were not significantly associated with any of the factors. CONCLUSIONS The study results revealed the influence of socioeconomic and cultural factors related to the different causes of cirrhosis of the liver in our environment.
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Affiliation(s)
- F Roesch-Dietlen
- Departamento de Gastroenterología, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Ver., México.
| | - M González-Santes
- Facultad de Bioanálisis, Universidad Veracruzana, Veracruz, Ver., México
| | - Y J Sánchez-Maza
- Departamento de Anestesiología, Hospital General Dr. Eduardo Liceaga, Secretaría de Salud, Ciudad de México, México
| | - F Díaz-Roesch
- Departamento de Gastroenterología, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Ver., México
| | - A D Cano-Contreras
- Departamento de Gastroenterología, Hospital Juárez de México, Ciudad de México, México
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Ver., México
| | - K R García-Zermeño
- Laboratorio de Fisiología Digestiva y Motilidad, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Ver., México
| | - L Salgado-Vergara
- Servicio Social, Facultad de Medicina, Universidad Veracruzana, Veracruz, Ver., México
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Ver., México
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26
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Barton JC, Barton JC, Adams PC. Prevalence and characteristics of anti-HCV positivity and chronic hepatitis C virus infection in HFE p.C282Y homozygotes. Ann Hepatol 2020; 18:354-359. [PMID: 31056361 DOI: 10.1016/j.aohep.2018.11.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 10/30/2018] [Accepted: 11/28/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Observations of hepatitis C virus (HCV) infection in adults with hemochromatosis are limited. MATERIALS AND METHODS We determined associations of serum ferritin (SF) with anti-HCV in non-Hispanic white North American adults in a post-screening examination. Cases included p.C282Y homozygotes (regardless of screening transferrin saturation (TS) and SF) and participants (regardless of HFE genotype) with high screening TS/SF. Controls included participants without p.C282Y or p.H63D who had normal screening TS/SF. Participants with elevated alanine aminotransferase underwent anti-HCV testing. We determined prevalence of chronic HCV infection in consecutive Alabama and Ontario referred adults with HFE p.C282Y homozygosity. RESULTS In post-screening participants, anti-HCV prevalence was 0.3% [95% CI: 0.02, 2.2] in 294 p.C282Y homozygotes, 9.5% [7.2, 12.3] in 560 Cases without p.C282Y homozygosity, and 0.7% [0.2, 2.3] in 403 Controls. Anti-HCV was detected in 7.2% of 745 participants with and 0.8% of 512 participants without elevated SF (odds ratio 9.9 [3.6, 27.6]; p<0.0001). Chronic HCV infection prevalence in 961 referred patients was 1.0% (10/961) [95% confidence interval (CI): 0.5, 2.0]. Ten patients with chronic HCV infection had median age 45y (range 29-67) and median SF 1163μg/L (range 303-2001). Five of eight (62.5%) patients had biopsy-proven cirrhosis. CONCLUSIONS Odds ratio of anti-HCV was increased in post-screening participants with elevated SF. Prevalence of anti-HCV in post-screening participants with HFE p.C282Y homozygosity and chronic HCV infection in referred adults with HFE p.C282Y homozygosity in North America is similar to that of Control participants with HFE wt/wt and normal screening TS/SF.
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Affiliation(s)
- James C Barton
- Southern Iron Disorders Center, Birmingham, Birmingham, AL, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| | | | - Paul C Adams
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
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27
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Ganesan M, Eikenberry A, Poluektova LY, Kharbanda KK, Osna NA. Role of alcohol in pathogenesis of hepatitis B virus infection. World J Gastroenterol 2020; 26:883-903. [PMID: 32206001 PMCID: PMC7081008 DOI: 10.3748/wjg.v26.i9.883] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/09/2020] [Accepted: 02/14/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and alcohol abuse often contribute to the development of end-stage liver disease. Alcohol abuse not only causes rapid progression of liver disease in HBV infected patients but also allows HBV to persist chronically. Importantly, the mechanism by which alcohol promotes the progression of HBV-associated liver disease are not completely understood. Potential mechanisms include a suppressed immune response, oxidative stress, endoplasmic reticulum and Golgi apparatus stresses, and increased HBV replication. Certainly, more research is necessary to gain a better understanding of these mechanisms such that treatment(s) to prevent rapid liver disease progression in alcohol-abusing HBV patients could be developed. In this review, we discuss the aforementioned factors for the higher risk of liver diseases in alcohol-induced HBV pathogenies and suggest the areas for future studies in this field.
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Affiliation(s)
- Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Allison Eikenberry
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Larisa Y Poluektova
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
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28
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Wu J, Wu D, Ma K, Wang T, Shi G, Shao J, Wang C, Yan G. Paeonol ameliorates murine alcohol liver disease via mycobiota-mediated Dectin-1/IL-1β signaling pathway. J Leukoc Biol 2020; 108:199-214. [PMID: 32129526 DOI: 10.1002/jlb.3ma0120-325rr] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 01/25/2020] [Accepted: 02/07/2020] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is caused by long-term consumption of alcohol and has become an important social and medical problem. Intestinal fungal flora (mycobiota) play an important role in ALD, so we used the mycobiota as an entry point to explore the mechanism of action of Paeonol against ALD. Here, we found that Paeonol is effective against ALD inflammatory lesions and relieves liver fat lesions. Furthermore, we found that after the treatment of Paeonol, the fungal dysbiosis is improved, and the fungal abundance is reduced, and the translocation of β-glucan to the liver and its mediated Dectin-1/IL-1β signaling pathway is blocked. Our study shows that paeonol ameliorated acute ALD-related inflammatory injury to the liver by alleviating intestinal fungal dysbiosis and inhibiting the mycobiota-mediated Dectin-1/IL-1β signaling pathway.
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Affiliation(s)
- Jiadi Wu
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Daqiang Wu
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei, China
| | - Kelong Ma
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Tianming Wang
- Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei, China
| | - Gaoxiang Shi
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Jing Shao
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei, China
| | - Changzhong Wang
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei, China
| | - Guiming Yan
- Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei, China
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29
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Zhou Z, Qi J, Kim JW, You MJ, Lim CW, Kim B. AK-1, a Sirt2 inhibitor, alleviates carbon tetrachloride-induced hepatotoxicity in vivo and in vitro. Toxicol Mech Methods 2020; 30:324-335. [PMID: 32063085 DOI: 10.1080/15376516.2020.1729915] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background/Aim: Acute liver injury (ALI) is a life-threatening clinical syndrome that is usually caused by toxic chemicals, drugs, or pathogen infections. Sirtuin2 (Sirt2), an NAD+-dependent deacetylase, appears to play detrimental roles in liver injury. Here, we evaluated the therapeutic application targeting Sirt2 in carbon tetrachloride (CCl4)-induced ALI, by using AK-1 (a Sirt2 inhibitor).Methods: For in vivo experiments, a single injection of CCl4 was used to induce ALI. One hour later, mice were intraperitoneally injected with AK-1 and were sacrificed 24 h after CCl4 administration. For in vitro experiments, primary mouse hepatocytes were used to determine the effects of AK-1 on oxidative stress and hepatocellular death induced by CCl4.Results: AK-1 alleviated CCl4-induced ALI as confirmed by histopathologic analysis, and decreased levels of serum biochemicals and inflammatory cytokines. Although it barely affected the expression of hepatic cytochrome P450 enzymes, AK-1 attenuated CCl4-induced oxidative stress and its related cell death. Mechanistically, Sirt2 inhibition significantly increased the nuclear protein level of nuclear factor erythroid 2-related factor 2 (Nrf2), and meanwhile decreased phosphorylation of c-Jun N-terminal kinases (JNK), in normal and injured livers. Similar results were observed in vitro. AK-1 significantly attenuated CCl4-induced cytotoxicity and oxidative stress by up-regulating the activity of Nrf2, and down-regulating JNK signaling in hepatocytes.Conclusions: Our results suggest that AK-1 treatment attenuated oxidative stress and cell death in the ALI model, at least partially, via activating Nrf2 and inhibiting JNK signaling, and that Sirt2 inhibition might be a potential approach to cure ALI.
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Affiliation(s)
- Zixiong Zhou
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
| | - Jing Qi
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
| | - Jong-Won Kim
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
| | - Myung-Jo You
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
| | - Chae Woong Lim
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
| | - Bumseok Kim
- Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan, South Korea
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30
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Hermosa S, Goutzamanis S, Doyle J, Higgs P. Reducing alcohol-related harm in people recently treated for hepatitis C. Aust J Prim Health 2019; 25:193-194. [PMID: 31196383 DOI: 10.1071/py19074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 05/08/2019] [Indexed: 02/28/2024]
Affiliation(s)
- Sasha Hermosa
- Behaviours and Health Risks Program, Burnet Institute, 85 Commercial Road, Melbourne, Vic. 3004, Australia; and Department of Epidemiology and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, Vic. 3004, Australia; and Corresponding author
| | - Stelliana Goutzamanis
- Behaviours and Health Risks Program, Burnet Institute, 85 Commercial Road, Melbourne, Vic. 3004, Australia; and Department of Epidemiology and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, Vic. 3004, Australia
| | - Joseph Doyle
- Behaviours and Health Risks Program, Burnet Institute, 85 Commercial Road, Melbourne, Vic. 3004, Australia; and Department of Epidemiology and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, Vic. 3004, Australia; and Department of Infectious Diseases, Alfred Health, 55 Commercial Road, Melbourne, Vic. 3004, Australia
| | - Peter Higgs
- Behaviours and Health Risks Program, Burnet Institute, 85 Commercial Road, Melbourne, Vic. 3004, Australia; and Department of Public Health, La Trobe University, 360 Collins Street, Melbourne, Vic. 3000, Australia
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Santos SGRD, Mattos AA, Guimarães MM, Boger BDS, Coral GP. Alcohol Consumption Influences Clinical Outcome in Patients Admitted to a Referral Center for Liver Disease. Ann Hepatol 2019; 17:470-475. [PMID: 29735785 DOI: 10.5604/01.3001.0011.7391] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Excessive alcohol consumption is a public health concern worldwide and has been associated with high mortality rates. This study aimed to determine the prevalence of alcohol consumption and its influence on the prognosis of hospitalized cirrhotic patients in a tertiary care hospital. MATERIAL AND METHODS We reviewed the medical records of all patients with hepatic cirrosis admitted between January 2009 and December 2014, in a referral center for liver disease in southern Brazil. Data on clinical outcomes, associated conditions, infections, and mortality were collected and compared between alcoholic and nonalcoholic patients. RESULTS The sample consisted of 388 patients; 259 (66.7%) were men. One hundred fifty-two (39.2%) were classified as heavy use of alcohol. Most alcoholic patients were men (n = 144; 94.7%). Mean age was 55.6 ± 8.9 years. Hepatic decompensations and infections were more prevalent in alcoholic patient. Spontaneous bacterial peritonitis and respiratory tract infection accounted for most of the infections. Excessive alcohol consumption was associated with mortality (P = 0.009) in multivariate analysis. CONCLUSION On the present study, the prevalence of heavy use of alcohol was high and associated with a poorer prognosis in hospitalized cirrhotic patients, increasing the risk of infection and death.
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Affiliation(s)
- Suyan G R Dos Santos
- Postgraduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | - Angelo A Mattos
- Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil
| | - Marcela M Guimarães
- Postgraduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | - Bibiana de S Boger
- Postgraduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | - Gabriela P Coral
- Postgraduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
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Wang WJ, Xiao P, Xu HQ, Niu JQ, Gao YH. Growing burden of alcoholic liver disease in China: A review. World J Gastroenterol 2019; 25:1445-1456. [PMID: 30948908 PMCID: PMC6441911 DOI: 10.3748/wjg.v25.i12.1445] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 02/22/2019] [Accepted: 03/01/2019] [Indexed: 02/06/2023] Open
Abstract
Explosive economic growth and increasing social openness in China over the last 30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease (ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology, pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.
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Affiliation(s)
- Wen-Jun Wang
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Peng Xiao
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Hong-Qin Xu
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Jun-Qi Niu
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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Ohashi K, Pimienta M, Seki E. Alcoholic liver disease: A current molecular and clinical perspective. LIVER RESEARCH 2018; 2:161-172. [PMID: 31214376 PMCID: PMC6581514 DOI: 10.1016/j.livres.2018.11.002] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Heavy alcohol use is the cause of alcoholic liver disease (ALD). The ALD spectrum ranges from alcoholic steatosis to steatohepatitis, fibrosis, and cirrhosis. In Western countries, approximately 50% of cirrhosis-related deaths are due to alcohol use. While alcoholic cirrhosis is no longer considered a completely irreversible condition, no effective anti-fibrotic therapies are currently available. Another significant clinical aspect of ALD is alcoholic hepatitis (AH). AH is an acute inflammatory condition that is often comorbid with cirrhosis, and severe AH has a high mortality rate. Therapeutic options for ALD are limited. The established treatment for AH is corticosteroids, which improve short-term survival but do not affect long-term survival. Liver transplantation is a curative treatment option for alcoholic cirrhosis and AH, but patients must abstain from alcohol use for 6 months to qualify. Additional effective therapies are needed. The molecular mechanisms underlying ALD are complex and have not been fully elucidated. Various molecules, signaling pathways, and crosstalk between multiple hepatic and extrahepatic cells contribute to ALD progression. This review highlights established and emerging concepts in ALD clinicopathology, their underlying molecular mechanisms, and current and future ALD treatment options.
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Affiliation(s)
- Koichiro Ohashi
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michael Pimienta
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA,University of California San Diego, School of Medicine, La Jolla, CA, USA
| | - Ekihiro Seki
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA,University of California San Diego, School of Medicine, La Jolla, CA, USA,Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA,Corresponding author. Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., (E. Seki)
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Siqueira FM, Ferreira VL, Borba HHL, Pontarolo R. Quality of life of Brazilian chronic hepatitis C patients treated with interferon-free therapies. Rev Inst Med Trop Sao Paulo 2018; 60:e72. [PMID: 30462795 PMCID: PMC6235428 DOI: 10.1590/s1678-9946201860072] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/17/2018] [Indexed: 02/07/2023] Open
Abstract
Due to the severity of chronic hepatitis C, there are multiple factors that can negatively affect the quality of life of infected patients. The aim of this study was to evaluate changes in the health-related quality of life (HRQoL) in patients under second-generation direct-acting antiviral (DAA) (interferon-free) therapies and to assess treatment effectiveness. This was an observational study conducted in Curitiba (Brazil) using two instruments (a generic and a specific) for measuring the quality of life in patients with chronic hepatitis C, the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) for liver disease evaluation. The study included patients receiving any interferon-free therapy for hepatitis C treatment during 2016 and 2017. Data were collected before, during, and after treatment regarding the two questionnaires, effectiveness and safety. Fifty-six patients fulfilled all eligibility criteria and were included for analysis. Sustained virological response was obtained in 88% of the patients. They were mainly genotype 1, cirrhotic and treated with sofosbuvir combined with daclatasvir or sofosbuvir with simeprevir. Improvement in the quality of life was observed for several domains in both questionnaires (p < 0.05) in the comparison before and after treatment. Patients receiving sofosbuvir with daclatasvir had significantly lower scores compared to the group receiving sofosbuvir with simeprevir. Second-generation DAA therapies were effective and have considerably increased the HRQoL of patients with chronic hepatitis C virus.
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Affiliation(s)
- Fabiane Mateus Siqueira
- Universidade Federal do Paraná, Programa de Pós-Graduação em Assistência Farmacêutica, Curitiba, Paraná, Brazil
| | - Vinicius Lins Ferreira
- Universidade Federal do Paraná, Programa de Pós-Graduação em Ciências Farmacêuticas, Curitiba, Paraná, Brazil
| | - Helena Hiemisch Lobo Borba
- Universidade Federal do Paraná, Programa de Pós-Graduação em Ciências Farmacêuticas, Curitiba, Paraná, Brazil
| | - Roberto Pontarolo
- Universidade Federal do Paraná, Programa de Pós-Graduação em Assistência Farmacêutica, Curitiba, Paraná, Brazil.,Universidade Federal do Paraná, Programa de Pós-Graduação em Ciências Farmacêuticas, Curitiba, Paraná, Brazil
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Thursz M, Gual A, Lackner C, Mathurin P, Moreno C, Spahr L, Sterneck M, Cortez-Pinto H. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69:154-181. [PMID: 29628280 DOI: 10.1016/j.jhep.2018.03.018] [Citation(s) in RCA: 563] [Impact Index Per Article: 80.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 12/12/2022]
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Mansberg K, Kull K, Salupere R, Prükk T, Margus B, Kariis T, Remmel T, Suurmaa K, Ott K, Jaago K, Šmidt J. A Population-Based Surveillance Study on the Epidemiology of Hepatitis C in Estonia. ACTA ACUST UNITED AC 2018; 54:medicina54010009. [PMID: 30344240 PMCID: PMC6037246 DOI: 10.3390/medicina54010009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 03/20/2018] [Accepted: 03/21/2018] [Indexed: 02/07/2023]
Abstract
Background and objective: The hepatitis C virus (HCV)-infected patients serve as a reservoir for transmission of the disease to others and are at risk of developing chronic hepatitis C, cirrhosis, and hepatocellular carcinoma. Although the epidemiological data of high rate HCV infection have been obtained in many countries, such data are insufficient in Estonia. Therefore, the aim of the study was to analyze country-specific data on HCV patients. Materials and methods: Data about age, gender, diagnosis, possible risk factors, coinfections, HCV genotypes, liver fibrosis stages and extrahepatic manifestations were collected from 518 patients. Results: The most common risk factors for hepatitis C were injection drug use and tattooing in the 30–39 and 40–49 year age groups, and blood transfusion in the 50–59 and 60–69 year age groups. The other risk factors established were profession-related factors and sexual contact. The prevailing viral genotype among the HCV infected patients was genotype 1 (69% of the patients) followed by genotype 3 (25%). Genotypes 1 and 3 correlated with blood transfusions before 1994, drug injections and tattooing. Conclusions: Our study provides the best representation of genotype distribution across Estonia. As a result of the study, valuable data has been collected on hepatitis C patients in Estonia.
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Affiliation(s)
- Kairi Mansberg
- Department of Gastroenterology, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
- Internal Disease Clinic, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
| | - Karin Kull
- Department of Gastroenterology, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
- Internal Disease Clinic, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
| | - Riina Salupere
- Department of Gastroenterology, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
- Internal Disease Clinic, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
| | - Tiina Prükk
- Department of Gastroenterology, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
- Internal Disease Clinic, Tartu University Hospital, University of Tartu, 51014 Tartu, Estonia.
| | - Benno Margus
- Department of Gastroenterology, East Tallinn Central Hospital, 10138 Tallinn, Estonia.
| | - Toomas Kariis
- Department of Gastroenterology, East Tallinn Central Hospital, 10138 Tallinn, Estonia.
| | - Triin Remmel
- Department of Gastroenterology, East Tallinn Central Hospital, 10138 Tallinn, Estonia.
| | - Külliki Suurmaa
- Department of Gastroenterology and Infectios Diseases Clinic, West Tallinn Central Hospital, 10138 Tallinn, Estonia.
| | - Kristi Ott
- Department of Gastroenterology and Infectios Diseases Clinic, West Tallinn Central Hospital, 10138 Tallinn, Estonia.
| | - Krista Jaago
- Internal Disease Clinic, Pärnu Hospital, 80010 Pärnu, Estonia.
| | - Jelena Šmidt
- Internal Disease Clinic, East Viru Central Hospital, 31024 Kohtla-Järve, Estonia.
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Jumonji: Welcome to the World of Interferon Signaling in Alcohol and HCV. Cell Mol Gastroenterol Hepatol 2017; 5:163-164. [PMID: 29693044 PMCID: PMC5904047 DOI: 10.1016/j.jcmgh.2017.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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39
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Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J Gastroenterol 2017; 23:6549-6570. [PMID: 29085205 PMCID: PMC5643281 DOI: 10.3748/wjg.v23.i36.6549] [Citation(s) in RCA: 164] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 07/25/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.
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Affiliation(s)
- Sukhpreet Singh
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
- Department of Biochemistry and Molecular Biology, Nebraska Medical Center, Omaha, NE 68198, United States
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Chow J, Márka Z, Bartos I, Márka S, Kagan JC. Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral Infections. Cell Host Microbe 2017; 22:48-60.e5. [PMID: 28704652 PMCID: PMC5560172 DOI: 10.1016/j.chom.2017.06.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 03/16/2017] [Accepted: 06/20/2017] [Indexed: 02/07/2023]
Abstract
Asymptomatic infections often proceed undetected, yet can still prime the host to be sensitive to secondary environmental stress. While the mechanisms underlying disease caused by asymptomatic infections are unknown, it is believed that productive pathogen replication is required. We report that the environmental stress of carbon dioxide (CO2) anesthesia converts an asymptomatic rhabdovirus infection in Drosophila to one that is lethal. This lethality results from a pool of infectious virus in glial cells and is regulated by the antiviral RNAi pathway of the host. CO2 sensitivity is caused by the fusogenic activity of the viral glycoprotein, which results in fusion of neurons and glia. Expression of the viral glycoprotein, but not a fusion defective mutant, is sufficient to cause CO2 sensitivity, which can occur even in the absence of productive viral replication. These findings highlight how viral proteins, independent of pathogen replication, may predispose hosts to life-threatening environmental stress.
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Affiliation(s)
- Jonathan Chow
- Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA
| | - Zsuzsa Márka
- Department of Physics, Columbia University, New York, NY, USA
| | - Imre Bartos
- Department of Physics, Columbia University, New York, NY, USA
| | - Szabolcs Márka
- Department of Physics, Columbia University, New York, NY, USA
| | - Jonathan C Kagan
- Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA.
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Fung P, Pyrsopoulos N. Emerging concepts in alcoholic hepatitis. World J Hepatol 2017; 9:567-585. [PMID: 28515843 PMCID: PMC5411952 DOI: 10.4254/wjh.v9.i12.567] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 02/21/2017] [Accepted: 03/12/2017] [Indexed: 02/06/2023] Open
Abstract
Severe alcoholic hepatitis is implicated as a costly, worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended first-line treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.
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Affiliation(s)
- Phoenix Fung
- Phoenix Fung, Nikolaos Pyrsopoulos, Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Phoenix Fung, Nikolaos Pyrsopoulos, Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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Iida-Ueno A, Enomoto M, Tamori A, Kawada N. Hepatitis B virus infection and alcohol consumption. World J Gastroenterol 2017; 23:2651-2659. [PMID: 28487602 PMCID: PMC5403744 DOI: 10.3748/wjg.v23.i15.2651] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 01/25/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C. The mechanisms underlying the complex interaction between HBV and alcohol are not fully understood, and enhanced viral replication, increased oxidative stress and a weakened immune response could each play an important role in the development of HCC. It remains controversial whether HBV and alcohol synergistically increase the incidence of HCC. Herein, we review the currently available literature regarding the interaction of HBV infection and alcohol consumption on disease progression.
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Fujii H, Nishimoto N, Yamaguchi S, Kurai O, Miyano M, Ueda W, Oba H, Aoki T, Kawada N, Okawa K. The Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) is more useful than pre-existing laboratory tests for predicting hazardous drinking: a cross-sectional study. BMC Public Health 2016; 16:379. [PMID: 27165437 PMCID: PMC4862044 DOI: 10.1186/s12889-016-3053-6] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2015] [Accepted: 04/29/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking. METHODS A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. RESULTS Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant. CONCLUSIONS This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking.
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Affiliation(s)
- Hideki Fujii
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan.
| | - Naoki Nishimoto
- Department of Radiological Technology, Hokkaido University of Science, Maeda, Teine, Sapporo, Hokkaido, 006-8585, Japan
| | - Seiko Yamaguchi
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Osamu Kurai
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Masato Miyano
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Wataru Ueda
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Hiroko Oba
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Tetsuya Aoki
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Abeno, Osaka, 545-8585, Japan
| | - Kiyotaka Okawa
- Department of Gastroenterology and Hepatology, Osaka City Juso Hospital, Nonaka-kita, Yodogawa, Osaka, 532-0034, Japan
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