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Condon S, Levy C, Martin EF. Recurrent and De Novo Liver Disease After Liver Transplantation. Clin Liver Dis 2025; 29:313-335. [PMID: 40287274 DOI: 10.1016/j.cld.2024.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Disease recurrence after liver transplantation (LT) is common. Certain liver diseases such as autoimmune hepatitis and steatotic liver disease may appear de novo after LT. This review discusses post LT alcohol-associated liver disease, metabolic dysfunction-associated liver disease, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Both recurrent and de novo diseases are important causes of allograft failure.
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Affiliation(s)
- Sally Condon
- Transplant Hepatology/Gastroenterology, Swedish Organ Transplant Center, 1124 Columbia Street #600, Seattle, WA 98104, USA.
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA
| | - Eric F Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1801 NW 9th Avenue, 7th Floor, Miami, FL 33136, USA
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Liangpunsakul S, Krebs WB, Kwong AJ, Kwo PY, Brown RS, Lin W, Sussman NL. The impact of liver transplantation on endpoint selection in alcohol-associated hepatitis trials. Hepatol Commun 2025; 9:e0709. [PMID: 40304564 PMCID: PMC12045545 DOI: 10.1097/hc9.0000000000000709] [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: 01/14/2025] [Accepted: 03/17/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND Alcohol-associated hepatitis (AH) is a serious liver disease caused by heavy alcohol consumption with severe cases exhibiting a 90-day mortality rate of ~30%. No drugs have been approved for AH, and regulatory approval currently requires evidence of improved survival. The lack of effective drug therapies and high mortality rates have fueled interest in early liver transplantation (LT), which has a survival rate that exceeds 90%. However, LT is resource-intensive and is available only in expert centers, where most AH trials are conducted. As a result, LT is overrepresented in recent AH studies, leading to confounding and unresolved questions regarding valid endpoints in therapeutic AH trials. METHODS We propose methodological approaches to address the inclusion of LT in AH trials, supported by power calculations and data from the AHFIRM trial, a 300-patient multicenter study completed in late 2023. We demonstrate the impact of effect size, trial size, and statistical methods on trial design and interpretation. RESULTS Effect size plays a crucial role in power calculations. While 90-day survival is the most efficient endpoint, competing risk analysis, primary stratum analysis, and win ratio are valuable tests for assessing the role of LT. The combined endpoint of death or LT is the least efficient method and requires the largest trial population to achieve statistical significance. We recommend using multiple statistical methods with adjustments for multiplicity. CONCLUSIONS The adoption of early LT complicates the assessment of new therapies for AH. Statistical methods and endpoints are critical in power calculations and when assessing the efficacy of new therapeutic agents. We recommend mortality as the primary analysis complemented by hierarchical secondary analyses that avoid problems of multiplicity.
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Affiliation(s)
- Suthat Liangpunsakul
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | - Allison J. Kwong
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Paul Y. Kwo
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Robert S. Brown
- Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - WeiQi Lin
- Durect Corporation, Cupertino, California, USA
| | - Norman L. Sussman
- Durect Corporation, Cupertino, California, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
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Malmut L, Eickmeyer S, Rydberg L, Neal J, Lanphere J, Barker K. The role of rehabilitation across the continuum of liver disease from cirrhosis to transplantation and beyond: A narrative review. PM R 2025. [PMID: 40285684 DOI: 10.1002/pmrj.13384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 11/19/2024] [Accepted: 02/06/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVE The authors' objective with this narrative review is to explore the impact of rehabilitative interventions at each stage of liver disease. TYPE: Narrative review. LITERATURE SURVEY Literature search conducted in Medline, Embase, and Google Scholar databases. METHODOLOGY Articles were included if they were identified in one of the three database, written in English, peer-reviewed, and involved human participants without any restrictions on the publication date. Reference lists of these publications were also scrutinized for other articles that might be relevant. Elibigle articles were reviewed to determine whether they met inclusion crtieria. SYNTHESIS Authors synthesized findings in the eligible articles to create a narrative summary. CONCLUSIONS Chronic liver disease is a major cause of morbidity and mortality across the globe. Cirrhosis causes alterations in metabolic and circulatory functions that negatively affect nutritional status and exercise capacity. Frailty is identified in nearly half of patients with advanced liver disease and bears a poor prognosis. Exercise and nutritional interventions improve key components of physical frailty and quality of life in chronic liver disease and after liver transplantation. Early mobility is generally recommended following liver transplantation and deemed to be safe and feasible. Inpatient rehabilitation may be considered in patients who require ongoing daily medical management by a physician, demonstrate a significant functional decline from their baseline, tolerate intensive rehabilitation, and have functional goals that can be addressed by at least two skilled therapies. Rehabilitation is safe and improves outcomes at every stage of liver disease from cirrhosis to following transplantation. This literature review explores the impact of rehabilitative interventions at each stage of liver disease from cirrhosis to transplantation and beyond.
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Affiliation(s)
- Laura Malmut
- Department of Physical Medicine and Rehabilitation, MedStar National Rehabilitation Hospital, Washington, District of Columbia, USA
- Department of Physical Medicine and Rehabilitation, Georgetown University School of Medicine, Washington, District of Columbia, USA
| | - Sarah Eickmeyer
- Department of Physical Medicine and Rehabilitation, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Leslie Rydberg
- Department of Physical Medicine and Rehabilitation and Medical Education, Northwestern University Feinberg School of Medicine and the Shirley Ryan AbilityLab, Chicago, Illinois, USA
| | - Jacqueline Neal
- Physical Medicine and Rehabilitation, Jesse Brown VA, Chicago, Illinois, USA
- Department Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Julie Lanphere
- Rehabilitation Services, Neurosciences Department, Intermountain Health, Murray, Utah, USA
| | - Kim Barker
- Department of Physical Medicine and Rehabilitation, UT Southwestern Medical Center, Dallas, Texas, USA
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Lo CH, Verma R, Amin R, Manne V, Saab S. Rural-Urban Disparities in Mortality Related to Alcohol-Associated Liver Disease by Race/Ethnicity in the United States From 1999 to 2022. Dig Dis Sci 2025:10.1007/s10620-025-08979-z. [PMID: 40229526 DOI: 10.1007/s10620-025-08979-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Accepted: 03/08/2025] [Indexed: 04/16/2025]
Abstract
INTRODUCTION Mortality related to alcohol-associated liver disease (ALD) has been increasing over the past two decades, especially in racial and ethnic minorities and those living in rural areas. The interaction between rurality, race and ethnicity in mortality disparities is unclear. METHODS This cross-sectional study extracted data from the Underlying Cause of Death database of CDC Wide-Ranging Online Database for Epidemiological Research (1999-2022). We estimated the age-adjusted mortality rates (AAMRs) for ALD among adults 25 years and older. We calculated the average annual percentage change (AAPC) using the Joinpoint regression program. RESULTS There were 436,814 deaths related to ALD among US adults with rising mortality from 1999 (AAMR, 6.7) to 2022 (AAMR, 12.5) (AAPC, 2.7%). American Indian and Alaska Native (AI/AN) individuals had the highest mortality in 2022 (AAMR, 76.8), followed by Hispanic individuals (AAMR, 14.1). Mortality increases in non-Hispanic White (NHW) individuals (AAPC, 4.0%) surpassed that of non-Hispanic Black (NHB) individuals (AAPC, 0.4%). The increase in AAMR was more pronounced in rural areas (AAPC, 4.1%) than large metropolitan areas (AAPC, 2.0%). For NHW, AI/AN, and Hispanic individuals, AAMRs in rural areas had greater increases than in large metropolitan areas. AAMRs remained largely stable in large metropolitan (AAPC, - 0.6%) and rural areas for NHB individuals (AAPC, 0.1%). DISCUSSION There were significant and widening rural-urban disparities in ALD-related mortality among NHW, AI/AN, and Hispanic individuals. Mortality in NHB individuals remained largely stable. Targeted resources and efforts are essential to address the growing mortality burden in select populations.
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Affiliation(s)
- Chun-Han Lo
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
| | - Renuka Verma
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
| | - Rajan Amin
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
- Division of Gastroenterology, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
| | - Vignan Manne
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
- Division of Gastroenterology, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA, USA.
- Department of Surgery, Pfleger Liver Institute, University of California at Los Angeles (UCLA), 100 Medical Plaza, Suite 700, Los Angeles, CA, 90095, USA.
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Kim D, Danpanichkul P, Wijarnpreecha K, Cholankeril G, Loomba R, Ahmed A. Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023. Clin Mol Hepatol 2025; 31:382-393. [PMID: 39610192 PMCID: PMC12016658 DOI: 10.3350/cmh.2024.0987] [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: 11/03/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND/AIMS Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US. METHODS Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature. RESULTS The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4-36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI 30.4-33.4), MetALD 2.2% (95% CI 1.8-2.6), and ALD 0.8% (95% CI 0.6-1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era. CONCLUSION While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, AZ, USA
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Rohit Loomba
- Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Calleri A, Shah VH. Interleukin-1 Inhibition in Alcohol-associated Hepatitis: Are We Hitting the Right Target? Clin Gastroenterol Hepatol 2025; 23:713-714. [PMID: 39447948 DOI: 10.1016/j.cgh.2024.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024]
Affiliation(s)
- Alberto Calleri
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota.
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Cotter TG, Anouti A, Zhang B, Rady ED, Patel M, Patel S, Ellis DJ, Lieber SR, Rich NE, O'Leary JG, Mitchell MC, Singal AG. Disparities in Alcohol-Associated Liver Disease Hospital Encounters Amongst a Texas-Based Cohort of Patients. Aliment Pharmacol Ther 2025; 61:988-999. [PMID: 39821471 PMCID: PMC11869159 DOI: 10.1111/apt.18477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/07/2024] [Accepted: 12/20/2024] [Indexed: 01/19/2025]
Abstract
INTRODUCTION Alcohol-associated liver disease (ALD) disproportionately impacts men, racial and ethnic minorities, and individuals of low socioeconomic status; however, it's unclear how recent increases in ALD burden have impacted these disparities. We aimed to describe trends in racial, ethnic and socioeconomic disparities in alcohol-associated hospital encounters. METHODS We conducted a retrospective cohort study of adult hospital encounters with alcohol-associated diagnoses from three health systems between January 2016 and December 2021. The cohort was divided into three eras: a 'Historical Era,' (Oct 2016-June 2018, used only for trends); 'Era 1' (July 2018-March 2020); and 'Era 2' (April 2020-December 2021). Kaplan Meier and Cox regression analyses were performed to identify factors associated with overall survival. RESULTS We identified 19,295 individuals with alcohol-associated encounters (44.7% White, 29.8% Hispanic, and 21.8% non-Hispanic Black (NHB) individuals), with a greater increase observed between eras 1 and 2 than the historical era and Era 1 (8.7% vs. 5.0%, p < 0.01). By age and sex, the greatest increases in encounters were observed in the youngest and oldest females but only the oldest males. By race and ethnicity, Hispanic individuals had greater increases in encounters compared to Black and White individuals (14.8% vs. 7.5% and 6.3%, p < 0.01). Older age (aSHR: 1.03, 95% CI: 1.03-1.0), higher MELD (aSHR: 1.08, 95% CI: 1.0-1.09), hepatic encephalopathy (aSHR: 1.42, 95% CI: 1.06-1.90), and hepatocellular carcinoma (HCC) (aSHR: 3.20, 95% CI: 2.29-4.49) were associated with increased mortality. CONCLUSION The highest increases of alcohol-associated encounters were observed amongst young Hispanic and NHB women, highlighting variation in trends by age, sex, race and ethnicity. These disparities merit further investigation to elucidate underlying mechanisms and develop tailored interventions to improve ALD burden and outcomes.
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Affiliation(s)
- Thomas G. Cotter
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Ahmad Anouti
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Bill Zhang
- Department of Internal MedicineUT Southwestern Medical CentreDallasTexasUSA
| | - Elias D. Rady
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Mausam Patel
- Department of Internal MedicineUT Southwestern Medical CentreDallasTexasUSA
| | - Suraj Patel
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Daniel J. Ellis
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Sarah R. Lieber
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Nicole E. Rich
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Jacqueline G. O'Leary
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Mack C. Mitchell
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Amit G. Singal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
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Yamazaki T, Schnabl B. Acute alcohol-associated hepatitis: Latest findings in non-invasive biomarkers and treatment. Liver Int 2025; 45:e15608. [PMID: 37183549 PMCID: PMC10646153 DOI: 10.1111/liv.15608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/15/2023] [Accepted: 05/03/2023] [Indexed: 05/16/2023]
Abstract
Acute alcohol-associated hepatitis (AH) is a syndrome that occurs in heavy and long-term drinkers and results in severe jaundice and liver failure. The mortality rate in severe cases is 20%-50% at 28 days, and in cases that do not improve despite appropriately timed corticosteroid therapy, the mortality rate reaches 70% at 6 months. The only curative treatment is early liver transplantation, but less than 2% of patients with severe AH are eligible. In order to improve the prognosis, diagnostic tools are needed to detect appropriate cases at risk of severe conditions, and new therapies need to be developed that can replace corticosteroids. Recent research has revealed that the pathogenesis of AH involves a complex of factors, including changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity. Non-invasive diagnostic tools focusing on these specific pathologies have been reported in recent years. In addition, several novel agents targeting specific pathways are currently being developed and tested in clinical trials. This review will provide an overview of alcohol-associated hepatitis and focus on the latest diagnostic tools, particularly non-invasive biomarkers, and novel therapies.
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Affiliation(s)
- Tomoo Yamazaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Nagano, Matsumoto, Japan
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, VA San Diego Healthcare System, California, San Diego, USA
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Kim SR, Kim SK, Asai A, Nishikawa H. Comparison between Japan and Korea in liver transplantation: Focusing on a higher deceased donation rate in Korea. Hepatol Res 2025. [PMID: 40317651 DOI: 10.1111/hepr.14177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 01/08/2025] [Accepted: 01/22/2025] [Indexed: 05/07/2025]
Abstract
Over the past 30 years, liver transplantations (LTs) and deceased-donor LTs (DDLTs) have been higher in Korea than in Japan. In 2019, the number of DDLT reached 88 (22.3% of LTs) in Japan and 391 (24.7% of LTs) in Korea. The deceased-donor rate (per million population) was 0.70 in Japan and 7.56 in Korea. Presently, Korea is one of the Asian countries with the highest rate of DDLT. Factors conducive to the deceased donation rate in Korea encompass the socio-legal system, including the Korean Network for Organ Sharing, Korean Organ Donation Agency, the healthcare system and public awareness. During 2009-2019, two major indications of DDLT were hepatitis B cirrhosis and alcoholic liver disease in Korea, and acute liver failure and metabolic diseases in Japan. For living-donor LT, two major indications were hepatitis B cirrhosis and neoplastic diseases in Korea, and biliary atresia and neoplastic diseases in Japan. During the COVID-19 pandemic, the indications for DDLT in Korea were alcoholic liver disease and hepatitis B cirrhosis with a higher rate of alcoholic liver disease than during the pre-pandemic period. In 2021, the 5-year survival rate of DDLT was 66.5% in Korea compared with 82.6% in Japan, whereas that rate of living-donor LT in Korea reached 80.8% compared with 79.4% in Japan. To promote LT in Japan and Korea, mutual understanding and intercommunication between the two countries is crucial.
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Affiliation(s)
- Soo Ryang Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan
| | - Soo Ki Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan
| | - Akira Asai
- The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Hiroki Nishikawa
- The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
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Ochoa-Allemant P, Serper M, Wang RX, Tang H, Ghandour B, Khan S, Mahmud N. Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry. Hepatology 2025; 81:532-545. [PMID: 38683569 PMCID: PMC12036730 DOI: 10.1097/hep.0000000000000914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/15/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND AND AIMS The new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Waitlisting and liver transplantation for MetALD are not well defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assessing trends in waitlisting and transplant outcomes. APPROACH AND RESULTS We conducted a retrospective cohort study using the United Network for Organ Sharing registry, supplemented with detailed single-center data. We developed 5 candidate algorithms for SLD classification and calculated their diagnostic performance. Trends in waitlist registrations and transplants were estimated, and competing risk analyses and Cox regression models were conducted to assess waitlist removal and posttransplant outcomes among SLD phenotypes. The best-performing algorithm demonstrated substantial agreement (weighted kappa, 0.62) for SLD phenotypes, with acceptable sensitivity (73%) for MetALD. Between 2002 and 2022, waitlist registrations and transplants for MetALD increased 2.9-fold and 3.3-fold, respectively. Since 2013, there has been a significant increase in the absolute number of waitlist registrations (122 per year; 95% CI, 111-133) and transplants (107 per year; 95% CI, 94-120) for MetALD. Patients with MetALD experienced higher waitlist removal (adjusted subdistribution hazard ratio, 1.10; 95% CI, 1.03-1.17), all-cause mortality (adjusted hazard ratio, 1.13; 95% CI, 1.03-1.23), and graft failure (adjusted hazard ratio, 1.12; 95% CI, 1.03-1.21) than those with alcohol-associated liver disease. CONCLUSIONS We developed and validated an algorithm for identifying SLD phenotypes in UNOS. MetALD is the third leading etiology among those waitlisted and underwent transplantation, exhibiting worse pretransplantation and posttransplantation outcomes compared to alcohol-associated liver disease. Identifying and addressing factors determining poor outcomes is crucial in this patient population.
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Affiliation(s)
- Pedro Ochoa-Allemant
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Marina Serper
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Leonard David Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Roy X. Wang
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Helen Tang
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Bachir Ghandour
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sarem Khan
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nadim Mahmud
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Leonard David Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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11
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Vock DM, Humphreville V, Ramanathan KV, Adams AB, Lim N, Nguyen VH, Wothe JK, Chinnakotla S. The landscape of liver transplantation for patients with alcohol-associated liver disease in the United States. Liver Transpl 2025; 31:32-44. [PMID: 38727598 DOI: 10.1097/lvt.0000000000000394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 04/29/2024] [Indexed: 05/14/2024]
Abstract
Indications for liver transplants have expanded to include patients with alcohol-associated liver disease (ALD) over the last decade. Concurrently, the liver allocation policy was updated in February 2020 replacing the Donor Service Area with Acuity Circles (ACs). The aim is to compare the transplantation rate, waitlist outcomes, and posttransplant survival of candidates with ALD to non-ALD and assess differences in that effect after the implementation of the AC policy. Scientific Registry for Transplant Recipients data for adult candidates for liver transplant were reviewed from the post-AC era (February 4, 2020-March 1, 2022) and compared with an equivalent length of time before ACs were implemented. The adjusted transplant rates were significantly higher for those with ALD before AC, and this difference increased after AC implementation (transplant rate ratio comparing ALD to non-ALD = 1.20, 1.13, 1.61, and 1.32 for the Model for End-Stage Liver Disease categories 37-40, 33-36, 29-32, and 25-28, respectively, in the post-AC era, p < 0.05 for all). The adjusted likelihood of death/removal from the waitlist was lower for patients with ALD across all lower Model for End-Stage Liver Disease categories (adjusted subdistribution hazard ratio = 0.70, 0.81, 0.84, and 0.70 for the Model for End-Stage Liver Disease categories 25-28, 20-24, 15-19, 6-14, respectively, p < 0.05). Adjusted posttransplant survival was better for those with ALD (adjusted hazard ratio = 0.81, p < 0.05). Waiting list and posttransplant mortality tended to improve more for those with ALD since the implementation of AC but not significantly. ALD is a growing indication for liver transplantation. Although patients with ALD continue to have excellent posttransplant outcomes and lower waitlist mortality, candidates with ALD have higher adjusted transplant rates, and these differences have increased after AC implementation.
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Affiliation(s)
- David M Vock
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
| | - Vanessa Humphreville
- Liver Transplant Program, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Karthik V Ramanathan
- Liver Transplant Program, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Andrew B Adams
- Liver Transplant Program, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Nicholas Lim
- Liver Transplant Program, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Vinh H Nguyen
- Liver Transplant Program, Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Jillian K Wothe
- Liver Transplant Program, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Srinath Chinnakotla
- Liver Transplant Program, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
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12
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Heringer DL, Costa GPA, Weleff J, Rodrigues V, Sengupta S, Anand A. Racial and ethnic disparities in alcohol-associated liver disease hospitalizations in Brazil before and after the COVID-19 pandemic. Ann Hepatol 2024; 30:101742. [PMID: 39653118 DOI: 10.1016/j.aohep.2024.101742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 07/30/2024] [Accepted: 08/22/2024] [Indexed: 12/16/2024]
Abstract
INTRODUCTION AND OBJECTIVES The COVID-19 pandemic has resulted in a greater incidence of alcohol-associated liver disease (ALD) and simultaneously magnified health-related inequalities. We evaluated the impact of race and ethnicity on ALD-related hospitalizations in Brazil. MATERIALS AND METHODS An interrupted time series analysis was used to estimate ALD-related hospitalization in public hospitals in Brazil. Monthly hospitalization rates for 34 consecutive months before and after the point of interruption (March 2020) were calculated using the Sistema de Informações Hospitalares database across four ethnic groups: Black, Pardo, Black, and Pardo combined, and Others (White and Unknown Ethnicity). RESULTS A total of 84,787 ALD-related hospitalizations were recorded during the study period. The mean age of hospitalized patients was 53 years (SD=12.5); 83.6% were male. Immediately after the start of the pandemic, there was a statistically significant decrease in monthly ALD-related hospitalization rates for the whole population and for all ethnic groups. Subsequently, compared to pre-pandemic rates, there was a statistically significant trend increase in the referred hospitalization rates for the total population (0.065, 95% CI= 0.045 to 0.085, p<0.01), black population (0.0028, 95% CI= 0.006 to 0.050, p<0.05), pardo population (0.077, 95% CI= 0.063 to 0.090, p<0.01), and for black and pardo combined population (0.066, 95% CI= 0.053 to 0.079, p<0.01); however, the increase in hospitalization rates among the Others population (0.059, 95% CI= -0,014 to 0.133, p>0.1) was not statistically significant. CONCLUSIONS The pandemic impacted ALD-related monthly hospitalization rates and disproportionately impacted Black and Pardo populations in Brazil.
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Affiliation(s)
- Daniel L Heringer
- Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, SP, Brazil; Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, United States
| | | | - Jeremy Weleff
- Department of Psychiatry, Yale University School of Medicine, CT, United States; Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, United States; Department of Psychiatry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
| | - Victor Rodrigues
- Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, RJ 20950-000, Brazil
| | - Shreya Sengupta
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, United States.
| | - Akhil Anand
- Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, United States; Department of Psychiatry, University Hospitals Medical Center, Cleveland, OH, United States.
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13
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Åberg F, Jiang ZG, Cortez-Pinto H, Männistö V. Alcohol-associated liver disease-Global epidemiology. Hepatology 2024; 80:1307-1322. [PMID: 38640041 DOI: 10.1097/hep.0000000000000899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/23/2024] [Indexed: 04/21/2024]
Abstract
Alcohol-associated liver disease (ALD), as highlighted in this narrative review, is a major public health concern, increasingly impacting global disease burden and premature mortality. In 2019, ALD accounted for the loss of 11 million life-years worldwide. The rising number of deaths and disability-adjusted life-years attributed to ALD, particularly pronounced in the United States, are alarming. Projections suggest that the economic impact of ALD, as seen in the United States, could potentially double by 2040. ALD is increasingly prevalent among younger adults (20-45 y) and has become the leading cause of liver transplantation in both United States and Europe. During the COVID-19 pandemic, the existing trend was further amplified as high-risk drinking patterns coincided with a rise in hospital admissions for alcohol-associated hepatitis and increased ALD-related mortality. The prevalence of ALD is estimated at 3.5% in the general population, 26.0% among hazardous drinkers, and 55.1% among those with alcohol use disorders. Alarmingly, 5-year mortality rates for patients with ALD exceed 50%, with even higher rates in more advanced disease stages. Methodological challenges, such as underreporting, diagnostic difficulties, and variability in registry data quality, complicate the accurate assessment of the impact of ALD. Additionally, the contribution of alcohol to the progression of other liver diseases is often under acknowledged in health care registries, leading to a significant underestimation of its broader implications for liver health. Addressing the growing ALD concern requires robust public health initiatives, heightened awareness, refined diagnostic techniques, and comprehensive epidemiological studies. These measures are vital to tackle the increasing prevalence of ALD and mitigate its extensive impact on individuals and health care systems.
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Affiliation(s)
- Fredrik Åberg
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Z Gordon Jiang
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - Ville Männistö
- Department of Medicine, University of Eastern Finland, Kuopio, Finland
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
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14
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Simonetto DA, Winder GS, Connor AA, Terrault NA. Liver transplantation for alcohol-associated liver disease. Hepatology 2024; 80:1441-1461. [PMID: 38889100 DOI: 10.1097/hep.0000000000000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/31/2024] [Indexed: 06/20/2024]
Abstract
Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the United States. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short-term and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is a continued need to develop better tools to identify patients who may benefit from LT, improve the pretransplant and posttransplant management of ALD, and evaluate the impact of LT for ALD on the organ donation and transplantation systems. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions and highlight the knowledge gaps and research priorities in this field.
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Affiliation(s)
- Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ashton A Connor
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
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15
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Zhang W, Wong RJ. Epidemiology of Alcohol-Associated Liver Disease Including Increasing Burden in Young Adults and Females Especially Since Covid-19 Pandemic. Clin Liver Dis 2024; 28:589-600. [PMID: 39362709 DOI: 10.1016/j.cld.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (ALD) was already on the rise globally when the advent of coronavirus disease 2019 further accelerated this trend. ALD has emerged as the leading cause for liver transplantation in the United States. The pandemic has not only intensified the prevalence of ALD but has also highlighted significant disparities in its impact, particularly, among young adults and women. This review aims to dissect the complex landscape of ALD, focusing on gender, race, and emerging risk factors in the context of the current global health crisis.
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Affiliation(s)
- Wei Zhang
- Gastroenterology Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Stanford University School of Medicine, 3801 Miranda Avenue, GI-111, Palo Alto, CA 94304, USA.
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16
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Stewart SD, Manning WD, Gustafson KE, Kamp Dush C. Sexual and gender identities and alcohol use during the COVID-19 pandemic. PLoS One 2024; 19:e0308925. [PMID: 39241086 PMCID: PMC11379183 DOI: 10.1371/journal.pone.0308925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 08/01/2024] [Indexed: 09/08/2024] Open
Abstract
This study examined differences in alcohol use by sexual and gender identities during the COVID-19 pandemic, and assessed whether variation between groups was explained by pandemic-related stressors and minority stress. Data from 2,429 partnered adults in the National Couples' Health and Time Use Study (n = 3,593) collected from September 2020 to April 2021 were used to model drinking patterns (frequency, amount, and drinking to cope) by sexual and gender identities, COVID-19 stress and disruption, microaggressions, and supportive climate. Regression models indicated differences in drinking by gender and sexual identities, even controlling for demographic and socioeconomic factors. Gay, lesbian, and bisexual people had higher odds of drinking to cope with the pandemic than did heterosexual people, and cisgender men had higher odds than did cisgender women. Gay and lesbian people drank more regularly than did heterosexual people, as did cisgender men in relation to cisgender women. Exclusively bisexual people drank significantly more drinks than exclusively heterosexual people, and cisgender men drank significantly more drinks than did cisgender women and those who identified as trans/another gender identity. COVID-19 stress and minority stress were associated with greater alcohol consumption, but they did not account for these differentials. Moving forward, researchers will need to continuously assess these associations, as sources of discrimination and stress will persist beyond the pandemic. Although LGBTQ+ people have disproportionate sources of stress, they varied in how they used alcohol to cope. Potential sources of resilience among sexual and gender diverse individuals should be explored.
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Affiliation(s)
- Susan D. Stewart
- Department of Sociology and Criminal Justice, Iowa State University, Ames, Iowa, United States of America
| | - Wendy D. Manning
- Center for Family and Demographic Research and Department of Sociology, Bowling Green State University, Bowling Green, Ohio, United States of America
| | - Kristen E. Gustafson
- Center for Family and Demographic Research and Department of Sociology, Bowling Green State University, Bowling Green, Ohio, United States of America
| | - Claire Kamp Dush
- Minnesota Population Center and Department of Sociology, University of Minnesota, Minneapolis, Minnesota, United States of America
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17
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Narro GEC, Díaz LA, Ortega EK, Garín MFB, Reyes EC, Delfin PSM, Arab JP, Bataller R. Alcohol-related liver disease: A global perspective. Ann Hepatol 2024; 29:101499. [PMID: 38582247 DOI: 10.1016/j.aohep.2024.101499] [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: 03/06/2024] [Accepted: 03/07/2024] [Indexed: 04/08/2024]
Abstract
Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.
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Affiliation(s)
- Graciela Elia Castro Narro
- Hepatology and Transplant Unit, Hospital Médica Sur. Mexico City, Mexico; Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran". Mexico City, Mexico; Latin-American Association for the Study of the Liver (ALEH). Santiago de Chile, Chile.
| | - Luis Antonio Díaz
- Latin-American Association for the Study of the Liver (ALEH). Santiago de Chile, Chile; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile. Santiago, Chile
| | - Eric Kauffman Ortega
- Internal Medicine Department, Centenario Hospital Miguel Hidalgo. Aguascalientes, Mexico
| | - María Fernanda Bautista Garín
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran". Mexico City, Mexico
| | - Eira Cerda Reyes
- Investigation Department, Central Military Hospital. Mexico City, Mexico; Military School of Health Graduates, Mexico City, Mexico
| | | | - Juan Pablo Arab
- Latin-American Association for the Study of the Liver (ALEH). Santiago de Chile, Chile; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile. Santiago, Chile; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre. London, Ontario, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada.
| | - Ramón Bataller
- Liver Unit, Hospital Clinic. Institut d'Investigacions Biomediques August Pi i Sunyer (IDI-BAPS). Barcelona, Spain.
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18
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Wang Y, Huang Y, Sun C, Chung H, Taner CB, Yang L. Higher-Than-Expected Burden of Alcohol-Related Liver Diseases During COVID-19 Pandemic in the USA, with a Tapering Trend. J Gen Intern Med 2024; 39:2133-2141. [PMID: 38228988 PMCID: PMC11347505 DOI: 10.1007/s11606-023-08594-6] [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: 05/25/2023] [Accepted: 12/28/2023] [Indexed: 01/18/2024]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) pandemic has led to an increase in alcohol-related liver disease (ALD). The aim of this study was to evaluate the magnitude of ALD hospitalization surge during the pandemic in the USA. MAIN MEASURES A retrospective trend analysis of adult hospitalizations for ALD at acute care hospitals across the USA in 2016-2020 was conducted. Hospitalizations were identified using the International Classification of Diseases 10 codes for ALD and non-alcoholic-related liver disease. Outcomes measured included the predicted monthly volume of hospitalizations for ALD and inpatient mortality rates. KEY RESULTS During the 2020 pandemic, monthly ALD hospitalizations reached 10,247 representing a 20.7% increase compared to pre-pandemic monthly average of 8490. Additional 4163 ALD hospitalizations occurred during the pandemic, in addition to a pre-pandemic uptrend. The peak of excess ALD hospitalizations was from May to October (monthly excess of 1138) decreasing to monthly excess of 280 in November and December. The excess increase in ALD hospitalizations was primarily observed in young adults, totaling 5256 cases affecting both male (2101 excess cases) and females (2041 excess cases). The age-standardized monthly mortality rate during the pandemic was notably higher than expected at 0.9% (95% CI 0.4 to 1.4%). CONCLUSIONS The COVID-19 pandemic led to a significant increase in ALD hospitalizations, above and beyond the pre-existing upward trend, which tapered towards the end of 2020, suggesting a possible decline in the pandemic's impact. The excess increase in ALD hospitalizations was observed primarily in young adults and affected both males and females. These findings highlight the need for further attention to the long-term consequences of the pandemic.
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Affiliation(s)
- Yichen Wang
- Division of Hospital Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Yuting Huang
- Division of Gastroenterology & Hepatology, Mayo Clinic in Florida, Jacksonville, FL, USA
| | - Chenyu Sun
- Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Howard Chung
- Department of Medicine, NYU Grossman School of Medicine, New York City, NY, USA
| | - C Burcin Taner
- Department of Transplantation, Mayo Clinic in Florida, Jacksonville, FL, USA
| | - Liu Yang
- Department of Transplantation, Mayo Clinic in Florida, Jacksonville, FL, USA.
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19
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Yamazaki T, Kouno T, Hsu CL, Hartmann P, Mayo S, Zhang X, Stärkel P, Bosques-Padilla F, Verna EC, Abraldes JG, Brown RS, Vargas V, Altamirano J, Caballería J, Shawcross DL, Louvet A, Lucey MR, Mathurin P, Garcia-Tsao G, Bataller R, Schnabl B. Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis. Hepatology 2024; 80:403-417. [PMID: 38377466 PMCID: PMC11268475 DOI: 10.1097/hep.0000000000000777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 01/05/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND AND AIMS Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. APPROACH AND RESULTS The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group. CONCLUSIONS Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.
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Affiliation(s)
- Tomoo Yamazaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Tetsuya Kouno
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Cynthia L. Hsu
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA
| | - Phillipp Hartmann
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Division of Gastroenterology, Hepatology & Nutrition, Rady Children’s Hospital San Diego, San Diego, CA, USA
| | - Susan Mayo
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA
| | - Xinlian Zhang
- Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA
| | - Peter Stärkel
- Department of Hepatology and Gastroenterology, St. Luc University Hospital, Catholic University of Louvain, Brussels, Belgium
| | - Francisco Bosques-Padilla
- Hospital Universitario, Departamento de Gastroenterología, Universidad Autonoma de Nuevo Leon, Monterrey, México
| | - Elizabeth C. Verna
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Juan G. Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Robert S. Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA
| | - Victor Vargas
- Liver Unit, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jose Altamirano
- Liver Unit, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Juan Caballería
- Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Liver Unit, Hospital Clinic, Barcelona, Spain
| | - Debbie L. Shawcross
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Alexandre Louvet
- Service des Maladies de L’appareil Digestif et Unité INFINITE 1286, Hôpital Huriez, Lille, France
| | - Michael R. Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, WI, USA
| | - Philippe Mathurin
- Service des Maladies de L’appareil Digestif et Unité INFINITE 1286, Hôpital Huriez, Lille, France
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA; Section of Digestive Diseases, VA-CT Healthcare System, West Haven, CT, USA
| | - Ramon Bataller
- Liver Unit, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | | | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA
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Nasir N, Khanum I, Habib K, Wagley A, Arshad A, Majeed A. Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications. HEPATOLOGY FORUM 2024; 5:139-149. [PMID: 39006140 PMCID: PMC11237249 DOI: 10.14744/hf.2023.2023.0025] [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: 05/27/2023] [Revised: 07/25/2023] [Accepted: 11/02/2023] [Indexed: 07/16/2024]
Abstract
COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.
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Affiliation(s)
- Nosheen Nasir
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Iffat Khanum
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Kiren Habib
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Abdullah Wagley
- Research Facilitation Office, Medical College, Aga Khan University, Karachi, Pakistan
| | - Aleena Arshad
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Atif Majeed
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
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21
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Ayyala-Somayajula D, Dodge JL, Zhou K, Terrault NA, Yuan L. The impact of surging transplantation of alcohol-associated liver disease on transplantation for HCC and other indications. Hepatol Commun 2024; 8:e0455. [PMID: 38967588 PMCID: PMC11227353 DOI: 10.1097/hc9.0000000000000455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 04/01/2024] [Indexed: 07/06/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) for alcohol-associated liver disease (ALD) is increasing and may impact LT outcomes for patients listed for HCC and other indications. METHODS Using US adults listed for primary LT (grouped as ALD, HCC, and other) from October 8, 2015, to December 31, 2021, we examined the impact of center-level ALD LT volume (ATxV) on waitlist outcomes in 2 eras: Era 1 (6-month wait for HCC) and Era 2 (MMaT-3). The tertile distribution of ATxV (low to high) was derived from the listed candidates as Tertile 1 (T1): <28.4%, Tertile 2 (T2): 28.4%-37.6%, and Tertile 3 (T3): >37.6% ALD LTs per year. Cumulative incidence of waitlist death and LT within 18 months from listing by LT indication were compared using the Gray test, stratified on eras and ATxV tertiles. Multivariable competing risk regression estimated the adjusted subhazard ratios (sHRs) for the risk of waitlist mortality and LT with interaction effects of ATxV by LT indication (interaction p). RESULTS Of 56,596 candidates listed, the cumulative waitlist mortality for those with HCC and other was higher and their LT probability was lower in high (T3) ATxV centers, compared to low (T1) ATxV centers in Era 2. However, compared to ALD (sHR: 0.92 [0.66-1.26]), the adjusted waitlist mortality for HCC (sHR: 1.15 [0.96-1.38], interaction p = 0.22) and other (sHR: 1.13 [0.87-1.46], interaction p = 0.16) were no different suggesting no differential impact of ATxV on the waitlist mortality. The adjusted LT probability for HCC (sHR: 0.89 [0.72-1.11], interaction p = 0.08) did not differ by AtxV while it was lower for other (sHR: 0.82 [0.67-1.01], interaction p = 0.02) compared to ALD (sHR: 1.04 [0.80-1.34]) suggesting a differential impact of ATxV on LT probability. CONCLUSIONS The high volume of LT for ALD does not impact waitlist mortality for HCC and others but affects LT probability for other in the MMAT-3 era warranting continued monitoring.
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Affiliation(s)
- Divya Ayyala-Somayajula
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jennifer L. Dodge
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA
| | - Kali Zhou
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Liyun Yuan
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Mellinger JL, Winder GS, Fernandez AC, Asefah H, Zikmund-Fisher BJ. Critical misconceptions and knowledge gaps regarding alcohol cessation and risk of relapse in alcohol-related liver disease patients: A qualitative mental models study. JOURNAL OF SUBSTANCE USE AND ADDICTION TREATMENT 2024; 161:209292. [PMID: 38364995 DOI: 10.1016/j.josat.2024.209292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 09/27/2023] [Accepted: 01/11/2024] [Indexed: 02/18/2024]
Abstract
INTRODUCTION Despite the mortality benefits of alcohol cessation and alcohol treatment, few patients with alcohol-related liver disease (ALD) get such treatment. To understand reasons for low treatment rates, we performed a qualitative mental models study to explore how ALD patients understand factors influencing alcohol cessation, relapse and their liver health. METHODS Using a mental models framework, we interviewed experts in alcohol use disorder (AUD) and ALD to determine factors influencing alcohol cessation, risk of relapse and liver health. An expert influence diagram was constructed and used to develop a patient interview guide. We recruited participants with ALD enrolled in hepatology or transplant clinics at a single tertiary-care center. We conducted interviews either face-to-face or by phone, per participant preference. We transcribed all interviews verbatim and analyzed them using combined deductive coding schema based on both the interview guide and emergent coding. RESULTS 25 (10 women, 15 men) participants with a mean age of 57 years completed interviews. 68 % had decompensated cirrhosis. Major omissions included gender (as a factor in alcohol use or liver disease) and the influence of benzodiazepines/opioids on relapse. Misconceptions were common, in particular the idea that the absence of urges to drink meant participants were safe from relapse. Conceptual differences from the expert model emerged as well. Participants tended to view the self as primary and the only thing that could influence relapse in many cases, resulting in a linear mental model with few nodes influencing alcohol cessation. Participants' risky drinking signals (i.e., elevated liver enzymes) differed from known definitions of hazardous or high-risk drinking, which largely emphasize dose of alcohol consumed irrespective of consequences. Finally, participants sometimes viewed stopping on one's own as the primary means of stopping alcohol use, not recognizing the many other nodes in the influence diagram impacting ability to stop alcohol. CONCLUSION Patients with ALD had critical misconceptions, omissions, and conceptual reorganizations in their mental models of the ability to stop alcohol use. Attention to these differences may allow clinicians and researchers to craft more impactful interventions to improve rates of alcohol abstinence and AUD treatment engagement.
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Affiliation(s)
- Jessica L Mellinger
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, United States of America; Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, United States of America.
| | - Gerald Scott Winder
- Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, United States of America; University of Michigan Department of Surgery, Michigan Medicine, Ann Arbor, MI, United States of America; University of Michigan Department of Neurology, Michigan Medicine, Ann Arbor, MI, United States of America
| | - Anne C Fernandez
- Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, United States of America; University of Michigan Addiction Treatment Service, Michigan Medicine, Ann Arbor, MI, United States of America
| | - Haila Asefah
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, United States of America
| | - Brian J Zikmund-Fisher
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, United States of America; Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America
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23
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Blaney HL, Khalid MB, Yang AH, Asif BA, Vittal A, Kamal N, Wright EC, Abijo T, Koh C, George D, Goldman D, Horneffer Y, Diazgranados N, Heller T. Hepatology consultation is associated with decreased early return to alcohol use after discharge from an inpatient alcohol use disorder treatment program. Hepatol Commun 2024; 8:e0414. [PMID: 38619432 PMCID: PMC11019822 DOI: 10.1097/hc9.0000000000000414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 12/20/2023] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Alcohol cessation is the only intervention that both prevents and halts the progressions of alcohol-associated liver disease. The aim of this study was to assess the relationship between a return to alcohol use and consultation with hepatology in treatment-seeking patients with alcohol use disorder (AUD). METHODS Two hundred forty-two patients with AUD were enrolled in an inpatient treatment program, with hepatology consultation provided for 143 (59%) patients at the request of the primary team. Patients not seen by hepatology served as controls. The primary outcome was any alcohol use after discharge assessed using AUDIT-C at 26 weeks after discharge. RESULTS For the primary endpoint, AUDIT at week 26, 61% of the hepatology group and 28% of the controls completed the questionnaire (p=0.07). For the secondary endpoint at week 52, these numbers were 22% and 11% (p = 0.6). At week 26, 39 (45%) patients in the hepatology group versus 31 (70%) controls (p = 0.006) returned to alcohol use. Patients evaluated by hepatology had decreased rates of hazardous alcohol use compared to controls, with 36 (41%) versus 29 (66%) (p = 0.008) of the patients, respectively, reporting hazardous use. There were no significant differences in baseline characteristics between groups and no difference in rates of prescribing AUD therapy. There was no difference in outcomes at 52 weeks. CONCLUSIONS Patients evaluated by hepatology had significantly lower rates of return to alcohol use and lower rates of hazardous drinking at 26 weeks but not at 52 weeks. These findings suggest that hepatology evaluation during inpatient treatment of AUD may lead to decreased rates of early return to alcohol use.
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Affiliation(s)
- Hanna L. Blaney
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Mian B. Khalid
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Alexander H. Yang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Bilal A. Asif
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Anusha Vittal
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Natasha Kamal
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Elizabeth C. Wright
- Office of the Director, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Tomilowo Abijo
- Office of the Director, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Chris Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - David George
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - David Goldman
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Yvonne Horneffer
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Nancy Diazgranados
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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24
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Ramirez-Cadiz C, Blaney H, Kubanek N, Díaz LA, Loomba R, Skladany L, Arab JP. Review article: Current indications and selection criteria for early liver transplantation in severe alcohol-associated hepatitis. Aliment Pharmacol Ther 2024; 59:1049-1061. [PMID: 38475893 DOI: 10.1111/apt.17948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 10/17/2023] [Accepted: 03/03/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND Alcohol-associated hepatitis (AH) is a severe inflammatory form of alcohol-associated liver disease (ALD) that carries a high mortality rate. Early liver transplantation for severe AH is increasingly available. However, specific criteria for referral and selection remain a subject of debate. AIMS To provide a narrative review of the natural history, diagnostic criteria and indications for referral for early liver transplantation for severe AH. METHODS We searched PubMed for articles published through August 2023. Key search terms were 'alcoholic hepatitis,' 'alcohol-associated hepatitis,' 'abstinence,' 'alcohol relapse,' and 'liver transplantation.' RESULTS Previously, a six-month period of alcohol abstinence was required before patients with ALD were considered for liver transplantation. However, studies in recent years have demonstrated that, among carefully selected patients, patients who received early transplants have much higher survival rates than patients with similarly severe disease who did not undergo transplants (77% vs. 23%). Despite these successes, early liver transplantation remains controversial, as these patients have typically not undergone treatment for alcohol use disorder, with the ensuing risk of returning to alcohol use. CONCLUSIONS While early liver transplantation for AH has survival benefits, many patients would not have received treatment for alcohol use disorder. An integrated approach to evaluating candidacy for early liver transplantation is needed.
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Affiliation(s)
- Carolina Ramirez-Cadiz
- Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Hanna Blaney
- Division of Gastroenterology and Hepatology, University of Maryland, College Park, Maryland, USA
| | - Natalia Kubanek
- Division of Hepatology, Gastroenterology and Liver Transplantation, Department of Internal Medicine II, Slovak Medical University Faculty of Medicine, F. D. Roosevelt University Hospital, Banska Bystrica, Slovak Republic
| | - Luis Antonio Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Rohit Loomba
- Division of Gastroenterology, University of California at San Diego, San Diego, California, USA
| | - Lubomir Skladany
- Division of Hepatology, Gastroenterology and Liver Transplantation, Department of Internal Medicine II, Slovak Medical University Faculty of Medicine, F. D. Roosevelt University Hospital, Banska Bystrica, Slovak Republic
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
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25
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Okumura K, Dhand A, Misawa R, Sogawa H, Veillette G, Nishida S. The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States. J Clin Exp Hepatol 2024; 14:101296. [PMID: 38544764 PMCID: PMC10964071 DOI: 10.1016/j.jceh.2023.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 10/17/2023] [Indexed: 03/03/2025] Open
Abstract
Background New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Methods Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Results Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P < 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P < 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P < 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P < 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. Conclusions The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
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26
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Branagan WT, Norvell JP. Assessment and Evaluation of Alcohol Use Disorder in Liver Transplant. Transplantation 2024; 108:654-661. [PMID: 37408098 DOI: 10.1097/tp.0000000000004722] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
Alcohol-related liver disease is the most common indication for liver transplantation. It is essential for providers in transplantation to be informed of the state of the science in evaluation of alcohol use disorder (AUD). This review examines the broad range of approaches to the evaluation of AUD ranging from traditional interview approaches to recent literature on artificial intelligence models. The empirical support for methods of evaluation is examined. The authors discuss the use of each method in the context of patients seeking a liver transplant for alcohol-related liver disease. This review emphasizes the importance of using objective assessments so that transplant centers make evidence-based decisions and reduce cognitive bias. The review concludes with a proposed assessment battery for evaluation and bridges to future directions in the field of AUD assessment in liver transplantation.
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Affiliation(s)
- William T Branagan
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - J P Norvell
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
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27
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Ladner DP, Gmeiner M, Hasjim BJ, Mazumder N, Kang R, Parker E, Stephen J, Polineni P, Chorniy A, Zhao L, VanWagner LB, Ackermann RT, Manski CF. Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018. PLoS One 2024; 19:e0298887. [PMID: 38408083 PMCID: PMC10896513 DOI: 10.1371/journal.pone.0298887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 01/31/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. METHODS In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. RESULTS Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. CONCLUSION Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.
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Affiliation(s)
- Daniela P. Ladner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Surgery, Division of Organ Transplantation, Northwestern University, Chicago, IL, United States of America
| | - Michael Gmeiner
- Department of Economics, London School of Economics, London, United Kingdom
| | - Bima J. Hasjim
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
| | - Nikhilesh Mazumder
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Medicine, Division of Hepatology, University of Michigan, Ann Arbor, MI, United States of America
| | - Raymond Kang
- Institute for Public Health and Medicine (IPHAM), Northwestern University, Chicago, IL, United States of America
| | | | - John Stephen
- Department of Preventive Medicine, Northwestern University, Chicago, IL, United States of America
| | - Praneet Polineni
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
| | - Anna Chorniy
- Department of Medical Social Sciences and Buehler Center for Health Policy and Economics, Northwestern University, Chicago, IL, United States of America
| | - Lihui Zhao
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Preventive Medicine, Northwestern University, Chicago, IL, United States of America
| | - Lisa B. VanWagner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, United States of America
| | - Ronald T. Ackermann
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Institute for Public Health and Medicine (IPHAM), Northwestern University, Chicago, IL, United States of America
| | - Charles F. Manski
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Economics and Institute for Policy Research, Northwestern University, Evanston, IL, United States of America
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28
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Michalak A, Lach T, Szczygieł K, Cichoż-Lach H. COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023? Int J Mol Sci 2024; 25:2212. [PMID: 38396888 PMCID: PMC10888568 DOI: 10.3390/ijms25042212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.
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Affiliation(s)
- Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Tomasz Lach
- Department of Orthopedics and Traumatology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Karolina Szczygieł
- Clinical Dietetics Unit, Department of Bioanalytics, Medical University of Lublin, Chodźki 7, 20-093 Lublin, Poland;
| | - Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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29
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Almazan E, Dixon J, Gerstenblith A, Andrews S, Flanary J, Cameron AM, Gurakar A, Chen PH. Between-hospital care referrals for severe alcohol-related liver disease during the COVID-19 pandemic, 2020 to 2022. Alcohol Alcohol 2024; 59:agad071. [PMID: 37873970 DOI: 10.1093/alcalc/agad071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/20/2023] [Accepted: 10/03/2023] [Indexed: 10/25/2023] Open
Abstract
Increased alcohol consumption during the coronavirus disease 2019 pandemic is projected to impact alcohol-related liver disease (ALD) morbidity and mortality. Inter-hospital escalation-of-care referral requests to our tertiary-care hepatology unit were analyzed from January 2020 through December 2022. Most requests to our center were for ALD with an increase in requests from intermediate care units, suggestive of higher acuity illness.
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Affiliation(s)
- Erik Almazan
- Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Juliette Dixon
- Department of Care Management, Johns Hopkins Hospital, Baltimore, MD, United States
| | - Avi Gerstenblith
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sarah Andrews
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - James Flanary
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Ahmet Gurakar
- Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Po-Hung Chen
- Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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30
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Jophlin LL, Singal AK, Bataller R, Wong RJ, Sauer BG, Terrault NA, Shah VH. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol 2024; 119:30-54. [PMID: 38174913 PMCID: PMC11040545 DOI: 10.14309/ajg.0000000000002572] [Citation(s) in RCA: 54] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 10/04/2023] [Indexed: 01/05/2024]
Abstract
ABSTRACT Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.
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Affiliation(s)
- Loretta L. Jophlin
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville Health, Louisville, Kentucky, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Ramon Bataller
- Liver Unit, Department of Digestive and Metabolic Diseases, Hospital Clinic, Barcelona, Spain
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | - Bryan G. Sauer
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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31
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Aby ES, Vogel AS, Winters AC. Intersection of Coronavirus Disease 2019 and Alcohol-associated Liver Disease: A Review of Emerging Trends and Implications. Clin Ther 2023; 45:1164-1170. [PMID: 37758533 DOI: 10.1016/j.clinthera.2023.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/04/2023] [Accepted: 08/24/2023] [Indexed: 09/29/2023]
Abstract
PURPOSE This review will provide an overview of alcohol use and alcohol associated liver disease (ALD) prior to the coronavirus disease 2019 (COVID-19) pandemic and the impact of the pandemic on alcohol use and ALD. Furthermore, this review will explore strategies to mitigate the growing disease burden of AUD and ALD. METHODS A search using PubMed was performed for articles on topics related to alcohol use, ALD, and COVID-19. The literature was reviewed and pertinent sources were used for this narrative review. FINDINGS In the United States (US), excessive alcohol use is the third leading cause of preventable death. Prior to the COVID-19 pandemic, the increasing prevalence of alcohol use disorder (AUD) and ALD in the US had already constituted a public health crisis given the association between alcohol misuse, AUD, and ALD with significant medical, economic, and societal burdens. The COVID-19 pandemic led to increased alcohol consumption and downstream consequences, including increased prevalence of AUD, ALD, ALD-related hospitalization and death, and liver transplantation for ALD. IMPLICATIONS There is a critical need for additional, multi-pronged interventions to mitigate the mortality and morbidity linked to ALD.
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Affiliation(s)
- Elizabeth S Aby
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota.
| | - Alexander S Vogel
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Adam C Winters
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
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Mazhar A, Alnimer L, Piper MS. Which patient should have preference for liver transplantation: ALD? Clin Liver Dis (Hoboken) 2023; 22:238-242. [PMID: 38143811 PMCID: PMC10745244 DOI: 10.1097/cld.0000000000000009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/18/2022] [Indexed: 12/26/2023] Open
Abstract
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Gonzalez HC, Nimri FM, Lu M, Zhou Y, Rupp LB, Trudeau S, Gordon SC. Alcohol-related hepatitis admissions decline in 2021 after a 2020 surge attributed to the COVID-19 pandemic. Hepatol Int 2023; 17:1637-1644. [PMID: 37505324 DOI: 10.1007/s12072-023-10569-y] [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: 02/22/2023] [Accepted: 07/07/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVE We previously investigated the impact of the COVID-19 pandemic on alcohol-related liver disease (ARLD), finding that admissions for alcoholic hepatitis (AH) increased by 50% in the summer of 2020 compared to the same period in 2016-2019. We have now expanded our analysis to consider full years' data and evaluate how rates changed in 2021. We also sought to identify factors associated with ICU admissions, need for dialysis, liver transplant evaluations, and death. METHODS Using retrospective data, we identified patients admitted to our four Detroit, Michigan area hospitals for acute ARLD for three periods pre-COVID (2016-February 2020), early COVID (June-December 2020), and late COVID (2021). Clustered logistic regression was performed to study rates of AH admissions across the three eras, where the patient was defined as the cluster and the analysis accounted for multiple encounters per cluster. A similar regression approach, univariate followed by multivariable analysis, was also used to study associations between patient characteristics and outcomes during hospitalization for AH. RESULTS AH-related admissions declined significantly from the early COVID to late COVID eras (OR 0.68, 95% CL 0.52, 0.88), returning to levels similar to that of the pre- COVID period (OR 1.18, 95% CL 0.96, 1.47). In multivariable analysis, baseline MELD score was associated with ICU admission, initiation of dialysis, transplant evaluation, and death while hospitalized for AH. Female patients were at almost twice the risk of death during admission compared to male patients (aOR 1.81, 95% CL 1.1, 2.98). Increasing age was associated with slightly lower odds of transplant (aOR 0.97, 95% CL 0.94, 1) and higher odds of death (aOR 1.03, 95% CL 1.01. 1.06). CONCLUSION After a spike in AH-related admissions during the first summer of the COVID-19 pandemic, rates declined significantly in 2021, returning to pre-pandemic levels.
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Affiliation(s)
- Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, MI, USA.
- School of Medicine, Wayne State University, Detroit, MI, USA.
- Transplant Hepatology, Henry Ford Health, 2799 West Grand Blvd, Detroit, MI, 48202, USA.
| | - Faisal M Nimri
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, MI, USA
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health, Detroit, MI, USA
| | - Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health, Detroit, MI, USA
| | - Loralee B Rupp
- Department of Health Policy and Health Systems Research, Henry Ford Health, Detroit, MI, USA
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health, Detroit, MI, USA
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, MI, USA
- School of Medicine, Wayne State University, Detroit, MI, USA
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Okumura K, Dhand A, Misawa R, Sogawa H, Veillette G, Nishida S. The effects of acuity circle policy on racial disparity in liver transplantation. Surgery 2023; 174:1436-1444. [PMID: 37827898 DOI: 10.1016/j.surg.2023.09.002] [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: 03/03/2023] [Revised: 08/03/2023] [Accepted: 09/05/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND A new deceased donor liver allocation policy using an acuity circle-based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. METHODS We conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post-acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. RESULTS Acuity circle-policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post-liver transplantation mortality and liver graft failure in both periods. CONCLUSION Although the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York. https://twitter.com/KenjiOkumura_MD
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York. https://twitter.com/DhandAbhay
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York. https://twitter.com/HiroNewYork
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York.
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Taylor-Robinson SD, Morgan MY. COVID-19 and the Liver: A Complex and Evolving Picture. Hepat Med 2023; 15:209-220. [PMID: 37965296 PMCID: PMC10641025 DOI: 10.2147/hmer.s384172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/28/2023] [Indexed: 11/16/2023] Open
Abstract
Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, other organs, such as the liver, are also affected. In this overview, the effects of SARS-CoV-2 infection on the liver in both healthy people and in those with pre-existing liver disease are documented; the relationship between coronavirus disease 19 (COVID-19) vaccination and liver injury is examined; the mechanism of SARS-CoV-2-associated liver injury is explored; and the long-term consequences of COVID-19 are delineated, both in people with and without pre-existing liver disease.
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Affiliation(s)
- Simon D Taylor-Robinson
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Public Health, Busitema University and Mbale Clinical Research Institute, Mbale, Uganda
| | - Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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Wang Y, Huang Y, Zheng T, Sun C, Yang K, Pang M. Gastrointestinal hospitalization during COVID-19 pandemic in the United States: Analysis of a nationwide inpatient sample. J Gastroenterol Hepatol 2023; 38:1971-1979. [PMID: 37581244 DOI: 10.1111/jgh.16318] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 06/12/2023] [Accepted: 07/22/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND AND AIM We aim to systematically investigate gastrointestinal (GI) hospitalizations in the United States during the early phase of the COVID-19 pandemic on a national level and the consequence that may inform practice and policies. METHODS A retrospective cross-sectional analysis of adult hospitalizations with GI-related diagnoses or procedures in the United States in 2020 was used, with hospitalizations from 2016 to 2019 used for contextual information. RESULTS Hospitalizations with principal and secondary GI diagnoses decreased by 13.3% and 8.2% from 2019 to 2020, respectively. Most GI diagnoses decreased in 2020, with a few exceptions including alcoholic liver disease (increased by 7.8% as a principal diagnosis) and acute liver failure (increased by 11.6% as a secondary diagnosis). The mortality rate of hospitalizations with GI disease increased in 2020 compared with 2019 (for principal diagnosis: adjusted odds ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001; for secondary diagnosis: adjusted odds ratio 1.10, 95% confidence interval 1.07-1.13, P < 0.001). Most GI procedures decreased except for a notable 8.3% increase in gastrostomy. The per-GI-hospitalization rate of procedures increased for hospitalizations with a principal GI diagnosis (56.4% vs 55.6%, P = 0.003) or unchanged for hospitalizations with secondary GI diagnoses (18.3% vs 18.2%, P = 0.512). CONCLUSION The COVID-19 pandemic resulted in a decrease in the volume of GI hospitalizations and procedures in 2020, but there was an increase in the mortality rate and some specific diagnoses including alcoholic liver disease and acute liver failure. These findings will likely enlighten future research and healthcare resource allocation for GI diseases.
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Affiliation(s)
- Yichen Wang
- Mercy Internal Medicine Service, Trinity Health of New England, Springfield, Massachusetts, USA
| | - Yuting Huang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Ting Zheng
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Chenyu Sun
- Department of Thyroid and Breast Surgery, The Second Hospital of Anhui Medical University, He Fei, China
| | - Keming Yang
- Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Maoyin Pang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
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Marlowe N, Lam D, Liangpunsakul S. Epidemic within a pandemic: Alcohol-associated hepatitis and COVID-19. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:1883-1889. [PMID: 37553753 DOI: 10.1111/acer.15162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 07/28/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND There was an increase in alcoholic beverage sales during the peak of the COVID pandemic in the United States. However, little is known about the impact of SARS-CoV-2 infection among hospitalized alcohol-associated hepatitis (AH) patients. METHODS We analyzed the available National Inpatient Data (NIS) data from 2020 to determine mortality and healthcare utilization among hospitalized AH patients with and without COVID-19 in the United States. RESULTS We observed a ~15.6% increase in cases of hospitalized AH patients from 136,620 in 2019 to 157,885 in 2020, a significant increase from an average of 5.5% per annum despite an 8.7% decline in US hospital admissions over the same time span. Men younger than 40 were the fastest growing AH group, with a 23% increase in 2020. Approximately 1.8% of hospitalized AH patients had a SARS-CoV-2 infection, which significantly worsened the mortality among patients with AH (11.4% vs. 4.1%, p < 0.0001). This was especially true among older AH patients with concomitant conditions such as clinically apparent cirrhosis, acute renal failure, upper gastrointestinal bleeding, and sepsis. AH patients with COVID-19 also had a longer length of stay (8.6 vs. 6.1 days, p < 0.0001) and higher hospital charges during the stay ($93,670 vs. $66,283, p < 0.0001) than those without COVID-19. CONCLUSION Our study highlights the rise in AH cases during the COVID-19 pandemic. Screening and appropriate management of excessive alcohol use and preventive measures such as COVID-19 vaccination should be considered to reduce morbidity and mortality among patients with AH.
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Affiliation(s)
| | - David Lam
- Pharma Analytics, San Anselmo, California, USA
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
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Manikat R, Ahmed A, Kim D. The Impact of Alcohol Consumption and Addiction on Liver Transplantation Programs in the COVID-19 Era. Hepat Med 2023; 15:141-149. [PMID: 37794854 PMCID: PMC10546995 DOI: 10.2147/hmer.s384070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/26/2023] [Indexed: 10/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has caused significant shifts in alcohol consumption patterns in the United States, with potential long-term implications for liver transplantation (LT) programs. Alcohol consumption has increased, particularly in women, leading to a rise in alcohol-related liver disease (ALD) and alcohol use disorder. Psychological distress associated with the pandemic may further exacerbate alcohol addiction. ALD is now the most common indication for LT, with higher disease severity and complex clinical presentations, demanding a fundamental transformation in LT programs. Multidisciplinary cooperation among medical specialists, telemedicine, and remote healthcare are essential strategies to address these challenges. However, barriers to telemedicine and costs must be overcome. Curbing alcohol consumption at the societal level and bolstering mental health programs to mitigate healthcare workforce moral injury are recommended to optimize patient care in the post-COVID-19 era. Adequate planning and compassionate management of finite resources will be crucial for the successful continuation of LT programs amidst the concerning trends in alcohol consumption and addiction.
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Affiliation(s)
- Richie Manikat
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
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Wang Y, Huang Y, Chase RC, Li T, Ramai D, Li S, Huang X, Antwi SO, Keaveny AP, Pang M. Global Burden of Digestive Diseases: A Systematic Analysis of the Global Burden of Diseases Study, 1990 to 2019. Gastroenterology 2023; 165:773-783.e15. [PMID: 37302558 DOI: 10.1053/j.gastro.2023.05.050] [Citation(s) in RCA: 62] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/05/2023] [Accepted: 05/10/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND & AIMS This study assessed the worldwide burden of digestive diseases between 1990 and 2019. METHODS We analyzed data from the Global Burden of Diseases study, covering 18 digestive diseases across 204 countries and territories. Key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change. RESULTS In 2019, there were 7.32 billion incidents and 2.86 billion prevalent cases of digestive diseases, resulting in 8 million deaths and 277 million DALYs lost. Little to no decrease in global age-standardized incidence and prevalence of digestive diseases was observed between 1990 and 2019, with 95,582 and 35,106 cases per 100,000 individuals in 2019, respectively. The age-standardized death rate was 102 per 100,000 individuals. Digestive diseases accounted for a significant portion of the overall disease burden, with more than one-third of prevalent cases having a digestive etiology. Enteric infections were the primary contributor to incidence, death, and DALYs lost, whereas cirrhosis and other chronic liver diseases had the highest prevalence rate. The burden of digestive diseases was inversely related to the sociodemographic index, with enteric infections being the predominant cause of death in low and low-middle quintiles and colorectal cancer in the high quintile. CONCLUSIONS Despite significant reductions in deaths and DALYs due to digestive diseases from 1990 to 2019, they remain prevalent. A significant disparity in the burden of digestive diseases exists among countries with different development levels.
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Affiliation(s)
- Yichen Wang
- Mercy Internal Medicine Service, Trinity Health of New England, Springfield, Massachusetts
| | - Yuting Huang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida
| | - Robert C Chase
- Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida
| | - Tian Li
- Department of Internal Medicine, State University of New York (SUNY) Downstate Health Sciences University, New York, New York
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, Utah
| | - Si Li
- Department of Internal Medicine, Temple University Hospital, Philadelphia, Pennsylvania
| | - Xiaoquan Huang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Samuel O Antwi
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Andrew P Keaveny
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida
| | - Maoyin Pang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
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Liava C, Ouranos K, Chatziioannou A, Kamenidou I, Kofinas A, Vasileiadou S, Antoniadis N, Katsanos G, Akriviadis E, Sinakos E. Impact and management of COVID-19 in liver transplant candidates and recipients. Ann Gastroenterol 2023; 36:477-489. [PMID: 37664224 PMCID: PMC10433260 DOI: 10.20524/aog.2023.0815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 05/07/2023] [Indexed: 09/05/2023] Open
Abstract
The COVID-19 outbreak has had severe consequences for global public health, medical communities, and the socioeconomic status of a considerable number of countries. The emergence of COVID-19 has also significantly impacted the world of liver transplantation (LT). Studies from transplantation centers around the world have shown that LTs during the COVID-19 pandemic have been restricted because of the high risk of serious COVID-19 infection in this population. According to the Centers for Disease Control and Prevention, patients with liver disease are considered at higher risk for severe COVID-19 infection. In March 2020, the American Association for the Study of Liver Diseases recommended that LT should be limited to emergency cases. The COVID-19 treatment guidelines published by the National Institutes of Health are being constantly updated according to new epidemiology trends and treatment regimens. Immunocompromised patients have a higher risk of developing severe disease or death from COVID-19 compared with the general population. In this review, we summarize the available evidence regarding treatment guidelines and considerations for the evaluation and management of LT candidates and recipients in the era of COVID-19. In addition, we present data regarding COVID-19 among LT patients in our local transplantation center.
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Affiliation(s)
- Christina Liava
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki (Christina Liava, Konstantinos Ouranos, Anthi Chatziioannou, Evangelos Akriviadis, Emmanouil Sinakos)
| | - Konstantinos Ouranos
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki (Christina Liava, Konstantinos Ouranos, Anthi Chatziioannou, Evangelos Akriviadis, Emmanouil Sinakos)
| | - Anthi Chatziioannou
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki (Christina Liava, Konstantinos Ouranos, Anthi Chatziioannou, Evangelos Akriviadis, Emmanouil Sinakos)
| | - Irene Kamenidou
- Department of Management Science and Technology, International Hellenic University, Kavala Campus (Irene Kamenidou)
| | - Athanasios Kofinas
- Department of Transplantation Surgery Clinic, Hippokratio Hospital, Aristotle University of Thessaloniki, (Athanasios Kofinas, Stella Vasileiadou, Nikolaos Antoniadis, Georgios Katsanos), Greece
| | - Stella Vasileiadou
- Department of Transplantation Surgery Clinic, Hippokratio Hospital, Aristotle University of Thessaloniki, (Athanasios Kofinas, Stella Vasileiadou, Nikolaos Antoniadis, Georgios Katsanos), Greece
| | - Nikolaos Antoniadis
- Department of Transplantation Surgery Clinic, Hippokratio Hospital, Aristotle University of Thessaloniki, (Athanasios Kofinas, Stella Vasileiadou, Nikolaos Antoniadis, Georgios Katsanos), Greece
| | - Georgios Katsanos
- Department of Transplantation Surgery Clinic, Hippokratio Hospital, Aristotle University of Thessaloniki, (Athanasios Kofinas, Stella Vasileiadou, Nikolaos Antoniadis, Georgios Katsanos), Greece
| | - Evangelos Akriviadis
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki (Christina Liava, Konstantinos Ouranos, Anthi Chatziioannou, Evangelos Akriviadis, Emmanouil Sinakos)
| | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki (Christina Liava, Konstantinos Ouranos, Anthi Chatziioannou, Evangelos Akriviadis, Emmanouil Sinakos)
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Moskatel LS, Slusky DJG. The impact of COVID-19 on alcohol sales and consumption in the United States: A retrospective, observational analysis. Alcohol 2023; 111:25-31. [PMID: 37230334 PMCID: PMC10202895 DOI: 10.1016/j.alcohol.2023.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 04/27/2023] [Accepted: 05/04/2023] [Indexed: 05/27/2023]
Abstract
Understanding the COVID-19 pandemic's effect on alcohol sales and consumption is critical in mitigating alcohol abuse and morbidity. We sought to determine how the onset of the COVID-19 pandemic and changes in viral incidence affected alcohol sales and consumption in the United States. We conducted a retrospective observational analysis regressing National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcohol sales data and Behavioral Risk Factor Surveillance System (BRFSS) survey data for 14 states for 2017 to 2020 with COVID-19 incidence in 2020 in the United States. The onset of the pandemic was associated with higher monthly alcohol sales per capita of 1.99 standard drinks (95% Confidence Interval: 0.63 to 3.34, p = 0.007). Increases of one COVID-19 case per 100 were associated with lower monthly alcohol sales per capita of 2.98 standard drinks (95% CI: -4.47 to -1.48, p = 0.001) as well as broad decreases in alcohol consumption, notably 0.17 fewer days per month with alcohol use (95% CI: -0.31 to -0.23, p = 0.008) and 0.14 fewer days per month of binge drinking (95% CI: -0.23 to -0.052, p < 0.001). The COVID-19 pandemic is associated with increased monthly average alcohol purchases, but higher viral incidence is linked to lower alcohol purchases and consumption. Continued monitoring is needed to mitigate the effects of higher population alcohol use during the pandemic.
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Affiliation(s)
- Leon S Moskatel
- Department of Neurology, Stanford Health Care, Palo Alto, CA, United States.
| | - David J G Slusky
- Department of Economics, University of Kansas, Lawrence, KS, United States; National Bureau of Economics Research, Cambridge, MA, United States; IZA Institute of Labor Economics, Bonn, Germany
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Lim N, Leventhal TM, Thomson MJ, Hassan M, Thompson J, Adams A, Chinnakotla S, Humphreville V, Kandaswamy R, Kirchner V, Pruett TL, Schuller L, McCarty M, Lake J. Protocolized screening and detection of occult alcohol use before and after liver transplant: Lessons learned from a quality improvement initiative. Clin Transplant 2023; 37:e15036. [PMID: 37218656 DOI: 10.1111/ctr.15036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 05/09/2023] [Accepted: 05/13/2023] [Indexed: 05/24/2023]
Abstract
INTRODUCTION Detection of alcohol (ETOH) use with biomarkers provides an opportunity to intervene and treat patients with alcohol use disorder before and after liver transplant (LT). We describe our center's experience using urine ethyl glucuronide (EtG) and serum phosphatidylethanol (PEth) in alcohol screening protocols. METHODS Single-center, retrospective review of patients presenting for LT evaluation, patients waitlisted for LT for alcohol-associated liver disease (ALD), and patients who received a LT for ALD over a 12-month period, from October 1, 2019 through September 30, 2020. Patients were followed from waitlisting to LT, or for up to 12 months post-LT. We monitored protocol adherence to screening for ETOH use- defined as completion of all possible tests over the follow-up period- at the initial LT visit, while on the LT waitlist and after LT. RESULTS During the study period, 227 patients were evaluated for LT (median age 57 years, 58% male, 78% white, 54.2% ALD). Thirty-one patients with ALD were placed on the waitlist, and 38 patients underwent LT for ALD during this time period. Protocolized adherence to screening for alcohol use was higher for PEth for all LT evaluation patients (191 [84.1%] vs. 146 [67%] eligible patients, p < .001), in patients with ALD waitlisted for LT (22 [71%] vs. 14 (48%] eligible patients, p = .04) and after LT for ALD, 20 (33 [86.8%] vs. 20 [52.6%] eligible patients, p < .01). Few patients with a positive test in any group completed chemical dependency treatment. CONCLUSIONS When screening for ETOH use in pre- and post-LT patients, protocol adherence is higher using PEth compared to EtG. While protocolized biomarker screening can detect recurrent ETOH use in this population, engagement of patients into chemical dependency treatment remains challenging.
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Affiliation(s)
- N Lim
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - T M Leventhal
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - M J Thomson
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - M Hassan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - J Thompson
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - A Adams
- Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - S Chinnakotla
- Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - V Humphreville
- Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - R Kandaswamy
- Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - V Kirchner
- Division of Abdominal Transplantation, Stanford University, Palo Alto, California, USA
| | - T L Pruett
- Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - L Schuller
- University of Minnesota Physicians, Minneapolis, Minnesota, USA
| | - M McCarty
- Complex Care Analytics, Fairview Health Services, Minneapolis, Minnesota, USA
| | - J Lake
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
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Shaikh A, Goli K, Lee TH, Rich NE, Benhammou JN, Keeling S, Kim D, Ahmed A, Goss J, Rana A, Singal AG, Kanwal F, Cholankeril G. Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era. Clin Gastroenterol Hepatol 2023; 21:2288-2297.e4. [PMID: 36521738 PMCID: PMC10686256 DOI: 10.1016/j.cgh.2022.11.038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/24/2022] [Accepted: 11/30/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS With the availability of DAA therapy, racial disparities in post-LT survival have improved.
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Affiliation(s)
- Anjiya Shaikh
- Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut
| | - Karthik Goli
- Department of Student Affairs, Baylor College of Medicine, Houston, Texas
| | - Tzu-Hao Lee
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Hepatology Program, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas
| | - Nicole E Rich
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Jihane N Benhammou
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles, Los Angeles, California
| | - Stephanie Keeling
- Department of Student Affairs, Baylor College of Medicine, Houston, Texas
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford, California
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford, California
| | - John Goss
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Abbas Rana
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Hepatology Program, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas.
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Lee BP, Terrault NA. Liver transplantation for alcohol-associated liver disease: A call for national standards of best practices to monitor and bridge disparities in access and outcomes. Am J Transplant 2023; 23:1097-1101. [PMID: 37023857 PMCID: PMC10524758 DOI: 10.1016/j.ajt.2023.03.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 03/17/2023] [Accepted: 03/29/2023] [Indexed: 04/08/2023]
Abstract
Early (ie, without a mandated abstinence period) liver transplantation for alcohol-associated liver disease is the fastest-growing indication for liver transplantation in the United States. Despite widespread adoption, there is no standardization of practice or policies across transplant centers, nor are there any quality metrics from regulatory organizations specific to alcohol, all of which have likely contributed to confirmed disparities in transplant access and patient outcomes. In this article, we propose new mandates and best practices that could be put forth by the organ procurement and transplantation network regarding processes related to candidate selection, monitoring of alcohol use, and services to prevent and treat harmful alcohol use among early transplant candidates and recipients. We hope that this article stimulates discussion and leads to policy changes to maximize equity and quality of transplant care.
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Affiliation(s)
- Brian P Lee
- Division of Gastroenterology and Liver Diseases, University of Southern California, Los Angeles, California, USA.
| | - Norah A Terrault
- Division of Gastroenterology and Liver Diseases, University of Southern California, Los Angeles, California, USA
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45
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Perreault G, Ching C, Nobel YR. COVID-19 in patients with liver disease and liver transplant: clinical implications, prevention, and management. Therap Adv Gastroenterol 2023; 16:17562848231188586. [PMID: 37521085 PMCID: PMC10372508 DOI: 10.1177/17562848231188586] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/02/2023] [Indexed: 08/01/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has had enormous implications for the care of patients with chronic liver disease (CLD), cirrhosis, and liver transplant (LT). Clinical outcomes of COVID-19 vary in patients with CLD and cirrhosis compared to healthy controls, and in patients with LT compared to patients without LT. Several special considerations apply to the approach to vaccination and treatment in patients with CLD and LT. The practice of liver transplantation has also been heavily impacted by the pandemic, including persistent reductions in living donor LT and increases in LT for an indication of alcohol-related liver disease. Recent medical society guidelines strive to standardize severe acute respiratory syndrome coronavirus 2 testing in donors and recipients and the approach to transplantation after recovered from COVID-19 infection, but certain controversies remain.
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Affiliation(s)
- Gabriel Perreault
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Charlotte Ching
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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46
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Terrault NA, Francoz C, Berenguer M, Charlton M, Heimbach J. Liver Transplantation 2023: Status Report, Current and Future Challenges. Clin Gastroenterol Hepatol 2023; 21:2150-2166. [PMID: 37084928 DOI: 10.1016/j.cgh.2023.04.005] [Citation(s) in RCA: 113] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 04/23/2023]
Abstract
Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.
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Affiliation(s)
- Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California.
| | - Claire Francoz
- Liver Intensive Care and Liver Transplantation Unit, Hepatology, Hospital Beaujon, Clichy, France
| | - Marina Berenguer
- Hepatology and Liver Transplantation Unit, Hospital Universitario la Fe - IIS La Fe Valencia; CiberEHD and University of Valencia, Valencia, Spain
| | - Michael Charlton
- Transplantation Institute, University of Chicago, Chicago, Illinois
| | - Julie Heimbach
- William von Liebig Center for Transplantation, Mayo Clinic Rochester, Minnesota
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47
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Kim D, Perumpail BJ, Wijarnpreecha K, Manikat R, Cholankeril G, Ahmed A. Trends in aetiology-based hospitalisation for cirrhosis before and during the COVID-19 pandemic in the United States. Aliment Pharmacol Ther 2023; 58:218-228. [PMID: 37189243 DOI: 10.1111/apt.17547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/10/2023] [Accepted: 04/26/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND AND AIMS Patients with pre-existing cirrhosis and exposure to coronavirus disease-19 (COVID-19) may portend a poor prognosis. We evaluated the temporal trends in aetiology-based hospitalisations and potential predictors of in-hospital mortality in hospitalisation with cirrhosis before and during the COVID-19 pandemic. METHODS Based on the US National Inpatient Sample 2019-2020, we determined quarterly trends in aetiology-based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in-hospital mortality in hospitalisation with cirrhosis. RESULTS We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID-19 era. Hospitalisation rates for alcohol-related liver disease (ALD)-related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%-5.1%), with a notably higher rate during the COVID-19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)-related cirrhosis decreased steadily with a trend of -1.4% of QPC (95% CI: -2.5% to -0.1%). Quarterly trends in the proportion of ALD- (QPC: 1.7%, 95% CI: 0.9%-2.6%) and nonalcoholic fatty liver disease-related (QPC: 0.7%, 95% CI: 0.1%-1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID-19 era and COVID-19 infection were independent predictors of in-hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV-related cirrhosis, ALD-related cirrhosis was associated with a 40% higher risk of in-hospital mortality. CONCLUSION In-hospital mortality in cirrhosis was higher in the COVID-19 era than in the pre-COVID-19 era. ALD is the leading aetiology-specific cause of in-hospital mortality in cirrhosis with an independent detrimental impact of the COVID-19 infection.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Brandon J Perumpail
- Department of Pediatrics, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, USA
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, Arizona, USA
| | - Richie Manikat
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - George Cholankeril
- Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
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48
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Goli K, Lymberopoulos P, Samuel R, Shaikh A, Parakadavil N, Kim D, Ahmed A, Goss JA, Rana A, Lee TH, Kanwal F, Cholankeril G. Posttransplant outcomes for alcohol-associated liver disease during the COVID-19 pandemic. Liver Transpl 2023; 29:777-780. [PMID: 36872590 PMCID: PMC10269682 DOI: 10.1097/lvt.0000000000000113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 02/07/2023] [Indexed: 03/07/2023]
Affiliation(s)
- Karthik Goli
- Department of Student Affairs, Baylor College of Medicine, Houston, Texas, USA
| | - Peter Lymberopoulos
- Department of Medicine, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, New York, USA
| | - Ronald Samuel
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Anjiya Shaikh
- Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Nisha Parakadavil
- Department of Biomedical and Health Sciences, Rutgers University, Newark, New Jersey, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - John A. Goss
- Hepatology Program, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Abbas Rana
- Hepatology Program, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Tzu-Hao Lee
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Hepatology Program, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Hepatology Program, Division of Abdominal Transplantation, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
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49
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Mellinger JL, Fernandez AC, Winder GS. Management of alcohol use disorder in patients with chronic liver disease. Hepatol Commun 2023; 7:e00145. [PMID: 37314739 DOI: 10.1097/hc9.0000000000000145] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 03/15/2023] [Indexed: 06/15/2023] Open
Abstract
Alcohol use disorder (AUD) rates have risen dramatically in the United States, resulting in increasing rates of alcohol-associated liver disease (ALD), but many patients struggle to access alcohol use treatment. AUD treatment improves outcomes, including mortality, and represents the most urgent means by which care can be improved for those with liver disease (including ALD and others) and AUD. AUD care for those with liver disease involves 3 steps: detecting alcohol use, diagnosing AUD, and directing patients to alcohol treatment. Detecting alcohol use can involve questioning during the clinical interview, the use of standardized alcohol use surveys, and alcohol biomarkers. Identifying and diagnosing AUD are interview-based processes that should ideally be performed by a trained addiction professional, but nonaddiction clinicians can use surveys to determine the severity of hazardous drinking. Referral to formal AUD treatment should be made, especially where more severe AUD is suspected or identified. Therapeutic modalities are numerous and include different forms of one-on-one psychotherapy, such as motivational enhancement therapy or cognitive behavior therapy, group therapy, community mutual aid societies (such as Alcoholics Anonymous), inpatient addiction treatment, and relapse prevention medications. Finally, integrated care approaches that build strong relationships between addiction professionals and hepatologists or medical providers caring for those with liver disease are crucial to improving care for this population.
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Affiliation(s)
- Jessica L Mellinger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA
- Department of Psychiatry, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Anne C Fernandez
- Department of Psychiatry, Michigan Medicine, Ann Arbor, Michigan, USA
| | - G Scott Winder
- Department of Psychiatry, Michigan Medicine, Ann Arbor, Michigan, USA
- Department of Surgery, Michigan Medicine, Ann Arbor, Michigan, USA
- Department of Neurology, Michigan Medicine, Ann Arbor, Michigan, USA
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50
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Tsoulfas G. COVID-19 and Liver Transplantation: Challenges and Opportunities. J Clin Transl Hepatol 2023; 11:521-522. [PMID: 36969897 PMCID: PMC10037510 DOI: 10.14218/jcth.2022.00038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/28/2022] [Accepted: 01/10/2023] [Indexed: 01/21/2023] Open
Affiliation(s)
- Georgios Tsoulfas
- Department of Transplantation Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
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