Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Arab, Juan Pablo; Díaz, Luis Antonio; Baeza, Natalia; Idalsoaga, Francisco; Fuentes‐López, Eduardo; Arnold, Jorge; Ramírez, Carolina A.; Morales-Arráez, Dalia; Ventura-Cots, Meritxell; Alvarado‐Tapias, Edilmar; Zhang, Wei; Clark, Virginia; Simonetto, Douglas A.; Ahn, Joseph; Buryska, Seth; Mehta, Tej I; Ştefănescu, Horia; Horhat, Adelina; Bumbu, Andreea; Dunn, Winston; Attar, Bashar; Agrawal, Rohit; Haque, Zohaib; Majeed, Muhammad; Cabezas, Joaquín; García-Carrera, Inés; Parker, Richard; Cuyàs, Berta; Poca, María; Soriano, Germán; Sarin, Shiv Kumar; Maiwall, Rakhi; Jalal, Prasun K.; Abdulsada, Saba; Tijera, M.F. Higuera-de la; Kulkarni, Anand V.; Rao, Padaki Nagaraja; Salazar, Patricia Guerra; Skladaný, Ľubomír; Bystrianska, Natália; Prado, Verónica; Clemente‐Sánchez, Ana; Rincón, Diego; Haider, Tehseen; Chacko, Kristina; Cairo, Fernando; Coelho, Marcela de Sousa; Romero, Gustavo; Pollarsky, Florencia; Restrepo, Juan Carlos; Castro-Sanchez, Susana; Toro, Luis; Yaquich, Pamela; Mendizábal, Manuel; Garrido, María Laura; Narvaez, Adrián; Bessone, Fernando; Marcelo, Julio Santiago; Piombino, Diego; Dirchwolf, Melisa; Arancibia, Juan Pablo; Altamirano, José; Kim, Won; Araújo, Roberta Chaves; Rojo, Andrés Duarte; Vargas, Vı́ctor; Rautou, P.-E.; Issoufaly, T.; Zamarripa, Felipe; Torre, Aldo; Lucey, Michael R.; Maury, Philippe; Louvet, Alexandre; García–Tsao, Guadalupe; Gonzalez, Jose A.; Verna, Elizabeth C.; Brown, Robert S.; Roblero, Juan Pablo; Abraldes, Juan G.; Arrese, Marco; Shah, Vijay H.; Kamath, Patrick S.; Singal, Ashwani K.; Bataller, Ramón

doi:10.1016/j.jhep.2021.06.019

Cited by 63 publications

(37 citation statements)

References 38 publications

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“…In this landmark retrospective, registry-based multicentric cohort study spanning four continents, the authors evaluated 3,380 adults with a clinical and/or histological diagnosis of alcoholic hepatitis (AH). 1 The clinical definition of AH was as per the National Institute on Alcohol Abuse and Alcoholism. 2 Corticosteroids are the only effective therapy for severe alcoholic hepatitis (sAH), defined by a model for end-stage liver disease (MELD) score >20.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Progress in Hepatology: Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Roy

Verma

2022

Journal of Clinical and Experimental Hepatology

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Progress in Hepatology: Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Roy

Verma

2022

Journal of Clinical and Experimental Hepatology

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“…Excessive alcohol consumption causes a significant public health problem with devastating consequences, including alcohol-associated liver disease (ALD) and alcohol-associated hepatitis [14][15][16]. This is an important cause of chronic liver disease in Latin America and is the leading cause of cirrhosis in Argentina, Brazil, Chile, Mexico, and Peru [17].…”

Section: The Burden Of Liver Diseases In Latin Americamentioning

confidence: 99%

Liver Diseases in Latin America: Current Status, Unmet Needs, and Opportunities for Improvement

Díaz

Ayares

Arnold

et al. 2022

Curr Treat Options Gastro

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Purpose of review To assess the current challenges regarding liver diseases, including the burden of disease, access to care, screening, and treatment needs in Latin America. Recent findings Latin America is a region with a rich multicultural heritage and important socioeconomic differences. The burden of liver diseases is high and mainly determined by a high level of alcohol intake and the surge of risk factors associated with NAFLD (i.e., sedentary lifestyles, broader access to highly processed foods, obesity, and type 2 diabetes mellitus). Hepatotropic viruses also play a role in the development of chronic liver diseases, although their comparative frequency has been decreasing over the last decades. There are important disparities in access to screening and treatment for liver diseases in Latin America, which are reflected in low accessLiver (E Tapper, Section Editor) to critical treatments such as direct-acting antiviral agents and drugs to treat hepatocellular carcinoma. Also, important barriers to liver transplantation are present in multiple countries, including a low deceased donors' rate and a lack of availability in several countries (especially in Central America). Our region also has disadvantages in research and education in liver diseases, which limits regional academic development and improvement in quality of care of liver diseases. Summary In order to tackle an increasing health burden due to liver diseases, Latin America urgently needs tailored interventions aiming to control the main risk factors for these disorders through the establishment of effective public health policies. Also, development of liver transplantation programs and improvement of medical education and research capabilities as well as extensive collaboration between all stakeholders are keys to address the liver disease agenda in the region. AbbreviationsACLF Acute-on-chronic liver failure ALD Alcohol-associated liver disease ALF Acute liver failure AUD Alcohol use disorder DALYs Disability-adjusted life-years DILI Drug-induced liver injury GDP Gross domestic product HBV Hepatitis B virus HCV Hepatitis C virus HDV Hepatitis delta virus HCC Hepatocellular carcinoma LT Liver transplantation MAFLD Metabolic dysfunction-associated fatty liver disease NAFLD Non-alcoholic fatty liver disease NASH Non-alcoholic steatohepatitis PHP Public health policies PNPLA3 Patatin-like phospholipase domain-containing 3 US United States USD United States Dollars WHO World Health Organization * Updated to 2019 + Updated to 2020 Country Population in 2019 GDP + Gini index* Life expectancy from birth (years)* Deceased donors' rate* DDLT rate* LDLT rate* Argentina 44,938,712

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“…Importantly, several studies have also now shown that corticosteroids retain this survival benefit in 'very severe' AH based on MDF 47 or even MELD, although the optimal window for treatment is likely between a MELD of 21 to 40. 50 Even amongst the individuals who are eligible for corticosteroids, roughly 40% will derive no benefit from corticosteroid therapy. To avoid prolonged exposure to corticosteroids, these 'steroid nonresponders' can be identified using the Lille score, a dynamic score which assesses the change in serum bilirubin on day 7 of treatment, to determine response.…”

Section: Corticosteroidsmentioning

confidence: 99%

“…Apart from having severe disease as determined by MDF ≥32 or Model for End‐Stage Liver Disease score (MELD) > 20, several relative contraindications need to be evaluated before initiation of corticosteroid therapy including uncontrolled infection, acute kidney injury and uncontrolled upper gastrointestinal bleeding. Importantly, several studies have also now shown that corticosteroids retain this survival benefit in ‘very severe’ AH based on MDF 47 or even MELD, although the optimal window for treatment is likely between a MELD of 21 to 40 50 …”

Section: Current Therapies For Ahmentioning

confidence: 99%

Review article: current and emerging therapies for acute alcohol‐associated hepatitis

Rattan

Shah

2022

Aliment Pharmacol Ther

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Summary Background Alcohol‐associated hepatitis is an acute manifestation of alcohol‐associated liver disease (ALD) and is associated with 30%–40% mortality at 28 days. Abstinence and corticosteroids are the mainstays of treatment, but the latter only improves short‐term mortality, so new and improved therapies remain an unmet need. Aims The aim was to review the pathophysiology of alcohol‐associated hepatitis and how various targets can be used by current and emerging therapies as treatment. Methods A thorough literature review was conducted on acute alcohol‐associated hepatitis, current therapies and therapies under investigation. Results With the increasing prevalence of alcohol use disorder and ALD, the burden of alcohol‐associated hepatitis is also expected to rise. The current understanding of alcohol‐associated hepatitis pathophysiology has led to clinical trials of several therapies involving IL‐1 antagonism, modification of the gut microbiome and liver regeneration. Conclusions Corticosteroid therapy for alcohol‐associated hepatitis is restricted in its applicability and has limited efficacy. Developing multidisciplinary, patient‐centred care models based on digital health technologies, in combination with continued discovery of novel therapies using multiomics data and computational biology techniques will be necessary to tackle the increasing burden of alcohol‐associated hepatitis.

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Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Cited by 63 publications

References 38 publications

WITHDRAWN: Progress in Hepatology: Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

WITHDRAWN: Progress in Hepatology: Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Liver Diseases in Latin America: Current Status, Unmet Needs, and Opportunities for Improvement

Review article: current and emerging therapies for acute alcohol‐associated hepatitis

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