Young corner
Alcohol-related liver disease: (Re)compensation of abstinence
Enfermedad hepática relacionada con el alcohol: la (re)compensación de la abstinencia
Joaquín Cabezasa,b,f,1,
, José Ignacio Fortea Ormaecheaa,b,f,1, Ángela Puente Sáncheza,b,f,1, Rocío Gallego-Duránc,d,f,1, Andrés Conthec,d,f,1, David Martí-Aguadoe,f,1
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a Servicio de Gastroenterología y Hepatología, Hospital Universitario Marqués de Valdecilla, Santander, Spain
b Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain
c SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Universidad de Sevilla, Sevilla, Spain
d Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
e Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain
f Servicio de Aparato Digestivo, Hospital Clínico Universitario de Valencia, INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain
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array:3 [ "entidad" => "Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Universidad de Sevilla, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Clínico Universitario de Valencia, INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad hepática relacionada con el alcohol: la (re)compensación de la abstinencia" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1615 "Ancho" => 2667 "Tamanyo" => 407290 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ALD management: focusing multi-target.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alcohol-related liver disease (ALD) is the leading cause of liver-related mortality and is often diagnosed at advanced stages due to the lack of early detection.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Research has predominantly focused on these advanced stages, highlighting the critical need for more evidence on the factors that drive disease progression during its initial, silent phase. Steatotic liver disease (SLD) encompasses a spectrum of pathological stages ranging from simple steatosis to varying degrees of inflammation and fibrosis, ultimately culminating in cirrhosis or advanced liver disease (with its various compensated and decompensated manifestations), and hepatocellular carcinoma. While excessive alcohol consumption is a primary driver of this progression, other factors, including components of metabolic syndrome and their complex interplay, significantly contribute to disease advancement, including the development of acute-on-chronic liver failure (ACLF). In the subsequent sections, we delve into the complexities of SLD management in the context of co-existing alcohol use and metabolic disorders, highlighting the role of occult alcohol consumption in decompensation or ACLF, we also review some strategies for managing alcohol use disorder to achieve abstinence and subsequent recompensation – a novel objective that we will also explore.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The coexistence of metabolic syndrome and alcohol use is common and has recently been termed metabolic-associated alcoholic liver disease (MetALD),<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> it complicates both diagnosis and management, requiring a comprehensive approach to address both conditions simultaneously. In both ALD and MetALD, achieving the goal of alcohol abstinence is essential. Notably, alcohol consumption is often underreported by patients with metabolic-dysfunction associated steatotic liver disease (MASLD),<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> highlighting the need for incorporating alcohol biomarkers<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> into routine clinical practice.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The use of objective alcohol biomarkers to promote abstinence is important not only when MASLD is present, but also in patients with cardiometabolic risk factors and alcohol consumption in the absence of SLD.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> Regarding alcohol biomarkers there are several of them widely available (i.e. AST/ALT, GGT, MCV, CDT) however they are not precise, need high amount of alcohol consumption to become positive. In the era of personalized medicine, we need more accurate tools to measure alcohol consumptions. Although we have ethyl-glucuronide that can be easily measure in urine, we must know that urine can be changed/diluted, bacterial or yeast contamination/infections can alter detection of this metabolite, and finally we can only detect the 3–5 days of alcohol intake. Therefore, we propose the use of phosphatidyl-ethanol<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> (PEth) in blood; it captures as long as 3 weeks of alcohol consumption and low consumption, allowing to clearly monitor abstinence and it can reveal low or moderate consumption. Unfortunately, it is expensive, and it needs complex spectrometry technics which in the end they are not widely available.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The effort dedicated to the development of these tools reflects the importance of achieving abstinence, an aspect that has been addressed in the recent retrospective registry-based study by Idalsoaga et al.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> They emphasize the critical importance of alcohol abstinence and the frequent underreporting of alcohol consumption among MASLD patients. Conducted at three university centers in Chile, the authors examined the relationship between active alcohol consumption and the development of ACLF using the EASL-CLIF consortium ACLF criteria in 320 patients with decompensated cirrhosis. The most common etiologies were ALD (36.7%) and MASLD (34.4%). The study found that 92 patients (28.7%) met the criteria for ACLF, particularly those with ALD and a history of alcohol intake. Additionally, 17% of patients with cirrhosis due to MASLD (this study uses previous definition of NAFLD) were found to have excessive alcohol consumption at admission. The presence of ACLF was linked to higher mortality rates and a shorter time to death, underscoring the need for early intervention and the promotion of alcohol abstinence in cirrhosis patients, regardless of the underlying cause.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The challenges of interventions in ALD cirrhosis and the consequences of failure to achieve prolonged abstinence have been evaluated in numerous studies. The difficulties and importance of theses interventions to promote alcohol abstinence is also evidenced in a key study of the French CIRRAL group.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Louvet et al. showed in a prospective cohort of 650 patients with compensated ALD, followed for a median of 97 months, that within a five-year period, up to 30.9% of the abstinent patients recurred in alcohol consumption. Furthermore, low alcohol consumption as low as an absolute cumulative amount of more than 25 glass-years during follow-up was independently associated with lower survival and with a trend toward lower liver event-free survival.</p><p id="par0030" class="elsevierStylePara elsevierViewall">To assess alcohol use disorder (AUD), the initial step is to use the AUDIT and AUDIT-C questionnaires.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> Following this assessment, patients should be supported in reducing alcohol consumption through brief intervention strategies, a practical approach endorsed by the French Guidelines for ALD management.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> Brief interventions are tailored for individuals who engage in risky alcohol use but exhibit minimal dependence. These interventions are relatively short, usually lasting about 15<span class="elsevierStyleHsp" style=""></span>min, and include the following components: 1. <span class="elsevierStyleItalic">Personalized interview</span>: The healthcare provider conducts a one-on-one discussion with the patient, focusing on their alcohol use patterns and the related consequences. 2. <span class="elsevierStyleItalic">Education and information</span>: The patient receives clear and concise information about what constitutes low-risk drinking and the potential health hazards of excessive alcohol consumption. 3. <span class="elsevierStyleItalic">Identifying high-risk situations</span>: The healthcare provider helps the patient recognize situations that might trigger problematic drinking and explores coping mechanisms to navigate these situations. 4. <span class="elsevierStyleItalic">Motivating change</span>: Motivational interviewing techniques are employed to enhance the patient's readiness and willingness to modify their drinking behavior. 5. <span class="elsevierStyleItalic">Personalized reduction plan</span>: The healthcare provider collaborates with the patient to create a tailored plan that outlines achievable goals and practical strategies for reducing alcohol intake.</p><p id="par0035" class="elsevierStylePara elsevierViewall">These five interventions have been shown to be effective in reducing alcohol consumption and its associated risks, making them an essential tool in clinical practice. Thus, training all specialists who manage ALD patients to deliver these interventions is crucial for future practice.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Achieving abstinence is key not only to prevent disease progression but also because it can induce disease regression. The Baveno VII consensus<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> established criteria for defining hepatic recompensation, which include the removal or control of the underlying cause of cirrhosis, resolution of ascites and hepatic encephalopathy without continued treatment, absence of variceal bleeding for at least 12 months, and sustained improvement in liver function markers (serum albumin, bilirubin, and INR). Recent findings by Hofer et al.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> indicate that patients with decompensated alcohol-related cirrhosis who maintain abstinence have a significant likelihood of achieving recompensation, which is linked to improved survival rates and reduced liver-related mortality. This positive prognostic impact has also been observed in patients with viral-related decompensated cirrhosis.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">13,14</span></a> However, defining “complete suppression of aetiology” remains challenging in the context of MetALD or MASLD. Future research must clarify whether recompensation criteria should incorporate specific thresholds for hepatic venous pressure gradient (HVPG) reduction or other biomarkers.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, abstinence is the cornerstone of managing both ALD and MetALD. It is essential for halting disease progression and achieving recompensation. A multidisciplinary, patient-centered approach<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> is crucial for addressing ALD and its comorbidities, emphasizing prevention and early detection (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). National initiatives, such as AEEH National Plan for Liver Health,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a> aim to comprehensively tackle liver disease from prevention and early detection to treatment. By fostering collaboration between scientific societies and patient associations, we can enhance awareness and prevention efforts, ultimately improving liver health outcomes.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Disclosure</span><p id="par0050" class="elsevierStylePara elsevierViewall">This manuscript and its figures have been polished for English language/picture design using LiverAI and Gemini Advanced.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This manuscript has no funding.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Disclosure" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">All authors are members of the Young Investigator Group of the Spanish Association for the Study of the Liver (AEEH).</p>" "identificador" => "fn0005" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1615 "Ancho" => 2667 "Tamanyo" => 407290 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ALD management: focusing multi-target.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0085" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alcohol-related liver disease. 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