Alcohol-related liver disease: (Re)compensation of abstinence

Cabezas, Joaquín; Fortea Ormaechea, José Ignacio; Puente Sánchez, Ángela; Gallego-Durán, Rocío; Conthe, Andrés; Martí-Aguado, David
doi:10.1016/j.gastrohep.2024.502263
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alcohol-related liver disease &#40;ALD&#41; is the leading cause of liver-related mortality and is often diagnosed at advanced stages due to the lack of early detection&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Research has predominantly focused on these advanced stages&#44; highlighting the critical need for more evidence on the factors that drive disease progression during its initial&#44; silent phase&#46; Steatotic liver disease &#40;SLD&#41; encompasses a spectrum of pathological stages ranging from simple steatosis to varying degrees of inflammation and fibrosis&#44; ultimately culminating in cirrhosis or advanced liver disease &#40;with its various compensated and decompensated manifestations&#41;&#44; and hepatocellular carcinoma&#46; While excessive alcohol consumption is a primary driver of this progression&#44; other factors&#44; including components of metabolic syndrome and their complex interplay&#44; significantly contribute to disease advancement&#44; including the development of acute-on-chronic liver failure &#40;ACLF&#41;&#46; In the subsequent sections&#44; we delve into the complexities of SLD management in the context of co-existing alcohol use and metabolic disorders&#44; highlighting the role of occult alcohol consumption in decompensation or ACLF&#44; we also review some strategies for managing alcohol use disorder to achieve abstinence and subsequent recompensation &#8211; a novel objective that we will also explore&#46;</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 &#40;MetALD&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> it complicates both diagnosis and management&#44; requiring a comprehensive approach to address both conditions simultaneously&#46; In both ALD and MetALD&#44; achieving the goal of alcohol abstinence is essential&#46; Notably&#44; alcohol consumption is often underreported by patients with metabolic-dysfunction associated steatotic liver disease &#40;MASLD&#41;&#44;<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&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The use of objective alcohol biomarkers to promote abstinence is important not only when MASLD is present&#44; but also in patients with cardiometabolic risk factors and alcohol consumption in the absence of SLD&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> Regarding alcohol biomarkers there are several of them widely available &#40;i&#46;e&#46; AST&#47;ALT&#44; GGT&#44; MCV&#44; CDT&#41; however they are not precise&#44; need high amount of alcohol consumption to become positive&#46; In the era of personalized medicine&#44; we need more accurate tools to measure alcohol consumptions&#46; Although we have ethyl-glucuronide that can be easily measure in urine&#44; we must know that urine can be changed&#47;diluted&#44; bacterial or yeast contamination&#47;infections can alter detection of this metabolite&#44; and finally we can only detect the 3&#8211;5 days of alcohol intake&#46; Therefore&#44; we propose the use of phosphatidyl-ethanol<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> &#40;PEth&#41; in blood&#59; it captures as long as 3 weeks of alcohol consumption and low consumption&#44; allowing to clearly monitor abstinence and it can reveal low or moderate consumption&#46; Unfortunately&#44; it is expensive&#44; and it needs complex spectrometry technics which in the end they are not widely available&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The effort dedicated to the development of these tools reflects the importance of achieving abstinence&#44; an aspect that has been addressed in the recent retrospective registry-based study by Idalsoaga et al&#46;<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&#46; Conducted at three university centers in Chile&#44; 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&#46; The most common etiologies were ALD &#40;36&#46;7&#37;&#41; and MASLD &#40;34&#46;4&#37;&#41;&#46; The study found that 92 patients &#40;28&#46;7&#37;&#41; met the criteria for ACLF&#44; particularly those with ALD and a history of alcohol intake&#46; Additionally&#44; 17&#37; of patients with cirrhosis due to MASLD &#40;this study uses previous definition of NAFLD&#41; were found to have excessive alcohol consumption at admission&#46; The presence of ACLF was linked to higher mortality rates and a shorter time to death&#44; underscoring the need for early intervention and the promotion of alcohol abstinence in cirrhosis patients&#44; regardless of the underlying cause&#46;</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&#46; The difficulties and importance of theses interventions to promote alcohol abstinence is also evidenced in a key study of the French CIRRAL group&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Louvet et al&#46; showed in a prospective cohort of 650 patients with compensated ALD&#44; followed for a median of 97 months&#44; that within a five-year period&#44; up to 30&#46;9&#37; of the abstinent patients recurred in alcohol consumption&#46; Furthermore&#44; 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&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To assess alcohol use disorder &#40;AUD&#41;&#44; the initial step is to use the AUDIT and AUDIT-C questionnaires&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> Following this assessment&#44; patients should be supported in reducing alcohol consumption through brief intervention strategies&#44; a practical approach endorsed by the French Guidelines for ALD management&#46;<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&#46; These interventions are relatively short&#44; usually lasting about 15<span class="elsevierStyleHsp" style=""></span>min&#44; and include the following components&#58; 1&#46; <span class="elsevierStyleItalic">Personalized interview</span>&#58; The healthcare provider conducts a one-on-one discussion with the patient&#44; focusing on their alcohol use patterns and the related consequences&#46; 2&#46; <span class="elsevierStyleItalic">Education and information</span>&#58; The patient receives clear and concise information about what constitutes low-risk drinking and the potential health hazards of excessive alcohol consumption&#46; 3&#46; <span class="elsevierStyleItalic">Identifying high-risk situations</span>&#58; The healthcare provider helps the patient recognize situations that might trigger problematic drinking and explores coping mechanisms to navigate these situations&#46; 4&#46; <span class="elsevierStyleItalic">Motivating change</span>&#58; Motivational interviewing techniques are employed to enhance the patient&#39;s readiness and willingness to modify their drinking behavior&#46; 5&#46; <span class="elsevierStyleItalic">Personalized reduction plan</span>&#58; The healthcare provider collaborates with the patient to create a tailored plan that outlines achievable goals and practical strategies for reducing alcohol intake&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">These five interventions have been shown to be effective in reducing alcohol consumption and its associated risks&#44; making them an essential tool in clinical practice&#46; Thus&#44; training all specialists who manage ALD patients to deliver these interventions is crucial for future practice&#46;</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&#46; The Baveno VII consensus<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> established criteria for defining hepatic recompensation&#44; which include the removal or control of the underlying cause of cirrhosis&#44; resolution of ascites and hepatic encephalopathy without continued treatment&#44; absence of variceal bleeding for at least 12 months&#44; and sustained improvement in liver function markers &#40;serum albumin&#44; bilirubin&#44; and INR&#41;&#46; Recent findings by Hofer et al&#46;<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&#44; which is linked to improved survival rates and reduced liver-related mortality&#46; This positive prognostic impact has also been observed in patients with viral-related decompensated cirrhosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">13&#44;14</span></a> However&#44; defining &#8220;complete suppression of aetiology&#8221; remains challenging in the context of MetALD or MASLD&#46; Future research must clarify whether recompensation criteria should incorporate specific thresholds for hepatic venous pressure gradient &#40;HVPG&#41; reduction or other biomarkers&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; abstinence is the cornerstone of managing both ALD and MetALD&#46; It is essential for halting disease progression and achieving recompensation&#46; A multidisciplinary&#44; patient-centered approach<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> is crucial for addressing ALD and its comorbidities&#44; emphasizing prevention and early detection &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; National initiatives&#44; such as AEEH National Plan for Liver Health&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a> aim to comprehensively tackle liver disease from prevention and early detection to treatment&#46; By fostering collaboration between scientific societies and patient associations&#44; we can enhance awareness and prevention efforts&#44; ultimately improving liver health outcomes&#46;</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&#47;picture design using LiverAI and Gemini Advanced&#46;</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&#46;</p></span></span>"
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