The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

GREM1 is required to maintain cellular heterogeneity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1-4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3-5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7 as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1 inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1 overexpression caused an almost complete 'epithelialization' of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1 was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial-mesenchymal transition transcription factors Snai1 (also known as Snail) and Snai2 (also known as Slug) in the epithelial cell compartment, therefore restricting epithelial-mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.

Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak.

The heart develops from 2 sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay combined with genetic lineage tracing and live imaging, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Moreover, a subset of atrial progenitors are gradually incorporated in posterior locations of the FHF. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract cells originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single-cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are prepatterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function, and disease.

Destination Matters More: Relapse following Hospital-Based Treatment of Substance Use Disorders With and Without Co-Occurring Disorders.

OBJECTIVES: Addressing substance use in psychiatric care encounters significant barriers, but the emergence of specialized services offers an opportunity to advance and scale up the integration of addiction services within psychiatric settings. However, research gaps still exist in this field, particularly in understanding the substance relapse rates of people with co-occurring disorders after a psychiatric hospitalization. This study aimed to investigate and compare the relapse rates of patients under inpatient care with exclusively addiction-related issues and those with co-occurring disorders after a hospitalization in a psychiatric ward and gain insights into differences in outcomes for these two patient groups. METHODS: This retrospective analysis examined electronic medical records of patients admitted to the Acute Psychiatry Ward of the Hospital Clinic of Barcelona with a substance use disorder diagnosis between January 2019 and February 2021. Cox regression was used to identify variables independently associated with the first relapse episode. RESULTS: From a total of 318 admissions (79.2% with psychiatric comorbidity), 76.1% relapsed during the study follow-up, with a median survival time of 54 days. Younger age, female gender, voluntary admission, and outpatient follow-up were independently associated with relapse. The presence of a co-occurring disorder was not associated with relapse. CONCLUSION: This study highlights the need for interventions aimed at improving post-discharge abstinence rates for addiction-related hospitalizations. It also challenges the notion that co-occurring disorders automatically imply a worsened prognosis and emphasizes the importance of addressing addiction and psychiatric comorbidity in a comprehensive, integrated, and specialized manner.

Recent Advances in the Catalytic Synthesis of the Cyclopentene Core.

Five-membered carbocycles are ubiquitously found in natural products, pharmaceuticals, and other classes of organic compounds. Within this category, cyclopentenes deserve special attention due to their prevalence as targets and as well as key intermediates for synthesizing more complex molecules. Herein, we offer an overview summarizing some significant recent advances in the catalytic assembly of this structural motif. A great variety of synthetic methodologies and strategies are covered, including transition metal-catalyzed or organocatalyzed processes. Both inter- and intramolecular transformations are documented. On this ground, our expertise in the application of C-H functionalization reactions oriented towards the formation of this ring and its subsequent selective functionalization is embedded.

C-H Activation of Unbiased C(sp3 )-H Bonds: Gold(I)-Catalyzed Cycloisomerization of 1-Bromoalkynes.

Selective functionalization of non-activated C(sp3 )-H bonds is a major challenge in chemistry, so functional groups are often used to enhance reactivity. Here, we present a gold(I)-catalyzed C(sp3 )-H activation of 1-bromoalkynes without any sort of electronic, or conformational bias. The reaction proceeds regiospecifically and stereospecifically to the corresponding bromocyclopentene derivatives. The latter can be readily modified, comprising an excellent library of diverse 3D scaffolds for medicinal chemistry. In addition, a mechanistic study has shown that the reaction proceeds via a so far unknown mechanism: a concerted [1,5]-H shift / C-C bond formation involving a gold-stabilized vinylcation-like transition state.

Primary care provider expectations of addiction services and patients in Spain.

BACKGROUND: Primary care (PC) is crucial in the care of substance use disorder (SUD) patients. However, the relationship between PC and addiction settings is complex and collaboration issues stand out. Available evidence suggests that integration of SUD and PC services can improve physical and mental health of SUD patients and reduce health expenses. OBJECTIVE: To explore the experiences, views and attitudes of PC professionals towards the interaction between PC and SUD services. METHODS: Twenty-seven GPs took part in three focus groups. The focus group sessions were audio-taped, transcribed verbatim and analysed using reflexive thematic analysis. Recurrent themes were identified. RESULTS: Four main themes were devised: (1) Differences and specificities of SUD patients, (2) Interaction between providers of PC and addiction services, (3) Patient management (4) Addiction stigma. These main themes reflect the consideration that SUD patients are a specific group with specific care needs that yield specific challenges to GPs themselves. Improved training, availability of a shared medical record system, increased feedback between GP and addiction specialists and the efficiency of the circuit are to be considered the main priority for the majority of the participants. CONCLUSIONS: An efficient and effective referral circuit, with increased feedback and shared medical records is considered key to GPs. Its implementation should keep in mind the specific features of both SUD patients and GPs.

Abstinence Among Alcohol Use Disorder Patients During the COVID-19 Pandemic: Insights From Spain.

BACKGROUND: Patients with alcohol use disorder (AUD) are likely to suffer disproportionate harms related to the COVID-19 pandemic and related policy measures. While many surveys have been conducted, most are focused on drinking changes in the general population and validation with biological markers is lacking. METHOD: We performed a retrospective cohort study among patients with AUD attending a urine drug screening program. With mixed-effects logistic regression models, we assessed the probability of screening positive for ethyl glucuronide according to patients' main clinical characteristics and time of analysis (either prior to or after a lockdown was implemented in Spain). RESULTS: A total of 362 patients provided 2,040 urine samples (1,295 prior to lockdown, 745 during lockdown). The mean age of participants was 52.0 years (SD 12.6), and 69.2% were men. Of the 43% of patients tested for other drugs 22% screened positive. After adjusting for all covariates, the odds of screening positive for ethyl glucuronide during lockdown almost doubled (OR = 1.99, 95% CI 1.20 to 3.33, p = 0.008). Other significant covariates included testing positive for other drugs (OR = 10.79, 95% CI 4.60 to 26.97) and length of treatment (OR = 0.59, 95% CI 0.47 to 0.74). CONCLUSIONS: Our data support an association between the lockdown due to COVID-19 and increased alcohol use in patients with AUD. Thus, addiction healthcare systems could face significant challenges ahead. In light of these findings, it is essential to evaluate prospectively how patients with AUD are affected by the pandemic and how health systems respond to their needs.

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes.

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the most attractive methods undergoing wide-ranging development. In this review article, we discuss the most significant contributions made in this area during the last decade (2012-2021). The reactions reviewed in this work include chloro-, bromo-, iodo-, fluoro- and cyano-trifluoromethylation of alkenes and alkynes.

Gold-Catalyzed [3+2] Carbocycloaddition Reaction of Pinacol Alkenylboronates: Stereospecific Synthesis of Boryl-Functionalized Cyclopentene Derivatives.

Gold-catalysis has enabled new synthetic opportunities in the chemistry of vinyldiazo compounds. Herein, we report the gold-catalyzed reaction of stabilized vinyldiazo compounds with pinacol alkenylboronates to provide boryl-functionalized cyclopentene derivatives through a formal [3+2] carbocycloaddition reaction, a very unusual pathway in alkenylboronate chemistry. This reaction proceeds with high regio- and stereoselectivity. The synthetic usefulness of the resulting borylated cyclopentene derivatives toward the synthesis of densely functionalized cyclopentanoids is also demonstrated.

Role of Alcohol and Drug Detection by Regular Urine Sample Testing in pre-transplant evaluation for Alcohol Liver Disease. / Papel de la detección regular de sustancias en orina en pacientes en valoración pre-transplante hepático por hepatopatía alcohólica.

Alcohol Liver Disease (ALD) is one of the most prevalent conditions leading to liver transplantation for end-stage liver disease. There is lacking evidence of regular urine screening testing (RUST) impact on survival or liver transplantation of ALD patients. The aims of this study were to compare the sensitivity of RUST, to assess its impact on survival and liver transplantation, and to evaluate factors associated with adherence to RUST. We performed a single-centered retrospective study (N = 84) with ALD candidates for liver transplantation. Demographic, biochemical and clinical variables were recorded at baseline. Adherence to RUST was evaluated during follow-up. The sensitivity of both RUST and self-reports were calculated for all drugs. Multivariable logistic and survival regression analyses were performed to explore associated factors and the impact of adherence to RUST, and positive results on survival. RUST had high sensitivity for identifying active drinkers (76.9%), smokers (78.9%) and cannabis users (83.3%). High adherence to RUST was inversely associated with mortality during follow-up. Presence of personality disorders negatively impacted (OR 0.29, CI 95% 0.08-0.97) adherence to RUST. Both RUST and self-reports should be carried out in this setting. Professionals involved in liver transplantation programs must promote adherence to RUST, primarily in patients with personality disorders.

La enfermedad hepática alcohólica (EHA) es una de las causas más frecuentes de trasplante hepático en enfermedad hepática terminal. No hay evidencia de impacto de la detección regular de sustancias en orina (DRSO) sobre la supervivencia de los pacientes con EHA. Los objetivos de este estudio fueron comparar la sensibilidad de la DRSO, evaluar su impacto en la supervivencia y en el trasplante de hígado, y evaluar el impacto de la adherencia a la DRSO. Realizamos un estudio retrospectivo (N = 84) con candidatos para trasplante de hígado por EHA. Registramos las variables demográficas, bioquímicas y clínicas al inicio del estudio. Evaluamos la adherencia a la DRSO durante el seguimiento. Calculamos la sensibilidad tanto de la DRSO como de las declaraciones de los pacientes para todas las sustancias. Realizamos análisis multivariables (regresión logística) y de supervivencia para explorar los factores asociados y el impacto de la adherencia a la DRSO, y de los resultados positivos en la DRSO sobre la supervivencia. La DRSO tuvo una alta sensibilidad para identificar bebedores activos (76,9%), fumadores (78,9%) y consumidores de cannabis (83,3%). Alta adherencia a la DRSO tuvo una asociación inversa con mortalidad durante el seguimiento. La presencia de trastornos de la personalidad tuvo un impacto negativo (RM ,29, IC 95% ,08-,97) sobre la adherencia a la DRSO. Tanto la DRSO como las declaraciones deben llevarse a cabo en este perfil de pacientes. Los profesionales que participan en programas de trasplante hepático deben promover el cumplimiento de la DRSO, principalmente en pacientes con trastornos de la personalidad.

Pauson-Khand reaction of fluorinated compounds.

The Pauson-Khand reaction (PKR) is one of the key methods for the construction of cyclopentenone derivatives, which can in turn undergo diverse chemical transformations to yield more complex biologically active molecules. Despite the increasing availability of fluorinated building blocks and methodologies to incorporate fluorine in compounds with biological interest, there have been few significant advances focused on the fluoro-Pauson-Khand reaction, both in the inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular and intramolecular fluoro-Pauson-Khand reaction, with special attention to the PKR of enynes containing a fluoride moiety.

Copper-Catalyzed Regioselective Synthesis of (E)-ß-Fluorovinyl Sulfones.

Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed (E)-ß-fluorovinyl sulfones via a simple copper-catalyzed addition of hydrogen fluoride to alkynyl sulfone starting materials in varying yields and E/Z selectivities. The hydrogenation of these products was also explored and compared with the hydrogenation of the related Z isomers. These new products may find interesting applications, given the versatility of vinyl sulfones in chemical synthesis and the unique properties of vinyl fluorides in biological settings.

"Diazepam loading": ¿Can a strategy for preventing alcohol withdrawal be used to treat benzodiazepine use disorder? / "Carga de diazepam": ¿puede una estrategia para prevenir abstinencia al alcohol usarse con éxito para tratar la dependencia a benzodiacepinas?

Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are widely used to treat insomnia and anxiety, despite having long-term adverse side effects. (Fortea González, Oriolo, Balcells Oliveró, Sánchez Del Valle & Castellvi, 2017). As with alcohol, continued use can lead to tolerance and dependence phenomena. Discontinuation in such cases can produce abstinence symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y Murnion, 2015).

Las benzodiacepinas se usan para tratar la abstinencia alcohólica siguiendo varias estrategias: dosis descendiente, dosis de carga, tratamiento en función de sintomatología. La carga de diazepam ha demostrado ser un tratamiento válido para la abstinencia alcohólica en ensayos controlados aleatorizados. Tras una búsqueda bibliográfica no sistemática, no hemos encontrado antecedentes en la literatura de una estrategia de carga de diazepam sin posterior administración de benzodiacepinas para el tratamiento de la abstinencia a éstas. Describimos el caso de una desintoxicación de benzodiacepinas utilizando una situación preestablecida de carga de diazepam. La paciente tenía una larga historia de dependencia a benzodiazepinas que se había tratado previamente con escaso éxito con dosis descendiente de clonazepam. El día anterior al ingreso hospitalario, realizó sobreingesta de unos 200 mg de diazepam con finalidad suicida. Se decidió utilizar una estrategia de carga de diazepam para tratar el síndrome abstinencial. Así, no se administraron posteriores dosis de benzodiacepinas, considerando la sobreingesta de 200 mg de diazepam como dosis de carga única. En esta experiencia, la carga de diazepam resultó ser una estrategia válida y rápida para tratar una dependencia a las benzodiacepinas resistente. Los trastornos por uso de benzodiacepinas son un relevante problema de salud pública, en contraste con los escasos avances obtenidos en su tratamiento. Tal vez valdría la pena empezar por revisar y actualizar antiguas estrategias.

Remediation therapy in patients with alcohol use disorders and neurocognitive disorders: A Pilot Study. / Terapia de rehabilitación cognitiva en pacientes con trastorno por consumo de alcohol y trastorno neurocognitivo. Estudio piloto.

Many alcohol-dependent patients suffer from cognitive impairment of variable severity, manifested by alterations in retrograde and anterograde memory, visuospatial processing, cognitive abilities and attention, some of which are reversible. In this context, cognitive remediation therapies could significantly improve patients' performance; therefore, these are considered a valuable alternative. The aim of this study was to implement cognitive remediation therapy in patients with alcohol dependence and cognitive impairment and evaluate its viability and effectiveness. The participants were sixteen abstinent, alcohol-dependent patients (mean age of 59 years, 63% males) from the Addictive Behaviours Unit of a tertiary hospital. Over 6 months, a nurse led 1-hour weekly sessions (24 sessions in total) during which exercises for improving functional, social and cognitive performance were completed. Patients were assessed at baseline, at the end of the study and 6 months later, using the Mini-Mental State Examination (MMSE) and the Memory Alteration Test (M@T). Their respective scores were 26.4 (SD 3.16), 29 (SD 1.67) and 27 (SD 3.1) for the MMSE and 38.7 (SD 6.81), 45.7 (SD 5.6) and 41.1 (SD 7.86) for the M@T. Changes were assessed with both Friedman and Wilcoxon signed-rank tests, with mostly statistically significant differences (p < 0.05). Assistance and satisfaction were high. Therefore, the therapy was viable, widely accepted and effective.

El deterioro cognitivo es común en los pacientes alcohólicos. Éste se manifiesta por alteraciones en la memoria anterógrada y retrógrada, el procesamiento visual-espacial, y en las habilidades cognitivas y la atención, siendo algunas reversibles. Las terapias de rehabilitación cognitiva podrían mejorar el rendimiento de los pacientes, siendo una alternativa terapéutica de interés. El objetivo de este estudio piloto fue evaluar la implementación, viabilidad y efectividad de la terapia de rehabilitación cognitiva en pacientes con dependencia al alcohol y deterioro cognitivo asociado. Se trata de un estudio piloto con 16 pacientes (63% hombres, edad media de 59 años) seguidos en la Unidad de Conductas Adictivas de un hospital de tercer nivel. Siendo la abstinencia un requisito para la inclusión, durante 6 meses una enfermera realizó sesiones semanales de una hora (24 sesiones), realizándose ejercicios de psico-estimulación para la mejora del rendimiento cognitivo, funcional y social. Se evaluó a los pacientes al inicio, al final y pasados 6 meses, mediante las escalas MMSE (test Mini-mental de Lobo) y T@M (test de Alteración de Memoria). Sus puntuaciones medias respectivas fueron 26.4 (DE 3,16), 29 (DE 1,67) y 27 (DE 3,1) para MMSE y 38,7 (DE 6,81), 45,7 (DE 5,6) y 41,1 (DE 7,86) para T@M. Los datos se analizaron mediante la prueba de Friedman y se comparon los distintos periodos temporales mediante la prueba de rangos con signo de Wilcoxon, siendo la mayoría de comparaciones significativas (p < 0,05). La asistencia y la satisfacción fueron elevadas. Así pues, la terapia fue viable, ampliamente aceptada y mostró ser efectiva.

One Year Clinical Correlates of EtG Positive Urine Screening in Alcohol-Dependent Patients: A Survival Analysis.

AIMS: Little evidence exists supporting the efficacy of regular alcohol urine screening (RAUS) in the management of alcohol dependence, despite recent improvements in urine biomarkers. In this study, we aimed at investigating 1 year, differential clinical correlates between a positive and a negative baseline urine ethyl glucuronide (EtG) screening. METHODS: Alcohol-dependent outpatients participating in a previous cross-sectional study where EtG and ethanol diagnostic performances were compared in a double blind design were included. After 1 year, the presence of relapse, the number of hospitalizations and whether patients had abandoned treatment or not were assessed from electronic medical records. A survival analysis was conducted to compare time to relapse between EtG negative and positive subjects. Regression models were performed to compare the mean number of days hospitalized between groups, the risk of being lost to follow-up and treatment expenses. RESULTS: Of note, 152 patients (mean age 52, 67% males) were included. The mean time to relapse was of 163 days in EtG positive subjects, compared to 329 days in those with a negative result. In the Cox-regression model, only EtG positivity yielded significant results, with a hazard ratio of 5:3 (95% CI: 3.1-9.1). EtG positive was also the only significant predictor of a greater number of hospitalization days and treatment expenses. Younger age was the only variable predicting a greater risk of treatment abandonment. CONCLUSION: RAUS with sensible biomarkers could improve clinicians' ability to assess patients' relapse risk. Further prospective studies will have to determine if this can be translated into a better prevention capacity. SHORT SUMMARY: Positive urine screenings, when conducted with highly sensible alcohol biomarkers, significantly indicate a greater risk of relapse in alcohol-dependent patients and have the capacity to predict a greater risk of hospitalization and greater treatment expenses.

Self-management and Shared Decision-Making in Alcohol Dependence via a Mobile App: a Pilot Study.

PURPOSE: Mobile applications (apps) have created new opportunities in the field of alcohol dependence (AD) within new paradigms of shared decision-making and self-management. The aim of this study is to report the results of a pilot study testing the usability of and satisfaction with a mobile app (called SIDEAL) in AD patients. METHODS: Adult AD outpatients were included. SIDEAL was installed on patients' personal phones. The Timeline Followback (TLFB) method for the preceding 6 weeks was administered both at baseline and after 6 weeks (end of the study). Self-reports from the app were also assessed at the end of the study and compared to data provided by the TLFB. An online questionnaire about usability and satisfaction was administered to participants after completion of the study. Exploratory efficacy analyses were conducted. RESULTS: Twenty-four patients were included (mean age 48 years (SD 11.3), women 50%). Most patients (22/24) selected a goal to reduce their consumption. Patients used the self-register module of the app for an average of 80% of the study days. The consumption and medication self-register modules were the most valued, as along with the weekly feedback provided by the app about participants' weekly rate of usage. Participants' satisfaction with the app was high. Significant reductions were observed in alcohol consumption (binge drinking days in the last 6 weeks declined from 25 (SD 18.6) to 5.8 (SD 8), p < 0.001; mean daily alcohol consumption in standard units declined from 6.5 (SD 4.3) to 1.9 (SD 1.8), p < 0.001). On most days (88%), patients achieved their self-imposed objectives. CONCLUSION: SIDEAL is a well-accepted and highly used app by AD patients that could improve their efficacy in managing their AD. Further larger, randomized studies are warranted.

Autoimmune-Mediated Psychosis: A Case of Susac Syndrome in a Drug User.

OBJECTIVE: Susac syndrome, a rare disorder, is thought to be mediated by autoantibodies. One of the potential targets of these autoantibodies could be an antigen in the microvessels of the brain, the retina, and the inner ear leading to central nervous system (CNS) alterations, visual disturbances, and hearing deficits. Our aim is to expand clinicians' diagnostic options when facing psychosis due to medical conditions. METHODS: A case report was conducted for this study. RESULTS: This paper reports the case of a young male drug user who presented with psychosis, confusion and CNS vasculitis. First deemed to be drug-induced CNS vasculitis, it was finally diagnosed as Susac syndrome. CONCLUSIONS: Although an infrequent entity, Susac syndrome should remain an option in the differential diagnosis of several neurological and psychiatric presentations.

Treatment of alcohol use disorders in patients with alcoholic liver disease.

Alcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatment for ALD is achieving total alcohol abstinence and preventing relapse; medical and surgical treatments for ALD are limited when drinking continues. This narrative review summarizes current treatments for AUDs with a particular emphasis to the treatment of AUDs in patients with ALD. Medical management, psychosocial and pharmacological interventions are analyzed, underlying limits and options in AUD patients. Finally, this review discusses the most appropriate setting for the management of AUD patients with advanced liver disease as well as the indications for liver transplantation in AUD patients.