Alcohol withdrawal syndrome (AWS) develops in patients with alcohol use disorder (AUD) and physical dependence after abrupt cessation or substantial reduction of sustained heavy alcohol use. It is common and potentially life-threatening in general medical practice. Characteristic features include tremor, autonomic activation, anxiety, insomnia, perceptual disturbances, seizures, and delirium tremens. This practical review aims to guide internists in early recognition, risk stratification, monitoring, pharmacological treatment, and transition to longitudinal AUD care. Most hospitalized patients can be managed effectively when physicians identify early high-risk features, select an appropriate level of monitoring, and use approved first-line therapy. Supportive care, including thiamine, hydration, electrolyte correction, and reassessment for differential diagnoses, is essential. Benzodiazepines remain the standard of care for moderate to severe withdrawal, but decisions should reflect withdrawal history, current severity, comorbidity, and symptom-scale limitations in medically complex patients. Benzodiazepine-based protocols include symptom-triggered therapy, fixed-dose therapy, and front loading; choosing among them should depend on the patient's risk profile, ability to participate in symptom scoring, and monitoring environment. Phenobarbital is increasingly used within standardized, closely monitored hospital protocols with appropriate expertise, whereas clomethiazole and sodium oxybate remain region-specific alternatives in some European countries. This review also emphasizes delirium tremens and refractory withdrawal, including when higher-acuity care and adjunctive sedatives should be considered. Hospitalization should be used to initiate treatment for AUD and reduce recurrent withdrawal, readmission, and mortality.

BACKGROUND:The pharmacological management of alcohol use disorder (AUD) currently includes six medications approved by different regulatory agencies worldwide: acamprosate (ACM), naltrexone (NTX), nalmefene (NMF), disulfiram (DF), baclofen, and sodium oxybate (SO). Their optimal use should be aligned with the main aims of treatment, namely reduction of alcohol consumption and maintenance of complete abstinence. OBJECTIVES:This brief review summarizes the role of these six approved medications in AUD treatment and proposes practical treatment algorithms according to treatment goals, mechanisms of action, and clinically relevant outcomes. METHODS:A focused narrative review of the literature was conducted, prioritizing meta-analyses, systematic reviews, randomized controlled trials, and relevant regulatory documents. Evidence on efficacy, safety, tolerability, and clinical applicability was interpreted pragmatically to support first-, second-, and third-line pharmacological strategies. RESULTS:For reducing alcohol intake, NMF or NTX are proposed as first-line pharmacotherapies, with baclofen considered as a second-line option when these agents are partially effective or ineffective. For maintaining abstinence, ACM is proposed as a first-line strategy. In selected clinical settings, including severe AUD, protracted alcohol withdrawal syndrome, high motivation for aversive treatment, or liver disease, SO, baclofen, DF, or NTX may serve as second-line options. Combined pharmacotherapy may be considered in highly adherent patients, whereas off-label drugs remain third-line options for refractory cases. CONCLUSIONS:Improved knowledge of the efficacy, safety, and tolerability of the six approved medications may support more appropriate, individualized, and goal-oriented pharmacological management of patients with AUD. The proposed algorithms are intended as pragmatic tools to aid clinical decision-making rather than as formal guidelines.

Alcohol-related liver disease (ALD) is one of the most prevalent causes of liver disease. It is the leading cause of cirrhosis, accounting for almost 60%. Moreover, it is the leading cause of liver transplant. Hepatologists are underpreparated to diagnose and treat alcohol use disorder (AUD) despite its high prevalence. The aim of this narrative review is to suggest a cultural and organizational change of a hepatology unit. This narrative review is based on a detailed analysis of the scientific literature published before January 31st, 2025 and examining the most recent papers on alcohol-related liver disease and hepatology unit organization (PubMed, Web of Science, Scopus, Google Scholar). Hepatology Unit must acquire alcohol and social skills autonomously. In association with liver injury treatment, it is necessary to set up addiction therapy in relation to liver damage severity and manage social vulnerability. The latter significantly influences the therapeutic path (mainly in case of inclusion on the list for a liver transplant). Therefore, in addition to cultural change (AUD skills), it is mandatory that the new organization provides the introduction of an authentic multi-professional activity, the formal caregiver and the self-help groups facilitator. The ability to identify hazardous/harmful alcohol consumption or alcohol use disorder is necessary. This is essential to clinically define steatotic liver disease. If this does not happen, the clinical outcome is compromised. Identification of a low-risk alcohol consumption in case of metabolic associated steatotic liver disease is necessary. In fact, it is known that ethanol in case of metabolic syndrome induces fibrogenesis at low dosage. Competence to manage harmful alcohol consumption and AUD is necessary (pharmacotherapy: intoxication, craving, withdrawal syndrome and psychotherapy). It is necessary to manage family and social problems that may prohibit inclusion in the liver transplantation list. Training and support of informal caregivers is necessary (introduction of the formal caregiver). Collaboration with self-help groups associations is necessary (introduction of the self-help groups facilitator). Collaboration with associations or charities for the management of fragile patients affected by AUD (homeless, migrants, prisoners, etc.).

Metabolic-dysfunction associated steatotic liver disease (MASLD) includes diagnostic criteria such as overweight/ obesity, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). MASLD is a subtype of steatotic liver disease (SLD). MASLD is characterized by SLD plus one or more cardiovascular disease (CVD) risks. Metabolic and alcohol-related liver disease (MetALD) is characterized by an alcohol consumption between 20-40 g/day for females and 30-50 gr/day for males and alcohol related liver disease (ALD) is characterized by an alcohol consumption >40 g/day for females and >50 g/day for males. Synergism or a supra-additive interaction between alcohol consumption (AC) and metabolic factors is well known. The aim of this narrative review is to explore the following points: 1) it is mandatory early identification of AC and it is necessary to also identify low dosage of AC; 2) all SLD subtypes increase cardiovascular and oncologic risk; 3) fibrosis is the most important predictor of long term survival. For this reason early liver fibrosis (LF) detection is crucial to reduce hepatic and extra hepatic pathology and motivate the patient to change lifestyle. This narrative review is based on a detailed analysis of the scientific literature published before December 31, 2024 and examining the most recent guidelines on SLD (PubMed, Web of Science, Scopus, Google Scholar). From the data reported in the present narrative review, the following emerges: 1) due to the significant synergistic effect between SLD and alcohol, the cut-off to distinguish MASLD and MetALD should be reduced to 10 g/day for women and 20 g/day for men; 2) it is useful to identify even low doses of consumption. The most appropriate suggestion is total alcohol abstinence (especially in cases with high oncological risk) and even light AC increases the risk of morbidity and mortality expecially in young people; 3) it is necessary to identify LF early and improve lifestyle; 4) cardiometabolic risk factors are present in >90% of subjects with all subtypes of SLD (mainly ALD) and therefore, cardiologists and hepatologists must cooperate; 5) all subjects who come to our attention for the first time (altered liver function, MS, T2DM, CVDs) must undergo ultrasonography with elastography. Subsequent oncologic surveillance beyond rigid schemes must be decided on a case-by-case basis. In cirrhotic patients and in non-cirrhotic patients at high clinical risk, in our opinion surveillance is semi-annual (especially in the presence of T2DM and/or AC). In light of epidemiological data, in medium-low risk cases, for prudence, surveillance can be annual. It is appropriate to raise awareness among health-care professionals and the broader public that SLD is a major risk factor for liver and non-liver disease. It is necessary to combat SLD with prevention and early detection. Early detection of steatosis and fibrosis is a motivating factor for lifestyle correction. The latter represents both primary prevention and therapy in the case of early pathology. This leads to a reduction in cases of decompensated liver disease, cardiovascular and oncologic pathologies with better management of economic resources.

Ann Ist Super Sanità 2024 | Vol. 60, No. 4: 252-257 DOI: 10.4415/ANN_24_04_03 In the originally published version of this manuscript, an error occurred in the reporting of the dosage of disulfiram (DF) (Methods section, page 253). The correct sentence should read:"All patients failed to achieve abstinence either with SO (101 patients) or DF (25 patients) alone, so they were treated with oral doses of SO (50-100 mg/kg of body weight, tid), and DF (200 mg daily) in combination for 12 weeks"instead of:"All patients failed to achieve abstinence either with SO (101 patients) or DF (25 patients) alone, so they were treated with oral doses of SO (50-100 mg/kg of body weight, tid), and DF (250 mg daily) in combination for 12 weeks."We apologize for this error and any confusion it may have caused.

BACKGROUND:Disulfiram, acamprosate (ACM), naltrexone, and nalmefene are medications currently approved for the treatment of Alcohol Use Disorder (AUD). Baclofen and sodium oxybate (SO) have been approved for the treatment of AUD and alcohol withdrawal syndrome in France and Italy, respectively. However, concerning the effectiveness of combined therapies for AUD, data from the current literature are contrasting. AIMS:To investigate the outcomes of combined therapy of SO and ACM for the maintenance of alcohol abstinence. METHODS:A sample of 48 AUD patients consecutively enrolled and treated with SO (50-100 mg/kg of body weight, t.i.d.) plus ACM (666 mg three times daily; with dosage reduced in patients with body weight <60 kg) was observed for 12 weeks. RESULTS:At the 3-month visit, continuous abstinence from alcohol was maintained by 34 patients (70.8%). Fifteen patients (31.3%) reported side effects like nausea, dizziness, and abdominal pain, with no significant differences between abstinent and not abstinent patients. CONCLUSION:SO plus ACM may be an effective and safe pharmacological combination for maintaining alcohol abstinence in AUD patients. Future ad hoc clinical trials are needed to test this therapeutic association for AUD treatment.

Background: Colds are widespread infectious diseases that affect daily life, increasing healthcare costs and limiting productivity. Objectives: The aim of this study was to investigate the effects of a dietary supplement containing specific probiotic strains (L. plantarum PBS067, L. acidophilus PBS066, B. lactis BL050) on cold symptom relief, immune response enhancement, and quality of life. Methods This randomized, double-blind, placebo-controlled trial included 65 healthy volunteers (age range: 18-44 years), divided into two groups: 40 received the probiotic treatment (with vitamins and bulking agents), and 25 received placebo (vitamins and bulking agents only) for 12 weeks. Cold symptoms and systemic inflammation were assessed at three time points (baseline T0, post-treatment T1, and 6 weeks after treatment T2). Results: Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7% for Placebo, p < 0.05). At T1, fever and muscle pain occurred in 20% of participants in the Probiotic group vs. 28% and 44% in the Placebo group, respectively (p < 0.05 for muscle pain vs. Placebo). For muscle pain, a trend was maintained also at T2 (17.5% vs. 20%). The pro-inflammatory cytokine IFN-γ levels significantly decreased in the Probiotic group vs. T0 (p < 0.0001 at T1 and p < 0.01 at T2), while they increased in the Placebo group (22.279 ± 3.538 vs. 19.432 ± 3.143 pg/mL, p = NS). Although not statistically significant, at T1 the Probiotic group had higher levels of IL-10 vs. T0 (266.98 ± 78.432 vs. 240.967 ± 70.238, pg/mL p = NS). Conclusions: The probiotic mix effectively alleviated cold symptoms and reduced pro-inflammatory cytokine levels, suggesting anti-inflammatory effects.

The need for objective diagnostic tools in people with alcohol intake abuse is one of the major needs in daily clinical practice. Determination of blood alcohol concentration is commonly used in cases of suspected acute alcohol intoxication, especially in the emergency room. A dose-dependent correlation between alcohol consumption and mean corpuscular volume (MCV) is a known index of excessive alcohol intake. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently elevated (2-4 times above normal) in patients with alcohol use disorder and an AST/ALT ratio >2 is indicative of alcohol-related liver disease. Several studies highlighted a positive correlation between alcohol consumption and serum gamma-glutamyl transferase (γGT) levels, with increased values in about 75% of patients drinking >60 g/day of ethanol for at least 5 weeks. Also, 60-80 g of alcohol per day for a minimum of 2 weeks can result in increased carbohydrate-deficient transferrin (CDT) levels (normally less than 2% of total transferrin). Complete abstinence from alcohol leads to a normalization of CDT values in approximately 2-3 weeks. Ethyl glucuronide (EtG) is detectable in urine from a minimum of 6 hours up to a maximum of 100 hours after alcohol intake. In-vitro studies showed that the levels of phosphatidylethanol (PEth) in human red blood cells were proportional to ethanol concentration and exposure time, suggesting an important role in differentiating abstinence from unhealthy drinking. γGT and CDT are the most useful markers for monitoring chronic alcohol abstinence, whereas blood alcohol concentration and urinary EtG are the most valuable indexes of acute alcohol consumption. In conclusion, no specific laboratory marker alone is reliable to identify patients with alcohol abuse, thus the best diagnostic strategy includes combined index use in addition to other screening tools (i.e., clinical history/context and questionnaires).

Background: Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described. However, the research is moving fast, and new data regarding pathogenic pathways, patients’ classification, potential candidate biomarkers, and dietary interventions are emerging. Methods: This literature review aims to address the state of the art and summarize the latest updates in this field from 2019 to date. Results and Conclusions: Clinical studies regarding NCGWS in the last five years are reported to shed light on this complex condition and to guide specialists towards a more in-depth, prompt, and objective diagnosis.

Introduction. Disulfiram (DF), acamprosate, naltrexone, baclofen and sodium oxybate (SO) are currently the medications approved for the treatment of alcohol use disorder (AUD). In this context, combined pharmacological interventions and sex differences are an interesting area in the treatment of non-responder AUD patients. Aim. To evaluate the efficacy of SO in combination with DF in maintaining alcohol abstinence in patients with AUD who failed to achieve abstinence either with SO or DF alone. Methods and results. 126 detoxified AUD patients, previously treated with only SO or DF, were retrospectively enrolled from 2018 to 2022. At the end of treatment, a higher number of females than males (74.1% vs 66.3%: p=0.03) maintained continuous abstinence from alcohol, and all the females responded completely or partially to the treatment. Conclusions. This study shows that the combination of SO and DF may be considered a further pharmacological opportunity for AUD patients (particularly in females) who do not respond to mono-therapy.

BACKGROUND:Acute pancreatitis can be a severe disease that significantly impacts patients' quality of life and outcome. The clinical course is variable and predictive scoring systems have a debated role in early prognosis. This study aims to compare the prognostic accuracy of Balthazar, BISAP, HAPS and SOFA scores in the prediction of in-hospital mortality in patients with acute pancreatitis.METHODS:This is a retrospective, single-center cohort study conducted in the Emergency Department of a third-level university hospital. Patients aged >18 years admitted from 1st January 2018 to 31st December 2021 for the first episode of acute pancreatitis were included.RESULTS:A total of 385 patients (mean age of 65.4 years and 1.8% in-hospital mortality) were studied. Balthazar, BISAP and SOFA scores were significantly higher in patients with in-hospital mortality and AUROCs were equal to 0.95 (95% CI 0.91-0.99, P<0.001), 0.96 (95% CI 0.89-1, P=0.001), 0.91 (95% CI 0.81-1, P=0.001) with no differences among them and absence of in-hospital mortality in patients with HAPS=0.CONCLUSIONS:Our data support the concept that clinical prediction scores can be useful for risk stratification in the Emergency Department. However, no single score has shown superiority in predicting acute pancreatitis-related in-hospital mortality among tested tools.

Since the rise of awareness of gluten/wheat-related disorders in the academic and clinical field in the last few decades, misinformation regarding the gluten-free diet (GFD) and its impact on health has been spreading among the general population. Despite the established link between gluten and celiac disease (CD), where a GFD is mandatory to reach clinical and histological remission, things are more complicated when it comes to non-celiac gluten/wheat sensitivity (NCGWS) and other autoimmune/dysimmune disorders. In the last conditions, a beneficial effect of gluten withdrawal has not been properly assessed, but still is often suggested without strong supporting evidence. In this context, women have always been exposed, more than men, to higher social pressure related to nutritional behaviors and greater engagement in controlling body weight. With this narrative review, we aim to summarize current evidence on the adherence to a GFD, with particular attention to the impact on women’s health.

Alcoholic liver disease (ALD) is currently, worldwide, the second most common cause of human fatalities every year. Alcohol use disorders (AUDs) lead to 80% of hepatotoxic deaths, and about 40% of cases of cirrhosis are alcohol-related. An acceptable daily intake (ADI) of ethanol is hard to establish and studies somewhat controversially recommend a variety of dosages of ADI, whilst others regard any intake as dangerous. Steatohepatitis should be viewed as "the rate limiting step": generally, it can be overcome by abstinence, although in some patients, abstinence has little effect, with the risk of fibrosis, leading in some cases to hepatocellular carcinoma (HCC). Chronic alcoholism can also cause hypercortisolism, specifically pseudo-Cushing Syndrome, whose diagnosis is challenging. If fibrosis is spotted early, patients may be enrolled in detoxification programs to achieve abstinence. Treatment drugs include silybin, metadoxine and adenosyl methionine. Nutrition and the proper use of micronutrients are important, albeit often overlooked in ALD treatment. Other drugs, with promising antifibrotic effects, are now being studied. This review deals with the clinical and pathogenetic aspects of alcohol-related liver fibrosis and suggests possible future strategies to prevent cirrhosis.

INTRODUCTION:Worldwide, almost 1.2 million people drive under the influence of alcohol. However, early identification of alcohol use disorder (AUD) in subjects driving under the influence (DUI) of alcohol is seldom achieved. AIM:The aim of our retrospective study is to investigate the presence of AUD in a population of DUI subjects who had their driving license suspended, and if they were following a specific rehabilitation program. METHODS AND RESULTS:750 subjects were retrospectively enrolled from 2018 to 2021. DSM-V to assess AUD was used. Forty-eight (6.4%) subjects presented a diagnosis of AUD, after one month they showed a statistically significant reduction of carbohydrate-deficient transferrin (CDT) (p<0.0001); however, none were following a program for the treatment of AUD. CONCLUSIONS:This outpatient setting may be considered a place of primary and secondary prevention where DUI subjects with a diagnosis of AUD may be entrusted to a Centre in order to follow rehabilitation treatment.

Introduction: During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the “gold standard” for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. Rationale: We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30–45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, “as needed” short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5–25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than “as needed” therapy throughout the 24 hours. Patient concerns: Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. Diagnosis: Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. Interventions: In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. Outcomes: SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). Conclusion: Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

AIMS:Alcohol use disorder (AUD) is a common mental disorder characterized by sex-gender differences (SGDs). The present study was aimed at evaluating attitudes displayed by Italian AUD treatment services towards investigating the presence of SGDs in their patients and implementing gender-specific treatments for female AUD patients. METHODS:Potential SGDs were initially investigated in a sample of AUD outpatients, subsequently followed by a national survey on the adoption of specific interventions for female AUD outpatients. RESULTS:The presence of SGDs was confirmed in a sample of 525 (332 men; 193 women) AUD outpatients, including a higher prevalence of anxiety and mood disorders, and episodes of violence and trauma among female AUD outpatients compared to males. Despite the presence of these SGDs, only <20% of a total of 217 Italian AUD treatment services reported the implementation of specific strategies for female AUD outpatients. The majority of services (94%) reported investigating episodes of violence and/or trauma, largely resorting to specific procedures only when these issues were detected. CONCLUSIONS:Our findings confirm the presence of SGDs among AUD outpatients, including a higher prevalence of anxiety and mood disorders and episodes of violence and trauma among females compared with males. However, only a small number of services have adopted a gender medicine approach in AUD treatment. These results underline the urgency of investigating the specific needs of female, male, and non-binary AUD patients in order to personalize and enhance the effectiveness and appeal of AUD treatment.

Alcohol habit represents a major public health problem, being a chief cause of both morbidity and mortality. Binge drinking, a particularly dangerous alcohol intake pattern, has been growing in the last years, especially in younger people. Alcohol use disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V) as the spectrum of a maladaptive pattern of alcohol intake with a noteworthy clinical impact. It is important to underline that no amount of alcohol is risk-free. The present review analyzes and discusses the evolution of alcohol habit, the complex clinical burden and the future perspectives with an interdisciplinary approach.