Alcohol-related diseases: from metabolism to the main effect on the body.

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

Alcohol use disorders and liver fibrosis: an update.

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.

Liver involvement in presence of heart disease and heart involvement in presence of liver disease: a conundrum.

Data from literature show a cross-talk between the heart and liver during diseases which primarily involve one of the two organs, but data regarding this relationship are scant. Aim of this study was to investigate this relationship. In this narrative review we critically explored the most recent literature on this topic using PubMed and Medline and examining the most recent studies about liver involvement in heart failure and heart involvement in course of liver disease. Patients with acute and chronic heart failure and those who undergo heart transplatation (HT) manifest various signs of liver damage with a rate of incidence which is higher in candidates for left ventricular assist device. In presence of cardiogenic shock a very marked hepatocellular necrosis may occur while in the setting of chronic heart failure congestive hepatopathy and-or the so-called cardiac cirrhosis are observed. On the other side in presence of chronic liver disease and in case of liver transplantation (LT) heart functions may be altered and cirrhotic cardiomyopathy, which is a syndrome characterized by systolic, diastolic and electrophysiological abnormalities may occur. In this review we have analyzed the relationship between heart and liver disease, even in case of LT and HT. Furthermore we have underscored the effects of chronic alcoholism and of systemic disorders such as hemochromatosis and amyloidosis on both heart and liver.

Alcohol and cancer: a denied association the statement of the Italian society on alcohol (Società Italiana di Alcologia-SIA).

Alcohol consumption (AC) is carcinogenic to humans. The Italian Society on Alcohol (Società Italiana di Alcologia) defines excessive AC as anything greater than zero. It is not appropriate to associate AC with cardiovascular disease prevention. This is for prudence and to protect public health. It also asks to include information on alcohol labels that AC is associated with cancer.

Corrected and republished from: Metabolic associated liver disease.

Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.

Alcohol use disorders, self-help groups as a supplement to pharmacological and psychological therapy? A retrospective study in a population with alcohol related liver disease.

BACKGROUND: According to the new criteria in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V), the prevalence of alcohol use disorders (AUDs) is 20-30% in men and 10-15% in women worldwide 2,3. The anticraving therapy/ psychotherapy combination is currently used routinely in clinical practice. However, the results after one year are unsatisfactory. Meta-analytic studies found failure rates of 57 to 75%. These percentages vary in relation to the intensity and length of the treatment. In addition, the abstinence rates gradually decrease over time. In this study, the clinical outcome of alcohol related liver disease (ALD) patients who spontaneously attended self-help groups (SHGs) (club of alcoholics in treatment - multi-family community/ alcoholics anonymous) regularly versus those who did not want to start the path or did not complete it was evaluated. METHODS: 1337 alcohol use disorder patients affected by compensated alcohol related liver disease followed prospectively from January 2005 to December 2010, were retrospectively assessed. 231 patients were enrolled: 74 attended self-help groups assiduously, 27 attended sporadically and 130 refused participation in SHGs. RESULTS: Constant attendance at SHGs compared to non-attendance allows for a significant increase (<0.0001) in the period of sobriety found in the median of distribution. Frequent attendance at SHGs is effectively "preventive", reducing the fraction of relapses by about 30%. The percentage of cases of cirrhosis is significantly different (p = 0.0007) between those who have regularly attended SHG meetings (about 1% of patients) and those who have never attended or only occasionally (various percentages between 21 and 31% of patients); in both groups the incidence of new cases would seem to be 0.014 cases/ year. Similar difference in percentages regarding the onset of hepatocellular carcinomas (HCCs), although with a lower level of significance (p = 0.017) among those who attended regularly, 4% of patients with an incidence of 0.006 cases/ year, compared to those who have never attended or only occasionally: over 14% of patients with an incidence of 0.022 cases/ year. CONCLUSIONS: This study suggests the importance of attending SHGs not only for the long-term achievement of alcoholic abstention, but also in positively influencing the course of alcohol-related diseases.

Alcohol consumption, alcohol use disorder and organ transplantation.

BACKGROUND: In the present experience we have evaluated the link alcohol consumption/alcohol use disorder (AUD) and organ transplantation (OT) in order to provide adequate suggestions. METHODS: The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before August 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines / position papers of the scientific societies. RESULTS: With regard to the liver transplantation, there are position papers/ guidelines that clearly define indications and contraindications for including the AUD patient in the transplant list. One of the major difficulties in this area is psychosocial assessment which can be influenced by stigma. To solve this problem it is necessary to use objective tools. However, this assessment should be carried out after providing the patient and family adequate tools to be able to create or recreate reliable socio-family support. This behavior should also be used in the case of other OTs. For the latter, however, adequate guidelines must be created which at the moment do not exist or if there are, as in the case of heart transplantation, they are not sufficient. CONCLUSIONS: 1) Even in the absence of obvious alcohol addiction, use alcohol use disorder identification test. 2) Include the addiction specialist in the multidisciplinary transplant team. 3) Provide family members with the tools necessary to better support the patient. They are patients with alcohol use disorder/ possible presence of psychopathological manifestations and alcohol-related pathology (cirrhosis, cardiomyopathy, liver-kidney disfunction, etc). 4) Cardiovascular and oncologic surveillance post-OT. 5) For the selection of patients to be included in the list for non-LT (heart, lung, kidney, multivisceral, etc) it is mandatory to include the diagnosis and treatment of AUDs in the guidelines. What has already been indicated for LT may be useful. Timing of alcoholic abstention in relation to clinical severity, optimal psychosocial activity, anti-craving therapy in relation to the type of underlying disease and clinical severity. 9) Close collaboration between scientific societies is required to better manage AUD patients who need OT.

Economic Burden of Non-Alcoholic Steatohepatitis (NASH) Among Diabetic Population in Italy: Analysis and Perspectives.

Background: Aim of our study is to evaluate the economic impact of NASH among diabetic population in Italy and potential benefits of treatments that can slow the disease progression. Methods: A Markov model was conducted from the Italian National Healthcare System perspective reporting results at 3, 5, 10 and 15 years. The model included NASH and T2DM patients with all stages of fibrosis (F0-F3), compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplant (LT), post-LT and death. A 1-year model cycle length was considered, with each patient passing through the stages and exiting the model when reached one of mortality states. Transition probabilities and annual cost related to health states were derived from published literature. Moreover, the model made it possible to develop a scenario analysis to simulate the impact of treatments capable of slowing the disease progression in phases F0-F4 (CC). Results: The results highlighted an economic burden of NASH in T2DM patients of approximately € 1.4 billion, € 3.1 billion, and € 9.4 billion, respectively, after 3, 5 and 10 years, reaching about € 17.3 billion after 15 years. The slowing down of the progression in the early stages of the disease (fibrosis F0-CC) has led to significant savings corresponding to € 2.3 billion at 15 years. These savings were generated by the reduction of the patients in the advanced stages of the disease, which is linked to a reduction in deaths, equal to 92,208 deaths avoided over a 15-year time horizon. Conclusion: Patients with NASH and T2DM reported an important burden in Italy. It is important to investigate the potential clinical and economic benefits of antidiabetic drugs that have been shown to be effective in preventing the transition to advanced disease, simultaneously acting on the therapeutic goals of diabetic disease.

Alcohol use disorder identification test renamed GLU GLU test in an area of nord-west of Italy. Preliminary descriptive results.

INTRODUCTION: The first two causes of liver cirrhosis and hepatocellular carcinoma are alcoholic and dysmetabolic. In the early stages alcohol related liver disease (ALD) is silent. For this reason, more efforts should be made to identify early individuals with hazardous/harmful alcohol consumption (AC). Alcohol use disorder identification test (AUDIT) is a validated test. METHODS: ASL3 (Ligurian Local Health Company 3) has included the AUDIT renamed GLU-GLU Test on its institutional website dedicated to citizens (https://www.asl3.liguria.it/). The renaming was carried out to bring citizens closer to the Test with greater ease. Especially younger citizens. At the end of the compilation of the test, the calculator provides the citizen with his score: in relation to his possible risk band, provides him with the appropriate advice. In case of a score higher than 7 ultrasonography and elastography (2D-SWE) is proposed. RESULTS: from December 15, 2021 to July 15, 2022, 270 asymptomatic subjects requested a medical examination autonomously, without the indication of a health worker. In 167 the score found hazardous AC, in 65 harmful AC and in 38 alcohol addiction. In case of hazardous AC fibrosis grade 1-2 was evidenced in 16.7%, fibrosis grade 3 in 4.8% and fibrosis grade 4 in 3.6% of subjects. In case of harmful AC fibrosis grade 1-2 was evidenced in 37%, grade 3 in 9%, grade 4 in 6%. In this group an HCC nodule was diagnosed. In case of alcohol addiction, fibrosis grade 1-2 was evidenced in 73.6%, grade 3 in 10.5% and grade 4 in 10.5%. CONCLUSIONS: this preliminary experience clearly tells us that it is possible to make an early diagnosis of fibrosis and HCC starting from the AC reported autonomously by citizens.

Alcohol, smoke, cannabis, new psychoactive substances, and non-prescribed drugs consumption among school student in an area of Nord-West of Italy.

BACKGROUND: Alcohol and/or substance use disorders are known to be a significant phenomenon in the Western world. The aim of the present study was to evaluate the consumption of alcohol, cigarette smoking, cannabis, new psychoactive substances (NSP) / non prescribed drug (NPD) in a student population in the north-west of Italy (metropolitan area of Genoa). METHODS: Fourteen comprehensive schools in the metropolitan area of Genoa (Italy) have requested to participate in the education for correct lifestyles meetings (from December 16, 2021, to May 30, 2022). Before each meeting, a meeting was held with the reference teachers: 3805 students aged 9 to 17 were involved. The group was divided by age group: 9-11, 12-13, 14-15 and 16-17 years. Before the lesson, the students were given a questionnaire relating to various topics related to lifestyle or resulting from an incorrect lifestyle (alcohol consumption, cigarette smoking, cannabis, NPS/NPD, psychological path). The questionnaire was anonymous and was approved by the teachers in the preparation phase of the meeting. RESULTS: Logistic regression analysis found that cannabis use in the age of 14-15 increases the risk of consuming NPD/NPD by more than 26 times (odd ratio 26.3012; 95% CI 15.9656 to 43.3275; P<0.0001). In the age of 16-17, this risk increases approximately 14 times (odd ratio 14.0625; 95% CI 6.1729 to 32.0360; P<0.0001). In the age of 14-15 years, cannabis consumption, alcohol consumption >2 alcoholic units (AUs) on one occasion, NPD increases the probability of the need for a psychological path (cannabis: odds ratio 14.0254, 95% CI 10.9-17.9, P<0.0001; alcohol: odds ratio 3.68, 95% CI 3-4.4, P<0.0001; NPS/NPD: odds ratio 20.98, 16.4-38.4, P<0.0001). In the age of 14-15 and 16-17 years, respectively, 53% (95% CI 50-58%) and 68% (95% CI 66-71%) of students declared that they had neither the parents nor the psychologist of having used alcohol and/or substances. CONCLUSIONS: These data should be useful to policy makers to implement prevention and health promotion policies through teaching (education for correct lifestyles) to be permanently included in school programs and to be recognized in the curricular path.

Beyond biologics: advanced therapies in inflammatory bowel diseases.

INTRODUCTION: Inflammatory bowel diseases (IBDs) are conditions affecting the gut at different levels characterized by an abnormal activation of the intestinal immune system. In this narrative review, we will provide the reader with an update on the efficacy and safety of new pharmacological strategies to treat IBD patients. EVIDENCE ACQUISITION: We performed a thorough literature review via PubMed, EMBASE, MEDLINE and Science Direct databases addressing studies reporting on new therapies for IBD management published in the last ten years (January 2010-December 2020). Data from pharmaceutical companies and abstracts of conferences/meetings have also been considered. EVIDENCE SYNTHESIS: The discovery of monoclonal antibodies blocking pro-inflammatory cytokines, e.g., tumor necrosis factor-α (TNF-α) radically changed the management of IBDs. Anti-TNF-α agents represent the prototype molecule of "biologics"/"biologicals." These compounds have significantly improved the therapeutic management of IBDs refractory to standard medications as they provide clinical remission, mucosal healing and prevent extra-intestinal manifestations. However, about 50% of patients treated with biologicals experienced drawbacks, including primary failure or loss of response, requiring new effective treatments. Translational studies have identified new strategies, different from the TNF-α blockade, and new molecules, e.g. sphingosine-1-phosphate agonists and the JAK kinase inhibitors, have been proposed as potential therapeutic options for IBDs. CONCLUSIONS: With the availability of novel approaches reviewed in this article, physicians and especially gastroenterologists will increase the therapeutic options to provide a better management of IBD patients, particularly those poorly responsive to biologicals.