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.

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 use disorder and liver transplant: new perspectives and critical issues.

Alcoholic liver disease is a consolidated indication for liver transplantation, but many unsolved issues can be highlighted. Patients with alcohol use disorder develop peculiar comorbidities that can become contraindications for transplantation. Moreover, a number of social and psychological patterns should be evaluated to select candidates with a low risk of alcohol relapse and adequate post-transplant adherence. In this context, the 6-month rule is too rigid to be widely applied. A short period of abstinence (1 to 3 months) is useful to estimate recovery of liver function and, possibly to avoid transplant. Cardiovascular disorders and extra-hepatic malignancies represent the main clinical issues after transplant. Patients transplanted due to alcoholic disease are a major risk for other liver diseases. Severe corticosteroid-resistant alcoholic acute hepatitis is a debated indication for transplant. However, available data indicate that well-selected patients have excellent post-transplant outcomes. Behavioral therapy, continued psychological support and a multidisciplinary team are essential to achieve and maintain complete alcohol abstinence during the transplant process. Alcoholic liver disease is an excellent indication for a liver transplant but patients with alcohol use disorder deserve a personalized approach and dedicated resources.

Alcohol-related chronic exocrine pancreatic insufficiency: diagnosis and therapeutic management. A proposal for treatment by the Italian Association for the Study of the Pancreas (AISP) and the Italian Society of Alcohology (SIA).

Current estimates of the prevalence of chronic pancreatitis, one of the most common causes of exocrine pancreatic insufficiency, are in the range of 3-10 per 100,000 people in many parts of the world. Alcohol consumption is a very important risk factor for exocrine pancreatic insufficiency and is involved in nearly half of all cases. The main hypothesis regarding the role of chronic alcohol consumption in pancreatitis is that there must be additional environmental or genetic risk factors involved for ongoing damage to occur. Treatment of patients with alcohol-related exocrine pancreatic insufficiency is complex, as the patient has two concomitant pathologies, alcohol-use disorder (AUD) and exocrine pancreatic insufficiency/chronic pancreatitis. Alcohol abstinence is the starting point for treatment, although even this along with the most advanced therapies allow only a slowdown in progression rather than restoration of function. This position paper of the Italian Association for the Study of the Pancreas and the Italian Society of Alcohology provides an overview of the pathogenesis of alcohol-related pancreatitis and discuss diagnostic issues. Treatment options for both exocrine pancreatic insufficiency/chronic pancreatitis (with a focus on pancreatic enzyme replacement therapy) and AUD (acamprosate, disulfiram, oral naltrexone, long-acting injectable naltrexone, sodium oxybate, nalmefene, baclofen, and psychosocial interventions) are also reviewed.

Addiction disorders: a need for change. Proposal for a new management. Position paper of SIA, Italian Society on Alcohol.

Various epidemiological and biological evaluations and the recent publication of the DSM-V (diagnostic and statistical manual of mental disorders) has imposed on the scientific community a period of reflection on the diagnosis and treatment of what in the DSM-IV was defined as "addiction". To date, the term "addiction" has been replaced by the DSM-5, because there is no global scientific consensus that has unequivocally characterized its clinical characteristics. This, we will talk about substance/alcohol use disorders (SUDs/AUDs) and disorders related to behavioral alterations (DBA) that can generate organic diseases, mental disorders, and social problems. In the first psychotic episode 40-70% of subjects meet the criteria of a SUDs/AUDs, excluding tobacco dependence. Substances can not only be the cause of a psychotic onset, but they can also disrupt a psychotic picture or interfere with drug therapy. The pharmacodynamic profiles of many substances are able to provoke the phenomenology of the main psychotic symptoms in a way that can be superimposed onto those presented by psychotic subjects without a history of SUDs/AUDs. The Department of Addictions (DAs) must not be absorbed by or incorporated into the Departments of Mental Health (DMH), with which, however, precise operational cooperation protocols will have to be defined and maintained, but it will have to maintain its own autonomy and independent connotation. Addiction Medicine is a discipline that brings together elements of public health, prevention, internal medicine, clinical pharmacology, neurology, and even psychiatry. The inclusion of the DAs in those of DMH refers purely to a problem of pathology that has to do with lifestyle, choices, and behaviors. These, over time, show their dysfunctionality and only then do related problems emerge. Moreover, epidemiological, social, and clinical motivations impose the creation of alcohological teams dedicated to alcohol-related activities. The collaboration with self-help-groups (SHGs) is mandatory. The action of SHGs is accredited in numerous international recommendations both on the basis of consensus and evidence in the literature.

[Acute alcoholic hepatitis.] / Epatite alcolica acuta.

Chronic alcohol related liver disease is characterized by a cascade of events defined as follows: steatosis, steatohepatitis/steatofibrosi, cirrhosis and hepatocellular carcinoma. On one of these histologic patterns may overlap acute alcoholic hepatitis (AAE) (mild, moderate, severe). Severe AAE can cause a severe clinical picture: jaundice with a duration of less than three months, jaundice in the first decompensation event, serum bilirubin higher than 5 mg/dL, ratio AST/ALT >2:1, AST less than 500 IU/L ALT <300 IU/L, neutrophil leukocytosis and increased GGT. In addition, it is possible the presence of encephalopathy, fever, fatigue, coagulopathy. The onset can also be characterized by portal hypertension-related complications. An extremely severe clinical condition is the superposition of an acute insult to a chronic framework, not necessarily a cirrhotic one. This condition has been termed acute on chronic (acute on chronic liver failure - ACLF:), and it is possible to have a SIRS (systemic inflammation response syndrome) with a multi-organ system involvement. The diagnosis, in selected cases, can be confirmed by a transjugular biopsy that allows to reach a histologic prognostic stratification. Several indices are used for the assessment of prognosis and in particular the MDF and the MELD. In our clinical practice we use the MELD. In case of ACLF, the consortium organ failure score (CLIF-C OFS) is used. The therapy is characterized by alcohol abstention, and, in severe forms (MDF >32 and MELD >21) with absence of contraindications, it is possible to use steroids therapy. If a positive answers cannot be obtained, an early liver transplantation is proposed. This possibility, after a careful selection, now is promoted by several authors.

Alcohol, caffeine, and nicotine consumption in adolescents: hair analysis versus self-report.

BACKGROUND: Clinical reliability of self-reported data for alcohol, caffeine, and nicotine consumptions is lacking, particularly in adolescents. OBJECTIVES: To compare a self-report questionnaire and hair analysis to assess the reliability and effectiveness of the self-report. METHODS: A cross-sectional study on 14-15-year-old Italian students (n = 874, 38% males, 62% females) was performed comparing self-reported data to hair analysis. The latter quantified hair concentrations of caffeine, nicotine, cotinine, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEEs) using mass spectrometry. RESULTS: Concordance between self-report and hair testing ranged from good to poor across substances and levels of use: poor for heavy alcohol intake (EtG: k = 0.36, 20 positive cases by hair analysis, false negative by self-report, 2.3% of total sample; FAEE k = 0.31, 25 positive cases, 2.9% of total sample); fair to poor for active smokers (k = 0.40, 125 positive cases, 14.3% of total sample); and moderate for caffeine (k = 0.57, 56 positive cases, 6.4% of total sample). CONCLUSIONS: Epidemiological studies on alcohol, caffeine, and nicotine consumption in adolescents may benefit from the inclusion of toxicological analysis on hair samples to overcome the under-reporting phenomenon of questionnaires and detect more cases of problematic substance use.

Hepatocellular carcinoma: diagnosis and proposal of treatment.

Hepatocellular carcinoma (HCC) ranks third among the causes of cancer deaths globally. The most frequent causes are the hepatitis C virus (HCV), a combination of alcohol/HCV and metabolic syndrome (MS). The introduction of new pharmaceutical drugs that inhibit protease will bring a relative increase in the number of cases of HCC that are linked to the consumption of alcohol and MS. The latest development in the diagnostic sector is the total recognition of the contrast-enhanced ultrasound diagnostic algorithm. In the treatment sector we are moving on from the Barcelona criteria. With nodules up to 3 cm in size and with favorable anatomical and clinical conditions, the first treatment choice is percutaneous ablation. The first choice for nodules that are 3-5 cm in size is still hepatic resection (HR). For cases that fall completely within the Milan criteria with portal hypertension and compromised liver function the first treatment choice, in the total absence of any contraindications, is certainly LT. Intermediate forms of HCC are the most complicated as the stratification of patients is particularly relevant. TACE certainly no longer represents the only choice. HR is preferable where possible. According to the individual case and during down-staging, LT may be proposed. In some cases both locoregional ablative approaches and sorafenib can be used. In advanced cases with preserved function, the best treatment is still sorafenib. The treatment of HCC is complex because of the extreme anatomic-clinical variability of the cases. The key to a successful and effective approach is the creation of a true multi-disciplinary group in which the various players have the opportunity to express their own opinion. This is an indispensable prerequisite for a successful synthesis.

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

[Alcohol, cardiovascular prevention and cancer]. / Alcol, prevenzione cardiovascolare e cancro.

It is well known that light to moderate drinking (10-25 g/day) has a protective effect on ischaemic heart disease. This effect seems independent of the type of alcoholic beverage. Recently, the International Agency for Research on Cancer (World Health Organization) stated that alcoholic beverages are carcinogenic for human (oral cavity, pharynx, larynx, oesophagus, colorectum, liver and breast). There is a dose-response relationship between alcohol and cancer in that the risk of cancer increases proportionally with alcohol consumption. Low doses of alcohol (10 g/day) are associated with an increased risk for oral cavity, pharynx, larynx, oesophagus and breast cancer. Therefore, a physically active lifestyle and a healthy diet are more effective in preventing ischaemic heart disease than a low level of alcohol consumption.

Priapus is happier with Venus than with Bacchus.

INTRODUCTION: The relationship between alcohol consumption and erectile function is still not completely clarified. AIM: Aims of the present study are to explore a number of biological and clinical correlates of alcohol consumption in a sample of men consulting for sexual dysfunction, and to verify possible associations with the incidence of major adverse cardiovascular events (MACEs). METHODS: A consecutive series of 1956 (mean age 55 ± 11.9 years old) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N = 1687) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES: Different clinical, biochemical, instrumental (penile Doppler ultrasound [PCDU]), and intrapsychic (Middlesex Hospital Questionnaire [MHQ]) were evaluated. We considered alcohol abuse more than three drinks per day. RESULTS: Among the patients studied 81% reported no or mild (<4 drinks/day) alcohol consumption whereas 14.3% and 3.9% declared a moderate (4-6 drinks/day) or severe (>6 drinks/day) alcohol abuse, respectively. After adjustment for confounders, both moderate or severe alcohol abuse was associated with low perceived partner's sexual desire, worse couple relationship, and smoking abuse. Furthermore, moderate and severe alcohol abuse was associated with low prolactin and thyroid-stimulating hormone levels, as well as an increase in triglycerides and total cholesterol levels. Penile blood flow was reduced in moderate and severe alcohol drinkers even after adjustment for confounders. In the longitudinal study, after adjusting for confounding factors, any kind of alcohol abuse was independently associated with a higher incidence of MACE (hazard ratio = 2.043 [1.059-3.943]; P < 0.0001). CONCLUSIONS: Our findings demonstrate that, in subjects consulting for erectile dysfunction, severe alcohol consumption is associated with a worse sexual function and a higher incidence of MACE.

Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells.

BACKGROUND & AIMS: Accumulating evidence indicates that acetaldehyde (AcCHO) is one of the main mediators of fibrogenesis in alcoholic liver disease. AcCHO stimulates synthesis of fibrillar collagens in hepatic stellate cells, but the molecular events directly involved in the activation of collagen genes are debatable. METHODS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that is expressed in stellate cells, and its activation by specific ligands inhibits collagen synthesis. In this study, we evaluated the effects of AcCHO on PPARgamma transcriptional activity and its correlation with the AcCHO-induced collagen synthesis in hepatic stellate cells. RESULTS: AcCHO treatment inhibited ligand-dependent and -independent PPARgamma transcriptional activity, and this effect was correlated with an increased phosphorylation of a mitogen-activated protein kinase site at serine 84 of the human PPARgamma. Transfection of the PPARgammaSer84Ala mutant completely prevented the effect of AcCHO on PPARgamma activity and in parallel abrogated the induction of collagen gene expression by AcCHO. The effect of AcCHO on PPARgamma activity and phosphorylation was blocked by extracellular signal-regulated kinase (ERK) 1/2 and protein kinase C (PKC)delta inhibitors as well as by catalase, suggesting that hydrogen peroxide is involved in the molecular cascade responsible for PPARgamma phosphorylation via activation of the PKCdelta/ERK pathway. Furthermore, inhibition of c-Abl completely abrogated the effect of AcCHO on either PPARgamma function or collagen synthesis; in addition, expression of the PPARgammaSer84Ala mutant prevented the profibrogenic signals mediated by c-Abl activation. CONCLUSIONS: Our results showed that the induction of collagen expression by AcCHO in stellate cells is dependent on PPARgamma phosphorylation induced by a hydrogen peroxide-mediated activation of the profibrogenic c-Abl signaling pathway.