Commentary: Metabolic associated liver disease: an inevitable terminological evolution in real practice.

In real practice, the patient with liver disease is often the carrier of multiple etiological factors, such as metabolic syndrome (MS) and alcohol consumption (AC). Their co-presence is often underestimated as AC is not adequately studied. AC is a contributing cause of MS and alcoholic and nonalcoholic liver disease have a substantially overlapping histopathological picture. Moreover, AC and MS are the cause (and the contributing cause) of extra-hepatic morbidity and mortality. It can be concluded that the possible simplification of terminology at metabolic associated liver disease (MALD) facilitates better communication and cooperation between scientific societies and specialists belonging to different medical sectors, facilitates early identification of related hepatic and extra-hepatic pathology, allows to "see the person in a unitary way", to create leaner healthcare pathways, to reduce the hospitalization rate with relative cost-benefit advantage and to create unitary prevention and health promotion policies.

Identification of harmful drinking in subjects who have had their driving license suspended due to alcohol use: a retrospective Italian study.

OBJECTIVE: Early identification of Harmful Drinking (HD) is difficult, and underestimated. The aim of our retrospective study was to investigate the presence of HD in a population of subjects who had their driving license suspended due to driving under the influence of alcohol. MATERIALS AND METHODS: We retrospectively recruited 979 subjects. During the first appointment (T0), clinical and laboratory characteristics of patients were evaluated, and the AUDIT questionnaire was administered. Two groups were then defined: Harmful Drinking (HD) and non-HD, and all subjects underwent a brief interview for 5-10 minutes before being assigned to a group. RESULTS: 95.9% of our sample were identified as non-HD, whereas 4.1% of them were HD; twenty-one (2.1%) of the HD underwent a control appointment (T1), and 17 (1.7%) of them were diagnosed with alcohol use disorder (AUD); there was a statistically significant reduction in mean daily alcohol intake (p<0.009), and in the mean values of the blood markers of HD between T0 and T1 in HD. CONCLUSIONS: The present study shows that 4.1%, and 1.7% of subjects presented a diagnosis of HD and AUD, respectively, and their entry in a protocol of drinking monitoring proved beneficial in reducing alcohol intake. Thus, the implementation of strict surveillance of subjects found driving under the influence of alcohol involving a network of professional figures (from police forces to specialists in alcohol addiction treatment) may help to detect and to treat subjects with HD and AUD, and to monitor their alcohol use over time.

The undertreatment of alcohol-related liver diseases among people with alcohol use disorder.

Harmful and hazardous alcohol consumption is one of the most significant public health problems in Italy and Europe. Habitual excessive consumption and occasional excessive consumption, known as binge drinking, are the two main risk behaviours related to alcohol. Harmful drinking and alcohol dependence have strong social repercussions in terms of their social and economic impact and contribution to productivity losses. In addition, the terms alcohol abuse and alcohol dependence have been recently substituted by the only term of alcohol use disorder (AUD). The issues presented in this review demonstrate that excessive alcohol consumption is a growing public health concern and an appropriate national action plan is needed to increase the prevention of harmful and hazardous consumption and encourage patients to seek healthcare. To date, the main problem is the under-treatment of the population at risk, manifested as the time-lag between the onset of AUD and the first clinical detection. In order to address this, the Screening, Brief Intervention, and Referral to Treatment (SBIRT) strategy has been shared across countries in Europe and is supported by a Systematic Review of Reviews on SBIRT in primary healthcare. Unfortunately, there are still obstacles in the implementation of this approach. The main problem would appear to be general practitioners' difficulty in carrying out accurate and widespread screening, because they may minimize the problem. A more concerted effort in the training of healthcare professionals could address this by enabling the creation of renewed networks for the early identification of harmful and hazardous drinkers. These networks could prevent the occurrence of avoidable alcohol-related conditions, such as alcohol-related liver disease (ALD), while allowing for the timely implementation of evidence-based brief interventions.

Treatment of alcohol dependence: recent progress and reduction of consumption.

Alcohol dependence (AD) is a major public health problem. Currently, three drugs for the treatment of AD have been approved by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA): acamprosate, disulfiram, and oral naltrexone. The FDA also approved the use of long-acting injectable naltrexone. In Austria and in Italy sodium oxybate is also approved. The EMA's Committee for Medicinal Products for Human Use has recently granted marketing authorization for nalmefene for the reduction of alcohol consumption. Many patients, while accepting the problem, are unable or unwilling to completely stop consuming alcohol, leading to an inevitable deterioration over time of their psycho-physical state, and social and family relationships. It is appropriate to offer these patients the opportunity to significantly reduce their consumption of alcohol. The reduction may be an opportunity to prepare the individual for achieving complete abstinence. Abstinence should always be the main goal. Currently, nalmefene is the only drug that has been authorized for the reduction of alcohol consumption. Its association with psycho-social support is mandatory; it is taken on an "as-needed" basis, which should preferably be 1-2 hours before the possible intake of alcohol. The trials showed a significant reduction in alcohol consumption, which resulted in a significant reduction in morbidity and mortality. Reducing consumption allows a decrease in the progression of numerous alcohol-induced chronic diseases, as well as a reduction in psycho-physical damage, acts of violence, motor vehicle accidents, and accidents at work, which in turn means fewer healthcare costs.

Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view.

The alcoholic liver disease (ALD) is the leading cause of death from liver failure in Italy and worldwide. Ethanol abstention, a healthy diet, and a significant improvement of life-style are the mainstay of treatment for this disease. Currently, we do not have effective therapeutic options are at our disposal to restore and maintain an improved clinical status. Silymarin is a complementary and alternative medicine often prescribed and self-prescribed; it has anti-oxidant, anti-inflammatory, anti-fibrotic, and metabolic properties. It improves the laboratoristic values and the ultrasonographic grading of liver disease in case of steatosis/steatohepatitis. S-adenosyl-L-methionine (SAMe) is the principal biological methyl donor, and it is also a precursor of glutathione (GSH), essential for the anti-oxidant pathways. SAMe is particularly important for opposing the toxicity of free radicals generated by various toxins, including alcohol. An association between Silymarin and SAMe (labelled as a dietary supplement) has been recently brought to market, and seems to be promising. It could be beneficial in such cases of alcoholic hepathopathies. New therapeutic options are needed by hepatologists to successfully overcome a constantly growing disease.

Alcoholic hepatitis.

Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey's Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT.

Recurrent hepatitis C and non-alcoholic fatty liver disease in transplanted patients: a review.

Non-alcoholic fatty liver disease (NAFLD) is a common occurrence after orthotopic liver transplantation (OLT). The association steatosis/HCV determines important implications for clinical practice: steatosis accelerates the progression of fibrosis and reduces the likelihood of obtaining a sustained virological response (SVR) with antiviral therapy. In post-transplant HCV patients we have evidenced a strong correlation between body mass index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis. In subjects with BMI <25 and TGC <160 ng/mL, the chance of SVR was 48 times higher than that of non response. The chances of SVR and sustained biochemical response for patients with percentage of steatosis <15 were 12 times higher than that with higher percentage of steatosis. We can conclude how the amount of steatosis be noted specifically in biopsy examination reports of patients with relapse chronic hepatitis C and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and the response to antiviral therapy.

Severe acute alcoholic hepatitis and hepatorenal syndrome: role of transjugular intrahepatic portosystemic stent shunt.

Acute Alcoholic Hepatitis (AAH) is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol. Mild to moderate forms of AAH frequently respond to alcoholic abstinence, whereas severe AAH is characterized by a poor prognosis. Up to 40% of these patients die within 6 months upon symptoms onset. This high rate of mortality is due to different factors: liver failure, severe infections, and portal hypertension with variceal bleeding and hepatorenal syndrome (HRS). In AAH, HRS is a common complication that leads to the death of more than 90% of the patients within 3 months, unless they had been liver transplanted. Transjugular Intrahepatic Portosystemic Stent Shunt (TIPS) has been increasingly used in the management of portal hypertension and its complications, and, it might become a valuable option in patients with HRS awaiting LT. This study has taken into consideration 9 consecutive patients affected by severe AHH with HRS suitable for TIPS. We have determined serum creatinine, blood urea nitrogen, serum sodium, sodium urinary excretion and urine volume in all patients, before the intervention, 7 days and 30 days after TIPS. Seven patients were transplanted within 6 months. After TIPS, the renal function improved with significant reduction in serum creatinine and increase in urine volume. We can conclude that TIPS is a valuable option in patients with severe AAH complicated by HRS and are waiting for liver transplantation.

Human carcinogenesis and alcohol in hepato-gastroenterology.

Alcohol consumption is one of the top-10 risks for worldwide burden of disease. The International Agency for Research for Cancer affirmed that there was evidence for the carcinogenicity of ethanol in animals and classified alcohol consumption as carcinogenic for humans. Alcohol consumption causes cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum, liver, pancreas and female breast. Most alcohol-induced diseases increases in a linear fashion as intake increases: oral, oesophagus and colon cancer fall into this pattern: very little is known about safe margins of alcohol consumption. Given the linear dose-response relation between alcohol intake and risk of cancer, control of heavy drinking remains the main target for cancer control. European Code Against Cancer recommends keeping daily consumption within two drinks (20 g [corrected] of alcohol/day) for man and one drink for women and US Department of Health and Human Services suggest as a low risk, a maximum of 10 g [corrected] of alcohol a day in man and half of this in women.

Relationship between laboratory parameters and intensive care unit stay post-liver transplantation: proposal of a model.

UNLABELLED: The aim of this study was to create a model that forecasted the stay in the intensive care unit in post-liver transplantation. METHODS: Twenty-three consecutive patients who underwent liver transplantation provided samples for serum sodium, serum creatinine, total bilirubin, cholesterol, aspartate and alanine aminotransferase, alkaline phosphatase (ALP), albumin, and platelet count for correlation together with age at transplantation in a Pearson correlation model with intensive care unit stay. Multivariate analysis used a regression model to evaluate the relationship between the dependent variable "intensive care unit stay" and the predictor variables that were correlated by a Pearson correlation test. To test the acceptability and strength of the model, analyses of variance was performed and a multiple correlation coefficient R was calculated for the model. RESULTS: Pearson correlation test showed a strong correlation between intensive care unit stay and creatinine (correlation coefficient = 0.34, P = .03), serum sodium (correlation coefficient = -0.42, P < .01), and total bilirubin (correlation coefficient = -0.29, P = .06). Other variables showed no significant correlation, namely correlation coefficients < 0.24 (P > .1). The final model to evaluate the relationship between the dependent variable "intensive care unit stay" and laboratory parameters included ALP, serum creatinine, serum sodium, and total bilirubin as well as a correction for age. CONCLUSIONS: The most significant parameters were total bilirubin, serum creatinine, and serum sodium. The proposal model significantly correlated with the variable "intensive care unit stay." Such data are particularly important since increased intensive care unit stay correlates with a significant reduction in 1-year survival rate.

Gastric precancerous changes: carcinogenesis, clinical behaviour immunophenotype study and surveillance.

Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Two-thirds of the GC patients are diagnosed in advanced stages, when surgery can only be a palliative. When the diagnosis is made at an early stage, the surgical treatment results in 10 years survival rates are higher than 85%. From the critical evaluation of the literature data we can affirm that there are some obstacles to an exclusive acceptance of the idea that the relation of Helicobacter pylori (H. pylori) infection with noninvasive (formerly dysplasia) or invasive neoplastic modifications solely develop by means of chronic gastritis with its atrophic evolution and achlorhydria. Intestinal metaplasia as a precursor of GC has been overemphasized and doubts persist about the real necessity to operate histologically a subdivision into subtypes. The extent of the metaplastic process is probably more important that the metaplastic subtype. The evaluation of the clinical behaviour shows how low grade noninvasive neoplasia is associated with or progressed to GC in about 9% of cases, while high grade noninvasive neoplasia is associated with or progressed to GC in about 75% of cases, thus proving to be a real histological marker of GC. The subdivision of the cases according to the TNM classification demonstrates that, in most of the cases, early GC is present (43/45: 95.5%). An appropriate endoscopy follow-up with biopsies according to well defined criteria increases the likelihood of invasive neoplasia being detected in its early stage with a better postsurgical prognosis. Noninvasive neoplasia is characterized by severe alterations of the immunophenotype profile in association with a high proliferation index and frequent p53 mutations. The choice to address the patients to surgical intervention could be made not only on the basis of histochemical techniques, but also with the help of immunohistochemical evaluations.

Combination hepatitis C virus antigen and antibody immunoassay as a new tool for early diagnosis of infection.

Reduction of the window period of hepatitis C virus (HCV) infection represents an important goal in the transfusional and diagnostic setting. A prototype assay designed to simultaneously detect circulating HCV antigen and anti-HCV, has been developed. Aim of this study was to evaluate the performance of this new assay in terms of specificity and sensitivity and to compare its efficacy with commercial assays. To evaluate the specificity of the assay, 400 samples from the general population and 100 'difficult' sera, negative for anti-HCV, were tested. To assess sensitivity, the new test was used on 76 PCR-positive and anti-HCV negative sera, seven natural or commercial seroconversion panels that included 17 RNA-positive and anti-HCV negative sera and 31 anti-HCV positive sera, 20 weak anti-HCV positive sera, 80 viraemic and anti-HCV-positive sera from patients infected with different subtypes and 10 sera from patients with HBV-HCV or HIV-HCV co-infections. Of 500 anti-HCV negative samples, 499 (99.8%) were negative with a cut-off index <0.5, while one sample was within the grey zone. Of the 93 HCV-RNA positive and anti-HCV negative sera from patients and panels, 85 (91.4%) resulted positive, and one had the cut-off index in the grey zone. The reduction in the diagnostic window period observed with the new test and HCV-RNA assays were equal, on average, to 24 and 34.4 days respectively. All anti-HCV positive sera were positive. The new assay shows high sensitivity and specificity and could be a useful tool not only in the diagnostic setting, where procedures to reduce the window period, such as antigen or HCV-RNA detection, are not currently recommended, but also in the screening of blood donations, when nucleic acid technologies is not feasible because of costs, organization, emergency and/or logistic difficulties.