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Background: Leaks are the major complication associated with laparoscopic sleeve gastrectomy. Objective: The study aimed to assess the efficacy and safety of specifically designed large covered metal stents for the management of post-laparoscopic sleeve gastrectomy leaks. Methods: Prospectively collected databases from three Italian Endoscopy Units were reviewed. The primary outcome of the study was to evaluate the clinical success of stents placement, defined as complete resolution of clinical and laboratory signs of sepsis with radiological evidence of leak closure. Secondary outcomes were stent-related adverse events and mortality. Results: Twenty-one patients (67% females, mean age 45 years) were included in the study and a total of 26 stents were placed. Technical success of stent placement was achieved in all cases (100%). Clinical success was observed in 85.5% of patients. Stent-related adverse events occurred in 9 patients (43%), with stent migration as the most frequent complication (33%). Adverse events were more frequently observed in patients who had undergone bariatric surgery prior to laparoscopic sleeve gastrectomy compared to patients without previous surgery (83% et al. 27%, p=0.018). Conclusion: The placement of specifically designed covered metal stents appears to be an effective and safe therapeutic approach for post-laparoscopic sleeve gastrectomy leaks. Stent migration can be a frequent complication.

Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p<0.000). Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

Introduction: The first case of infection by SARS-CoV-2 (i.e., COVID-19) has been officially recorded by the Italian National Health Service on February 21st, 2020. Lombardy was the first Italian region to be affected by the pandemic. Subsequently, the entire Northern part of Italy recorded a high number of cases, while the South was hit following the migratory waves. On March 8th, the Italian Government has issued a decree that imposed a total lockdown, defining it as a state of isolation and restricting access in Lombardy and the other 14 provinces of Northern Italy. Methods: We analyzed the virus trend in the period between February 24thand September 8th, 2020, focusing on Calabria, with regards to the following items: new positives, change of total positives, and total cases. Furthermore, we included other information, such as the incubation period, symptom resolution period, quarantine period. Results: On March 27th, the epidemic curve spiked with 101 new positive cases validating the hypothesis that this abnormal event was related to the displacement of non-residents people, living in the Northern part of Italy, to the home regions in the South. The epidemic curve showed a decreasing trend in the period after lockdown, proving the effectiveness of this measure. From the end of the lockdown May 04thto September 8th, the registered trend was -94.51%. A negative growth rate indicates that the number of new positive cases is lower than the number of healed patients. Conclusion: This study describes the effectiveness of the Italian Government policy, particularly the role of lockdown, for the containment of SARS-CoV-2 contagion in Calabria, a region with a low SARS-CoV-2 infection rate within the registered period.

Background: Severe postoperative pain is principally managed by opioids. While effective, opioids do not provide adequate relief in many patients and cause many side effects, including antinociceptive tolerance and opioid-induced hyperalgesia. To evaluate if a combination of intravenous Magnesium, Lidocaine, Ketorolac (MLK cocktail) is a useful rescue therapy through synergistic pharmacological mechanisms for acute pain relief. We present the intravenous combination of magnesium, lidocaine, and ketorolac (MLK cocktail) as a possible rescue for opioid insensitive severe post-operative pain. Materials and Methods: The principal settings were the post-operative care unit (PACU) and the surgical ward. We retrospectively analyzed the electronic medical record and anesthesia documents of 14 patients experiencing severe postoperative pain, >7/10 visual-analogue pain score (VAS), despite receiving at least 8 mg of intravenous morphine milligram equivalents (MME) after arrival in the LAC+USC Medical Center PACU between September 2012 and January 2013. The data reviewed included patients’ demographics, disease etiology, surgical procedure, opioids received perioperatively, and visual-analogue pain scores before and after each analgesic received, and after the MLK cocktail. The a priori primary outcome and a posteriori secondary outcome of this study are mean visual-analogue pain score and morphine milligram equivalent dose administered per hour, respectively. The main tool evaluated has been VAS score. Results: In patients who failed to respond to opioid analgesics, administration of the MLK cocktail improved the VAS pain scores immediately from 9.4 ± 1.0 to 3.6 ± 3.5. The MLK cocktail also decreased the MME doses/hour in the immediate 12 hours postoperative period from 12.4 ± 5.6 to 1.1 ± 0.9. Conclusion: In patients experiencing opioid-resistant severe postoperative pain, the magnesium, lidocaine, and ketorolac combination may be an effective nonopioid rescue therapy. Additionally, magnesium, lidocaine, and ketorolac may be utilized in cases complicated by either antinociceptive tolerance or opioid-induced hyperalgesia and can restore opioid responsiveness.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that poses several challenges in terms of clinical diagnosis and investigation of molecular etiology. The lack of knowledge on the pathogenic mechanisms underlying ASD has hampered the clinical trials that so far have tried to target ASD behavioral symptoms. In order to improve our understanding of the molecular abnormalities associated with ASD, a deeper and more extensive genetic profiling of targeted individuals with ASD was needed. Methods: The recent availability of new and more powerful sequencing technologies (third-generation sequencing) has allowed to develop novel strategies for the characterization of comprehensive genetic profiles of individuals with ASD. In particular, this review will describe integrated approaches based on the combination of various omics technologies that will lead to a better stratification of targeted cohorts for the design of clinical trials in ASD. Results: In order to analyze the big data collected by assays such as the whole genome, epigenome, transcriptome, and proteome, it is critical to develop an efficient computational infrastructure. Machine learning models are instrumental to identify non-linear relationships between the omics technologies and, therefore, establish a functional informative network among the different data sources. Conclusion: The potential advantage provided by these new integrated omics-based strategies is better characterization of the genetic background of ASD cohorts, to identify novel molecular targets for drug development, and ultimately offer a more personalized approach in the design of clinical trials for ASD.

Introduction: Corona virus is a group of viruses that cause diseases in mammals and birds. In humans, these families of viruses can cause respiratory infections from a mild form to fatal. It is preferably called coronavirus. Formally, it is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) and this disease is called coronavirus disease 2019 (COVID-19). SARS-CoV-2 is infectious in humans and the world health organization has announced COVID-19 as pandemic disease. Tocilizumab is a biological agent that inhibits the cytokine, interleukin 6 (IL-6 inhibitor). As SARS-CoV-2 infection leads to the development of cytokine storm syndrome, the drug, tocilizumab, seems to have a positive effect on patients with COVID-19. Aim: To analyze and review the possible effects and efficacy of the tocilizumab (monoclonal antibody against IL-6 receptors) in SARS-CoV-2 patients. Materials and Methods: A search was carried out for all recent review articles, which were used to study the SARS-CoV-2 disease and their characteristics. Furthermore, we have analyzed the most recent research articles on monoclonal antibody against IL-6 receptors (tocilizumab) and their possible clinical effects in COVID-19 and its’ clinical trials. Results: COVID-19 is a disease caused by SARS-CoV-2 infection. It is a life threatening condition, which can give rise to fatal outcomes if left untreated. However, there are no approved treatments for COVID-19 globally. Furthermore, we can conclude that SARS-CoV-2 is associated with the worsening of lung conditions, characterized by interstitial pneumonia with acute respiratory distress syndrome as a result of cytokine storm syndrome. According to available research data, tocilizumab, a recombinant humanized anti-human monoclonal antibody of IgG1Τ (gamma 1, kappa), can improve patient’s condition from cytokine storm syndrome by inhibiting the IL-6 (Interleukin 6) receptors. Conclusion: The rational use of the tocilizumab in severe and critically ill COVID-19 patients can prevent the development of irreversible lung injury and death of the patient. Three retrospective studies of Xiaoling Xu et al., Pan luo et al., and Paola Tonaiti et al. have shown the efficacy of tocilizumab in severe and critically ill COVID-19 patients. However, we need more randomized research studies with a significant number of patients which can confirm the promising results on tocilizumab treatment in COVID-19 patients. Moreover, ongoing clinical trails such as TOSCA, COVACTA results have not been published yet which are expected to give better and more significant results on tocilizumab’s effectiveness and safety.

Background and Aims: Liver cirrhosis (LC) of any origin has always been a source of several emergencies for physicians working at the Emergency Department (ER). LC patients can present with several complications that are sometimes difficult to recognize and treat. Thus, we reviewed the literature evidence for the diagnosis and management of several LC related emergencies. Methods: We conducted a search on the main medical databases for papers, reviews, metanalyses, case series, and RCTs using the following keywords and their associations: liver cirrhosis, variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepato-renal syndrome, emergency. Results: Main LC emergencies are upper gastrointestinal hemorrhage, decompensated ascites and spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome. Their management is partly medical and interventional. Very often, the final cure of some complications, such as hepato-renal syndrome, is represented by liver transplantation. Conclusion: Although LC prevalence is going to fall in the following years, due to HBV and HCV optimized treatments, its complications represent a significant admission percentage at the ER and challenge for physicians’ skills.

Background: In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12.5g per day) is still unknown. Objective: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset. Methods: To collect the scientific evidences regarding this topic the keywords “light alcohol drinking”, “light alcohol consumption” and “cancer”, were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded. Results: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed. Conclusion: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.

Background: Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. Methods: We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. Results: Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). Conclusion: RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.

Background: Clinical therapeutic trials are a fundamental tool for identifying and testing new categories of drugs useful for ensuring clinical benefit in patients with Inflammatory Bowel Diseases (IBD). A number of difficulties may affect the recruitment process in large clinical trials. Objectives: In order to increase the involvement of patients within clinical trials in IBD therapy, it is necessary to identify which factors could facilitate or discourage participation. The aim of this study was to evaluate the factors influencing the participation in clinical trials in a consecutive series of patients with IBD from a single referral center from Southern Italy. Methods: Consecutive patients with Crohn´s Disease (CD) and Ulcerative Colitis (UC) were recruited to complete a questionnaire dealing with their knowledge about clinical trials and attitudes towards participation. Patients also completed the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ) to investigate their Quality of Life (QoL). Demographic and clinical data were recorded. Results: Of the 145 consecutive patients invited to the survey, 132 completed the survey (91% response rate). Of them, 67% claimed their willingness to take part in a clinical therapeutic trial for IBD. Multivariate analysis showed a significant positive association between interest in clinical trials and previous experience (p = 0.014), high education (p < 0.001), poor QoL (p = 0.016), money retributions (p = 0.03) and informative materials (p = 0.02). On the other hand, a long-standing disease (p = 0.017), the possibility of receiving a placebo (p = 0.04) and the frequent colonoscopies required by the study protocol (p = 0.04) were significantly associated with the lack of interest in clinical trials. Conclusion: In a native local resident series of IBD patients, the majority of the patients were willing to participate in a clinical therapeutic trial. A long-standing disease, placebo and invasive procedures represented a barrier to enrollment while previous experience, high education, monetary compensation and adequate information could be facilitative. Knowing barriers and facilitators affecting participation in IBD clinical trials is of fundamental importance in order to increase the involvement of patients in research and explore new treatment opportunities.

Background: High-Flow through Nasal Cannula (HFNC) is a system delivering heated humidified air-oxygen mixture at a flow up to 60 L/min. Despite increasing evidence in hypoxemic acute respiratory failure, a few is currently known in chronic obstructive pulmonary disease (COPD) patients. Objective: To describe the rationale and physiologic advantages of HFNC in COPD patients, and to systematically review the literature on the use of HFNC in stable and exacerbated COPD patients, separately. Methods: A search strategy was launched on MEDLINE. Two authors separately screened all potential references. All (randomized, non-randomized and quasi-randomized) trials dealing with the use of HFNC in both stable and exacerbated COPD patients in MEDLINE have been included in the review. Results: Twenty-six studies have been included. HFNC: 1) provides heated and humidified airoxygen admixture; 2) washes out the anatomical dead space of the upper airway; 3) generates a small positive end-expiratory pressure; 4) guarantees a more stable inspired oxygen fraction, as compared to conventional oxygen therapy (COT); and 5) is more comfortable as compared to both COT and non-invasive ventilation (NIV). In stable COPD patients, HFNC improves gas exchange, the quality of life and dyspnea with a reduced cost of muscle energy expenditure, compared to COT. In exacerbated COPD patients, HFNC may be an alternative to NIV (in case of intolerance) and to COT at extubation or NIV withdrawal. Conclusion: Though evidence of superiority still lacks and further studies are necessary, HFNC might play a role in the treatment of both stable and exacerbated COPD patients.

Background: Blood cytokines affect the development of inflammatory processes in both normal and pathological states. We have studied changes in the concentration of interleukins (ILs) - 1β, IL-4, IL-10, IL-12B p40, transforming growth factor β (TGF β), tumor necrosis factor (TNF-α) in acute carrageenan-induced inflammation and degenerative-dystrophic changes of knee joint caused by monoiodoacetate-induced Osteoarthritis (OA) in experimental models on rats. We also investigated the change in the cytokine profile during prophylactic and therapeutic administration of chondroitin sulfate to animals under experimental conditions. Methods: The concentration of the cytokines was measured in blood serum by enzyme-linked immunosorbent assay. Results: The manifestation of articular lesions was characterized by a disturbance in the balance between proinflammatory (IL-1β, IL-12B p40, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF -β) cytokines. Conclusion: A reduction in the concentration of proinflammatory cytokines in blood serum after prophylactic and therapeutic administration of chondroitin sulfate to the rat with experimental models of acute inflammation of the hind limb and degenerative-dystrophic changes in the knee joint with OA is associated with anti-inflammatory and regenerative properties of the drug.

Background: Endoscopic ultrasound (EUS) has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. Method: We conducted a systematic review of the available English-language articles. Objective: The purpose of this review is to summarize the relevant applications of operative EUS. Results: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. The main indications of operative EUS, both diagnostic and therapeutic, are related to its ability to combine ultrasound imaging and safe and effective needle insertion into lesions originating from the gut wall and from organs nearby. In addition, technologic advancements of echoendoscopes with a therapeutic working-channel have allowed to perform several EUS-guided interventions, i.e. celiac plexus neurolysis, drainage of fluid collections, drainage of dilated biliary and pancreatic ducts, and vascular interventions.

Background: Endoscopic Ultrasound has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. Method: We conducted a systematic review of the available English-language articles. Objective: The purpose of this review is to summarize all the relevant indications to endoscopic ultrasound and analyze its relevant data in terms of accuracy and clinical outcomes. Results: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. Staging indications include gastroesophageal and rectal cancers. Diagnostic, staging and therapeutic indications include diseases of the pancreaticobiliary area. Finally, differential diagnosis of submucosal tumors represents another important indication to this technique.

Background: An intricate network of reciprocal interactions between adipose tissue and immune system have been largely demonstrated, leading to the well-accepted concept of insulin resistance as a low grade inflammatory state and, conversely, chronic high-grade inflammation as a dysmetabolic condition. Immune homeostasis is regulated by several players including the complement system, a complex protein network at the crossroad between the innate and adaptive arms of the human defences against pathogens. Objective: Complement C3 represents the nodal point of the complement cascade independently of the pathway recruited. Aim of this review is to collect the evidence supporting the role of complement C3 as a candidate biomarker of insulin resistance and other metabolic disorders. Methods: We reviewed the available evidence pointing to a role of complement system, and in particular complement C3, in insulin resistance and other cardiometabolic diseases including diabetes (T2D), hypertension, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Results: Compelling preclinical evidence demonstrated a role of adipose-tissue C3 and its cleavage products C3a and acylation stimulating protein (ASP) in adipose tissue inflammation and insulin resistance. To further support this hypothesis, several clinical studies, both cross-sectional and longitudinal, confirmed this association in independent cohorts. Moreover, preliminary evidence support a role of complement C3 in other cardiometabolic diseases such as hypertension, NAFLD and atherosclerosis. Conclusion: Future studies are needed to fully confirm the usefulness of C3 as a clinical biomarker and to establish accurate cut-off values. Moreover, the therapeutic potential of C3 modulation in either cardiometabolic and inflammatory diseases need to be investigated.

Background: Recent evidence demonstrated a potential role of complement C3 as a candidate biomarker of cardiometabolic risk in the general population. Objective: Aim of the present study was to investigate the correlation between complement C3 levels and comorbid Type 2 Diabetes (T2DM) in Rheumatoid Arthritis (RA) patients. Methods: For the present study, 40 consecutive diabetic RA patients (RA/T2DM+ group) and 80 consecutive RA patients without diabetes (RA/T2DM- group) were recruited. Results: Patients in the RA/T2DM+ group were significantly older (p < 0.0001), had a longer RA duration (p < 0.0001) and higher disease activity (p = 0.006) compared to controls. Moreover, patients in the RA/T2DM+ group had significantly higher levels of ESR (p < 0.0001), CRP (p < 0.0001) and complement C3 (p < 0.0001). A logistic regression model was built to ascertain the effect of selected variables (age, RA duration, BMI, ESR, C3, lnCRP, corticosteroid use) on the likelihood that patients have T2DM. Longer RA duration, ESR and C3 were associated with an increased likelihood of being classified as T2DM. Finally, we built ROC curves to evaluate the predictivity of RA duration, complement C3 and the combination of both variables on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.79 (p < 0.0001) for RA duration, 0.71 (p < 0.0001) for complement C3 and 0.89 (p < 0.0001) for the combination of both variables. Conclusion: According to our data complement C3 levels can predict the presence of T2DM in RA patients.

Background: Recent evidence demonstrated a potential role of complement C3 as a candidate biomarker of cardiometabolic risk in the general population. Objective: Aim of the present study was to investigate the correlation between complement C3 levels and comorbid Type 2 Diabetes (T2DM) in Rheumatoid Arthritis (RA) patients. Methods: For the present study, 40 consecutive diabetic RA patients (RA/T2DM+ group) and 80 consecutive RA patients without diabetes (RA/T2DM- group) were recruited. Results: Patients in the RA/T2DM+ group were significantly older (p < 0.0001), had a longer RA duration (p < 0.0001) and higher disease activity (p = 0.006) compared to controls. Moreover, patients in the RA/T2DM+ group had significantly higher levels of ESR (p < 0.0001), CRP (p < 0.0001) and complement C3 (p < 0.0001). A logistic regression model was built to ascertain the effect of selected variables (age, RA duration, BMI, ESR, C3, lnCRP, corticosteroid use) on the likelihood that patients have T2DM. Longer RA duration, ESR and C3 were associated with an increased likelihood of being classified as T2DM. Finally, we built ROC curves to evaluate the predictivity of RA duration, complement C3 and the combination of both variables on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.79 (p < 0.0001) for RA duration, 0.71 (p < 0.0001) for complement C3 and 0.89 (p < 0.0001) for the combination of both variables. Conclusion: According to our data complement C3 levels can predict the presence of T2DM in RA patients.

Background and Rationale of Study: The real-life data of triple therapy-based treatment in patients with chronic hepatitis C were investigated in this survey of 12 clinical centers of southern Italy. This retrospective study analyzed data from 176 consecutive patients. Methods: 125 (70%) patients were treated with telaprevir, and 51(30%) with boceprevir. There were no differences in demographic characteristics between the groups. The degree of Liver Fibrosis (LF) was evaluated according to Liver Biopsy (LB) and/or Transient Elastography (TE). 53/176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were treatment naïve, and the remaining were not: 92 were non-responders (52, 84%), 63 relapsed (35,79%), and 5 discontinued treatment (2, 8%). Results: Overall, the rapid Virological Response (RVR) rate was 67.6%. Of the 103 patients who had follow-up for at least 12 weeks after the end of treatment, 61 (59, 2%) achieved a Sustained Virological Response (SVR). According to multivariate analysis for SVR, RVR was the only independent predictive factor of SVR, irrespective of the degree of LF and the type of response to previous treatments. In telaprevir-treated patients, the rate of RVR was similar in patients with F0-F2, F3 and F4 fibrosis (85%, 84%, 78%, respectively), and the SVR rates among RVR patients was similar irrespective of LF. Conclusions: Data from this real-life study confirm the efficacy reported in clinical trials, although cirrhosis appears to play a smaller role in influencing treatment efficacy. Moreover, RVR is the only independent predictive factor of response regardless of cirrhosis. Based on RVR and for patients with cirrhosis, a shorter therapy might be considered, at least with telaprevir-based therapy.

Liver biopsy due to the limitations is not recommended for all patients with suspected Alcoholic Liver Disease (ALD) but useful for establishing the stage and severity of ALD, in case of aggressive forms or severe steatohepatitis requiring specific therapies, for distinguishing comorbid liver pathology. Procedure is invasive and that’s why associated with some potential adverse effects and complications which may be minor (pain or vagal reactions, transient hypotension) or major such as visceral perforation, bile peritonitis or significant bleeding. The typical histological features in patients with ALD include steatosis, hepatocellular damage (ballooning and/or Mallory-Denk bodies), lobular inflammation with basically polymorphonuclear cells infiltration, with a variable degree of fibrosis and lobular distortion that may progress to cirrhosis which confers a high risk of complications (ascites, variceal bleeding, hepatic encephalopathy, renal failure and bacterial infections).

Alcohol is considered one of the most common hepatotoxin, and chronic alcoholic liver disease is affecting millions of subjects worldwide. The three most frequently manifestations of alcoholic liver disease are steatosis, acute alcoholic hepatitis and liver cirrhosis. The diagnosis of Alcoholic Liver Diseases (ALD) is made by clinical and laboratory analysis. Actually do not exist a single laboratory test able to confirm the diagnosis of ALD, but in the last years several serum markers and laboratory abnormalities have been discovered in these patients. In particular the combination of tests and markers can increase the diagnostic accuracy, for this reason the last studies are focusing on the development of serum biomarkers panel able to diagnose alcohol-related liver damage.

Alcohol represents the oldest substance of abuse known, existed at least as early as the Neolithic period. In the present era, almost half of the world’s population consumes alcohol and it represents the third largest risk factor for disease and disability and the most prevalent cause of advanced liver disease worldwide. In fact, when alcohol consumption reaches “unsafe quantities” an Alcoholic Liver Disease (ALD) is very likely. ALD comprises a large spectrum of diseases, ranging from simple steatosis to steatohepatitis with fibrosis and cirrhosis. Alcohol related cirrhosis is responsible of almost 50% of all cirrhosis-related and 1% of all-cause deaths worldwide. Even if ALD and alcoholic cirrhosis represent a large part of liver diseases, to know exactly the global burden of these phenomena is very difficult. This is mostly due to diagnostic and nosological issues, being ALD represented by several types of diseases and the diagnosis very often based on voluntary questionnaires. Also the natural history of ALD is somewhat difficult to predict, since there is not a definite evolution between the various stages of the disease and, indeed, they may coexist in a single subject. In this brief review we will report on the global burden of ALD, the principal factors influencing its prevalence among populations and the different presentations of its natural history.

Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD.

Alcohol represents the oldest substance of abuse known and Alcoholic Liver Disease (ALD) is the most common cause of chronic liver disease worldwide. The ALD includes a wide spectrum of injury and may lead progressively from simple steatosis to frank cirrhosis. The ALD diagnosis may be hard and it is mainly defined by the history of chronic alcohol intake, physical and laboratory abnormalities suggestive of liver disease. Abstinence is the cornerstone of ALD therapy. Although the burden on health of ALD is not negligible, in the last decades few therapeutic advances have been made. Because of the complex pathogenetic mechanisms, the therapy of ALD and especially of severe Alcoholic Hepatitis (AH), represents a thorny problem in the clinical practice. In severe forms of acute AH, some specific drug treatments, including glucorticoids or pentoxifylline, have been defined and are, at the moment, recommended by international guidelines. On the contrary, specific long-term treatments of ALD, aimed at stopping the progression of fibrosis, are not yet approved.

Alcoholic and virus C hepatitis currently represent the main causes of chronic liver disease worldwide. Every year many people die and are subjected to complex hospitalization and medical assistance due to these pathologies. Alcoholic liver disease and hepatitis C virus chronic infection are often present in the same patient. These two pathologies sinergically act in determining the onset and progression of liver damage that, from the chronic hepatitis staging, may rapidly progress to fibrosis, cirrhosis and hepatocellular carcinoma. In this review we analysed physiopathological aspects and biomolecular interactions that relate ethanol and hepatitis C virus in determining liver damage; moreover we took into account the effect on the natural history of liver disease deriving from the co-presence of these pathologies. Therefore we paid particular attention to the ability of ethanol and hepatitis C virus to in inducing oxidative stress or lipid accumulation, and analyzed the basic mechanisms of fibrogenesis that both diseases have got, amplified by their co-presence in the same patient. Finally we paid attention to the oncogenetic mechanisms inducing hepatocellular carcinoma and variability of response to antiviral therapy that derives from alcohol abuse in a subject affected by C hepatitis.

Background: Chronic ethyl alcohol consuming is well known independent negative predictor of unfavorable natural course and therapy outcome of Chronic Hepatitis C (CHC) infection. Objective: The aim of the present study was to clarify the impact of alcohol consumption on fibrosis rate progression in patients with CHC and Sustained Virologic Response (SVR) rates in patients undergoing treatment with pegylated interferon and ribavirin. Method: This cross sectional retrospective study included 807 CHC patients underwent liver biopsy and hospitalized at Clinical center of Vojvodina, Novi Sad, Serbia. According to the alcohol consumption equal or greater than 50 g/day prior to liver biopsy, patients were divided into two groups. We compared demographic, clinical, virologic and histopathological markers of CHC, as well as response to antiviral therapy. Results: We find statistically significant difference (p=0.001) in gender, but not in age (p=0.081), estimated duration of the CHC (p=0.470) and hepatitis C genotype (p=0.545) between two groups. Among patients with CHC who consume alcohol ≥50 g/day there were significantly higher incidence of intravenous drug users (p=0.000). Binary logistic regression showed that the only independent predictors of moderate to severe fibrosis (fibrosis ≥2) were age (p=0.000) and alcohol use (p=0.027). There was not statistically significant difference in SVR rate between two groups (p=0.810). Conclusion: We believe that this good result in treatment outcome was the consequence of proper selection of patients based primarily on regulations of Republic of Serbia on the necessity of abstinence from the use of alcohol and psychoactive substances at least one year before starting antiviral therapy.

The Gastrointestinal (GI) tract is one of the most affected systems by alcohol consumption. Alcohol can affect the esophagus in several ways: induces mucosal inflammation, increases the risk for Barrett esophagus and esophageal cancer, and also impairs the esophageal motility. Numerous studies have reported an increased prevalence of Gastroesophageal Reflux Disease (GERD) or erosive esophagitis in alcoholics. Some alcoholics exhibit an abnormality of esophageal motility known as a “nutcracker esophagus”. Alcohol effect on gastric motility depends on the alcohol concentration. In general, beverages with high alcohol concentrations (i.e., above 15 percent) appear to inhibit gastric motility and low alcohol doses (wine and beer) accelerate gastric emptying. Also, acute administration of ethanol inhibits the gastric emptying, while chronic administration of a large dose of alcohol accelerates gastric motility. The effect of alcohol on small bowel motility differs according to the type of consumption (acute or chronic). Acute administration of alcohol has been found to inhibit small bowel transit and chronic administration of a large dose of alcohol accelerates small bowel transit. This article reviews some of the below findings.

The gut–liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic/toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine. Several recent evidences from the literature show how gut microbiota composition can be altered by alcohol, affects IP and can be modulated by several nonpharmacological and pharmacological agents, becoming the target for ALD treatment. In this review we describe the definition of ALD, gut microbiota composition in healthy and ALD, definition and role of IP in ALD physiopathology and emerging evidences on gut microbiota modulation in ALD treatment from preliminary clinical and non-clinical studies.

Background: Non-Cirrhotic Portal Hypertension (NCPH) is a rare but potentially fatal liver disorder described in patients treated with anti-retroviral therapy for Human Immunodeficiency Virus (HIV). In particular, the most important predisposing factor to its development has been identified as prolonged exposure to Didanosine (ddI). The clinical entity of NCPH is characterized by an increase in portal pressure due to pre- or intra-hepatic causes, in absence of liver cirrhosis. However, the exact pathogenesis remains poorly understood, and due to its rarity, the diagnosis is often delayed. Objective: We herein report a case in which ddI administration, with concomitant spontaneous bacterial peritonitis by Streptococcus agalactiae, has induced NCPH in a HIV male patient. Conclusion: NPCH should be suspected when HIV patient with an history of ddI treatment presents liver decompensation.

Rosmarinus officinalis L. (Lamiaceae), popularly known as rosemary, is used for food flavoring, and in folk medicine, as an antispasmodic, analgesic, anti-rheumatic, diuretic, and antiepileptic agent. Rosemary is an herb widely used in folk medicine, cosmetics, and phytotherapy and for flavoring of food products. Studies have focused on various biological activities of the secondary metabolites of this plant, such as rosmarinic acid, which have powerful antioxidant, hepato-protective, antimicrobial, anti-nociceptive, and anti-inflammatory properties.

Liver biopsy, since 1883, when were first performed, became the gold standard to confirm the earlier stages of fibrosis and grading of non-alcoholic fatty liver disease (NAFLD) and for distinguishing simple steatosis from non- alcoholic steatohepatitis (NASH). General limitations of liver biopsy are sampling error and inter- and intraobserver variability. Also procedure is invasive and that’s why associated with some potential adverse effects and complications which may be minor (pain or vagal reactions, transient hypotension) or major such as visceral perforation, bile peritonitis or significant bleeding. Presence of steatosis, hepatocellular injury in the form of ballooning, lobular inflammation and perisinusoidal fibrosis, usually with a zone 3 distribution are considered to be most important histological features of adult NAFLD which may differ from bariatric surgery or pediatric patients. In addition, grading and staging and current semiquantitative systems for NAFLD assessment are discussed.

One of the most common hepatic manifestations of the metabolic syndrome is non-alcoholic fatty liver disease (NAFLD). This disease varies from simple steatosis to cirrhosis and hepatocellular carcinoma. Different molecules secreted from adipose tissue such as adiponectin, leptin, resistin and visfatin and pro-inflammatory cytokines such as tumour necrosis factor-, and interleukins, can be involved in the pathogenesis of NAFLD. In this review we describe the role of these adipokines and cytokines in the pathogenesis of NAFLD. We comment on their potential use as non-invasive biomarkers of steatosis and fibrosis, and their potential therapeutic role.

Non Alcoholic Fatty Liver Disease (NAFLD), defined as the presence of a significant amount of lipid accumulation in the liver (at least in 5% of hepatocytes), represents a challenging issue for the Hepatologists. NAFLD is not represented by a single entity, but rather by two different entities that have different natural history and evolution that range from simple fat accumulation in the liver (without any consequence), to necroinflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The reason of these differences has to be found in the host characteristics and associated risk factors. Globally, its prevalence among liver diseases, and in the general population, is rising in the recent years along with its associated conditions: obesity, insulin resistance, metabolic syndrome and diabetes. This increment, together with the reported clinical conditions, may be accounted for changes in dietary habits and the increase of sedentary lifestyle. Its diffusion seems to be pandemic, given that it is beginning to affect the populations in the developing world due to the spread of Western lifestyle. This is particularly worrying in young adults and children in what seems to have become the main cause of liver disease. Even if the real rate of global incidence of NAFLD are not known, its worldwide prevalence in general population is estimated to be 20-30% in Western Countries and 5-18% in Asia and it is increasing over time. In this review we will report on the global and regional prevalence of NAFLD, the principal risk factors and the natural history of its different presentations.

Non-alcoholic fatty liver disease (NAFLD) is a global problem and one of the most common liver diseases in the world. Various pharmacological and non-pharmacological therapies seem to be non-effective and the patients are often advised not to expect a positive outcome. Hence, even in the modern Western society many patients reach for traditional herbal products. Silymarin, a lipophilic extract derived from milk thistle (Silybum marianum) has been used in liver and bile disorders for centuries. Strong antifibrotic, antioxidant, antiviral and anti-inflammatory activities of silymarin joined with its metabolic effect proven in vitro make it ideal as a drug candidate in the therapy of NAFLD. Several recent randomized clinical studies have demonstrated that silymarin versus placebo significantly contributes to amelioration of the liver condition affected by NAFLD since it reduces steatosis severity, liver ballooning and fibrosis, followed by lowered aminotransferase levels in both short and long lasting therapies. Silymarin is also as efficient as an insulin sensitizer in the NAFLD therapy, but with less adverse effects. Phase III clinical trials have confirmed silymarin to be currently the best medication for the NAFLD patients, but the problems associated with its standardization, formulation and dosage are yet to be solved. However, green tea (Camellia sinensis) and licorice (Glycyrrhiza glabra) root extracts have also been studied in the clinical trials in the therapy of NAFLD patients. Some other herbal products, which have been tested on animals and have the potential to be used in clinical trials, are briefly summarized in this paper.