Background
Many concerns about liver transplantation in alcoholic patients are related to the risk of alcohol recidivism. Starting from 2002, an Alcohol Addiction Unit (AAU) was formed within the ...liver transplant center for the management of alcoholic patients affected by end‐stage liver disease and included in the waiting list for transplantation. We evaluated retrospectively the impact of the AAU on alcohol recidivism after transplantation. The relationship between alcohol recidivism and the duration of alcohol abstinence before transplant was evaluated as well.
Methods
Between 1995 and 2010, 92 cirrhotic alcoholic patients underwent liver transplantation. Clinical evaluation and management of alcohol use in these patients was provided by psychiatrists with expertise in addiction medicine not affiliated to the liver transplant center before 2002 (n = 37; group A), or by the clinical staff of the AAU within the liver transplant center starting from 2002 (n = 55; group B).
Results
Group B, as compared with group A, showed a significantly lower prevalence of alcohol recidivism (16.4 vs. 35.1%; p = 0.038) and a significantly lower mortality (14.5 vs. 37.8%; p = 0.01). Furthermore, an analysis of group B patients with either ≥6 or <6 months of alcohol abstinence before transplantation showed no difference in the rate of alcohol recidivism (21.1 vs. 15.4%; p = ns).
Conclusions
The presence of an AAU within a liver transplant center reduces the risk of alcohol recidivism after transplantation. A pretransplant abstinence period <6 months might be considered, at least in selected patients managed by an AAU.
Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, ...the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies.
Abstract Purpose We assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib. Patients and ...methods Thirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child–Pugh class A) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression, unacceptable toxicity, death or patient/physician decision to discontinue. The primary end-point was safety; secondary end-points included efficacy (including time to progression and overall survival). Results The median treatment duration was 19.5 weeks (range 2–103). At data cutoff, three patients remained on treatment. Reasons for discontinuation were adverse events ( n = 20), disease progression ( n = 10), consent withdrawal ( n = 2) and death ( n = 1). Seventeen patients required dose reductions (mostly for adverse events n = 15); 35 patients had treatment interruption (mostly for adverse events n = 32 or patient error n = 11). The most frequent treatment-related adverse events were hand–foot skin reaction (any grade n = 19; grade ⩾3 n = 5), diarrhoea ( n = 19; n = 2), fatigue ( n = 19; n = 6), hypothyroidism ( n = 15; n = 0), anorexia ( n = 13; n = 0), hypertension ( n = 13; n = 1), nausea ( n = 12; n = 0) and voice changes ( n = 10; n = 0). Disease control was achieved in 26 patients (partial response n = 1; stable disease n = 25). Median time to progression was 4.3 months. Median overall survival was 13.8 months. Conclusion Regorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib.
Ulcerative colitis(UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the "forgotten ...organ", Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle(Ec N) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor?(Ardeypharm Gmb H, Herdecke, Germany and Ec N, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of Ec N 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of Ec N.
The proximity of the endoscopic ultrasound (EUS) transducer to the pancreas and the possibility to place needles or other accessories into a target located adjacent to the wall of the GI tract have ...encouraged researchers to develop various EUS‐guided local treatments directed towards pancreatic neuroendocrine neoplasms (PanNENs). The use of pre‐operative EUS‐guided tattooing or fiducial marker placement to facilitate intraoperative tumor localization has proven effective in reducing operative time of laparoscopic surgeries. To reduce the mortality and morbidity rates of surgical resection, which is presently the mainstay treatment of PanNENs. EUS‐guided loco‐regional treatments, such as injection of alcohol and radiofrequency ablation have been proposed and results are hitherto promising. The present paper summarizes currently available data in the field of EUS‐guided interventions to pancreatic neuroendocrine tumors, as well as possible future applications.
Portal vein thrombosis (PVT) represents a well-known complication during the natural course of liver cirrhosis (LC), ranging from asymptomatic cases to life-threating conditions related to portal ...hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development. However, PVT occurrence remains unpredictable and many issues regarding its natural history, prognostic significance and treatment are still elusive. In particular although spontaneous resolution or disease stability occur in most cases of PVT, factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet. Moreover, PVT impact on LC outcome is still debated, as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression. Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases, even if the safer therapeutic option and the optimal therapy duration are still unknown. Nevertheless, their impact on mortality rates should be addressed more extensively. In this review we present the most debated questions regarding PVT, whose answers should come from prospective cohort studies and large sample-size randomized trials.
The interactions between diet, gut microbiota, and irritable bowel syndrome (IBS) have many complex mechanisms that are not fully understood. Food additives are one component of the modern human diet ...that deserves attention from science and government policies. This review aims at identifying the current knowledge about the impact of food additives on gut microbiota and their potential role in the development of IBS. To date, few data on the effect of food additives on gut microbiota in IBS patients are available. However, exposure to food additives could induce the dysbiosis and dysregulation of gut homeostasis with an alteration of the gut barrier and activation of the immune response. These microbial changes could exacerbate the gut symptoms associated with IBS, such as visceral pain, low-grade inflammation, and changes in bowel habits. Some additives (polyols) are excluded in the low fermentable oligo-, di- and monosaccharide, and polyol (FODMAP), diets for IBS patients. Even if most studies have been performed in animals, and human studies are required, many artificial sweeteners, emulsifiers, and food colorants could represent a potential hidden driver of IBS, through gut microbiota alterations. Consequently, food additives should be preventively avoided in the diet as well as dietary supplements for patients with IBS.
Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular ...disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment.
There is increasing evidence for a correlation between intestinal microbiota, bacterial translocation and hepatic steatosis. Intestinal microbiota affects nutrient absorption and energy homeostasis. ...Altered intestinal permeability may favor the passage of bacteriaderived compounds into systemic circulation, causing a systemic inflammatory state, characteristic of the metabolic syndrome. The interaction between intestinal permeability and luminal bacteria is involved in the pathogenesis and evolution of non-alcoholic liver disease. Microbiota pharmacological modulation could be a promising tool for a new therapeutical approach to non-alcoholic fatty liver disease.
Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID ...patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.
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