Alcoholic disease: Liver and beyond Rocco, Alba; Compare, Debora; Angrisani, Debora ...
World journal of gastroenterology,
10/2014, Volume:
20, Issue:
40
Journal Article
Open access
The harmful use of alcohol is a worldwide problem.It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability;it is a causal factor of 60 ...types of diseases and injuries and a concurrent cause of at least 200 others.Liver is the main organ responsible for metabolizing ethanol,thus it has been considered for long time the major victim of the harmful use of alcohol.Ethanol and its bioactive products,acetaldehyde-acetate,fatty acid ethanol esters,ethanol-protein adducts,have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver.A similar mechanism has been postulated for the alcohol-related pancreatic damage.Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the"necrosis-fibrosis"sequence that finally leads to atrophy and fibrosis,morphological hallmarks of alcoholic chronic pancreatitis.Even if less attention has been paid to the upper and lower gastrointestinal tract,ethanol produces harmful effects by inducing:(1)direct damaging of the mucosa of the esophagus and stomach;(2)modification of thesphincterial pressure and impairment of motility;and(3)alteration of gastric acid output.In the intestine,ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system.Notably,disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage.This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver,pancreas and gastrointestinal tract.
The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which ...probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.
Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting.
At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment.
LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.
Although the prevalence of gastric cancer(GC) progressively decreased during the last decades,due to improved dietary habit,introduction of food refrigeration and recovered socio-economic level,it ...still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs,that rises many relevant concerns taking into account its worldwide variability,natural history,diagnostic tools,therapeutic strategies,and cost-effectiveness. Intestinal-type,the most frequent GC histotype,develops through a multistep process triggered by Helicobacter pylori(H. pylori) and progressing from gastritis to atrophy,intestinal metaplasia(IM),and dysplasia. However,the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore,it remains unclear who should be screened,when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries,at high prevalence of GC and the high-risk subjects in western countries,at low prevalence of GC.As far as concern surveillance,currently,we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach,the patients at higher risk,the best timing and the cost-effectiveness.Anyway,patients with corpus atrophic gastritis,extensive incomplete IM and dysplasia should enter a surveillance program.At present,screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.
Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal ...nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH. Treatment of PNH with the complement inhibitor eculizumab (Soliris
®
) prevented both recurrences of episodes of intravascular hemolysis and liver enzyme alteration. This is the first known published case of PNH-associated hepatitis.
The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has ...dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.
Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC ...development holds immense potential to revolutionize patients’ treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.
Many patients with inflammatory bowel disease (IBD) restrict dairy products to control their symptoms. The aim of the study was to investigate the prevalence of lactose intolerance assessed with ...hydrogen breath test (H-BT) in IBD patients in clinical remission compared to a sex, age and BMI matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910 CC (wildtype) and the intermediate phenotype LCT-22018 CT and LCT-13910 AG; finally, we assess the correlation between genotype and H-BT. A total of 54 IBD patients and 69 control who underwent clinical evaluation, H-BT and genetic test were enrolled. H-BT was positive in 64.8% IBD patients and 62.3% control (
= 0.3). The wild-type genotype was found in 85.2% IBD patients while CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 9.3%, 1.8% and 3.7%. In the control group, the wild-type genotype, CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. Therefore, the wild-type and polymorphisms' prevalence did not differ between IBD population and control group (85.2% vs. 87%,
= 0.1) (14.8% vs. 13%,
= 0.7). The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73-16.29,
= 0.003) and in the IBD (OR 7.61, 95%CI 1.36-42.7,
= 0.02). The prevalence of lactose intolerance in IBD patients did not differ from that of control. Despite suggestive symptoms, about 1/3 of IBD patients are not lactose intolerant, thus not needing "a priori" elimination diet. This may encourage a rationale and balanced dietary management in IBD.
Background & Aims Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost ...saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. Methods We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n = 90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n = 90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. Results Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval CI, 84.0%–95.8%) and sequential therapies (93.3%; 95% CI, 86.9%–97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%–99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%–98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; −7.6% to 9.8%) and −1.0% in the per-protocol analysis (95% CI; −8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. Conclusions Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.
Eur J Clin Invest 2011; 41 (4): 380–386
Background Gastroesophageal reflux disease (GERD), including erosive reflux disease and non‐erosive reflux disease (NERD), is a chronic disease with a ...significant negative effect on quality of life. State‐of‐the‐art treatment involves proton pump inhibitors (PPIs). However, relapse of symptoms occurs in the majority of the patients who require recurrent or continuous therapy. Although PPIs are well tolerated, little information is available about gastrointestinal side effects.
Aim To evaluate the effects of long‐term PPI treatment on development of bowel symptoms and/or small intestinal bacterial overgrowth (SIBO).
Methods Patients with NERD not complaining of bowel symptoms were selected by upper endoscopy, 24‐h pH‐metry and a structured questionnaire concerning severity and frequency of bloating, flatulence, abdominal pain, diarrhoea and constipation. Patients were treated with esomeprazole 20 mg bid for 6 months. Prior to and after 8 weeks and 6 months of therapy, patients received the structured questionnaire and underwent evaluation of SIBO by glucose hydrogen breath test (GHBT).
Results Forty‐two patients with NERD were selected out of 554 eligible patients. After 8 weeks of PPI treatment, patients complained of bloating, flatulence, abdominal pain and diarrhoea in 43%, 17%, 7% and 2%, respectively. After 6 months, the incidence of bowel symptoms further increased and GHBT was found positive in 11/42 (26%) patients. By a post hoc analysis, a significant (P < 0·05) percentage of patients (8/42) met Rome III criteria for irritable bowel syndrome.
Conclusions Prolonged PPI treatment may produce bowel symptoms and SIBO; therefore, the strategy of step‐down or on‐demand PPI therapy should be encouraged in GERD.
Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed ...consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.
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