Eleni Tsiaousi

The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease.

Non‐alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD.

Malnutrition in end stage liver disease: Recommendations and nutritional support

Malnutrition has increasingly been acknowledged as an important prognostic factor which can influence the clinical outcome of patients suffering from end‐stage liver disease (ESLD). Despite the fact that malnutrition is not included in the Child–Pugh classification, its presence should alert clinicians to the same extent as do other complications, such as ascites and hepatic encephalopathy. The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill‐balanced metabolic state are multiple and they intertwine. Inadequate offer of nutrients, the hypermetabolic state in cirrhosis, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are the main reasons that disrupt the metabolic balance in ESLD. Identifying patients that are approaching the state of malnutrition by simple and easily applied methods is necessary in order to provide nutritional support to those that need it most. According to the European Society for Clinical Nutrition and Metabolism, simple bedside methods such as Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of cirrhotic patients. Correcting the nutrient deficit of the affected patients is mandatory. Avoidance of alcohol and excess fat and ingestion of 4–6 meals/day containing carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral feeding and/or use of special formulae such as branched‐chain amino acid‐enriched nutrient mixtures are often recommended. Enteral nutrition improves nutritional status and liver function, reduces complications, prolongs survival and is therefore indicated.

Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease

The aim of the study was the evaluation of serum vitamin B12 and folate levels in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and their association with the disease severity. Thirty patients with biopsy-proven NAFLD and 24 healthy controls matched for gender, age, body mass index and waist circumference were recruited. Blood samples for vitamin B12, folate, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance was calculated. There was no difference in serum vitamin B12 and folate levels between groups. Neither vitamin B12 nor folate levels were significantly different within any histological category, including steatosis grade, fibrosis stage, lobular inflammation, portal inflammation and ballooning. In conclusion, similar vitamin B12 and folate levels were observed in non-alcoholic steatohepatitis and non-alcoholic fatty liver patients, and controls. Furthermore, vitamin B12 and folate levels were not associated with either insulin resistance or the severity of liver disease.

4,4′-Methylenedianiline-induced hepatitis in an industrial worker: Case report and review of the literature

4,4′-Methylenedianiline (MDA) is a chemical used in manufacturing and insulation processes and is a well-known hepatotoxin. We report the case of a 42-year-old construction-site worker who was accidentally exposed to large amounts of MDA and developed acute liver damage. The clinical course is described, with particular emphasis on the timely identification of the underlying cause and prompt management that led to an uneventful recovery. We review the relevant literature and discuss the safety measures necessary to minimize similar occupational hazards in industrial workers.

Letter: is Helicobacter pylori behind Barrett's oesophagus and colorectal neoplasms?

SIRS, Andrichi et al.’s meta-analysis showed that Barrett’s oesophagus (BO) was associated with an increased risk of both colorectal adenomas and colorectal cancer (CRC). They concluded that if the risk estimates for CRC in BO patients reflects a real relationship, an established association will warrant a search for common genetic or environmental risk factors. Some genetic alterations are common in both conditions; we initially found that specialised intestinal metaplasia indicating BO appeared in a significant percentage of patients with colon tumours (12/23) compared with controls (2/14) and was associated with increased oesophageal mucosal expression of oncogenes Ki-67 and p53/Bcl-2 that indicated mainly increased proliferation leading to oncogenesis. In this regard, Helicobacter pylori infection may be considered a promoter of both diseases. Our and others’ data indicate that H. pylori infection might contribute to oesophageal adenocarcinoma progress in subpopulations with gastro-oesophageal reflux disease and BO. In this respect, gastrin, induced by H. pylori infection, is an oncogenic growth factor contributing to oesophageal, gastric and colon carcinogenesis and, in particular, playing a potential causal effect on neoplastic progression in BO and left side CRC showing, for instance, anti-apoptotic activity through upregulation of the anti-apoptotic Bcl-2 and stimulation of mutagenic and tumourigenic cyclooxygenase-2 expression. Moreover, H. pylori infection is mostly frequent in colonic adenomas and tumour tissues (documented by immunohistochemical stain) and is accompanied by increased cell proliferation (mainly enhanced Ki-67 and Bcl-2 expression) and impaired apoptotic (decreased Bax) processes, thereby indicating its potential pathogenetic role. Apart from upper gastrointestinal tract (UGT), H. pylori infection might also cause chronic inflammatory colon mucosal damage and stimulate cancer stem cells and/or recruit bone-marrow–derived stem cells, which may ultimately facilitate UGT and colon tumour formation and progression. However, further studies are needed to elucidate the proposed pathophysiological mechanisms involved in H. pylori-associated colon oncogenesis; its eradication might inhibit these oncogenic processes.

A Case of Churg-Strauss Syndrome Revealed by Eosinophilic Gastroenteritis

Churg-Strauss syndrome (CSS) is a rare and usually underrecognized entity that often manifests late in the process of the disease. The syndrome is a small vessel-necrotizing vasculitis characterized by asthma, extravascular necrotizing granulomas, hypereosinophilia, and lung infiltrates [1]. According to the classification of CSS by the American College of Rheumatology, the presence of four or more of the criteria required to establish a diagnosis of CSS yield a sensitivity of 99.7% for CSS [2, 3] (Table 1). The annual incidence of the disease ranges between 0.5 and 6.8 per million inhabitants. The average age of the patient at diagnosis is 50 years; there is no sex predominance, and the annual incidence among asthma patients ranges from 0 to 97 per million [1]. The pathogenesis and etiology of CSS remain unclear, but the disease is most likely autoimmune, at least for those 30–40% anti-neutrophil cytoplasmic antibodies (ANCA)positive patients [4].

Helicobacter pylori might contribute to cancer and/or bone marrow-derived stem cell-related gastrointestinal oncogenesis

Helicobacter pylori might contribute to cancer and/or bone marrow-derived stem cell-related gastrointestinal oncogenesis

Helicobacter pylori infection in a Greek cohort with biliary disease.

SIR, In a recent study, Helaly et al.1 showed that Helicobacter pylori infection might be an aetiological factor leading to cholecystitis; gastric colonisation with H. pylori could be a source for gall bladder infection, and the organism may act as a lithogenic component, especially in the context of pure pigmented gallstones. In this regard, using serological anti-H. pylori IgG antibodies, our own relative data indicate presence of past and/or current H. pylori infection in 63/123 (51.2%) patients (64 females, mean age: 63 years) with calcular biliary and pancreatic diseases (cholecystitis/cholangitis and pancreatitis, respectively).2 Moreover, histological presence of H. pylori infection was detected in gall bladder tissue (by cresyl fast violet staining) in 19.3% of Greek cholecystectomised patients (all female).3 Although Helaly et al. report that the pathways of H. pylori penetration into the bile have not been completely explained, they comment that “the possibility is the translocation from the duodenum via Oddi’s sphincter and, moreover, bacterial antigen penetration into the portal circulation and lymphatic vessels is also possible”.1 We also considered the possible pathways of H. pylori migration and colonisation in the biliary tract and its potential involvement in inflammatory biliary diseases.2 Among the risk factors involved in gall bladder stone development, the inflammatory process plays an essential role; chronic biliary inflammation can also contribute to gall bladder cancer.4 In this regard, H. pylori infection could affect the pathophysiology of gall bladder stone creation and its complications, including cholecystitis, cholangitis, pancreatitis and even biliary cancer by the following mechanisms: i) Releasing large amounts of proinflammatory and vasoactive substances, such as interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-α (TNFα) or eicosanoids (leukotrienes, prostaglandins catalysed by cyclo-oxygenase enzymes), and acute-phase proteins (fibrinogen, C-reactive protein) involved in a number of inflammatory diseases,5 also including gall bladder disorders;6 H. pylori could indirectly affect extragastric tissues possibly including the gall bladder through the release of numerous cytokines such as TNFα acting at a distance;7 ii) Producing oxidative stress and circulating lipid peroxides5 also involved in gall bladder disease;6 for instance, increased production of oxygen and lipoperoxide free radicals and macrophage inflammatory cytokines (IL-6, IL-1α, TNFα) have been reported in blood in gallstone disease female patients, indicating the macrophages’ dominant role in the inflammatory and oxidative response during gall bladder stone disease in postmenopausal women;6 iii) Influencing the apoptotic process,5 also involved in chronic calculous cholecystitis and gall bladder oncogenesis;4 seropositivity to H. pylori proteins is associated with an increased risk of biliary tract cancer.8 In addition, H. pylori-induced vacA cytotoxin promotes intracellular survival of the bacterium, modulates host immune responses and induces autophagy.9 Subsequently, H. pylori, as an intracellular microorganism, invades and replicates in the cells. The autophagy induction by H. pylori is not only found in macrophages but also in dendritic cells (also expressed in acute and chronic cholecystitis)10 and gastric epithelial cells.9 The bacterium’s residence inside the infected cells will increase its resistance to antimicrobial treatment, avoid neutralisation by anti-H. pylori antibodies, impair antigen presentation, and alter the cellular immune response.9 In turn, the potential influx of activated monocytes infected with H. pylori in the gall bladder may lead to gall bladder-related pathologies; a comparable potential influx of activated monocytes infected with H. pylori through the disrupted blood-brain barrier, induced by several H. pylori-related mediators, in the brain (‘Trojan Horse’ pathway) might also lead to brain pathologies.9 Moreover, comparable to H. pylori translocation from the duodenum via Oddi’s sphincter to the biliary tract, mentioned by Helaly et al.,1 this bacterium may reach the brain through the oral cavity (which appears to act as a permanent reservoir for H. pylori)-nasal cavity-olfactory neuroepithelium pathway, causing central nervous system pathologies.11 Therefore, H. pylori eradication may have a positive impact on H. pylori-related gall bladder and other tissue pathologies. As there is lack of literature showing any demonstrable evidence to support the aforementioned H. pylori-related mechanisms involved in the pathophysiology of gall bladder diseases, large-scale studies are necessary to elucidate these fields. J. Kountouras, E. Tsiaousi, S. Trigonis, C. Zavos, G. Kouklakis Department of Gastroenterology Second Medical Clinic Aristotle University of Thessaloniki Ippokration Hospital Thessaloniki Macedonia Greece