Adipokines in Nonalcoholic Steatohepatitis: From Pathogenesis to Implications in Diagnosis and Therapy

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from benign steatosis to end-stage liver disease. The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to involve a multiple-hit process with the first hit being the accumulation of liver fat which is followed by the development of necroinflammation and fibrosis. There is mounting evidence that cytokines secreted from adipose tissue, namely, adipokines, are implicated in the pathogenesis and progression of NAFLD. In the current review, we explore the role of these adipokines, particularly leptin, adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as elucidated in experimental models and clinical practice. We also comment on their potential use as noninvasive markers for differentiating simple fatty liver from NASH as well as on their potential future therapeutic role in patients with NASH

Elastography for Hepatic Fibrosis Severity in Chronic Hepatitis B or C

AIMS: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients. METHODS: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak's classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0-1 (n = 30), 2-3 (n = 20), 4-6 (n = 25), respectively. RESULTS: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p < 0.001). The diagnostic accuracy of elastography for severe fibrosis and cirrhosis was excellent [area under the receiver operating characteristic (AUROC) curve 0.938 vs. 0.948], but it was not optimal for mild fibrosis (AUROC 0.78). Values of 7.5, 9.0 and 12 kPa had a sensitivity and specificity for severe fibrosis/cirrhosis of 96, 84 and 60%, and 76, 90 and 94%, respectively. The median stiffness value in cirrhotic patients (score 5-6) was 16.6 kPa (7.7-48). No differences in accuracy of elastography between CHB or CHC patients were found. Cutoff was 12.5 kPa for cirrhosis; 10/75 patients (13%) were misclassified. CONCLUSION: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation

Helicobacter pylori (H pylori) infection in Greece: the changing prevalence during a ten-year period and its antigenic profile

BACKGROUND: To evaluate changes in H pylori infection prevalence in Greece during a ten-year period, and to examine its antigenic profile. METHODS: Three groups of patients were studied. Group O-87: Banked serum samples of 200 consecutive adult outpatients, from the Hepato-Gastroenterology clinic of a teaching hospital at Athens, collected in 1987. Group O-97: Serum samples of 201 similarly selected outpatients from the same Unit, collected in 1997. Group BD-97: Serum samples of 120 consecutive blood donors from the same hospital, collected in 1997. H pylori IgG antibody seroprevalence was studied by a quantitative ELISA. Antigenic profile was studied by western-blot IgG assay, in 62 IgG positive patients of O-97 and BD-97. Results were analyzed by conventional statistics and multivariate regression analysis. RESULTS: The H pylori seroprevalence increased with age in the three tested groups. In O-97, seroprevalence did not differ from that, in BD-97. On the contrary, there was a significant decrease in seropositivity between O-87 and O-97 (59.5% vs 49.2%, p = 0.039). Multiple regression analysis showed that age over 35 years (OR:3.45, 95% CI:1.59–7.49, p = 0.002) and year of patients' selection – that is 1987 or 1997 – (OR:1.73, 95% CI:1.14–2.65 for 1987, p = 0.010), were independent risk factors of H pylori infection. The seroprevalence of CagA+ and VacA+ strains was 77.4% and 58.5%, respectively, and type I(CagA+/VacA+) strains were significantly more common than type II(CagA-/VacA-) strains (59.7% vs 22.6%, p < 0.001). CONCLUSIONS: During a ten-year period, we found a significant decrease of H pylori infection in Greece and our data support the birth cohort phenomenon as an explanation for the age-dependent increase of H pylori infection. The prevalence of CagA and/or VacA positive strains is relatively high, in a country with low incidence of gastric cancer

Tissue detection of natural killer cells in colorectal adenocarcinoma

BACKGROUND: Natural killer (NK) cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. METHODS: Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57). The number of immunopositive cells (%) was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. RESULTS: NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031). CONCLUSIONS: Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages

Jejunogastric intussusception presented with hematemesis: a case presentation and review of the literature

BACKGROUND: Jejunogastric intussusception (JGI) is a rare but potentially very serious complication of gastrectomy or gastrojejunostomy. To avoid mortality early diagnosis and prompt surgical intervention is mandatory. CASE PRESENTATION: A young man presented with epigastric pain and bilous vomiting followed by hematemesis,10 years after vagotomy and gastrojejunostomy for a bleeding duodenal ulcer. Emergency endoscopy showed JGI and the CT scan of the abdomen was compatible with this diagnosis. At laparotomy a retrograde type II, JGI was confirmed and managed by reduction of JGI without intestinal resection. Postoperative recovery was uneventful. CONCLUSIONS: JGI is a rare condition and less than 200 cases have been published since its first description in 1914. The clinical picture is almost diagnostic. Endoscopy performed by someone familiar with this rare entity is certainly diagnostic and CT-Scan of the abdomen could also help. There is no medical treatment for acute JGI and the correct treatment is surgical intervention as soon as possible

The evolving role of leptin and adiponectin in chronic liver diseases

Leptin and adiponectin, the main metabolic products of adipose tissue, have been implicated in a wide spectrum of human diseases. Given the frequent presence of hepatic steatosis in several chronic liver diseases, there is currently increasing interest in the role of these adipokines in the development of hepatic steatosis and also in necroinflammation and fibrosis, mostly in patients with nonalcoholic fatty liver disease or chronic hepatitis C. According to experimental data, reduced adiponectin levels and increased leptin levels associated with leptin resistance, which are usually observed in obese patients with or without metabolic syndrome, may result in fat accumulation in the liver and in the enhancement of liver inflammation and mostly fibrogenesis. Increased leptin and decreased adiponectin serum levels have been detected initially in patients with nonalcoholic steatohepatitis and more recently in patients with chronic hepatitis C compared to healthy controls in most but not all studies, while the data on the associations between these adipokine levels and the severity of hepatic steatosis or fibrosis are still rather conflicting. However, several potential confounding parameters were not evaluated in all studies. Therefore, the associations between adipokines and liver histological lesions and their effects on liver cells should be evaluated further in prospective, carefully designed studies, including larger cohorts of patients with detailed assessment of metabolic and other potential confounding factors

Pseudohyperkalemia in Serum: A New Insight into an Old Phenomenon

Pseudohyperkalemia, a rise in serum potassium concentration with concurrently normal plasma potassium concentration, is an in vitro phenomenon that was first described 50 years ago. It was originally attributed to the release of potassium from platelets during platelet aggregation and degranulation, and a significant correlation between pseudohyperkalemia and platelet count was established. During the last decade, new data were added to this phenomenon. In particular, pseudohyperkalemia was defined when serum potassium concentration exceeded that of plasma by more than 0.4 mmol/L provided that samples are collected under strict techniques, remain at room temperature and are tested within 1 hour from blood specimen collection. Moreover, it is positively correlated to (1) thrombocytosis due to the release of potassium from platelet granules during coagulation, (2) erythrocytosis due to the dilution of the released potassium in smaller volumes of serum, and (3) the presence of activated platelets, which have the capability of aggregation at a higher speed and release more potassium during degranulation. However, pseudohyperkalemia may be “masked” when in a state of hypokalemia because potassium moves back into the intracellular space in vitro, and the phenomenon is ameliorated or even not detected