Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

IgG4 related disease in a seven year old girl with multiple organ involvement: A rare presentation.

Autoimmune pancreatitis has been described as a pancreatic manifestation of immunoglobulin G4-related disease, which is characterized by typical histopathologic, radiologic, and clinical features. Immunoglobulin G4-related disease is usually accompanied by elevated serum immunoglobulin G4 level, and can involve multiple organ/systems. Immunoglobulin G4-related disease has rarely been reported in pediatric population. There are few reports of inflammatory bowel disease in association with immunoglobulin G4-related disease. We describe a 7-year-old girl who presented with pancreatitis and concurrent sclerosing cholangitis, and developed bloody diarrhea during follow-up. An endoscopic examination revealed inflammatory bowel disease, and later lacrimal gland involvement was also recognized. She was diagnosed as having immunoglobulin G4-related disease, and her clinical signs and symptoms improved dramatically after steroid treatment. Hence, awareness of the clinical picture is important and early diagnosis can prevent fibrosis and organ damage.

Gastrointestinal sarcoidosis presenting with malabsorption at an early age.

Sarcoidosis is a chronic multisystemic granulomatous disease that predominantly involves the thoracic lymph nodes and lungs and primarily occurs in young adults. Isolated extrapulmonary localization is uncommon in adults, and exceptionally rare in the pediatric age group. A 4-year-old male patient with chronic diarrhea and abdominal distention for the last 8 months is presented. Endoscopic biopsies, obtained during gastroscopy and colonoscopy, revealed noncaseating granulomas in all segments of the gastrointestinal tract. A noncaseating granuloma was also demonstrated in the liver biopsy. Granulomatous inflammation of both the gastrointestinal system and liver along with elevated serum angiotensin-converting enzyme were consistent with sarcoidosis. The peculiarity of our pediatric sarcoidosis was the involvement of whole gastrointestinal system, which is exceptionally rare in all age groups. Furthermore, this is the youngest case in the literature with gastrointestinal and hepatic sarcoidosis in the absence of pulmonary involvement at onset.

Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience.

BACKGROUND: It has been reported that 5-50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. OBJECTIVE: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. METHODS: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. RESULTS: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. CONCLUSIONS: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.

A Rare Complication of Giardiasis in Children: Protein-losing Enteropathy.

Protein-losing enteropathy may develop as a complication of a wide spectrum of diseases. Three cases of giardiasis that presented with acute onset of hypoalbuminemia were documented, and resolution of protein loss after treatment was also confirmed. Thus, chronic enteric infections should be considered as an etiology of severe intestinal protein loss, particularly in children.

Hepatic apoptotic markers are not predictors for the virological response to interferon-based therapy in chronic hepatitis C patients.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The majority of cases involving HCV infection develop into chronic hepatitis because of a failure to develop an effective immune response. Apoptosis of the hepatocytes plays a significant role in the pathogenesis of HCV infection: the interaction between the Fas antigen on hepatocytes and the Fas ligand on T cells corresponds to the main mechanism for hepatocyte damage. Interferon (IFN)-α has antiviral, immunoregulatory, and antiproliferative properties, and apoptosis seems to be a critical event in the action mechanisms of both IFNs. In this study, we aimed to detect any relationship between apoptotic markers in the liver and the response to the treatment. MATERIALS AND METHODS: The study included 180 chronic HCV patients treated with IFN and ribavirin in four centers. Apoptotic markers (Fas, Fas ligand, Fas-associated death domain, caspases 3, 8, and 9, and in-situ apoptosis) were studied in the liver. The age, sex of the patients, response to therapy, ALT level, viral load, and genotype were recorded. RESULTS: The results of the study showed that the histological activity index and fibrosis correlated with CD95 staining density, caspase-8 intensiveness, and portal and parenchymal Fas ligand scores. The apoptotic parameters of the responsive cases were not significantly different from those of the unresponsive cases. CONCLUSION: The apoptotic parameters studied in liver tissue are associated with inflammation and fibrosis; however, these parameters may not predict response to treatment.

Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease.

OBJECTIVE: Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA. RESULTS: Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively. CONCLUSIONS: Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.

Impact of Helicobacter pylori eradication on the anti-secretory efficacy of lansoprazole in gastroesophageal reflux disease patients.

BACKGROUND: Helicobacter pylori eradication was recommended for the prevention of atrophic gastritis in gastroesophageal reflux disease (GERD) patients on long-term omeprazole treatment. It has been also shown that the treatment with proton pump inhibitors produces lower intragastric pH after H. pylori eradication in subjects with peptic ulcer and healthy individuals. The aim of the present study was to test the hypothesis of whether the efficacy of lansoprazole is reduced after the eradication of H. pylori in GERD patients with peptic esophagitis. METHODS: Eight-hour intragastric pH recordings were performed before and after an 8-day course of lansoprazole (30 mg once daily) in 10 H. pylori-positive male patients with reflux esophagitis and were repeated after the H. pylori eradication. Intragastric acidity was measured by using an antimony electrode placed 10 cm below the cardia. RESULTS: Baseline median preprandial, post-prandial, total intragastric pH and the percentage of time with pH < 3 were not different before and after H. pylori eradication without lansoprazole treatment. During lansoprazole treatment, median post-prandial intragastric pH was lower (4 vs 2.7; P < 0.05) and the percentage of time with pH < 3 was longer (3.4%vs 41.8%; P < 0.05) after H. pylori eradication. Median total intragastric pH tended to be lower after eradication but no difference was found in preprandial median pH. CONCLUSIONS: In patients with reflux esophagitis treated with lansoprazole, intragastric pH increased significantly when H. pylori was present, especially in the post-prandial period, whereas baseline pH remained unchanged after H. pylori eradication.

Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury.

BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs are two major causes of gastric injury but the effect of H. pylori eradication on the development of aspirin-induced gastric mucosal injury is unclear. The aim of the present study was to investigate the effect of Helicobacter pylori eradication on gastroduodenal mucosal injury induced by antithrombotic doses of aspirin. METHODS: Patients who had been planned to start on medium-dose aspirin (300 mg) for any kind of indication were included in the study. All subjects underwent upper gastrointestinal endoscopy for determination of H. pylori status and Lanza score. The H. pylori-positive patients were randomized to receive either aspirin + eradication (omeprazole 20 mg b.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks) or aspirin + placebo eradication. Endoscopic reassessment was done 4 months after the onset of aspirin or when symptoms developed. RESULTS: Thirty-two patients (placebo group n = 16, H. pylori-eradicated group n = 16) completed the study and Lanza scores of both groups were similar before treatment. Lanza scores significantly increased in the placebo group (0.69 +/- 0.87 vs 2.25 +/- 1.3, P < 0.0001) and did not change in the H. pylori-eradicated group after aspirin treatment (0.43 +/- 0.72 vs 0.75 +/- 0.93, P > 0.05). CONCLUSION: Helicobacter pylori eradication may prevent medium-dose aspirin-induced gastroduodenal mucosal injury.