Characteristics of allergic colitis in breast-fed infants in the absence of cow's milk allergy

AIM: To investigate the characteristics of mucosal le-sions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. METHODS: In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimi-nation diet for cow's milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as con-trols. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with differ-ent nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. RESULTS: Iron deficiency, peripheral eosinophilia andthrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4±3.2 μmol/L vs 13.7±4.7 μmol/L, P<0.001; 0.67±0.49 G/L vs 0.33±0.17 G/L, P<0.001; 474±123 G/L vs 376±89 G/L, P<0.001, respectively). At colonosco-py, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 contin-ued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when com-pared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients ex-hibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessa-tion of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. CONCLUSION: Infant hematochezia, after cow's milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnor-mality. Formula feeding results in shorter time to cessa-tion of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia.

Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease

AIM： To investigate intestinal alkaline phosphatase （iAP） in the intestinal mucosa of children with inflammatory bowel disease （IBD）. METHODS： Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls. In IBD patients, specimens were obtainedboth from inflamed and non-inflamed areas. The lAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. Tissue localiza- tion of lAP and Toll-like receptor （TLR） 4 was investi- gated by immunofluorescent staining. RESULTS： The lAP protein level in the inflamed muco- sa of children with Crohn＇s disease （CD） and ulcerative colitis （UC） was significantly decreased when compared with controls （both P 〈 0.05）. Similarly, we found a significantly decreased level of lAP protein in the in- flamed mucosa in CD compared with non-inflamed mucosa in CD （P 〈 0.05）. In addition, the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD （P 〈 0.05）. lAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls, lAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significant- ly different from that in non-inflamed colonic mucosa with CD. Expression of lAP mRNA in patients with non- inflamed mucosa and in controls were similar. Co-local- ization of lAP with TLR4 showed intense staining with a dotted-like pattern, lAP was present in the inflamed and non-inflamed mucosa of patients with CD, UC, and in control biopsy specimens, irrespective of whether it was present in the terminal ileum or in the colon. However, the fluorescent signal of TLR4 was more pro- nounced in the colon compared with the terminal ileum in all groups studied. CONCLUSION： Lower than normal lAP protein levels in inflamed mucosa of IBD patients may indicate a role for lAP in inflammatory lesions in IBD. Based on our results, administration of exogenous lAP enzyme to pa- tients with the active form of IBD may be a therapeutic option.

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn&#x02019;s disease (CD) and the effect of transforming growth factor-&#x003b2; (TGF-&#x003b2;) on these miRs in duodenal epithelial and fibroblast cells.METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-&#x003b2; (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 &#x000b1; 0.50 vs CD intact: 0.62 &#x000b1; 0.26, P &#x02264; 0.01) and to the control group (CD inflamed: 3.21 &#x000b1; 0.50 vs C: 1.00 &#x000b1; 0.33, P &#x02264; 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 &#x000b1; 1.02 vs Control: 1.00 &#x000b1; 0.40, P &#x02264; 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-&#x003b2; treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-&#x003b2;: 0.7 &#x000b1; 0.083 vs Control: 1 &#x000b1; 0.09, P &#x02264; 0.05) and also the expression of miR-146a (TGF-&#x003b2;: 0.67 &#x000b1; 0.04 vs Control: 1 &#x000b1; 0.15, P &#x02264; 0.01) and miR-155 (TGF-&#x003b2;: 0.72 &#x000b1; 0.09 vs Control: 1 &#x000b1; 0.06, P &#x02264; 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-&#x003b2; treatment did not influence the expression of miR-122.CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-&#x003b2; plays an important role in the regulation of the expression of these miRs.

Rising plasma nociceptin level during development of HCC:A case report

AIM:Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC),relatively few reports are available on HCC in primary biliary cirrhosis.High plasma nociceptin (N/OFQ) level has been shown in Wilson disease and in patients with acute and chronic pain. METHODS:We report a follow-up case of HCC,which developed in a patient with primary biliary cirrhosis.The tumor appeared 18 years after the diagnosis of PBC and led to death within two years.Alfa fetoprotein and serum nociceptin levels were monitored before and during the development of HCC. Nociceptin content was also measured in the tumor tissue. RESULTS:The importance and the curiosity of the presented case was the novel finding of the progressive elevation of plasma nociceptin level up to 17-fold (172 pg/mL) above the baseline (9.2±1.8 pg/mL),parallel with the elevation of alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development.Nociceptin content was more than 15-fold higher in the neoplastic tissue (0.16 pg/mg) than that in the tumor- free liver tissue samples (0.01 pg/mg) taken during the autopsy. CONCLUSION:Results are in concordance with our previous observation that a very high plasma nociceptin level may be considered as an indicator for hepatocellular carcinoma.

mi R-122 negatively correlates with liver fibrosis as detected by histology and FibroScan

AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections(types B, C), 19 with autoimmune liver diseases(autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology(alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNAisolation, expression levels of mi R-21, mi R-122, mi R-214, mi R-221, mi R-222, and mi R-224 were determined using Taq Man Micro RNA Assays applying mi R-140 as the reference. Selection of mi RNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of mi RNAs was correlated with fibrosis stage and liver stiffness(LS) value measured by transient elastography, as well as with serum alanine aminotransferase(ALT) level.RESULTS: The expression of individual mi RNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of mi R-122 in stage F4 was statistically significant(P < 0.04). When analyzing mi RNA expression in relation to fibrosis, levels of mi R-122 and mi R-221 showed negative correlations with fibrosis stage, and mi R-122 was found to correlate negatively and mi R-224 positively with LS values(all P < 0.05). ALT levels displayed a positive correlation with mi R-21(P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between mi R-122 and fibrosis stage and LS values(P < 0.05), and in the samples of chronic viral hepatitis, between mi R-221 and fibrosis stage(P < 0.01), whereas mi R-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases(P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values(P < 0.01) when etiology of fibrosis was not taken into account.CONCLUSION: Reduced expression of mi R-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.

Changes in lipid metabolism in chronic hepatitis C

AIM: To investigate the relationship between certain biochemical parameters of lipid metabolism in the serum and steatosis in the liver.METHODS: The grade of steatosis (0-3) and histological activity index (HAI, 0-18) in liver biopsy specimens were correlated with serum alanine aminotransferase (ALT), total cholesterol and triglyceride levels in 142 patients with chronic hepatitis C (CH-C), and 28 patients with non-alcoholic fatty liver disease (NAFLD) without hepatitis C virus (HCV) infection. The serum parameters were further correlated with 1 797 age and sex matched control patients without any liver diseases.RESULTS: Steatosis was detected in 90 out of 142 specimens (63%) with CH-C. The ALT levels correlated with the grade of steatosis, both in patients with CH-C and NAFLD (P＜0.01). Inserting the score values of steatosis as part of the HAI, correlation with the ALT level (P＜0.00001) was found. The triglyceride and cholesterol levels were significantly lower in patients with CH-C (with and without steatosis), compared to the NAFLD group and to the virus-free control groups.CONCLUSION: Our study confirms the importance of liver steatosis in CH-C which correlates with lower lipid levels in the sera. Inclusion of the score of steatosis into HAI, in case of CH-C might reflect the alterations in the liver tissue more precisely, while correlating with the ALT enzyme elevation.

Elevated miR-33a and miR-224 in steatotic chronic hepatitis Cliver biopsies

AIM: To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues.

Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: A case report

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome： photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.

Changing trends in penetrating keratoplasty indications at a tertiary eye care center in Budapest,Hungary between 2006 and 2017

AIM:To analyze the changing trends in penetrating keratoplasty(PKP)indications.METHODS:This retrospective study included all patients with PKP between 2006 and 2017.Patients were classified using histological diagnoses.Our groups were as the following:pseudophakic or aphakic bullous keratopathy,regraft,acute necrotizing and ulcerative keratitis,keratoconus,Fuchs'dystrophy,corneal dystrophy other than Fuchs',corneal scar,other diagnoses and failed endothelial keratoplasty graft.Additionally,two different time-periods(2006-2012 and 2013-2017)were analysed.RESULTS:Totally 1721 histological analyses of 1214 patients were available for review.The diagnoses were pseudophakic or aphakic bullous keratopathy in 487(28.3%),regraft in 443(25.7%),acute necrotizing and ulcerative keratitis in 313(18.2%),corneal scar in 153(8.9%),keratoconus in 140(8.1%).Fuchs'dystrophy in 61(3.5%),corneal dystrophy other than Fuchs'in 46(2.7%),other diagnoses in 44(2.6%)and failed endothelial keratoplasty graft in 34(2.0%)cases.From the first to the second analysed time-period,incidence of acute necrotizing and ulcerative keratitis,corneal scar,Fuchs'dystrophy increased(P<0.032 for all)and incidence of keratoconus significantly decreased(P=0.015).CONCLUSION:Pseudophakic or aphakic bullous keratopathy is the leading indication for PKP,followed by regraft and acute necrotizing and ulcerative keratitis.