AIMTo analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients.METHODSDuring a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury.RESULTSTwo hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued.CONCLUSIONLiver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

Many urethral pathologies require surgical interventions. Although the commonly used surgical techniques are still being developed, complications such as the urethral strictures often occur and repeated surgery is needed. Tissue engineering of the urethral tissue, using autologous stem cells and appropriate scaffolds, represents promising technique to overcome these complications. In our experiment, we focused on the differentiation of adipose tissue‐derived stem cells seeded on the collagen/hyaluronan scaffolds into urothelial and smooth muscle cells. Differentiation culture media containing keratinocyte serum‐free medium with 2 % fetal bovine serum (FBS) and 30 ng/mL EGF, and D‐MEM with 10 % FBS, 2.5 ng/mL TGF‐β and 5 ng/mL PDGF were used to induce urothelial and smooth muscle differentiation, respectively. After two weeks of cultivation, cells were analyzed by scanning electron microscope (JEOL 7500F) for morphological features. Expression of the uroplakin 2 (UPK2) gene, keratin 2 gene (KRT2), ACTA 2 gene, and calponin 1 gene (CNN1) was tested in order to determine successful differentiation by quantitative Real‐Time PCR. Obtained results showed attachment of the cells on scaffold surface. The increased levels of UPK2 and KRT2 confirmed urothelial differentiation and expression of ACTA 2 and CNN1 confirmed smooth muscle differentiation. On the basis of obtained results, it can be emphasized that collagen/ hyaluronan scaffolds colonized by adipose tissue‐derived stem cells after performing further tests dealing with biosafety may have promising potential for tissue engineering of the urethra.Support or Funding InformationSupported by grant APVV no. 15‐0111.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.