Platelet-Rich stroma from Crohn's disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls.

BACKGROUND: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls. METHODS: Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis. RESULTS: Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*105 cells/mL versus non-IBD 12.20 ± 3.39*105). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples. CONCLUSIONS: The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products.

Quantitative HBV DNA and AST are strong predictors for survival after HCC detection in chronic HBV patients.

Hepatitis B virus infection (HBV) is an important co-factor in the development of hepatocellular carcinoma (HCC). We studied whether quantitative HBV DNA at time of HCC detection influences survival of HCC patients. All diagnosed HCC cases between 2000 and 2008 at our university-based reference centre were analysed to determine the influence of hepatitis B viral load on overall survival. Clinical and virological findings were evaluated in univariate and multivariate analyses, survival rates were assessed for HCC patients with a high viral load (HBV DNA ≥10(5) copies/ml) and low viral load (HBV DNA <10(5) copies/ml). HCC was diagnosed in 597 patients, including 98 patients with HBV. The group of 37 patients (38%) who had a high viral load contained more HBeAg-positive patients, had lower serum albumin levels and higher serum aspartate aminotransferase (AST ) and alanine aminotransferase (ALT ) levels. The one- and five-year survival rates of HCC patients with a high viral load were 58% and 11% and for HCC patients with a low viral load 70% and 35%, respectively. In multivariate analysis a higher AST level and higher viral load were significantly associated with shorter overall survival (HR=2.30; p=0.018, HR=1.22; p=0.015, respectively). HBeAg positivity, low albumin level or high AST or ALT levels in HCC patients are associated with a higher HBV DNA . HBV DNA level at detection is associated with overall survival of HCC patients. These findings support the concept that after HCC detection adequate suppression of HBV DNA by nucleoside analogue therapy may improve survival.

Systemic treatment in hepatocellular carcinoma; 'A small step for man...'.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. In localised disease, orthotopic liver transplantation, surgical resection or local ablations are the mainstay of treatment. In unresectable or metastatic HCC, systemic therapy has unfortunately yielded disappointing results and therefore until recently was generally considered to be ineffective. Most patients with HCC have an underlying liver disease and many drugs may exacerbate the underlying liver disease. Recently, two randomised phase II trials with sorafenib in patients with advanced or metastatic HCC have shown a significant increase in progression free and overall survival of approximately two months, which is an absolute novum for this disease. Sorafenib is therefore now considered a viable treatment option in patients with unresectable or metastatic HCC, a good performance status and Child-Pugh A liver cirrhosis. Despite this very promising result, of major concern is the treatment-related toxicity as observed in these and other trials by sorafenib treatment. However, the important first significant survival benefit by systemic treatment has generated hope for the development of new treatment strategies which will be more efficacious, have favourable toxicity profiles and will further extend survival of this still highly lethal disease.