Group 2 innate lymphoid cells exhibit progressively higher levels of activation during worsening of liver fibrosis.

INTRODUCTION: The interleukin-33/interleukin-13 pathway is involved in the immunopathology of liver fibrosis and recently characterized group 2 innate lymphoid cells (ILC2) were identified as profibrotic immune cells in the liver of mouse models. Our aim was to elucidate whether ILC2 might be present in human liver tissue and whether ILC2 contribute to liver fibrosis. MATERIALS AND METHODS: To identify ILC2 in liver tissue and blood, we purified mononuclear immune cells from needle biopsies, cirrhotic explant specimen, and paired peripheral blood samples. Cell suspensions were incubated with specific markers for ILC2 and analyzed by flow cytometry. The CD69 marker was included to assess the activation level of ILC2. In addition, we determined the IL-33 plasma level. RESULTS: Results were correlated with the METAVIR fibrotic score of patients enrolled in this study. We detected ILC2 in a higher percentage of CD45+ cells in liver tissue than in paired peripheral blood. The number of ILC2 was significantly increased in fibrotic tissue, but only slightly increased in paired peripheral blood. A higher percentage of CD69+ ILC2 was observed in fibrotic tissue, and this increase correlates positively with aggravation of liver fibrosis measured by fibrotic METAVIR score. A higher level of plasma IL-33 was only detected in samples obtained from cirrhotic patients. CONCLUSION: Our study indicates that ILC2 are present in the human liver and are activated in tissue contributing to the immunopathology of human liver fibrosis, independently of the etiology; which might be a potential new therapeutic target.

MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure.

Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the need and appropriate timing of orthotopic liver transplantation (OLT). In this study we investigated the prognostic efficacy of King's College criteria, Clichy's criteria, Model for End-Stage Liver Disease (MELD), and Pediatric End-Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with medical therapy (18%), death without OLT (15%), and receipt of a liver transplant were similar in adults (n = 64) and children (n = 56). MELD scores were significantly higher in patients who died compared to those who survived without OLT, both in adults (38 +/- 7 vs. 26 +/- 7, P = 0.0003) and children (39 +/- 7 vs. 23 +/- 6, P = 0.0004). Using logistic regression analysis in this cohort of patients, concordance statistics were significantly higher for MELD (0.95) and PELD (0.99) when compared to King's College (0.74) and Clichy's criteria (0.68). When data was analyzed in a Cox model including patients receiving transplants and censoring the time from admission, the concordance statistic for MELD (0.77) and PELD (0.79) remained significantly higher than that of King's College criteria but not higher than that of Clichy's criteria. In conclusion, this study is the first to show that MELD and PELD are superior to King's College and Clichy's criteria to assess prognosis in FHF. However, because data was generated from a single center and included a rather low number of patients who survived or died without OLT, further confirmation of our findings is required.

How common is delayed cyclosporine absorption following liver transplantation?

The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA > or =10 mg/kg/day (C(2) monitoring) and in 15 maintenance patients. Patients were categorized as 'normal' absorbers (C(2) exceeding C(4) and C(6)) or 'delayed' absorbers (C(4) or C(6) exceeding C(2)), and as 'good' (>800 ng/mL at C(0), C(2), C(4), or C(6)) or 'poor' absorbers (C(0), C(2), C(4) and C(6) <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had 'normal' CsA absorption and 12 (44%) 'delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6/15, 40%) or delayed (5/12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C(4). Mean C(0) level was significantly higher in delayed absorbers (282 +/- 96 ng/mL) than in normal absorbers (185 +/- 88 ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C(2) > C(4)) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C(4) in addition to C(2) differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided.