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Lai Q.,Catholic University of Louvain | Lai Q.,Azienda Universitario ospedaliera Pisana | Castro Santa E.,Catholic University of Louvain | Castro Santa E.,National Center for Liver Transplantation and Hepatobiliary Surgery | And 5 more authors.
Transplant International | Year: 2014

There is increasing evidence that systemic inflammation markers like neutrophil (NLR) and platelet-to-lymphocyte ratios (PLR) may play a role in the outcome of hepatocellular cancer (HCC). Between January 1994 and March 2012, 181 patients with HCC were registered on the transplant waiting list: 35 (19.3%) patients dropped out during the waiting period and 146 (80.7%) patients underwent liver transplantation (LT). The median follow-up of this patient cohort was 4.2 years (IQR: 1.8-8.3). On c-statistics, the last NLR (AUROC = 67.4; P = 0.05) was the best predictor of dropout. The last PLR had an intermediate statistical ability (AUROC = 66.1; P = 0.07) to predict post-LT tumor recurrence. Patients with a NLR value >5.4 had poor 5-year intention-to-treat (ITT) survival rates (48.2 vs. 64.5%; P = 0.02). Conversely, PLR better stratified patients in relation to tumor-free survival (TFS) (80.7 vs. 91.6%; P = 0.02). NLR is a good predictor for the risk of dropout, while PLR is a good predictor for the risk of post-LT recurrence. Use of these markers, which are all available before LT, may represent an additional tool to refine the selection criteria of HCC liver recipients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.


Micco L.,University College London | Micco L.,University of Bologna | Peppa D.,University College London | Loggi E.,University of Bologna | And 11 more authors.
Journal of Hepatology | Year: 2013

Background & Aims: A better understanding of the immunomodulatory effects of PegIFNα therapy could allow more rational optimisation of future therapeutic approaches in chronic HBV infection. In this study, we evaluated dynamic changes in the innate and adaptive arms of the immune system induced by PegIFNα. Methods: PBMC were obtained from a cohort of patients with eAg-negative CHB before, during and after PegIFNα treatment. The number, phenotype and function of global and virus-specific T cells and NK cells were analyzed by flow cytometry and serum cytokines by ELISA or CBA. Results: The absolute number of CD8 T cells was strikingly reduced on PegIFNα therapy (p <0.001), with a predominant loss of end-stage effectors, including CMV-specific CD8 T cells. There was no significant recovery of the exhausted HBV-specific CD8 T cell response. By contrast, PegIFNα was able to potently and cumulatively drive the proliferation and expansion in absolute numbers of CD56bright NK cell numbers (p <0.001), with induction of the pro-proliferative cytokine IL-15. Expanded CD56bright NK cells showed enhanced expression of activation markers and the activating receptor NKp46, accompanied by augmentation of TRAIL and IFN-γ expression (p <0.001). Peak virological response (temporal within individual patients and cross-sectional within the cohort) correlated with the degree of expansion of functional CD56bright NK cells. Conclusions: IFN-α mediates divergent effects on the innate and adaptive arms of the immune system in vivo. The efficacy of PegIFNα may be limited by its depleting effect on CD8 T cells; conversely, it can cumulatively drive proliferation, activation and antiviral potential of CD56bright NK cells. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Mirnezami R.,Imperial College London | Mirnezami A.H.,University of Southampton | Chandrakumaran K.,Basingstoke and North Hampshire Hospital NHS Trust | Abu Hilal M.,University of Southampton | And 3 more authors.
HPB | Year: 2011

Background: Laparoscopic liver resection (LLR) is now considered a feasible alternative to open liver resection (OLR) in selected patients. Nevertheless studies comparing LLR and OLR are few and concerns remain about long-term oncological equivalence. The present study compares outcomes with LLR vs. OLR using meta-analytical methods. Methods: Electronic literature searches were conducted to identify studies comparing LLR and OLR. Short-term outcomes evaluated included operating time, blood loss, length of hospital stay, peri-operative morbidity and resection margin status. Longer-term outcomes included local and distant recurrence, and overall (OS) and disease-free survival (DFS). Meta-analyses were performed using the Mantel-Haenszel method and Cohen's d method, with results expressed as odds ratio (OR) or standardized mean difference (SMD), respectively, with 95% confidence intervals (CI). Results: Twenty-six studies met the inclusion criteria with a population of 1678 patients. LLR resulted in longer operating time, but reduced blood loss, portal clamp time, overall and liver-specific complications, ileus and length of stay. No difference was found between LLR and OLR for oncological outcomes. Discussion: LLR has short-term advantages and seemingly equivalent long-term outcomes and can be considered a feasible alternative to open surgery in experienced hands. © 2011 International Hepato-Pancreato-Biliary Association.


Lerut J.P.,Catholic University of Louvain | Pinheiro R.S.,Catholic University of Louvain | Lai Q.,Catholic University of Louvain | Stouffs V.,Catholic University of Louvain | And 8 more authors.
Annals of Surgery | Year: 2014

Objective: To investigate the safety of minimal immunosuppression (IS) in liver transplantation (LT). Background: The lack of long-term follow-up studies, including pathologic data, has led to a protean handling of IS in LT. Methods: Between February 2000 and September 2004, 156 adults were enrolled in a prospective, randomized, double-blind, placebo-controlled minimization trial comparing tacrolimus placebo (TAC-PLAC) and TAC shortterm steroid (TAC-STER) IS. All patients had a minimum clinical, biochemical, and histological follow-up of 5 years. Results: Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1% and 82.1% (P = 0.89) and 74.2% and 76.9% (P = 0.90), respectively. Five-year biopsies were available in 112 (89.6%) of 125 survivors. Twelve patients refused a biopsy because of their excellent evolution; tissue material was insufficient in 1 patient; 11 had normal liver tests; and 2 patients had developed alcoholic and secondary biliary cirrhosis. Histology was normal in 44 (39.3%) patients; 35 (31.3%) had disease recurrence. The remaining biopsies showed nonspecific chronic hepatitis (14.3%), mild inflammatory infiltrates (10.7%), and steatosis (3.5%). All findings were equally distributed between both groups. In each group, 3 patients (4.8%) presented with acute cellular rejection after the first year and only 1 (0.9%) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis. Arterial hypertension, diabetes mellitus, renal insufficiency, hypercholesterolemia, gout, and obesity were equally low in both groups. Conclusions: Excellent long-term results can be obtained under minimal IS and absence of steroids. TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up. Copyright © 2014 by Lippincott Williams & Wilkins.


Sidhu R.,Gastroenterology and Liver Unit | McAlindon M.E.,Gastroenterology and Liver Unit | Drew K.,Gastroenterology and Liver Unit | Hardcastle S.,Gastroenterology and Liver Unit | And 2 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2012

OBJECTIVE: There are few centres that offer all forms of small-bowel endoscopic modalities [capsule endoscopy (CE), push enteroscopy (PE), double-balloon enteroscopy (DBE) or single-balloon enteroscopy and intraoperative enteroscopy (IOE)]. Previous investigators have suggested that DBE may be more cost-effective as the first-line investigation. We evaluated the relationship among four modalities of small-bowel endoscopy in terms of demand, diagnostic yield, patient management and tolerability. METHODS: Data were collected on patients who underwent PE and IOE since January 2002, CE since June 2002 and DBE since July 2006. These included age, sex, indication of referral, comorbidity, previous investigations and diagnosis obtained, including subsequent management change. RESULTS: Demand for CE and DBE increased every year. A total of 1431 CEs, 247 PEs, 102 DBEs and 17 IOEs were performed over 93 months. The diagnostic yield was 88% for IOE compared with 34.6% for CE, 34.5% for PE and 43% for DBE (P<0.001). Management was altered by CE in 25%, by PE in 19% and by DBE in 33% of patients. However, 44% of patients who underwent DBE found the procedure difficult to tolerate. In 2009, for every 17 CEs performed, one patient underwent DBE locally. CONCLUSION: This is the first series to report the clinical experience of four modalities of small-bowel endoscopy from a single centre. The use of CE as first-line investigation, followed by PE/DBE or IOE, is potentially both less invasive and tolerable. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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