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Role of monocytes and macrophages in experimental and human acute liver failure

World Journal of Gastroenterology 2010年第15期16卷 1811-1819页

作者： Lucia A Possamai Charalambos Gustav Antoniades Quentin M Anstee Alberto Quaglia Diego Vergani Mark Thursz julia wendon Antiviral Centre 10th Floor QEQM building St Mary’s Hospital Imperial College London Institute of Liver Studies King’s College Hospital

Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.

关键词： Monocyte Macrophage Acute liver failure Inflammation Monocyte chemoattractant protein-1/ chemokine (C-C motif) receptor-2 Cytokine

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Impact of comorbidity on waiting list and post-transplant outcomes in patients undergoing liver retransplantation

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World Journal of Hepatology 2017年第20期9卷 884-895页

作者： Mohammad A B Al-Freah Carl Moran Matthew R Foxton Kosh Agarwal julia A wendon Nigel D Heaton Michael A Heneghan Institute of Liver Studies King’s College HospitalLondon SE5 9RSUnited Kingdom

AIM To determine the impact of Charlson comorbidity index(CCI) on waiting list(WL) and post liver retransplantation(LRT) *** Comparative study of all adult patients assessed for primary liver transplant(PLT)(n = 1090) and patients assessed for LRT(n = 150), 2000-2007 at our centre. Demographic, clinical and laboratory variables were recorded. RESULTS Median age for all patients was 53 years and 66% were men. Median model for end stage liver disease(MELD) score was 15. Median follow-up was 7- years. For retransplant patients, 84(56%) had ≥ 1 comorbidity. The most common comorbidity was renal impairment in 66(44.3%). WL mortality was higher in patients with ≥ 1 comorbidity(76% vs 53%, P = 0.044). CCI(OR = 2.688, 95%CI: 1.222-5.912, P = 0.014) was independently associated with WL mortality. Patients with MELD score ≥ 18 had inferior WL survival(LogRank 6.469, P = 0.011). On multivariate analysis,CCI(OR = 2.823, 95%CI: 1.563-5101, P = 0.001), MELD score ≥ 18(OR 2.506, 95%CI: 1.044-6.018, P = 0.04), and requirement for organ support prior to LRT(P < 0.05) were associated with reduced post-LRT survival. Donor/graft parameters were not associated with survival(P = NS). Post-LRT mortality progressively increased according to the number of transplanted grafts(Log-Rank 18.455, P < 0.001). Post-LRT patient survival at 1-, 3- and 5-years were significantly inferior to those of PLT at 88% vs 73%, P < 0.001, 81% vs 71%, P = 0.018 and 69% vs 55%, P = 0.006, respectively. CONCLUSION Comorbidity increases WL and post-LRT mortality. Patients with MELD ≥ 18 have increased WL mortality. Patients with comorbidity or MELD ≥ 18 may benefit from earlier LRT. LRT for ≥ 3 grafts may not represent appropriate use of donated grafts.

关键词： Hepatic Organ Outcome Diabetes Renal

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Clinical management of acute liver failure: Results of an international multi-center survey

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World Journal of Gastroenterology 2016年第33期22卷 7595-7603页

作者： Liane Rabinowich julia wendon William Bernal Oren Shibolet Liver Unit Department of GastroenterologyTel-Aviv Medical Center and Tel-Aviv University Liver Intensive Therapy Unit Institute of Liver StudiesKing’s College Hospital

AIM To assess the practice of caring for acute liver failure(ALF) patients in varying geographic locations and medical *** Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed,treating between 300 and 500 ALF cases and performing over 100 liver transplants(LT) for ALF annually. The questions pertained to details of the institution and their clinical activity,standards of care,referral and admission,wardbased care versus intensive care unit(ICU) as well as questions regarding liver transplantation- including criteria,limitations,and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted,treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers,particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamolrelated ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals,lactulose,nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure(ICP). ICP monitoring was employed in 12 centers,with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT,with a 90% post transplant survival to hospital disc

关键词： Acute liver failure Liver transplantation Intra-cranial pressure Hepatic encephalopathy

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