Faouzi Saliba

Acute liver failure (ALF) results in a multitude of complications that result in multi‐organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia‐producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non‐paracetamol cases appear robust while the criteria for paracetamol‐intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post‐LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.

Background and Aims To report 5‐year outcomes of the CERTITUDE study. Methods An observational study in patients with liver transplantation (LTx) compared the long‐term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6‐month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow‐up. Results Of the 143 enrolled patients, 119 completed the 5‐year follow‐up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, −15.53 ml/min/1.73 m 2 and EVR, –14.56 ml/min/1.73 m 2 ). In the treatment subgroups based on actual treatment received, renal function was preserved better in the EVR subgroup compared with other subgroups ( p = .051). Treated biopsy‐proven acute rejection was higher in the EVR group (15.4% vs. 6.4%); however, the majority of events were mild in severity. MACE occurred in 9.2% vs. 14.1% of patients in the EVR and TAC groups respectively ( p = .370). De novo cancer was reported in 14 and 5 patients in EVR and TAC groups respectively. Hepatocellular carcinoma (HCC) recurrence was observed in the TAC group alone ( n = 4). Adverse events and treatment discontinuation owing to an adverse event were higher in the EVR group. Conclusions The CERTITUDE study demonstrated that EVR‐ and TAC‐based regimens have comparable efficacy, safety and tolerability up to 5 years post‐LTx.