Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe complication of liver cirrhosis associated with excess short-term mortality rates. Orthotopic liver transplantation (OLT) is a potentially life-saving therapeutic modality for acute-on-chronic liver failure patients, but selection of transplant candidates with an acceptable post-transplant outcome is difficult. AIM: To assess the risk of liver transplantation in patients with ACLF, and to determine parameters that predict post-transplant survival in this patient cohort. METHODS: We retrospectively analysed all 250 patients with cirrhosis who underwent their first liver transplantation between 2009 and 2014 at our institution, and assessed post-transplant outcomes. RESULTS: Of 250 cirrhotic liver transplant recipients, 98 patients fulfilled the diagnostic criteria for acute-on-chronic liver failure in the 3-month pre-transplant period. Compared to non-ACLF patients, ACLF was associated with significantly higher short-term morbidity and mortality after liver transplantation (90-day patient survival 96.1% non-ACLF vs 72.4% ACLF patients, P < 0.0001). Clinical improvement in the pre-transplant period, as defined by recovery of at least one previously failed organ system, was observed in 37 of 98 acute-on-chronic liver failure patients, mostly within several days after diagnosis. Most notably, clinical improvement prior to liver transplantation was associated with excellent post-transplant survival rates that approximated non-ACLF transplant recipients. Following the 90-day post-transplant period, patient survival and long-term graft functions were comparable between ACLF and non-ACLF liver transplant recipients for up to 5 years. CONCLUSIONS: Acute-on-chronic liver failure predicts adverse outcome after orthotopic liver transplantation. Given the dismal prognosis without transplantation, however, our results indicate that ACLF patients can be transplanted with comparably good outcomes, in particular patients who improve under conservative therapeutic measures.

Damage-associated molecular patterns in cancer: a double-edged sword.

Damage-associated molecular patterns (DAMPs) are released in response to cell death and stress, and are potent triggers of sterile inflammation. Recent evidence suggests that DAMPs may also have a key role in the development of cancer, as well as in the host response to cytotoxic anti-tumor therapy. As such, DAMPs may exert protective functions by alerting the immune system to the presence of dying tumor cells, thereby triggering immunogenic tumor cell death. On the other hand, cell death and release of DAMPs may also trigger chronic inflammation and, thereby promote the development or progression of tumors. Here, we will review the contribution of candidate DAMPs and their receptors, and discuss the evidence for DAMPs as tumor-promoting and anti-tumor effectors, as well as unsolved questions such as DAMP release from non-tumor cells as well as the existence of tumor-specific DAMPs.