F. Saliba

Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3.

BACKGROUND & AIMSnLiver transplantation (LT) for the most severely ill patients with cirrhosis, with multiple organ dysfunction (accurately assessed by the acute-on-chronic liver failure [ACLF] classification) remains controversial. We aimed to report the results of LT in patients with ACLF grade 3 and to compare these patients to non-transplanted patients with cirrhosis and multiple organ dysfunction as well as to patients transplanted with lower ACLF grade.nnnMETHODSnAll patients with ACLF-3 transplanted in three liver intensive care units (ICUs) were retrospectively included. Each patient with ACLF-3 was matched to a) non-transplanted patients hospitalized in the ICU with multiple organ dysfunction, or b) control patients transplanted with each of the lower ACLF grades (three groups).nnnRESULTSnSeventy-three patients were included. These severely ill patients were transplanted following management to stabilize their condition with a median of nine days after admission (progression of mean organ failure from 4.03 to 3.67, p=0.009). One-year survival of transplanted patients with ACLF-3 was higher than that of non-transplanted controls: 83.9 vs. 7.9%, p<0.0001. This high survival rate was not different from that of matched control patients with no ACLF (90%), ACLF-1 (82.3%) or ACLF-2 (86.2%). However, a higher rate of complications was observed (100 vs. 51.2 vs. 76.5 vs. 74.3%, respectively), with a longer hospital stay. The notion of a transplantation window is discussed.nnnCONCLUSIONSnLT strongly influences the survival of patients with cirrhosis and ACLF-3 with a 1-year survival similar to that of patients with a lower grade of ACLF. A rapid decision-making process is needed because of the short transplantation window suggesting that patients with ACLF-3 should be rapidly referred to a specific liver ICU. Lay summary: Liver transplantation improves survival of patients with very severe cirrhosis. These patients must be carefully monitored and managed in a specialized unit. The decision to transplant a patient must be quick to avoid a high risk of mortality.

823 INDETERMINATE CAUSES OF ACUTE LIVER FAILURE: INCIDENCE AND PREDICTIVE FACTORS OF SPONTANEOUS SURVIVAL AND AFTER LIVER TRANSPLANTATION (LT)

Methods: A retrospective study of patients with ALF admitted to a tertiary liver centre from 2001 to 2009 was done. We looked at the demographic data, clinical features, prognostic markers – King’s College Hospital (KCH) criteria and Model for End-Stage Liver Disease (MELD) score, and the outcome of these patients. Data was analysed using SPSS. Results: A total of 155 cases were reviewed. 63.9% were females and the mean age was 36.7±15.9 years. The causes of ALF include hepatitis B-related (23.2%), indeterminate (20.0%), nonparacetamol drug-induced liver injury (DILI) (18.7%), autoimmune liver disease (7.7%), acute paracetamol toxicity (7.1%), acute fatty liver of pregnancy (6.5%), dengue-related (5.2%), Wilson’s disease (4.7%), acute hepatitis A (1.3%), hepatitis C (1.9%) and acute Budd Chiari (1.9%). The overall survival rate was 27.1%. Even though 57.2% of the patients satisfied the KCH criteria, only 2 patients were transplanted with one survived. The spontaneous survival rate in patients who satisfied the KCH was 8.3% while in the group who did not satisfy the KCH, the survival rate was 52.9%. In the group where KCH was not applicable, the survival rate was 53.3%. The mean MELD score for patients who died was 30±7, while for patients who survived the score was 22±7. Multivariable logistic regression showed for any one point increase in MELD score, ORadj1.22 (CI 95%: 1.12, 1.32) for mortality. Conclusion: ALF patients with poor prognostic criteria had a high mortality in the absence of liver transplant. The three main causes of ALF in Malaysia were viral hepatitis B, indeterminate and nonparacetamol DILI.

Idiopathic Post Liver-Transplant Hepatitis Remains Obscure with Respect to Its Etiology and Relationship with Immunosuppressiona

Aim: Idiopathic post-liver transplant hepatitis (IPTH) can lead to late graft fibrosis. The treatment for IPTH is not clearly delineated. We aimed to approach its pathophysiology and predictive factors for fibrosis progression (FP). Methods: Patients whose IPTH was diagnosed in 2006 and had undergone at least one subsequent liver biopsy (LB) were included. The index LBs were reviewed and correlated with clinical, laboratory, C4d immunostaining retrospectively performed, and histological data on the most recent LBs. Results: Among the 299 post-transplant LBs, 37 presented IPTH. The index LBs mostly displayed mild fibrosis (65%) and activity (67.5%), and non-significant C4d immunostaining (i.e., weak, focal and/or portal stroma staining, 21.6%). Liver tests were normal in 46% of patients. Virological markers including Hepatitis E were negative. Antinuclear auto-antibodies were present concurrently in four patients and appeared later in two patients, together with features of autoimmune hepatitis (AIH) in one. Isolated AIH features appeared later in one patient. One patient displayed AIH features on the index LB, with negative auto-antibodies and elevated serum IgG. Fibrosis was stable, increased or decreased in 23, 11, and three patients, respectively. FP was less frequent in tacrolimus-treated patients (p = 0.022), more frequent in cyclosporine- (p = 0.035) and MMF-treated patients (p = 0.023), and not influenced by steroid-based treatment or increased overall immunosuppression or steroids. Under multivariate analysis, MMF remained an independent predictor of FP (p = 0.048). Conclusion: The physiopathology of IPTH remained unclear. Increasing steroid doses or overall immunosuppression did not prevent FP. The potential impact of MMF on FP will require prospective studies.

P0034 : Good outcome of patients transplanted with meld score greater than 30: Paul-brousse hospital experience

I/R injury remained more prominent in DBD grafts as compared to their DCD counterparts. Further, there was greater upregulation of pro-inflammatory ceramides in post-transfusion biopsies in DBD as compared to DCD allografts. Despite decreased inflammation, DCD allografts had significantly higher levels of cell death than DBD grafts, which correlated with the duration of warm ischemia time as well as significantly higher levels of aspartate aminotransferase (AST) in the serum of recipients of DCD livers in the acute posttransplant period. Conclusions: These data suggest that ischemia/reperfusion injury causes a non-inflammatory necrosis in DCD allografts with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD allografts and cell death in DCD allografts are unknown and warrant further investigation.

493 RESULTS OF LIVER RETRANSPLANTATION IN A MONOCENTRIC COHORT OF HCV INFECTED PATIENTS

quartile of LDLR mRNA expression in the PI biopsy survived with a significantly (Log-Rank test P < 0.05) better survival than those in the three lowest quartiles. Surviving graft (n = 34, median followup 44.8 months, range 8.6–72.3) had significantly higher LDLR (P < 0.01) and NPC1L1 (P < 0.05) mRNA expression in the PI biopsy and HMGCR (P < 0.05) mRNA expression in the PR biopsy than lost grafts (n = 13, median follow-up 6.0 months, range 0.03–43.7). Conclusions: In the settings of human liver transplantation: 1. hepatic LDLR mRNA is overexpressed immediately after graft reperfusion, suggesting an increased hepatocyte cholesterol uptake from blood; 2. hepatic upregulation of genes involved in cholesterol recruitment and synthesis is inversely related to the severity of IRI and is associated with better graft survival.

221 OUTCOME OF CIRRHOTIC PATIENTS ADMITTED TO THE LIVER ICU AND PREDICTIVE FACTORS OF MORTALITY: RESULTS OF A RECENT COHORT OF 308 PATIENTS

(p = 0.006), inotropic support (p = 0.006) and the absence of transplantation (p = 0.002) were significantly predictive of mortality. In the multivariate analysis, MELD score and need for inotropic support were major significant predictors of death while transplant free survival was significantly related to a MELD score <40 (OR:7.6; 95%CI: 2.2−26.2; p = 0.001), high fibrinogen level (OR: 3.2; 95%CI: 1.3−8.2; p = 0.01) and 3 MARS® treatments (OR: 6.3; 95%CI: 1.4−27.4; p = 0.01). Conclusion: In patients with fulminant hepatic failure awaiting liver transplantation, MELD score, inotropic support, fibrinogen and subsequent albumin dialysis therapy, outweighing liver transplantation, are major predictors of survival.