Outcomes of living versus deceased donor liver transplantation for acute liver failure in the United States.

Clinical outcomes for living donor liver transplantation (LDLT) for acute liver failure (ALF) in the United States remain to be determined. To address this gap in knowledge, we examined post-liver transplantation outcomes of adults with ALF undergoing LDLT and deceased donor liver transplantation (DDLT) in the United States. We analyzed Organ and Procurement and Transplantation Network data for adults with ALF who were listed for liver transplantation as status 1 or 1A and who underwent LDLT (N = 21) or DDLT (N = 2316) between October 1987 and April 2011. We found no strong evidence that the survival probabilities for adults with ALF who underwent LDLT were inferior to those who underwent DDLT (P = .764). In adults with ALF who underwent LDLT, 1- and 5-year survival probabilities were both 71%; for DDLT these probabilities were 79% and 71%, respectively. In adults with ALF, 1- and 5-year liver graft survival probabilities, respectively, were 62% and 57% for LDLT, and 74% and 66% for DDLT. In these series of adults with ALF who were listed as status 1 or 1A, patient and graft survival rates for LDLT were similar to those for DDLT. Our findings suggest that if deceased donor livers are unavailable, LDLT is an acceptable option in experienced centers for adults with ALF.

End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection.

Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

Simultaneous liver-kidney versus liver transplantation alone in patients with end-stage liver disease and kidney dysfunction not on dialysis.

BACKGROUND: Since implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined. METHODS: Organ Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between SLKT and post-liver transplant patient and graft survival. RESULTS: The study cohort comprised 5443 patients; 262 (5%) underwent SLKT and 5181 (95%) underwent LTA. Adjusting for potential confounders, patients who underwent SLKT were 34% less likely to die after liver transplantation than those who underwent LTA (hazard ratio [HR] = 0.66, P = .012) and 33% less likely to have liver graft failure than those who underwent LTA (HR = 0.67, P = .010). Among those who underwent SLKT, 1-, 3-, and 5-year kidney graft survival probabilities were 88%, 80%, and 77%, respectively. Black race and diabetes were associated with a higher likelihood of SLKT versus LTA; female sex, a higher eGFR, and higher MELD score reduced the likelihood of SLKT. CONCLUSIONS: Among those with ESLD and kidney dysfunction not on dialysis, post-liver transplant patient and liver graft survivals of patients who underwent SLKT were superior to those of patients who underwent LTA. Whether this reflects differences in the two groups that could not be adjusted in survival models or a specific effect of kidney dysfunction cannot be established.

The impact of nonalcoholic fatty liver disease and the metabolic syndrome on progression of fibrosis in patients with recurrent HCV after liver transplantation.

Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been shown to play a role in disease progression and response to therapy in patients with chronic hepatitis C virus (HCV) infection. The primary objective of this study was to evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were included in the study. Patients who had MS at the time of their first posttransplant biopsy were identified. The first and last posttransplant biopsies were assessed for the presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant biopsy. The mean FPR was 0.05+/-0.16 FU/mo in the presence of NAFLD compared to 0.07+/-0.10 FU/mo in its absence (P=.68) and 0.03+/-0.06 FU/mo in the presence of MS versus 0.10+/-0.15 FU/mo in its absence (P=.06). When FPR values were divided into two categories of <0.16 FU/mo or >or=0.16 FU/mo (below/above the 25% upper quartile) or <0.08 FU/mo or >or=0.08 FU/mo (below/above the 50% upper quartile), there was no correlation between FPR categories and the presence of NAFLD with or without MS, only MS, or the absence of both in the first liver transplant biopsy (P=.13). Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT in patients with treated hepatitis C after OLT.

Modulation of endothelial cell inflammatory integrins and stress markers with rh-factor VIIa in patients with advanced chronic hepatitis C.

Individuals with chronic hepatitis C (CHC) progress to cirrhosis and hepatic cancer. Individuals with advanced CHC are coagulopathic and can manifest fibrinolysis. The coagulopathy is a consequence of hepatocytic dysfunction. The fibrinolysis represents a response to local endothelial cell injury, and is of a low-grade. Based upon this hypothesis, the effect of the infusion of recombinant human factor VIIa (rh-FVIIa) on endothelial cell inflammatory integrins and measures of endothelial stress were determined in 17 individuals with advanced CHC. Immediately prior to the infusion of rh-FVIIa, the plasma levels of tissue factor (TF), Thrombomodulin (TM), human soluble ICAM-1 (hs-ICAM-1), human soluble VCAM-1 (hs-VCAM-1), human soluble L-Selectin (hs-L-Selectin), the prothrombin time and the activated partial thromboplastin time were determined. The same parameters were assayed at 5, 10, 30, 120, 240 and 360 min after infusion. TF and TM levels were very high at baseline consistent with a vascular endothelial stress response. Similarly hs-ICAM-1, hs-VCAM-1 as well as L-Selectin levels were increased. Thirty minutes after the infusion, a marked reduction in ICAM-1 and VCAM-1 and to a lesser degree L-Selectin levels was observed. This reduction persisted for 360 min. No change in measures of fibrinolysis [plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (t-TFPI), activated tissue factor pathway inhibitor (TFPIa), d-dimers (DD), FSP and fibrinogen levels] occurred. In addition, no change in plasma Annexin-V was observed. Based upon these data it can be concluded that: (1) rh-FVIIa corrects the coagulopathy seen in advanced CHC; (2) reduces endothelial cell injury and/or stress as evidenced by the TF, TM, hs-ICAM-1 and hs-VCAM-1 levels in plasma; (3) these changes in coagulation occurred without inducing a propagated vascular thrombosis.