Single-Center Experience in Pre-transplant Hepatitis C Virus (HCV) Treatment Among Living Donor Liver Transplant Candidates: Bridging the Direct-Acting Antivirals (DAA).

BACKGROUND Treatment with DAAs before deceased donor liver transplantation has been shown to be an effective strategy to prevent post-transplant HCV recurrence, with a 95% cure-rate among individuals who achieve undetectable HCV VL for ≥30 days pre- transplant. This strategy has not been evaluated in LDLT. MATERIAL AND METHODS We evaluated outcomes in LDLT recipients treated with DAAs pre-transplant and bridged with 4 weeks of post-transplant SOF. All cases of LDLT at Johns Hopkins (1/1/2014-3/1/15) were retrospectively reviewed. RESULTS There were 4 HCV+ LDLT cases treated with DAAs pre- and post-transplant. Pre-transplant DAA regimens included SOF plus SIM in 2 cases of HCC and SOF plus RBV in 2 cases of ESLD. All patients achieved negative VL by week 7 of treatment and all patients had at least 30 days of HCV RNA negativity at the time of LDLT. Patient 4 had a delay in LDLT due to uncontrolled pulmonary hypertension, and experienced viral breakthrough because of treatment interruption. Due to concerns for SOF resistance, a salvage regimen of LDV-SOF and SIM was used. Post-LDLT patients 1-3 received 4 weeks of SOF monotherapy and patient 4 received 14 weeks of LDV-SOF. Three patients achieved SVR12. One died from non-HCV related complications at 4 months post-LDLT. CONCLUSIONS Our preliminary experience suggests that bridging DAAs pre- and post-LDLT is an effective strategy to prevent HCV recurrence. With delays in transplant and prolonged use of SOF/RBV, there is a risk of viral breakthrough, but a salvage strategy of triple DAA therapy can be effective.

Ammonia Level and Mortality in Acute Liver Failure: A Single-Center Experience.

BACKGROUND Acute liver failure (ALF) is an emergent condition that requires intensive care and manifests in particular by significant elevation in serum ammonia level. Patients with ALF with concomitant renal failure experience a further rise in ammonia levels due to decreased kidney excretion. The aim of this study was to evaluate the relationship between elevated ammonia levels and mortality and to characterize the subgroup of ALF patients who develop acute kidney injury (AKI) and require renal replacement therapy. MATERIAL AND METHODS This was a retrospective study of 36 consecutive patients admitted to Johns Hopkins Hospital's intensive care units from December 2008 to May 2013 who presented with grade III and IV hepatic encephalopathy (HE). Patients who developed AKI and required hemodialysis (HD) were compared to those without AKI. Patients with chronic kidney disease were excluded. RESULTS Sixteen patients developed AKI and underwent HD (HD group). Median ammonia levels in the HD and non-HD groups were not significantly different (p=0.95). In the HD group, 4 patients underwent liver transplantation (LT) and 3 of them survived the hospitalization. Among the 12 HD patients who did not receive LT, 6 (50%) survived. Out of 20 non-HD patients, 3 were transplanted, all of whom survived the hospitalization. Among the 17 non-HD patients who did not receive LT, 14 (82%) survived. Admission ammonia level (>120 µmol/L) was associated with higher mortality rate (OR=7.188 [95% CI 1.3326-38.952], p=0.026) in all patients. CONCLUSIONS Admission ammonia level is predictive of mortality in ALF patients with grade 3-4 HE.