Sofosbuvir and Simeprevir Therapy for Recurrent Hepatitis C Infection After Liver Transplantation.

UNLABELLED: Antiviral therapy for recurrent hepatitis C in liver transplant recipients has been associated with low efficacy, poor tolerability, and drug-drug interactions. Recent approval of various hepatitis C direct-acting antivirals has resulted in improvement of these parameters. We evaluated the efficacy and safety of 12 week all-oral interferon- and ribavirin-free therapy with sofosbuvir and simeprevir. METHODS: Thirty-two genotype 1 liver transplant recipients with recurrent hepatitis C infection were retrospectively analyzed. All patients received 12 weeks of sofosbuvir 400 mg and simeprevir 150 mg orally daily. The primary endpoint was sustained virologic response 12 weeks after treatment. RESULTS: Sustained virologic response 12 weeks after treatment was achieved in 30 of 32 (94%; 95% confidence interval, 79-99%) patients. All patients enjoyed on-treatment virological response. Both patients who relapsed were cirrhotic, previously treated with Q80K polymorphism. Significant improvements in alkaline phosphatase, albumin, alanine aminotransferase levels, and platelets were seen at 12-week post therapy. Treatment was well tolerated. No grade 3 or 4 adverse events were noted. Headache and fatigue were the most common complaints. CONCLUSION: Combination of sofosbuvir and simeprevir for 12 weeks resulted in 94% sustained virological response-12 rates in patients with hepatitis C genotype 1 and was well tolerated.

Long-term nutrition and predictors of growth and weight gain following pediatric intestinal transplantation.

BACKGROUND: Advances in intestinal transplantation (ITx) have resulted in improved survival and the opportunity to examine nutritional outcomes. The aim of this study was to describe detailed, long-term nutritional results and identify positive predictors of growth and weight gain following pediatric ITx. METHODS: A single-center retrospective, Institutional Review Board-approved review of a prospective database was conducted. Inclusion criteria were ITx recipients 18 years or younger with survival of 6 months or more. Outcomes included anthropometric measurements and biochemical markers at 6, 12, 24, 36, and 48 months post-ITx. More than 25 ITx-related variables were analyzed as potential predictors of growth and weight gain. Statistical analysis was performed using chi-square test, t test, and analysis of variance. RESULTS: Between November 1991 and April 2007, 50 children received 55 ITx; 33 patients met eligibility criteria. Median age at ITx was 2.2 years, follow-up time was 3.8 years, and time from ITx to cessation of total parenteral nutrition was 31 days. The most common micronutrient deficiencies post-ITx were zinc, iron, and copper. Serum protein levels improved significantly over time. Weight gain occurred within 6 months and vertical growth within 12 months, although limited catch-up growth was seen. Early predictors of weight gain and growth included shorter hospitalization and absence of rejection. Long-term predictors were low steroid dosage, infrequent hospitalization, and the use of peptide-based formulas. CONCLUSIONS: This represents one of the largest and most comprehensive long-term studies on nutritional outcomes in pediatric ITx. Overall, positive growth and weight gain were seen as were micronutrient deficiencies. Numerous long-term nutritional challenges exist which require a multidisciplinary approach and future prospective studies.

Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants.

INTRODUCTION: Outcomes after intestinal transplantation (ITx) have steadily improved. There are few studies that assess factors associated with these enhanced results. The purpose of this study was to examine peri-ITx variables and survival. METHODS: A review of a prospectively maintained database was undertaken and included all patients undergoing ITx from 1991 to 2010. The study endpoints were patient and graft survival. Data collection included 44 variables. Survival was computed using Kaplan-Meier methods. Univariate analysis was conducted (log-rank test) with significance set at P less than or equal to 0.20. Multivariate analysis of significant variables was conducted using model reduction by backward elimination variable selection method with significance set at P less than 0.05. RESULTS: Eighty-eight patients received 106 ITx. The majority of recipients were male, Latino, and children. The leading causes of intestinal and liver failure were gastroschisis and parenteral nutrition. Grafts transplanted were isolated intestine (24%), liver-intestine (62%), and multivisceral (14%). Overall 1- and 5-year patient and graft survival were 80% and 65%, and 74% and 64%, respectively. Significant univariate survival predictors were weight less than 20 kg, children, liver-inclusive allograft, panel reactive antibody less than 20%, absence of donor-specific antibody, negative crossmatch, warm ischemia time less than 60 min, absence of recipient splenectomy, interleukin-2 receptor antagonist induction, and era. Significant multivariate survival predictors were absence of donor-specific antibody, absence of recipient splenectomy, and liver-inclusive graft type. CONCLUSION: This large, single-center ITx experience confirms a marked improvement in outcome over time. Several important factors were associated with survival, and these factors can potentially be adjusted before ITx. These findings should refocus future efforts on strategies to improve treatment and prevent graft loss.

Renal function impacts outcomes after intestinal transplantation.

BACKGROUND: Although renal dysfunction (RD) has been commonly associated with poor outcome after other solid organ transplants, it has not been studied in detail after intestinal transplantation (ITx). Here we provide a detailed analysis of renal function after ITx, and identify predictors of post-ITx RD. METHODS: A retrospective analysis of patients undergoing ITx from 1991 to 2006 was performed. For each patient, the estimated glomerular filtration rate (eGFR) was compared with the normal GFR for age and gender to obtain the percent of normal eGFR. Chi-square analysis and log-rank tests were used to identify categorical variables associated with RD (eGFR <75% of normal) and to determine if RD was predictive of post-ITx survival. RESULTS: Sixty-eight transplantations were performed in 62 patients. Overall patient survival at 1 and 5 years was 78% and 56%, respectively. Renal dysfunction was observed in 16% of patients post-ITx. The most frequent predictors of post-ITx RD were preoperative eGFR less than 75% of normal, pre-ITx location in the intensive care unit, and high-dose tacrolimus immunotherapy. An eGFR less than 75% of normal at days 7, 28, and 365 was predictive of poor patient survival (P<0.05). CONCLUSIONS: This study provides the first detailed analysis of renal function after ITx. We identified specific risk factors for the development of RD in the first year post-ITx and found a significant association of RD with decreased long-term survival. Given the strong correlation of RD with poor outcome, preserving renal function may be key to improving long-term outcomes in ITx recipients.