Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

OBJECTIVES: We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. MATERIALS AND METHODS: In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. RESULTS: Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. CONCLUSIONS: Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

BACKGROUND: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. METHODS: One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. RESULTS: One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. CONCLUSIONS: Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.

Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.

BACKGROUND/AIM: In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence. PATIENTS AND METHODS: A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed. RESULTS: A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years' post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007). CONCLUSIONS: This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.

The safety and efficacy of gastric fundal variceal obliteration using N-butyl-2-cyanoacrylate; the experience of a single canadian tertiary care centre.

BACKGROUND/AIM: Bleeding from Gastric Varices (GV) is not only life threatening, but also leads to many hospitalizations, contributes to morbidity and is resource intensive. GV are difficult to diagnose and their treatment can be challenging due to their location and complex structure. To assess the safety and efficacy of endoscopic gastric fundal variceal gluing using periodic endoscopic injections of N-butyl-2-cyanoacylate (NBCA) and to assess the utility of endoscopic ultrasound (EUS) in assessing for the eradication of GV post-NBCA treatment. MATERIALS AND METHODS: Analysis of prospectively collected data of a cohort of patients with GV who underwent periodic endoscopic variceal gluing from 2005 to 2011. Outcomes included success of GV obliteration, incidence of rebleeding, complications from the procedure, and analysis of factors that might predict GV rebleeding. The success of GV eradication was assessed by both EUS and direct endoscopy. RESULTS: The cohort consisted of 29 consecutive patients that had undergone NBCA injection for GV. The mean age was 60.8 years standard deviations (SD 13.3, range 20-81). The average follow-up was 28 months (SD 19.61, range 1-64) and the most common cause for GV was alcoholic liver cirrhosis (34.48%). A total of 91 sessions of NBCA injections were carried out for 29 patients (average of 3.14 sessions/patient, SD 1.79, range 1-8) with a total of 124 injections applied (average of 4.28 injections/patient, SD 3.09, range 1-13). 24 patients were treated for previously documented GV bleeding while five were treated for primary prevention. Overall, 79% of patients were free of rebleeding once three sessions of histoacryl ® injection were completed. None of the patients treated for primary prevention developed bleeding during follow-up. 11 of the 24 patients (46%) with previous bleeding however had rebleeding. 4/11 (36%) patients had GV rebleeding while awaiting scheduled additional NBCA sessions. 19/29 (60%) patients had complete eradication of GV, 11/19 (58%) documented by endoscopic assessment alone, 4/19 (21%) by EUS alone and 4/19 (21%) by both techniques. Two of the 11 (18%) patients that had rebleeding had recurrence of GV bleeding after documented eradication by EUS compared to 5/11 (45%) patients documented eradication by endoscopic assessment and 2/11 (18%) patients that had rebleeding after documented eradication by both modalities. Twenty five patients in total had documented residual GV by EUS (14, 56%), direct endoscopic assessment (18, 72%) or both modalities (9, 36%), two of which developed recurrent bleeding (13%). No immediate or long-term complications of NBCA injection occurred, nor any related endoscopic complications were reported in any of these cases during the time of follow-up. CONCLUSION: NBCA injection of GV is a safe and successful therapeutic intervention. A minimum of three endoscopic sessions is required to significantly decrease the risk of bleeding/rebleeding. In this small sample of patients, neither EUS nor direct endoscopic assessment was reliable in predicting the recurrence of GV bleeding.