Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus

AIM: To determine the safety profile of new hepatitis C virus(HCV) treatments in liver transplant(LT) recipients with recurrent HCV infection.METHODS: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events(SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIVinfected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. RESULTS: Median age of the 42 patients was 60 years [Interquartile Range(IQR): 56-65 years], 33%(14/42) were female, 21%(9/42) were Hispanic, and 9%(4/42) were Black. The median time from transplant to treatment initiation was 5.4 years(IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62%(8/13) patients, while 54%(7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31%(95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin(OR = 0.61 per g/d L, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate(OR = 0.95 per m L/min per 1.73 m^2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin(OR = 2.43 per mg/d L, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.CONCLUSION: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Bisphosphonates as potential adjuvants for patients withcancers of the digestive system

Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.