Tse, Chung Sang

Background: Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). Methods: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. Results: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. Conclusions: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

Linked ContentThis article is linked to Tse et al and Ma and Kotze paper. To view these articles visit https://doi.org/10.1111/apt.14829 and https://doi.org/10.1111/apt.14858.

SummaryBackgroundPrimary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure.AimTo evaluate the effect of biological therapies on PSC progression in IBD patients.MethodsWe performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t‐test (patients served as their own controls) ≤3 months before and 6‐8 and 12‐14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography.ResultsUse of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6‐8 months (P = 0.03; mean change −70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12‐14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6‐8 or 12‐14 months.ConclusionsCurrent evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

SummaryBackgroundUp to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post‐operative complications.AimWe sought to compare 30‐day postoperative infectious complication rate among vedolizumab‐treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy.MethodsA retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy.ResultsOne hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab‐treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty‐two vedolizumab‐treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab‐treated group experienced no difference in nonsurgical site infections (6% vs 5% anti‐TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002).ConclusionsTwenty‐six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30‐day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30‐day postoperative surgical site infection on multivariable analysis. While vedolizumab‐treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

Background: Physicians’ lack of comfort and skill in communicating about hospice care results in deficits and delays in hospice referrals. Preclinical exposure to hospice may lay a foundation to improve medical students’ knowledge and comfort with hospice care. Objective: To understand how preclinical medical student (MS)-2s respond both educationally and emotionally to a required hospice care experience (HCE). Design: Accompanied by hospice clinicians, MS-2s spent 3 hours seeing inpatient or home hospice patients followed by a 1-hour debriefing. Students submitted written reflections to e-mailed educational and emotional prompts. Setting/patients: Two hundred and two MS-2s from 2 academic cohorts completed the HCE at 1 of 2 hospice sites. Measurements: Written reflective responses were analyzed qualitatively, where salient themes extracted and responses were coded. Results: Ninety-two students submitted 175 responses to Prompt #1 (educational impact) and 85 students entered 85 responses to prompt #2 (emotional impact) of the HCE. Eleven themes were identified for prompt #1, most frequently focusing on hospice services and goals and hospice providers’ attitudes and skills. Prompt #2 elicited a diverse spectrum of emotional responses, spanning positive and negative emotions. Most often, students reported “no specified emotional reaction,” “sad/depressed,” “difficult /challenging,” “heartened/encouraged,” and “mixed emotions.” Conclusion: In an HCE, preclinical students reported learning core aspects of hospice care and experiencing a broad spectrum of emotional responses. These findings may assist educators in the planning of HCEs for preclinical students, including debriefing sessions with skilled clinicians and opportunities for triggered reflection.