Background & Aims
The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC.
Methods
A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015.
Results
A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p = 0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p <0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio = 8.5, 95% confidence interval = 3.90–18.49).
Conclusions
The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR.
Lay summary
The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.
BackgroundSingle-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable.MethodsWe conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function.ResultsWe screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months.ConclusionsOur multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/7-5-reading-prenner.html a video presentation of this article
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/7-5-interview-prenner.html the interview with the author
Background.
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the United States under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the United States for patients with HEHE remains understudied.
Methods.
This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From February 27, 2002 to January 31, 2018, 131 adults waitlisted for LT with HEHE were identified by free-text entry.
Results.
Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median model for end-stage liver disease score at LT was 7 ((interquartile range [IQR]: 6–11) and waiting time 78.5 days (IQR: 29.5–237.5). Unadjusted post-LT survival of HEHE recipients at 1-, 3-, and 5-years from LT was 88.6%, 78.9%, and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (P = 0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% versus 0.5%).
Conclusions.
The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT.
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