At this year's Liver Meeting, the 69th annual meeting of the American Association for the Study of Liver Diseases, several new concepts emerged, including novel treatment approaches to viral hepatitis that promise to alter clinical practice in the near future.
Hepatitis C Virus (HCV)
Impact of Direct-acting Antiviral Therapy on Donor Organ Availability and Outcome
Donor organ availability continues to limit the number of liver, kidney, and heart transplants performed in the United States. In the past, organs from HCV–infected donors were discarded. This practice had a significant impact. For example, although the prevalence of heart failure rose over the past decade, the number of annual heart transplants has remained unchanged. Thus, HCV-positive hearts that meet standard criteria for cardiac donation are an underutilized resource.
With the rising incidence of HCV infection and the growing number of HCV-positive organ donors, there is a time-sensitive and critical need to document both the efficacy and logistics surrounding successful use of HCV-positive organs for transplantation.
Bethea and colleagues set out to determine whether the preemptive administration of pangenotypic direct-acting antiviral (DAA) therapy could prevent the development of chronic HCV infection in HCV-negative cardiac transplant recipients receiving HCV-infected donor hearts. In this single-center, proof-of-concept trial, wait-listed patients who expressed a willingness to accept an HCV-positive donor were enrolled. If a patient received an offer for an HCV RNA–positive donor heart, preemptive DAA therapy with glecaprevir/pibrentasvir (GLE/PIB) was administered; the first treatment dose was given prior to transport to the operating room. Each patient then completed an 8-week course of GLE/PIB therapy post-transplant. All patients successfully achieved viral suppression with undetectable or nonquantifiable HCV RNA by day 7 following transplant. There were no treatment failures, and the HCV viral load following hospital discharge remained negative. No adverse drug reactions or interactions necessitated a lapse or cessation of therapy. Preliminary analysis indicated a decrease in time to transplant in patients willing to accept an HCV-positive heart. The investigators conclude that preemptive administration of pangenotypic DAA therapy has the potential to shorten heart transplant wait times and improve transplant outcomes.
Improved treatment of chronic HCV infection in the current era of DAA therapy is also expected to translate into improved outcomes from liver transplantation.
Young and colleagues evaluated trends in post-liver transplantation graft failure, death, and the need for re-transplantation before and after the availability of DAAs in the United States. Using the United Network for Organ Sharing registry, they stratified and compared outcomes in adults who underwent liver transplantation before the DAA era (2002-2013) or after the DAA era (2014 and later). Among 87,833 liver transplantation patients, 13% were HCV-infected (77% in the pre-DAA period and 23% in the post-DAA period), 32% experienced graft failure, 27% died during the study period, and 5% were re-transplanted. Compared with patients in the pre-DAA era, those undergoing liver transplantation in the post-DAA era had lower likelihood of graft failure. Although HCV-infected patients had a higher likelihood of graft failure compared with noninfected patients in the pre-DAA era, graft survival significantly improved for HCV-infected patients in the post-DAA era, to the extent that no significant difference in graft survival was observed between infected and noninfected patients.
Similar trends were observed when evaluating overall patient survival. Although HCV-infected patients had a higher likelihood of post-liver transplantation death in the pre-DAA era, this higher risk was no longer seen in the post-DAA era. Also, while patients in the post-DAA period were less likely to need re-transplant compared with those in the pre-DAA era, no significant differences were seen between HCV-infected and noninfected patients. The investigators summarized their findings by stating that the disparities in graft failure and overall death have disappeared in the post-DAA era, reflecting the impact of DAAs on improving post-liver transplantation outcomes among HCV-infected patients.
Impact of Imperfect Medication Adherence on Treatment
People who inject drugs (PWID) have a high risk for HCV acquisition and transmission, yet many are excluded from treatment owing to concerns as to whether they will adhere to the prescribed DAA regimen. This concern was recently addressed in a meta-analysis, which reported that across eight studies of people who reported recent injection drug use, 97% completed DAA treatment and 87% achieved a sustained virologic response (SVR).
Kattakuzhy and colleagues postulated that high rates of SVR could be obtained in a real-world setting of PWID despite imperfect medication adherence. In a single-center study, they evaluated the success of treatment of PWID with chronic HCV and opioid use disorder attending a harm-reduction, drop-in center in Washington, DC. Participants were prescribed sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks, with the medication dispensed monthly in 28 pill bottles. Of note, the majority of participants were men (75%) and unstably housed (51%). At screening, 57% of the participants reported injecting opioids at least daily. Of 66 patients who have reached week 24, 91% received the second bottle of SOF/VEL before running out, and 88% received the third bottle of SOF/VEL; 12% had an interruption in treatment ranging from 3 to 15 days. At week 4, HCV viral load was assessed in 62 patients, and 95% had HCV RNA of <200 IU/mL. In total, 89% of participants received 12 weeks of treatment. Of those who completed 12 weeks, 48% finished 1-7 days after the anticipated end of treatment and 16% finished more than 14 days late. SVR was significantly associated with having an HCV viral load of <200 IU/mL at week 4. The investigators noted that finishing treatment after 12 weeks did not impact SVR, even in those patients more than 14 days late. Their data indicate that people with recent drug use and those receiving opioid substitution therapy with HCV and ongoing opioid use have high rates of adherence, treatment completion, and SVR. Even with imperfect adherence, patients can achieve SVR with completion of treatment. As such, high-risk PWID should not be excluded from HCV treatment. The reduction in the pool of HCV-infected subjects may aid in reduction of transmission.
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Cite this: Viral Hepatitis: Five Highlights From the Liver Meeting - Medscape - Nov 29, 2018.