Recommendations for the treatment of HCV after liver transplantation are based on clinical trial data where available. We have tried to avoid extrapolation from studies performed in non-liver transplant patients, given the complexity associated with post-transplant immunosuppression. Therefore, treatment recommendations may differ from those for the non-transplant population and may differ from the treatment regimens currently eligible for prescription under the PBS (Table 7). None of the currently available DAAs in Australia include a specific indication for treating HCV after liver transplantation.
Clinical trial data are limited. The safety and efficacy of sofosbuvir plus velpatasvir has not been formally evaluated in the post-transplant setting but should be safe and effective. The role of ribavirin combined with sofosbuvir plus velpatasvir in the post-transplant setting is not clear, but it should be considered. In the SOLAR-1 study, treatment with sofosbuvir plus ledipasvir plus 1000/1200 mg of ribavirin daily for 12 or 24 weeks was studied in 162 post-transplant patients with HCV Gt 1 (31% with Child–Pugh A cirrhosis). SVR was observed in 96%–98% (157/162) and there was no significant difference between 12 and 24 weeks of treatment. Similar SVR results were found for the combination of sofosbuvir and daclatasvir plus ribavirin for 12 weeks in patients with HCV Gt 1 and post-transplant HCV recurrence in the ALLY-1 study. This regimen was also effective in 10 of 11 patients (91%) with Gt 3 and is the only currently available regimen suitable for people with Gt 3 HCV. It is therefore recommended for post-transplant patients with HCV Gt 3. Treatment was well tolerated in these studies and there were no clinically significant drug–drug interactions between sofosbuvir plus ledipasvir or sofosbuvir plus daclatasvir and calcineurin inhibitors or mTOR inhibitors.
The combination of glecaprevir plus pibrentasvir has been evaluated in the post-transplant setting. In the MAGELLAN-2 study, 80 liver transplant recipients and 20 kidney transplant recipients without cirrhosis were treated with glecaprevir plus pibrentasvir for 12 weeks. Patients with Gt 1, 2, 3, 4 and 6 HCV were included. SVR was observed in 98%, with one post-treatment relapse and one loss to follow-up. Treatment was well tolerated. One episode of mild rejection occurred that was assessed to be unrelated to drug–drug interactions.
Sofosbuvir plus velpatasvir plus voxilaprevir has not specifically been studied in post-transplant patients but should be used for people who did not respond to a prior DAA regimen, particularly one containing an NS5A inhibitor. As with all other DAA regimens in post-transplant patients, drug–drug interactions should be taken into consideration.
The combination of PrOD and ribavirin has been shown to be effective for the treatment of HCV infection after transplantation. However, now that there are multiple other treatment regimens suitable for this population with the benefits of shorter treatment duration, improved toxicity profile and improved drug–drug interaction profile, it is no longer a preferred regimen.