Direct Acting Antiviral Therapy After Liver Transplantation

Paul Y. Kwo

Disclosures

Curr Opin Gastroenterol. 2016;32(3):152-158. 

In This Article

Conclusion

Few populations have benefited as greatly from the DAA era as have postliver transplantations with chronic hepatitis. Prior to initiation of DAAs, survival rates for hepatitis C were lower than virtually all other indications for OLT. However, our current DAA agents now can be administered posttransplant with the expectation of SVR rates that are not different than those who are not posttransplant. In this era, no patient's graft should fail because of recurrent hepatitis C. The most robust treatment options are for genotype 1. The combination of sofosbuvir with ledipasvir, or daclatasvir/or simeprevir as well as the three DAA regimen paritaprevir, ombitasvir, dasabuvir, and ribavirin all lead to high sustained response rates in genotype 1 populations. At this time, sofosbuvir/ledipasvir and sofosbuvir/dacltasvir are given with ribavirin post-OLT for duration of 12 weeks. However, preliminary nonrandomized data suggest that a 24-week duration of daclatasvir and sofosbuvir with or without ribavirin is also highly effective and is a pan-genotypic option post-OLT. The optimal use of ribavirin with sofosbuvir and simeprevir has yet to be determined post-OLT though an ongoing trial will provide additional data (NCT02165189). High sustained response rates for genotype 1 may also be achieved with paritaprevir, ombitasvir, dasabuvir, and ribavirin for 24 weeks with subsequent preliminary data showing ribavirin is not required for genotype 1b individuals who were treatment naïve. For genotypes 2 and 3, there are limited data. The combination of sofosbuvir and ribavirin for 24 weeks has been shown to be effective in a small subset of genotype 3 infected individuals. The most robust data, though preliminary, is with sofosbuvir and daclatasvir with or without ribavirin for 12–24 weeks and it is this author's preference for a 24-week duration, regardless of genotype whether genotype 2 or 3, though genotype 2 naïve posttransplant patients will likely be successfully treated with 12 weeks of sofosbuvir/daclastasvir/ribavirin 600 mg. For genotype 4, the data are preliminary but likely ledipasvir/sofosbuvir with ribavirin, paritaprevir/omitasvir with ribavirin, sofosbuvir/daclatasvir with ribavirin, sofosbuvir/simeprevir with ribavirin will all be effective. It is this author's preference to use a 24-week duration until additional data are available. Still fewer data are available for genotypes 5 and 6 with likely treatment options being ledipasvir/sofosbuvir and sofosbuvir/daclatasvir Finally, the majority of posttransplant studies have incorporated ribavirin with DAAs. Suggested approaches are in Table 3. More data are needed on ribavirin free options for posttransplant patients though to date the doses have been better tolerated than when given with interferon. Given these successes, retransplantation rates for hepatitis C should become comparable to other indications for OLT.

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