الفهرس 
Hepatitis C VirusOnly 14 pages are availabe for public view
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Abstract
- HCV infection is the most common indication for liver transplantation in the United States (Kim et al., 2014).In addition, reinfection of the grafted liver is nearly universal in patients who are viremic at transplantation,conferring increased risk of accelerated disease progression and graft loss (Narang et al., 2010).
- The development of new direct acting antivirals constitutes a clinical revolution in the field of hepatitis C therapy and, most probably, in the history of Hepatology, difficult-to-treat patients, such as cirrhotics or patients in the peri-transplant setting, will clearly benefit from these therapies, particularly from interferon-free all-oral combinations (Lens et al., 2014).
- Multiple all-oral regimens with improved tolerability have achieved rates of sustained virologic response (SVR) exceeding 90% (Feld et al., 2014).
- The safety and efficacy profile of these DAA combinations is particularly relevant in those with HCV recurrence after liver transplantation (LT) (Lens et al., 2014).
- The pan-genotypic combination of daclatasvir and sofosbuvir, with or without ribavirin, has achieved high SVR rates (Nelson et al., 2015).
- Daclatasvir is an inhibitor of the HCV NS5A replication complex; sofosbuvir is a nucleotide inhibitor of the HCV NS5B polymerase (Gao et al., 2010).
- Both have favorable safety profiles and are dosed once daily, with few clinically significant drug-drug interactions, including a lack of interactions with cyclosporine or tacrolimus(Bifano et al., 2015).
- Many studies have demonastrated a decreased risk of HCC with antiviral treatment that was based on clinical trial data using INF based regimens,but recently results of studies linking the use of DAA therapy with an increased risk of HCC present an interesting dilemma for clinicians in that achieving SVR poses an additional risk to the patient (Hirmatsu et al., 2015).
- In the current study 40 patients were treated with combined sofosbuvir 400 mg anddaclatasvir 60 mg for 24 weeks.
- All patients received treatment at least 3 months following transplantation.
- 40 patients (100%) have good response to treatment during treatment and during follow up (SVR 12 was 100%).
- No abnormal side effects to treatment were detected.
- No drug-drug interactions were noted during treatment.
Conclusions
- Noninterferon-based therapies with oral DAA agents have revolutionized the treatment of HCV recurrence posttransplant. These regimens have consistently demonstrated high SVR rates, shorter treatment courses, and a more favorable side effect profile than interferon- based therapies.
- Although DAA agents are effective even in advanced liver disease, SVR rates seem diminished when compared with patients with minimal liver disease.
- Further studies are needed to clarify whether DAAs increase HCC incidence and to determine the natural history and baseline post-SVR HCC incidence according to the type of anti-HCV therapy in each specific patient population.
Recommendations
- Further evaluation of drug-drug interactions with calcineurin inhibitors will be needed as DAA use becomes more common.
- Studying for the optimal timming of starting treatment following transplantation is needed.
- Further evaluation of the outcomes of treating HCV before transplantation.