Interferon-free DAA combination is currently being tested in patients awaiting liver transplantation. In an open label single arm study, 61 patients awaiting LT with HCV cirrhosis, but with CTP score 7 or less, were treated with sofosbuvir (SOF), an NS5B nucleotide polymerase inhibitor, in combination with RBV [16]. Of the 43 patients who achieved pre-transplant viral levels of HCV RNA <25 IU/mL, 30 (70 %) were able to maintain a post-transplant virologic response at 12 weeks. Notably, recurrence of HCV was inversely related to the number of consecutive days of undetectable HCV RNA before transplantation. The main adverse reactions noted with this combination were fatigue, headache, and anemia due to RBV, but the drug discontinuation rates due to adverse events were low. In addition to treating patients before LT, there is anecdotal evidence of benefit by extending the therapy to immediate post-LT period if HCV RNA undetectability prior to LT is less than 30 days [17]. These anecdotal observations require further corroboration before such a strategy is recommended.

The cure rates in patients with well-compensated cirrhosis, whether treatment naïve or treatment experienced, with recently approved DAA regimens (Harvoni or Viekira Pak with or without RBV) is over 90 % with 12–24 weeks of treatment. Those with HCC and compensated HCV cirrhosis (Child A) could be treated with above regimens if there are no obvious contraindications. While SOF/ledipasvir (Harvoni) is contraindicated in people with renal failure, Viekira Pak could be used in the presence of renal failure, except those on dialysis. The side effect profile of these regimens is excellent with fatigue and headache being the most common side effects. When RBV is used, hemoglobin should be monitored closely especially in those with renal impairment. Use of these regimens in the pre-LT setting is preliminary in nature and requires further evaluation in larger studies. Moreover, the current studies comprised patients with compensated or mildly decompensated liver disease undergoing transplantation and studies involving patients with more advanced disease are currently in progress. The cure rates with DAA regimens in well-compensated cirrhosis (Child A) are shown in Table 4.2.

Another approach to chronic HCV patients who undergo LT is to treat them with antiviral agents immediately after LT before histological evidence of inflammation or fibrosis is established (i.e., begin treatment within 4 weeks after LT; this is also known as preemptive strategy). The rationale for such treatment is that fibrosis is absent in the early period after LT, and therefore these patients are more likely to respond antiviral therapy. The experience with interferon-based regimens immediately after LT showed that interferon-based regimens are poorly tolerated in the immediate postoperative period, and it is not very practical to treat these patients in the immediate postoperative period with interferon-based regimes (Table 4.3) when they have many other issues related to the transplant surgery. There is only anecdotal experience with DAA regimens in this setting, but we are likely to see more studies in this area in the near future.

Treatment with standard interferon, as a part of preemptive strategy, has been largely unsuccessful in reducing recurrence of HCV [18–20]. Peg IFN and RBV combination regimen for preemptive therapy after LT has shown better efficacy than interferon monotherapy, but the SVR rates for genotypes 1, 2, and 3 were not encouraging. In one study, only 51 of 124 patients were eligible for preemptive therapy suggesting that this therapy is difficult to administer in the immediate postoperative period [21]. Additionally, 27 % of patients had serious adverse events, 85 % required dose reductions, and 37 % required discontinuation of treatment [20]. The large PHOENIX study [22] evaluated the preemptive strategy using Peg IFN/RBV and concluded that rates of histological recurrence, graft loss, and death were similar in the active and control groups. Although adding TVR/BOC to conventional dual therapy (interferon/RBV) improved SVR rates [23], there are only anecdotal case reports of using these combinations as a preemptive strategy, and moreover, the higher rates of serious adverse reactions make these combinations unsuitable for preemptive treatment. Other drugs such as SOF and simeprevir (SMV) have not been studied for this purpose. Based on the current evidence, the preemptive therapy using interferon-based regimen is currently not recommended.

This approach is currently the most accepted method to treat patients transplanted for hepatitis C. The histological recurrence is established with a combination of invasive and noninvasive factors as discussed in the previous chapter. Most centers would currently recommend therapy only when there is established recurrence of progressive disease, but this strategy may change in the near future with the availability of safer DAA regimens. It is more than likely that most patients with HCV will be treated with these regimens, perhaps after 3–6 months post-LT, with an intention to cure HCV. Although interferon-based regimens are going to become obsolete, it will be discussed for historical perspective on this topic.