Delisting HCV-infected Liver Transplant Candidates Who Improved After Viral Eradication

Outcome 2 Years After Delisting

Giovanni Perricone; Christophe Duvoux; Marina Berenguer; Paolo A. Cortesi; Carmen Vinaixa; Rita Facchetti; Chiara Mazzarelli; Susanne-Rasoul Rockenschaub; Silvia Martini; Cristina Morelli; Sara Monico; Riccardo Volpes; Georges-Philippe Pageaux; Stefano Fagiuoli; Luca S. Belli; for the European Liver and Intestine Transplant Association (ELITA)

Disclosures

Liver International. 2018;38(12):2170-2177. 

In This Article

Discussion

The issue of 'delisting for clinical improvement' remained relevant for a period of time at the start of the DAA era. This, as a significant number of patients with decompensated cirrhosis on the waiting list for LT had not yet been treated with DAAs. Three European studies showed that "delisting for clinical improvement" was possible in 1 in 3 patients, provided that their MELD score was below 20; however, the long-term risk of further decompensation and HCC development after delisting could not be assessed because of short follow-up.[1,3] After only a few years of DAA use, fewer and fewer liver transplant candidates with HCV-related decompensated cirrhosis are now being considered for DAA therapy while on the waiting list. In fact, when DAAs are administered to patients with compensated cirrhosis, the progression of their liver disease can be generally halted and hepatic decompensation prevented. Hence, the number of patients requiring listing for LT is rapidly declining,[6] Even though, having information on the long-term outcome of delisted patients is still needed to aid clinicians in deciding whether to treat HCV-infected patients pre- or post-liver transplant.

The most interesting findings of this study are the following:

  1. DAAs given to liver transplant candidates with HCV infection and decompensated cirrhosis resulted in a remarkable clinical improvement permitting 'delisting' of almost one-third of treated patients. This percentage is greater than in the original study because of a number of patients being delisted after a long period of time from initial DAA administration. At delisting, the great majority (80%) were off diuretic therapy and none had clinical signs of encephalopathy.

  2. The risk of re-decompensation in the 44 patients who were delisted was low, with 3 patients requiring relisting for recurrent grade 3 ascites. These 3 patients at delisting were still on low-dose diuretics which represents a possible risk factor for subsequent relisting.

  3. The risk of developing HCC after delisting was also low (4.5%), with 2 Child-Pugh B patients experiencing such complication, which is in line to what observed in untreated patients.[7]

The present study corroborates the results of a similar study conducted in Spain by Pascasio[3] et al on a smaller cohort of 29 patients delisted for clinical improvement, with only 2 patients having to be relisted because of a single nodule of HCC less than 2 cm in diameter. At present, the largest series of patients with decompensated cirrhosis treated with DAAs outside the liver transplant setting is that of the English Expanded Access Program (EAP)[8] which included 406 patients, principally Child-Pugh B and with a median MELD score of 12. The majority of patients had reversal of liver decompensation after DAA therapy, with no evidence of an increased risk in liver malignancy. Another multicentre international study analysed 190 patients with Child-Pugh B or C cirrhosis treated with DAA therapy with an annual incidence of "de novo" HCC of 2.61%, which is lower than that observed in untreated patients with decompensated cirrhosis.[9] Very similar findings emerged in a study from Romano et al[7] with an annual incidence of HCC of 2.8% after DAAs in 215 Child-Pugh B patients. The authors stressed that one-third of their patients with "de novo" HCC developed a multifocal or infiltrative type of tumour. This was more frequent during rather than after DAA treatment and in patients who did not achieve SVR. Our findings are in alignment with what reported by Romano et al, as 3 of the 5 patients with no previous history of HCC developed a diffuse HCC after DAA therapy, 2 while waiting for a LT and a third one after being delisted. It cannot be excluded that in these 3 cases growth of HCC could be boosted by the microenvironment changes induced by DAAs. If these findings were confirmed by larger studies, the use of DAA pre-LT may need further consideration, particularly in patients with low probability of being delisted.

A number of limitations to the current study should be acknowledged. Firstly, the number of delisted patients is small to draw definitive conclusions, but more robust studies based on many more patients can no longer be planned, given the rapidly changing epidemiology of HCV infection. Secondly, should some patients re-decompensate long after being delisted, ageing may negate them to relisting. At present, this is not an issue but needs consideration for the future.

In conclusion, this study demonstrates that DAA therapy in liver transplant candidates with decompensated cirrhosis is effective and results in long-term improvement in liver function, giving 1 in 3 patients the possibility to delist with low risk for future liver-related complications.

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