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

Results

Between February 2014 and June 2015, 142 patients with DC, HCC negative, were treated with DAA therapy while on the waiting list for LT. Baseline features are reported in Table 1. Sixty-nine patients (48.6%) had a MELD score lower than 16. For these patients, the indication for LT was the presence of at least one of the following complications: chronic encephalopathy, refractory ascites/hydrothorax, uncontrolled bleeding, hepato-pulmonary syndrome, portopulmonary hypertension and severe malnutrition.

Clinical Outcome of the Entire Cohort

At the time of the analysis, 7 patients (4.9%) died while on the WL (5 of sepsis, 1 of massive bleeding and 1 of pulmonary embolism). Sixty-nine patients (48.6%) underwent LT. Of note, all patients who had a MELD score higher than 20 at start of DAA therapy and were not delisted have already received a liver graft (no purgatory effect). Thirteen patients (9.1%) were still on the WL and all had a MELD score equal or below 16 at the last visit. Forty-four patients (30.9%) were delisted because of clinical improvement. The 9 remaining patients were delisted or 'dropped out' for reasons not related to clinical improvement, 2 for LT refusal, 1 for a severe cardiac pathology, 2 for alcohol recidivism, 1 for complete portal vein, splenic vein and mesenteric veins thrombosis, 1 for heart failure after transjugular intrahepatic portosystemic (TIPS) placement, and 2 for a rapidly progressing HCC. The median (IQR) follow-up was 34.9 (29.8–39.5) months. See Figure 1.

Figure 1.

Patient disposition and outcome

Impact of DAA treatment on delisting for clinical improvement

Forty-four patients treated with DAA while on the waiting list showed a remarkable clinical improvement and were delisted. Their median MELD and Child-Pugh score at start of therapy were significantly lower than in non-delisted patients. At delisting, the great majority were Child-Pugh A (38/44 = 93%) with a MELD score lower than 12. By competing risk analysis, the cumulative incidence of delisting for clinical improvement at 48, 72 and 96 weeks after start of DAAs therapy, was 7%, 18% and 27% (Figure 2). Patients with a MELD score lower than 16 at start of therapy had almost 50% chance of being delisted for clinical improvement. The median (IQR) follow-up from start of therapy was 37.5 (34.6–41.7) months. The median (IQR) time from start of treatment to delisting was 14.8 (11.6–18.1) months. The median (IQR) follow-up after delisting was 22.1 (16.2–31.1) months.

Figure 2.

Competing risk cumulative incidence of delisting, dropping out, receiving a LT or death

Clinical Features of Patients Delisted for Clinical Improvement

The MELD and Child-Pugh scores at start of treatment, at delisting and at last follow-up in the 44 patients who were delisted are shown in Figure 3 and Table 2. Thirty-five patients (79.5%) had complete regression of ascites or other fluid retention and were off diuretic therapy. Nine patients (20.5%) maintained some fluid retention requiring low-dose diuretics. Patients with chronic HE, completely regressed with no medical therapy needed.

Figure 3.

Delisted patients: change of Child-Pugh and MELD score at start of therapy, at delisting and at last follow-up. The 3 red circles refer to patients who were relisted for recurrent grade 3 ascites, the yellow circle to the patient who developed a small HCC, and the black circle to the patient who died of a rapidly progressing HCC

Outcome in Delisted Patients

Four patients required relisting (9%) and 1 additional patient died after delisting because of a rapidly progressive HCC (1/44 = 2.3%). Three of the four relisted patients developed recurrent ascites and were among those on low-dose diuretic at delisting. On the other side, none of the 35 patients, who was off diuretics at delisting, had to be relisted for worsening ascites, to date. Hence, maintaining some fluid retention requiring low doses of diuretics at delisting emerged as a possible risk factor for worsening of ascites and relisting (P < .005). The fourth patient requiring relisting had a nodule of 1.3 cm HCC diagnosed 9 months after completing DAA therapy.

The patient who died after delisting was from Egypt and had skipped his scheduled ultrasound screening 6 months prior to diagnosis of large infiltrating HCC. One year prior to diagnosis, magnetic resonance imaging (MRI) was negative for HCC.

Patients Developing HCC in the Entire Cohort and Liver Transplant Outcomes

Overall, 5 Child-Pugh B patients developed HCC. In 3 cases HCC was diagnosed when patients were still on the waiting list, while in the remaining 2 cases after their delisting for clinical improvement. The timing of HCC diagnosis was between 6 and 18 months after completing DAA therapy. One patient was still viraemic at the time of the diagnosis of HCC, having relapsed after a 6-month course of SOF/RBV. To note, 3 in 5 patients presented an aggressive, infiltrative type HCC, which rapidly lead patients to death. No patient with HCC had diabetes.

Seventy patients received a liver graft, one of whom after being delisted for clinical improvement and then relisted for HCC. The Median MELD score at LT was 18. Eleven patients could not finish the planned duration of DAA treatment, all of them being aviremic at the time of LT. Four patients who had been treated with SOF/RBV pre-LT had a viral recurrence post-LT and were successfully retreated with a combination of SOF and NS5A inhibitor. Nine of the 70 patients (13%) who received a liver graft died, none from HCV recurrent disease.

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