Hepatitis C Late Relapse in Patients With Directly Acting Antiviral-related Sustained Virological Response at Week 12

Mariantonietta Pisaturo; Carmine Minichini; Mario Starace; Mara Caroprese; Margherita Macera; Giuseppina Brancaccio; Stefania De Pascalis; Antonella Santonicola; Alfonso Galeota Lanza; Rosa Zampino; Gaetano Cotticelli; Evangelista Sagnelli; Giovanni Battista Gaeta; Nicola Coppola

Disclosures

Liver International. 2019;39(5):844-853. 

In This Article

Results

The demographic, clinical and virological data of the 129 patients enrolled are summarized in Table 1. Ninety-one (70.5%) were males, and the median age was 64 years (range, 42-81). No patient was anti-HIV- and/or HBsAg-positive. The risk factor for the acquisition of parenteral infection was identified in 81 (62.8%). The majority (96 patients, 74.4%) had cirrhosis. The duration of the DAA therapy had a median of 12 weeks (range 1-48).

Of the 129 patients enrolled, 15 (11.6%) showed a non-response, 8 (6.2%) a virological breakthrough and 106 relapsed (82.2%). Of the 106 relapser patients, 99 (93.4%) experienced a relapse by week 12 after the discontinuation of DAA therapy, and 7 (6.6%) experienced a late relapse (after week 12). Nine of the 15 patients with a non-response were treated with a DAA regimen not active against their HCV genotype (one patient with HCV genotype 2 and eight with genotype 3 treated with paritaprevir-r plus ombitasvir and dasabuvir; Table 1). Moreover, 37 patients were treated with a suboptimal DAA regimen (one patient with HCV genotype 1a, 15 with 1b, 15 with 2 and six with 3 treated with sofosbuvir+ribavirin; Table 1).

The demographic, clinical and virological data of the seven patients with a late relapse are shown in Table 2. Cirrhosis was present in four patients, HCC in only one; all, but one, harboured the same genotype before the DAA regimen and at late relapse (patient #6 showed genotype 1b before the start of the DAA regimen and genotype 1a at week 24 after stopping); four had been treated with an optimal DAA regimen; none declared intravenous drug use or man to man sex or was under immunosuppressive treatment. After negativization of HCV-RNA by week 12, a relapse was identified at week 24 in four patients, at week 48 (HCV-RNA negative at week 24) in one and at week 72 (HCV-RNA negative at week 24 and 48) in two. The dynamics of HCV-RNA before, during and after DAA treatment in these seven patients are reported in the Figure S1. All patients showed at least one RAS, all in the NS5A region. A serum sample collected before the start of the DAA regimen was available for two patients (patient no. 2 and no. 7 of Table 2); the phylogenetic analysis region comparing the HCV NS3, NS5A and NS5B regions in sera collected before the DAA regimen and at the time of the late relapse demonstrated the same viral strain in both patients (Figures 1–3), suggesting a reactivation of HCV infection instead of re-infection; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re-infection cannot be excluded.

Figure 1.

NS3 phylogenetic analysis of patient #4 and patient #7 at baseline (B) and at relapse (R)

Figure 2.

NS5A phylogenetic analysis of patient #4 and patient #7 at baseline (B) and at relapse (R)

Figure 3.

NS5B phylogenetic analysis of patient #4 and patient #7 at baseline (B) and at relapse (R)

Supplementary Figure.

HCV load dynamic before, during and after DAA regimen

Table 3 shows the epidemiological, clinical and virological features of the patients according to the type of virological failure to DAA therapy. No differences in the demographic, clinical or virological features were observed between the patients with a different virological failure.

Considering the 106 patients with a relapse, the prevalence of patients with RASs was higher in the seven with a late relapse than in the 99 with a relapse by week 12. In fact, at least one RAS or RASs in all three regions of HCV were more frequently identified in the first group (100% vs 66.7%, P = 0.09; and 28.6% vs 5%, P = 0.06 respectively); however, because of the low number of patients with a late relapse, these differences were not significant to the statistical analysis. Moreover, a RAS in the NS5A region was observed in all patients with a late relapse and in 53 (53.5%, P = 0.018) in those with a relapse by week 12.

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