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Hepatitis C virus direct acting antivirals impact on renal function in the first 4 weeks of treatment

Taramasso, Lucia; Montanari, Lara; Di Biagio, Antonio

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doi: 10.1097/QAD.0000000000001804
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Rossi et al.[1] have recently highlighted how the estimated glomerular filtration rate (eGFR) decline in patients with sustained viral response after hepatitis C virus (HCV) treatment, although present, is not different from that of HIV/HCV coinfected patients who are not treated. We found this result very interesting and of great clinical significance, although, in that study, only 53% of patients received an interferon-free direct acting antiviral (DAA) [1] that is now the first line treatment for HCV. Definitive data on the real renal impact of DAA regimens are still scarce and seem to indicate a general tendency toward renal impairment in course of treatment [2–5], but, to our knowledge, a comparison between the eGFR trend pre-DAA and post-DAA treatment has not been performed so far.

We reviewed our single centre data, prospectively collected the years 2015 and 2016, and selected patients treated with an interferon-free DAA regimen with available creatinine measure 48 (±8) weeks before starting DAA (48WB), at the time of starting (baseline), 4 week after baseline (4WA) and 48 (±8) weeks after baseline (48WA).

The eGFR value was estimated according to the Chronic Kidney Disease Epidemiology Collaboration equation [6] and its trend across the study period was evaluated by a generalized linear model for repeated measures. Continual variables were expressed as means (±SD). Metavir stage of fibrosis was given according to stiffness evaluation by Fibroscan: F1 less than 7.1 kPa; F2 7.1–9.6 kPa; F3 more than 9.6–12.5 kPa; F4 more than 12.5 kPa. We found 126 patients with fully available data, 37 (29.4%) were women, mean age was 56.1 (±7.3) years. Eighty-six (68.2%) were HIV/HCV coinfected, all in combined antiretroviral therapy with HIV-RNA less than 200 copies/ml at baseline, and with mean CD4+ T-lymphocyte 588 (±323.6) cells/μl. Risk factors for infection were previous intravenous drug use in 84 (66.7%), hemotransfusion in 10 (7.9%), sexual transmission in five (4.0%) and unknown in 27 (21.4%) patients. Hypertension, diabetes and dyslipidemia were common comorbidities (18.9%, 10.2% and 18.1%, respectively). Metavir stage of fibrosis was F4 in 75 (59.5%) and F3 in 33 (26.2%) patients.

Overall, 63 (50.0%) patients were treated with sofosbuvir/ledipasvir, 36 (28.6%) with sofosbuvir/daclatasvir, 25 (19.8%) with ombitasvir/paritaprevir/ritonavir ± dasabuvir and two (1.6%) with sofosbuvir. Ribavirin was added as a part of anti-HCV treatment in 92 cases (73.0%).

Mean eGFR (ml/min/1.73 m2) was 91.9 (±17.6) at 48WB, 90.1 (±17.4) at baseline, 87.8 (±16.6) at 4WA, and 85.1 (±19.5) at 48WA, with a significant decreasing trend across the study period (P < 0.0001).

Pair comparison after Bonferroni adjustment revealed that the eGFR decline was significant between baseline and 4WA (P = 0.042), while eGFR changes between 48WB and baseline (P = 0.486) and between 4WA and 48WA (P = 0.121) were not. The decreasing trend was confirmed also when analyzing separately the subgroups of HIV/HCV coinfected patients (P = 0.001) and of HCV mono-infected (P = 0.011), and individuals with or without history of intravenous drug use (P = 0.002 and 0.004, respectively). After pair comparison in these subgroups of patients, the eGFR drop maintained significance only in the first 4 weeks of treatment (P = 0.034) in HIV-infected patients (Table 1).

Table 1
Table 1:
Estimated glomerular filtration rate changes in the study population, according to serostatus and history of illicit drug use.

Despite a renal function decline being expected with ageing, especially in HCV-infected patients [7], and as also found also in patients who are not treated for HCV [1], in our study, we found that the eGFR decline was more marked in the first 4 weeks following DAA initiation in HIV/HCV coinfected patients, whereas it was not significant in the year before the treatment, nor in the timeframe between week 4 and 48 after treatment. Thus, it is possible that, in studies evaluating more deferred follow-up, the decline might not be noticeable. We recognize that our sample size was limited and we lack power to detect all possible significant factors that may be associated with renal impairment. With this limit, the eGFR decline found in the first 4 weeks of DAA strongly suggests that DAA treatment can negatively influence the eGFR in HIV/HCV coinfected patients. We still do not know whether this worsening may be significant in the long-term, as we still lack long-term follow up of patients treated with DAA. Active surveillance and continual follow up of these patients are crucial not only for monitoring their long-term hepatic evolution, but also for defining what will be the future of the renal function in people who are treated now for HCV infection.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.

References

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