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We would like to thank Savale et al1Savale L. Chaumais M.C. Montani D. et al.Direct-acting antiviral medications for hepatitis C virus infection and pulmonary arterial hypertension.Chest. 2016; 150: 256-258Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar for their interest in our recent article in CHEST.2Renard S. Borentain P. Salaun E. et al.Severe pulmonary arterial hypertension in patients treated for hepatitis C with sofosbuvir.Chest. 2016; 149: e69-e73Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar They report three additional cases of newly diagnosed pulmonary arterial hypertension (PAH) occurring during direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.1Savale L. Chaumais M.C. Montani D. et al.Direct-acting antiviral medications for hepatitis C virus infection and pulmonary arterial hypertension.Chest. 2016; 150: 256-258Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar These observations underline the importance of systematic report of potential cardiopulmonary side effects related to DAA therapy. In their comment, Savale et al1Savale L. Chaumais M.C. Montani D. et al.Direct-acting antiviral medications for hepatitis C virus infection and pulmonary arterial hypertension.Chest. 2016; 150: 256-258Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar also report safety of DAA therapy in previous known patients with PAH. They did not observe any significant hemodynamics worsening after HCV treatment completion compared with pretherapeutic assessment.1Savale L. Chaumais M.C. Montani D. et al.Direct-acting antiviral medications for hepatitis C virus infection and pulmonary arterial hypertension.Chest. 2016; 150: 256-258Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar These data, collected in 13 patients, argue for a good tolerance of DAA therapy in this clinical setting. However, in our experience, we observed one case of PAH worsening occurring during DAA therapy. A 48-year-old HIV/1a genotype HCV coinfected cirrhotic woman with mild PAH on bosentan therapy received DAA therapy in our institution. Pretherapeutic noninvasive evaluation found World Health Organization (WHO) functional class (FC) II, systolic pulmonary arterial pressure (sPAP) estimated at 50 mm Hg, right ventricle (RV) of normal size, and brain natriuretic peptide level at 73 pg/mL. The patient started a DAA combination (sofosbuvir plus ledipasvir) for 24 weeks. Sixteen weeks after treatment initiation and 8 weeks after HCV suppression, the patient presented with dyspnea worsening (WHO FC III). Noninvasive results were sPAP at 86 mm Hg, with RV enlargement and brain natriuretic peptide level at 275 pg/mL. Despite this worsening, DAA was continued without PAH treatment modification. An early monitoring on DAA therapy revealed a regression of PAH with WHO FC II and sPAP at 50 mm Hg with normal RV size. This regression was confirmed 1 month after DAA cessation. The present case demonstrates that patients with PAH could experience a transient PAH worsening during DAA therapy. However, as reported here, spontaneous regression could be observed despite DAA continuation. Therefore, in accordance with Savale et al1Savale L. Chaumais M.C. Montani D. et al.Direct-acting antiviral medications for hepatitis C virus infection and pulmonary arterial hypertension.Chest. 2016; 150: 256-258Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, reported data suggest that DAA therapy remains usually safe in stable patients with PAH, but can be associated with PAH worsening. The long-term impact of DAA-induced HCV eradication in patients with PAH should be assessed. Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With SofosbuvirCHESTVol. 149Issue 3PreviewDevelopment of direct-acting antiviral agents against hepatitis C virus (HCV) has changed the management of chronic HCV infection. We report three cases of newly diagnosed or exacerbated pulmonary arterial hypertension (PAH) in patients treated with sofosbuvir. All patients had PAH-associated comorbidities (HIV coinfection in two, portal hypertension in one) and one was already being treated for PAH. At admission, all patients presented with syncope, World Health Organization functional class IV, right-sided heart failure, and extremely severe hemodynamic parameters. Full-Text PDF Direct-Acting Antiviral Medications for Hepatitis C Virus Infection and Pulmonary Arterial HypertensionCHESTVol. 150Issue 1PreviewWe read with interest the article by Renard et al1 in CHEST (March 2016) reporting newly diagnosed or worsening pulmonary arterial hypertension (PAH) in 3 patients treated with sofosbuvir for hepatitis C virus (HCV) infection. As discussed by the authors, the causal link between direct-acting antiviral (DAA) medications for HCV and PAH is difficult to confirm at this stage because all 3 patients had concomitant PAH risk factors (portal hypertension and/or HIV infection). To supplement these observations, we have collected all cases of PAH monitored in the French referral center for severe pulmonary hypertension with a history of DAA therapy. Full-Text PDF