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pegylated-interferon 2a 180<span class="elsevierStyleHsp" style=""></span>mcg&#47;week and ribavarin 1200&#47;day for a total of 48-weeks&#46; At the time of starting treatment&#44; the patient had a F3 degree of fibrosis determined by Fibroscan<span class="elsevierStyleSup">&#174;</span> &#40;9&#46;9<span class="elsevierStyleHsp" style=""></span>kPa&#41;&#44; a HCV VL of 5&#44;810&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#44; CT IL28B polymorphism&#44; a CD4 count of 544<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> &#40;32&#37;&#41;&#44; HIV VL &#60;20<span class="elsevierStyleHsp" style=""></span>copies&#47;ml&#44; ALT of 75<span class="elsevierStyleHsp" style=""></span>IU&#47;L and AST of 62<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; the rest of the analytical was normal&#46; During the following weeks&#44; he did not show relevant adverse events&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">At week 43&#44; the patient started having dyspnea and chest pain without fever&#44; symptoms that worsened in the following weeks&#46; The chest radiography showed bilateral diffuse interstitial lung disease&#44; ground-glass opacities and mediastinal lymphadenopathy&#46; Also&#44; a lung scan was performed and no findings of acute pulmonary embolism were observed&#46; The gas analysis showed&#58; pCO<span class="elsevierStyleInf">2</span>&#58; 31&#46;2<span class="elsevierStyleHsp" style=""></span>mmHg&#44; pO<span class="elsevierStyleInf">2</span>&#58; 68&#46;2<span class="elsevierStyleHsp" style=""></span>mmHg&#44; O<span class="elsevierStyleInf">2</span> saturation&#58; 95&#46;9&#37; and pH&#58; 7&#46;47&#44; and the biochemistry showed an angiotensin-converting enzyme value greater than 100&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two weeks later&#44; the patient presented clinical improvement &#40;after drug treatment with antibiotics and bronchodilators&#41; but with persistent injury in chest radiography&#44; so a thoracic CT was performed&#44; showing bilateral and diffuse ground-glass opacities&#44; multiple centrilobular micronodules &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and mediastinal lymphadenopathy&#46; Bronchoscopy was normal&#44; and transbronchial biopsy showed the presence of non-necrotizing granulomas&#46; Ziehl Neelsen&#44; and Groccott staining were negative&#44; as PCR and mycobacteria culture&#46; After completing HCV treatment&#44; the clinical course of the patient was favorable&#44; showing the following thoracic CT gradual improvement in lung and lymph node involvement&#44; and finally&#44; a year later&#44; the resolution of the disease &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">HCV VL values became undetectable at week 8 and remained undetectable 24 weeks after completion of HCV therapy&#44; reaching sustained viral response &#40;SVR&#41;&#46; In addition&#44; the liver function values normalized after 28 weeks of treatment &#40;ALT 31<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; AST&#58; 35<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#41;&#44; and remained within the normal range 24 weeks after completion of antiviral therapy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sarcoidosis is a granulomatous disease of unknown origin and multisystemic character&#44; in which lung&#44; liver&#44; lymphoid system and skin are the most affected organs&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Although its etiology is unknown&#44; probably an exaggerated response to various antigens as mycobacterias&#44; environmental agents or autoantigens&#44; produces an abnormal activation of CD4&#43; T cells&#44; activating peripheral blood monocytes&#44; and causing the formation of granulomas&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis of sarcoidosis is often a matter of exclusion&#44; as in our case&#59; there is no specific test for the condition&#46; All the findings of our case raised the possibility of a differential diagnosis of granulomatous inflammation caused by infection or sarcoidosis&#46; Findings on cultures for viral&#44; fungal and mycobacterial organisms were negative&#46; Radiological findings and clinical manifestations were consistent with an atypical pulmonary sarcoidosis&#46; Similar clinical findings were reported in other cases of sarcoidosis associated with interferon&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Interferon is a cytokine with immunomodulatory activity on T lymphocytes&#44; which is successfully used in the treatment of hepatitis C&#46; Several adverse effects have been described for interferon therapies&#44; like hematologic symptoms&#44; flu-like symptoms&#44; and cutaneous events&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> and although the exact mechanism of action is unknown&#44; interferon is also associated with the occurrence of certain immunological diseases like hemolytic anemia&#44; hypothyroidism&#44; and sarcoidosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;5</span></a> The majority of patients achieved spontaneous resolution of sarcoidosis after stopping treatment with interferon&#44; and there is also evidence of remission in spite of continuing treatment&#44; demonstrating that interferon may play a role in its appearance&#44; but not in the maintenance&#44; so the decision to continue treatment should be assessed depending on the risk-benefit balance&#46; In our case&#44; the patient continued the treatment until completion&#44; reaching SVR&#44; and showing clinical and radiological improvement since the end of treatment&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The systemic manifestations of sarcoidosis are usually treated with oral steroids&#44; but it often increases the hepatitis C viral load&#46; In this case&#44; it was not necessary to use corticosteroid treatment&#44; and sarcoidosis was resolved after stopping HCV treatment&#44; which may indicate the role of HCV treatment in his appearance&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although there are several articles about the relationship between sarcoidosis and interferon&#44; their relationship with ribavirin cannot be ruled&#44; because it can activate the Th1 helper lymphocytes&#44; or even with telaprevir&#44; this occurred in another case of sarcoidosis in a patient treated with telaprevir&#44; ribavirin and standard interferon 3 times per week&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">This case draws attention to this serious side effect that some patients may experience during the antiviral treatment&#44; and it is essential that the diagnosis of sarcoidosis is considered in patients with compatible clinical findings&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Letter to the Editor
Pulmonary sarcoidosis in the context of a telaprevir-based triple therapy for hepatitis C
D. Pérez Parentea,
Corresponding author
di_parente@hotmail.com

Corresponding author.
, M. Suárez Santamaríaa, S. Suárez Ordóñezb, L.E. Morano Amadoc
a Pharmacy Service, Hospital Meixoeiro, EOXI Vigo, Vigo, Spain
b Hematology Service, Hospital Meixoeiro, EOXI Vigo, Vigo, Spain
c Unit of Infectious Disease, Hospital Meixoeiro, EOXI Vigo, Vigo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We would like to present the first case of a patient coinfected with human immunodeficiency virus &#40;HIV&#41; and hepatitis C virus &#40;HCV&#41;&#44; diagnosed with pulmonary sarcoidosis in the context of a triple therapy with pegylated-interferon&#44; ribavirin and telaprevir&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 50-year-old man&#44; diagnosed with HIV in 1993&#44; stage A2&#44; treated with antiretroviral therapy&#58; tenofovir&#44; emtricitabine and raltegravir&#46; In 2004 was diagnosed with chronic hepatitis C&#44; genotype 1a with F2 degree of liver fibrosis&#44; and treated during 24 weeks with pegylated-interferon and ribavirin&#44; presenting partial response&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2013&#44; the patient was treated with telaprevir-based triple therapy according to the regimen&#58; telaprevir 2250<span class="elsevierStyleHsp" style=""></span>mg&#47;day for the first 12 weeks&#59; pegylated-interferon 2a 180<span class="elsevierStyleHsp" style=""></span>mcg&#47;week and ribavarin 1200&#47;day for a total of 48-weeks&#46; At the time of starting treatment&#44; the patient had a F3 degree of fibrosis determined by Fibroscan<span class="elsevierStyleSup">&#174;</span> &#40;9&#46;9<span class="elsevierStyleHsp" style=""></span>kPa&#41;&#44; a HCV VL of 5&#44;810&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#44; CT IL28B polymorphism&#44; a CD4 count of 544<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> &#40;32&#37;&#41;&#44; HIV VL &#60;20<span class="elsevierStyleHsp" style=""></span>copies&#47;ml&#44; ALT of 75<span class="elsevierStyleHsp" style=""></span>IU&#47;L and AST of 62<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; the rest of the analytical was normal&#46; During the following weeks&#44; he did not show relevant adverse events&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">At week 43&#44; the patient started having dyspnea and chest pain without fever&#44; symptoms that worsened in the following weeks&#46; The chest radiography showed bilateral diffuse interstitial lung disease&#44; ground-glass opacities and mediastinal lymphadenopathy&#46; Also&#44; a lung scan was performed and no findings of acute pulmonary embolism were observed&#46; The gas analysis showed&#58; pCO<span class="elsevierStyleInf">2</span>&#58; 31&#46;2<span class="elsevierStyleHsp" style=""></span>mmHg&#44; pO<span class="elsevierStyleInf">2</span>&#58; 68&#46;2<span class="elsevierStyleHsp" style=""></span>mmHg&#44; O<span class="elsevierStyleInf">2</span> saturation&#58; 95&#46;9&#37; and pH&#58; 7&#46;47&#44; and the biochemistry showed an angiotensin-converting enzyme value greater than 100&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two weeks later&#44; the patient presented clinical improvement &#40;after drug treatment with antibiotics and bronchodilators&#41; but with persistent injury in chest radiography&#44; so a thoracic CT was performed&#44; showing bilateral and diffuse ground-glass opacities&#44; multiple centrilobular micronodules &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and mediastinal lymphadenopathy&#46; Bronchoscopy was normal&#44; and transbronchial biopsy showed the presence of non-necrotizing granulomas&#46; Ziehl Neelsen&#44; and Groccott staining were negative&#44; as PCR and mycobacteria culture&#46; After completing HCV treatment&#44; the clinical course of the patient was favorable&#44; showing the following thoracic CT gradual improvement in lung and lymph node involvement&#44; and finally&#44; a year later&#44; the resolution of the disease &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">HCV VL values became undetectable at week 8 and remained undetectable 24 weeks after completion of HCV therapy&#44; reaching sustained viral response &#40;SVR&#41;&#46; In addition&#44; the liver function values normalized after 28 weeks of treatment &#40;ALT 31<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; AST&#58; 35<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#41;&#44; and remained within the normal range 24 weeks after completion of antiviral therapy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sarcoidosis is a granulomatous disease of unknown origin and multisystemic character&#44; in which lung&#44; liver&#44; lymphoid system and skin are the most affected organs&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Although its etiology is unknown&#44; probably an exaggerated response to various antigens as mycobacterias&#44; environmental agents or autoantigens&#44; produces an abnormal activation of CD4&#43; T cells&#44; activating peripheral blood monocytes&#44; and causing the formation of granulomas&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis of sarcoidosis is often a matter of exclusion&#44; as in our case&#59; there is no specific test for the condition&#46; All the findings of our case raised the possibility of a differential diagnosis of granulomatous inflammation caused by infection or sarcoidosis&#46; Findings on cultures for viral&#44; fungal and mycobacterial organisms were negative&#46; Radiological findings and clinical manifestations were consistent with an atypical pulmonary sarcoidosis&#46; Similar clinical findings were reported in other cases of sarcoidosis associated with interferon&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Interferon is a cytokine with immunomodulatory activity on T lymphocytes&#44; which is successfully used in the treatment of hepatitis C&#46; Several adverse effects have been described for interferon therapies&#44; like hematologic symptoms&#44; flu-like symptoms&#44; and cutaneous events&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> and although the exact mechanism of action is unknown&#44; interferon is also associated with the occurrence of certain immunological diseases like hemolytic anemia&#44; hypothyroidism&#44; and sarcoidosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;5</span></a> The majority of patients achieved spontaneous resolution of sarcoidosis after stopping treatment with interferon&#44; and there is also evidence of remission in spite of continuing treatment&#44; demonstrating that interferon may play a role in its appearance&#44; but not in the maintenance&#44; so the decision to continue treatment should be assessed depending on the risk-benefit balance&#46; In our case&#44; the patient continued the treatment until completion&#44; reaching SVR&#44; and showing clinical and radiological improvement since the end of treatment&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The systemic manifestations of sarcoidosis are usually treated with oral steroids&#44; but it often increases the hepatitis C viral load&#46; In this case&#44; it was not necessary to use corticosteroid treatment&#44; and sarcoidosis was resolved after stopping HCV treatment&#44; which may indicate the role of HCV treatment in his appearance&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although there are several articles about the relationship between sarcoidosis and interferon&#44; their relationship with ribavirin cannot be ruled&#44; because it can activate the Th1 helper lymphocytes&#44; or even with telaprevir&#44; this occurred in another case of sarcoidosis in a patient treated with telaprevir&#44; ribavirin and standard interferon 3 times per week&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">This case draws attention to this serious side effect that some patients may experience during the antiviral treatment&#44; and it is essential that the diagnosis of sarcoidosis is considered in patients with compatible clinical findings&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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ISSN: 21735115
Original language: English
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