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The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

Summary Background Direct‐acting anti‐viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. Aim To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Me...

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Published in:Alimentary pharmacology & therapeutics 2019-06, Vol.49 (11), p.1442-1447
Main Authors: El‐Serag, Hashem B., Christie, Israel C., Puenpatom, Amy, Castillo, Diana, Kanwal, Fasiha, Kramer, Jennifer R.
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Christie, Israel C.
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description Summary Background Direct‐acting anti‐viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. Aim To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Methods We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Results Of the 45 260 patients treated with DAA with mean follow‐up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10‐0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41‐0.90) and lichen planus (aHR = 0.46; 95% CI 0.30‐0.70), but not for non‐Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52‐1.43) or diabetes (aHR = 0.98; 95% CI 0.81‐1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11‐1.03). Conclusions Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non‐Hodgkin's lymphoma or diabetes.
doi_str_mv 10.1111/apt.15240
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However, the available data are limited. Aim To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Methods We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Results Of the 45 260 patients treated with DAA with mean follow‐up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10‐0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41‐0.90) and lichen planus (aHR = 0.46; 95% CI 0.30‐0.70), but not for non‐Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52‐1.43) or diabetes (aHR = 0.98; 95% CI 0.81‐1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11‐1.03). Conclusions Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non‐Hodgkin's lymphoma or diabetes.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.15240</identifier><identifier>PMID: 30932218</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Antiviral Agents - therapeutic use ; Cryoglobulinemia - etiology ; Cryoglobulinemia - prevention &amp; control ; Diabetes ; Diabetes mellitus ; Female ; Glomerulonephritis ; Glomerulonephritis - etiology ; Glomerulonephritis - prevention &amp; control ; Hepacivirus - drug effects ; Hepacivirus - genetics ; Hepatitis ; Hepatitis C ; Hepatitis C - complications ; Hepatitis C - drug therapy ; Hepatitis C - virology ; Humans ; Incidence ; Infections ; Lichen planus ; Lichen Planus - etiology ; Lichen Planus - prevention &amp; control ; Lymphoma ; Male ; Middle Aged ; Non-Hodgkin's lymphoma ; Porphyria ; Porphyria cutanea tarda ; Porphyria Cutanea Tarda - etiology ; Porphyria Cutanea Tarda - prevention &amp; control ; Regression analysis ; Retrospective Studies ; Ribonucleic acid ; Risk ; RNA ; Sustained Virologic Response ; Viruses</subject><ispartof>Alimentary pharmacology &amp; therapeutics, 2019-06, Vol.49 (11), p.1442-1447</ispartof><rights>2019 John Wiley &amp; Sons Ltd</rights><rights>2019 John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2019 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4540-9eff5666c04742dc4c845cb5dd9584658b211817ae0ecd2d1af7b353a270a6833</citedby><cites>FETCH-LOGICAL-c4540-9eff5666c04742dc4c845cb5dd9584658b211817ae0ecd2d1af7b353a270a6833</cites><orcidid>0000-0003-2953-4949 ; 0000-0001-5964-7579</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30932218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El‐Serag, Hashem B.</creatorcontrib><creatorcontrib>Christie, Israel C.</creatorcontrib><creatorcontrib>Puenpatom, Amy</creatorcontrib><creatorcontrib>Castillo, Diana</creatorcontrib><creatorcontrib>Kanwal, Fasiha</creatorcontrib><creatorcontrib>Kramer, Jennifer R.</creatorcontrib><title>The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection</title><title>Alimentary pharmacology &amp; therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary Background Direct‐acting anti‐viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. Aim To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Methods We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Results Of the 45 260 patients treated with DAA with mean follow‐up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10‐0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41‐0.90) and lichen planus (aHR = 0.46; 95% CI 0.30‐0.70), but not for non‐Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52‐1.43) or diabetes (aHR = 0.98; 95% CI 0.81‐1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11‐1.03). Conclusions Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non‐Hodgkin's lymphoma or diabetes.</description><subject>Antiviral Agents - therapeutic use</subject><subject>Cryoglobulinemia - etiology</subject><subject>Cryoglobulinemia - prevention &amp; control</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Female</subject><subject>Glomerulonephritis</subject><subject>Glomerulonephritis - etiology</subject><subject>Glomerulonephritis - prevention &amp; control</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - genetics</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C - complications</subject><subject>Hepatitis C - drug therapy</subject><subject>Hepatitis C - virology</subject><subject>Humans</subject><subject>Incidence</subject><subject>Infections</subject><subject>Lichen planus</subject><subject>Lichen Planus - etiology</subject><subject>Lichen Planus - prevention &amp; control</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Non-Hodgkin's lymphoma</subject><subject>Porphyria</subject><subject>Porphyria cutanea tarda</subject><subject>Porphyria Cutanea Tarda - etiology</subject><subject>Porphyria Cutanea Tarda - prevention &amp; control</subject><subject>Regression analysis</subject><subject>Retrospective Studies</subject><subject>Ribonucleic acid</subject><subject>Risk</subject><subject>RNA</subject><subject>Sustained Virologic Response</subject><subject>Viruses</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1DAURi0EokNhwQsgS2zKIq1_YidZVqMWkCqVxbCOPM5NxyVjB9spzK6PwJbX40m4IS0LJLyxrXt07id9hLzm7JTjOTNjPuVKlOwJWXGpVSGY1E_JigndFKLm8oi8SOmWMaYrJp6TI8kaKQSvV-TnZgcU-h5sTjT0NE0pG-eho3cuhiHcOGsGGiGNwSegOdDORYR_3f8wNjt_Q43PDn-II5h3EM14oMHPTxpd-jJb4XuOZgejyc7SvfGuB1yTHTrn8TLJLtE1dX7OgpOX5FlvhgSvHu5j8vnyYrP-UFxdv_-4Pr8qbKlKVjQYXmmtLSurUnS2tHWp7FZ1XaPqUqt6KziveWWAge1Ex01fbaWSRlTM6FrKY3KyeMcYvk6Yq927ZGEYjIcwpVYIxivOBWOIvv0HvQ1T9JgOKSG0lEo3SL1bKBtDShH6doxub-Kh5ayd-2qxr_ZPX8i-eTBO2z10f8nHghA4W4BvboDD_03t-afNovwN1xCjPQ</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>El‐Serag, Hashem B.</creator><creator>Christie, Israel C.</creator><creator>Puenpatom, Amy</creator><creator>Castillo, Diana</creator><creator>Kanwal, Fasiha</creator><creator>Kramer, Jennifer R.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2953-4949</orcidid><orcidid>https://orcid.org/0000-0001-5964-7579</orcidid></search><sort><creationdate>201906</creationdate><title>The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection</title><author>El‐Serag, Hashem B. ; Christie, Israel C. ; Puenpatom, Amy ; Castillo, Diana ; Kanwal, Fasiha ; Kramer, Jennifer R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4540-9eff5666c04742dc4c845cb5dd9584658b211817ae0ecd2d1af7b353a270a6833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antiviral Agents - therapeutic use</topic><topic>Cryoglobulinemia - etiology</topic><topic>Cryoglobulinemia - prevention &amp; control</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Female</topic><topic>Glomerulonephritis</topic><topic>Glomerulonephritis - etiology</topic><topic>Glomerulonephritis - prevention &amp; control</topic><topic>Hepacivirus - drug effects</topic><topic>Hepacivirus - genetics</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C - complications</topic><topic>Hepatitis C - drug therapy</topic><topic>Hepatitis C - virology</topic><topic>Humans</topic><topic>Incidence</topic><topic>Infections</topic><topic>Lichen planus</topic><topic>Lichen Planus - etiology</topic><topic>Lichen Planus - prevention &amp; control</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Non-Hodgkin's lymphoma</topic><topic>Porphyria</topic><topic>Porphyria cutanea tarda</topic><topic>Porphyria Cutanea Tarda - etiology</topic><topic>Porphyria Cutanea Tarda - prevention &amp; control</topic><topic>Regression analysis</topic><topic>Retrospective Studies</topic><topic>Ribonucleic acid</topic><topic>Risk</topic><topic>RNA</topic><topic>Sustained Virologic Response</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El‐Serag, Hashem B.</creatorcontrib><creatorcontrib>Christie, Israel C.</creatorcontrib><creatorcontrib>Puenpatom, Amy</creatorcontrib><creatorcontrib>Castillo, Diana</creatorcontrib><creatorcontrib>Kanwal, Fasiha</creatorcontrib><creatorcontrib>Kramer, Jennifer R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El‐Serag, Hashem B.</au><au>Christie, Israel C.</au><au>Puenpatom, Amy</au><au>Castillo, Diana</au><au>Kanwal, Fasiha</au><au>Kramer, Jennifer R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection</atitle><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2019-06</date><risdate>2019</risdate><volume>49</volume><issue>11</issue><spage>1442</spage><epage>1447</epage><pages>1442-1447</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Summary Background Direct‐acting anti‐viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. Aim To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Methods We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Results Of the 45 260 patients treated with DAA with mean follow‐up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10‐0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41‐0.90) and lichen planus (aHR = 0.46; 95% CI 0.30‐0.70), but not for non‐Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52‐1.43) or diabetes (aHR = 0.98; 95% CI 0.81‐1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11‐1.03). Conclusions Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non‐Hodgkin's lymphoma or diabetes.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30932218</pmid><doi>10.1111/apt.15240</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-2953-4949</orcidid><orcidid>https://orcid.org/0000-0001-5964-7579</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antiviral Agents - therapeutic use
Cryoglobulinemia - etiology
Cryoglobulinemia - prevention & control
Diabetes
Diabetes mellitus
Female
Glomerulonephritis
Glomerulonephritis - etiology
Glomerulonephritis - prevention & control
Hepacivirus - drug effects
Hepacivirus - genetics
Hepatitis
Hepatitis C
Hepatitis C - complications
Hepatitis C - drug therapy
Hepatitis C - virology
Humans
Incidence
Infections
Lichen planus
Lichen Planus - etiology
Lichen Planus - prevention & control
Lymphoma
Male
Middle Aged
Non-Hodgkin's lymphoma
Porphyria
Porphyria cutanea tarda
Porphyria Cutanea Tarda - etiology
Porphyria Cutanea Tarda - prevention & control
Regression analysis
Retrospective Studies
Ribonucleic acid
Risk
RNA
Sustained Virologic Response
Viruses
title The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection
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