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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EThere are few data regarding the efficacy and safety of simeprevir\u2005+\u2005sofosbuvir in patients with decompensated cirrhosis. Data from this study comparing this drug combination in patients with Child-Pugh B\/C cirrhosis with patients who received older treatment regimens suggest that recently approved all-oral therapies offer patients with decompensated cirrhosis a safer and more effective therapy than historical peginterferon-based therapies.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ehepatitis C virus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecirrhosis\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esimeprevir\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esofosbuvir\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EChild-Pugh score\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egastroenterology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EIn December 2013, the FDA approved both simeprevir (SMV) and sofosbuvir (SOF) as oral treatments for chronic hepatitis C virus (HCV), providing clinicians with off-label access to an all oral-regimen for HCV genotype 1. Subgroup data from the phase 2 COSMOS study [Lawitz E et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2014] showed that the combination of SMV\u2005+\u2005SOF with or without ribavirin (RBV) produced a 93% cure rate among people with Child-Pugh class A cirrhosis. However, the efficacy and safety of this drug combination with or without RBV among patients with worsening cirrhosis (Child-Pugh class B\/C) remained unknown.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EVarun Saxena, MD, University of California San Francisco School of Medicine, San Francisco, California, USA, presented data assessing the safety and efficacy of a 12-week combination of SMV\u2005+\u2005SOF with or without RBV in patients with cirrhosis Child-Pugh class B\/C. These patients were compared with matched treated and untreated controls. The treated controls had been treated with telaprevir or boceprevir plus interferon and RBV, which was the standard of care at the time that they were treated.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EFifty-five adults with HCV genotype 1 (cases) received the drug combination; RBV was included at the discretion of the physician. Each of the 55 cases was matched with up to 3 treated and untreated controls based on age, treatment center, model for end-stage liver disease (MELD), and Child-Pugh class. At baseline, cases had a median age of 61 years. About half of patients were women; 35% had diabetes; 58% had HCV genotype 1a; 62% had previous HCV treatment; and 89% had cirrhosis Child-Pugh class B.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt baseline, patients had a median MELD score of 12; 64% had ascites; 49% had any hepatic encephalopathy; 35% had varices; and 35% had been exposed to RBV, highlighting their high morbidity. The study\u2019s 2 primary outcomes were the percentage of patients who achieved a sustained virologic response at week 12 (SVR12) and a number of safety outcomes:\u003C\/p\u003E\u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\u003Cp id=\u0022p-6\u0022\u003Eearly treatment discontinuation,\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\u003Cp id=\u0022p-7\u0022\u003Eadverse events (AEs) requiring hospitalization,\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\u003Cp id=\u0022p-8\u0022\u003Einfections requiring antibiotics,\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\u003Cp id=\u0022p-9\u0022\u003Ehepatic decompensating events, and\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-5\u0022\u003E\u003Cp id=\u0022p-10\u0022\u003Edeath.\u003C\/p\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-11\u0022\u003EA total of 73% of the cases achieved SVR12. Of the 27% who did not, 3 patients had detectable HCV RNA at the end of treatment, and 12 patients relapsed after the end of treatment. Multivariate analysis revealed that the absence of hepatic encephalopathy and platelets \u2265\u2005100\u2005000\/mm\u003Csup\u003E3\u003C\/sup\u003E significantly predicted those patients likely to achieve SVR12 (OR, 3.37; 95% CI, 1.00 to 11.8; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.05; OR, 4.29; 95% CI, 1.14 to 16.1; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.02, respectively). Regarding safety, 11% of the cases discontinued treatment, and 11% discontinued treatment (of which 9% discontinued because of AEs); 22% were hospitalized due to AEs; 20% required antibiotics for infections; and 20% experienced hepatic decompensation. One patient died as the result of worsening liver and kidney function.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003E\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E compares the rates of HCV cure, early discontinuation, AEs, infections, and decompensation between the cases and the treated controls.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16787\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16787\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16787\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-13\u0022 class=\u0022first-child\u0022\u003ESMV\u2005+\u2005SOF Cases vs Treated Historical Controls\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003ECurrent guidelines from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America do not recommend the use of SMV and SOF in patients with Child-Pugh B\/C cirrhosis because of safety concerns [\u003Ca href=\u0022http:\/\/www.hcvguidelines.org\u0022\u003Ewww.hcvguidelines.org\u003C\/a\u003E. Accessed May 29, 2015]. However, Dr Saxena conjectured that these difficult patients (mostly those with Child-Pugh B cirrhosis) can be successfully treated and that data from this study may help inform future treatment recommendations.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/14\/18.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlhj1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlhj1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}