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As most of the available data were obtained from clinical trials, limited generalizability to the real\u2010world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real\u2010world setting. HRQoL of 1180 participants of the German Hepatitis C\u2010Registry was assessed by Short\u2010Form 36 (SF\u201036) questionnaires. Scores at post\u2010treatment weeks 12\u201324 (FU12\/24) were compared to baseline (BL). Changes of \u22652.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001, OR\u00a0=\u00a00.925) and PCS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001, OR\u00a0=\u00a00.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.023, OR\u00a0=\u00a01.518), increased GPT levels (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.005, OR\u00a0=\u00a00.626) and RBV containing therapy regimens (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.001, OR\u00a0=\u00a01.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV\u2010infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.<\/jats:p>","DOI":"10.1111\/jvh.13546","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T13:07:20Z","timestamp":1621343240000},"page":"1206-1218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Only partial improvement in health\u2010related quality of life after treatment of chronic hepatitis C virus infection with direct acting antivirals in a real\u2010world setting\u2014results from the German Hepatitis C\u2010Registry (DHC\u2010R)"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-0100","authenticated-orcid":false,"given":"Valerie","family":"Ohlendorf","sequence":"first","affiliation":[{"name":"Hannover Medical School Hannover 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