AUTHOR=Váncsa Szilárd , Németh Dávid , Hegyi Péter , Szakács Zsolt , Farkas Ádám , Kiss Szabolcs , Hegyi Péter Jenő , Kanjo Anna , Sarlós Patrícia , Erőss Bálint , Pár Gabriella 

TITLE=Diabetes Mellitus Increases the Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Therapy: Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.744512

DOI=10.3389/fmed.2021.744512

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing <italic>de novo</italic> HCC in HCV-infected patients after DAA treatment.</p><p><bold>Methods:</bold> This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of <italic>de novo</italic> HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis.</p><p><bold>Results:</bold> We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted (<italic>UHR</italic> = 1.44, CI: 1.15–1.79) and adjusted analyses (<italic>AHR</italic> = 1.31, <italic>CI</italic>: 1.06–1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted (<italic>UHR</italic> = 1.3, CI: 1.09–1.51) analysis; however, in adjusted results, the risk was non-significant (<italic>AHR</italic> = 1.07, CI: 0.89–1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted (<italic>AHR</italic> = 1.36, CI: 1.03–1.8), but not in unadjusted analysis (<italic>UHR</italic> = 1.11, CI: 0.8–1.42).</p><p><bold>Conclusions:</bold> DM is an independent risk factor of <italic>de novo</italic> HCC after DAA treatment in HCV-infected patients.</p><p><bold>Systematic Review Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457</ext-link>, identifier: CRD42021230457.</p>