Risk Factors for HCC after DAA-Induced HCV Cure

This retrospective multicenter cohort study conducted by the DAA Study in Hamamatsu group (DASH study group), involved 9 institutions (Hamamatsu University Hospital, Shimada General Medical Center, Seirei Hamamatsu General Hospital, Hamamatsu Medical Center, Iwata City Hospital, Shizuoka City Shizuoka Hospital, Minoru Medical Clinic, Tamakoshi Clinic, Elm Medical Clinic). The study was approved by the Ethics Committee of Hamamatsu University School of Medicine (approval number, 23-224). The study protocols conformed to the ethical guidelines of the Declaration of Helsinki. All patients provided written informed consent. Patients diagnosed with serogroup 1 chronic HCV infection who initiated IFN-free DAA regimens (DCV/ASV or sofosbuvir [SOF]/ledipasvir [LDV]) between August 2014 and December 2016 at nine affiliated institutions were enrolled. SVR was defined as absence of detectable HCV RNA at 24 weeks after treatment completion. No relapse of viremia was observed after 24 weeks in the patients who achieved SVR. Serum samples from healthy volunteers were also collected during the study period.
The exclusion criteria were as follows: (1) absence of sufficiently stored serum samples; (2) coinfection with either hepatitis B virus (HBV) or human immunodeficiency virus; (3) history of other chronic liver diseases (autoimmune hepatitis, primary biliary cholangitis, hemochromatosis, or Wilson’s disease); (4) history of HCC development at enrollment; (5) HCC development in the period up to 24 weeks after treatment completion, detected using ultrasonography (US), contrast-enhanced computed tomography (CT), or contrast-enhanced magnetic resonance imaging (MRI); (6) serum LOXL2 levels (see below) under the lower limit of quantification (LLQ). After exclusions, the data from 137 patients were retrospectively analyzed to identify risk factors for HCC development after achieving SVR (Fig. 4).Figure 4

Study Flowchart Illustrating the Patient Selection Process. The development of HCC was studied in patients with HCV who achieved SVR via DAA therapy. Abbreviations: ASV, asunaprevir; DAA, direct-acting antiviral; DCV, daclatasvir; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LDV, ledipasvir; LLQ, lower limit of quantification; LOXL2, lysyl oxidase-like 2; SOF, sofosbuvir; SVR, sustained virological response.