Hepatitis C virus-associated hepatocellular carcinoma as a second primary malignancy: exposing an overlooked presentation of liver cancer Dima Dandachi,1,2 Manal Hassan,3 Ahmed Kaseb,4 Georgios Angelidakis,2 Harrys A Torres2,4 1Department of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA; 2Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Epidemiology, The University of Texas Medical School, Houston, TX, USA; 4Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Introduction: Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. Antiviral therapy in patients with HCV infection reduces the risk of primary HCC development by 71%–75%. HCV-infected patients with different primary cancers are also at risk for HCC development as a second primary malignancy (HCC-SPM). Limited information is available on the occurrence and characteristics of HCC-SPM. Herein, we determine the prevalence and clinical features of HCV-associated HCC-SPM when compared to primary HCC. Materials and methods: Patients with HCV-associated HCC seen at MD Anderson Cancer Center (2011–2017) were enrolled in a prospective observational study. Patients with multiple cancers diagnosed simultaneously or with hepatitis B virus or HIV coinfections were excluded. At enrollment, patients completed a questionnaire on medical history and HCC risk factors. Information on demographics, comorbidities, HCV treatment, tumor characteristics, treatment modalities, and virologic and oncologic outcomes were extracted from the medical records. Results: Among 171 consecutive patients with HCV-associated HCC enrolled, 26 (15%) had HCC-SPM. Most of the underlying primary cancers were solid tumors (85%). In 12 (46%) of these patients, the diagnosis was made incidentally while undergoing surveillance for primary malignancies, and the majority (81%) had their primary cancer in remission. Most patients (72%) with documented HCV viral load had chronic viremia due to lack of diagnosis, lack of treatment, or prior unsuccessful treatment of HCV infection and only 28% had undetectable viral load following successful antiviral therapy. The overall median survival for both groups was 29 months (95% CI: 23–35) without difference between groups