Gender Matters: Characteristics of Hepatocellular Carcinoma in Women From a Large, Multicenter Study in the United States

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, affecting men to women at a ratio of about 4:1. Risk factors, characteristics, and outcomes for HCC in women in the United States remain poorly understood; therefore, we aim to explore gender differences further. METHODS: Patients diagnosed with HCC between January 2000 and June 2014 at 5 large centers were identified. Clinical information, tumor characteristics, and survival data were extracted manually. The presence of underlying cirrhosis was assessed based on published criteria. RESULTS: Of 5,327 patients with HCC in our cohort, 1,203 (22.6%) were women. There were important differences in the underlying etiology of liver disease between the 2 genders (P < 0.0001): women had a significantly higher frequency of nonalcoholic fatty liver disease (23% vs 12%) and lower frequency of alcoholic liver disease (5% vs 15%). The proportion of noncirrhotic HCC was significantly higher among women (17% vs 10%, P < 0.0001). Women had less-advanced HCC at presentation by tumor, node, metastasis staging (P < 0.0001) and a higher proportion within Milan criteria (39% vs 35%, P = 0.002). Women had a greater overall survival (2.5 ± 2.9 years vs 2.2 ± 2.7 years, P = 0.0031). DISCUSSION: The frequency of underlying nonalcoholic fatty liver disease and noncirrhotic HCC were significantly higher in women than men in this large cohort. Women presented with less-advanced HCC and had a greater overall survival. Further investigation is warranted to explore potential mechanisms and implications for these gender differences, especially with noncirrhotic HCC (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B535).