Increased prevalence but decreased survival of nonviral hepatocellular carcinoma compared to viral hepatocellular carcinoma in recent ten years

Abstract

Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.

Keywords: Alcoholic liver disease; Non alcoholic fatty liver disease; Non-viral hepatocellular carcinoma; Type 2 diabetes mellitus; Viral hepatocellular carcinoma.

Figure 1

Comparison between viral HCC and nonviral HCC in recent years. The prevalence of nonviral HCC increased significantly from 19.2% in 2011–2013 and 19.3% in 2014–2017 to 23.0% in 2018–2020 (P = 0.046).

Figure 2

Comparisons of overall survival in recent years. (A) The median survival was not attained in 2018–2020, which was better than those in 2014–2017 (median survival: 4.54 years) and 2011–2013 (median survival: 2.56 years) (P < 0.001). (B) For viral HCC, the median survival was not attained in 2018–2020, which was better than those in 2014–2017 (median survival: 5.21 years) and 2011–2013 (overall survival: 2.86 years) (P < 0.001). (C) For nonviral HCC, the median overall survival did not differ significantly between the different periods (P = 0.056).

Figure 3

Comparison of the overall survival between viral and nonviral HCC. (A) Viral HCC vs. nonviral HCC. The median survival durations in viral HCC and nonviral HCC were 4.58 years and 1.60 years, respectively, and there was no statistically significant difference between them (p < 0.001). (B) HBV, HCV, both HBV and HCV, nonviral HCC. We divided viral causes of HCC into HBV, HCV, and both HBV, and HCV. The median survival was better in HBV, HCV, and both HBV, and HCV (4.67 years, 4.55 years, 4.33 years, respectively) than in nonviral HCC (1.60 years) with each of the differences being statistically significant (all P < 0.001).

Figure 4

Comparison of early-stage survival between viral and nonviral HCC. (A) In early-stage HCC, namely BCLC stage 0, and stage A, the median survival was not attained in viral HCC and was 5.77 years in nonviral HCC. This parameter was significantly better in viral HCC (P < 0.001). (B) In BCLC stage B, the median survival was 4.25 years in viral HCC and 3.73 years in nonviral HCC (P = 0.067). (C) In BCLC stage C, the median survival was 0.56 years in viral HCC and 0.41 years in nonviral HCC (P = 0.048). (D) In BCLC stage D, the median survival was 0.14 years in viral HCC and 0.10 years in nonviral HCC (P = 0.214).