The irreversible HCV-associated risk of gastric cancer following interferon-based therapy: a joint study of hospital-based cases and nationwide population-based cohorts

Abstract

Background: Hepatitis C virus (HCV) infection causes many extrahepatic malignancies; whether it increases gastric cancer risk and the risk reverses after anti-HCV therapy remain elusive.

Method: A nationwide population-based cohort study of Taiwan National Health Insurance Research Database (TNHIRD) was conducted. In parallel, the risk factors and HCV-core-protein expressions were surveyed in gastric cancer patients from a tertiary care center.

Results: From 2003 to 2012, of 11,712,928 patients, three 1:4:4, propensity-score-matched TNHIRD cohorts including HCV-treated (7545 patients with interferon-based therapy ⩾ 6 months), HCV-untreated (n = 30,180), and HCV-uninfected cohorts (n = 30,180) were enrolled. The cumulative incidences of gastric cancer [HCV-treated: 0.452%; 95% confidence interval (CI): 0.149-1.136%; HCV-untreated: 0.472%; 95% CI: 0.274-0.776%; HCV-uninfected: 0.146%; 95% CI 0.071-0.280%] were lowest in HCV-uninfected cohort (p = 0.0028), but indifferent between treated and untreated cohorts. HCV infection [hazards ratio (HR): 2.364; 95% CI: 1.337-4.181], male sex (HR: 1.823; 95% CI: 1.09-3.05) and age ⩾ 49 years (HR: 3.066; 95% CI: 1.56-6.026) were associated with incident gastric cancers. Among 887 (males: 68.4%; mean age: 66.5 ± 12.9 years, 2008-2018) hospitalized gastric cancer patients, HCV Ab-positive rate was 7.8%. None of the investigated factors exhibited different rates between HCV Ab-positive and Ab-negative patients. No HCV-core-positive cells were demonstrated in gastric cancer tissues.

Conclusions: HCV infection, male sex and old age were risk factors for gastric cancer development. HCV-associated gastric cancer risk might be neither reversed by interferon-based therapy, nor associated with in situ HCV-core-related carcinogenesis.

Keywords: HCV; age; gastric cancer; sex.

Figure 1.

Flow chart of TNHIRD study participant selection. HBV, hepatitis B virus; HCV, hepatitis C virus; Peg-IFN, pegylated interferon; PS, propensity score; RNA, ribonucleic acid; TNHIRD, Taiwan National Health Insurance Research Database.

Figure 2.

Cumulative incidence of gastric cancers among three TNHIRD cohorts, including HCV-treated, HCV-untreated and HCV-uninfected cohorts. Cumulative incidence of gastric cancers among the three TNHIRD cohorts, including HCV-treated, HCV-untreated and HCV-uninfected cohorts (a) and between two TNHIRD cohorts including HCV-infected (pooled data of HCV-treated and HCV-untreated cohorts) and HCV-uninfected cohorts (b). HCV, hepatitis C virus; TNHIRD, Taiwan National Health Insurance Research Database.

Figure 3.

Forest plot of factors associated with incident gastric cancers in the TNHIRD cohorts. CI, confidence interval; COPD, chronic obstructive pulmonary disease; DM, diabetes; ESRD, end-stage renal disease; HCL, higher confidence limit; HCV, hepatitis C virus; HP, Helicobacter pylori; HR, hazards ratio; LCL, lower confidence limit; TNHIRD, Taiwan National Health Insurance Research Database.