In a Taiwanese study reported in the Journal of Clinical Oncology, Shen et al found that use of H1-antihistamines was associated with reduced risk of hepatocellular carcinoma in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV/HCV infection.
Study Details
The study involved data on 521,071 patients with HBV infection, 169,159 with HCV infection, and 39,016 with dual infection from Taiwan’s National Health Insurance Research Database for the period of January 2006 to December 2015. Antihistamine use was assessed as a time-varying covariate in analysis. Cumulative antihistamine dose was calculated by multiplying the number of pills dispensed by prescribed dose and dividing the value by the recorded days’ supply. Antihistamine use was defined by cumulative defined daily dose (cDDD)—ie, the sum of the daily prescribed dose, with antihistamine nonusers having cDDD < 28 and antihistamine users having cDDD ≥ 28. Cohorts were matched 1:1 to contain 127,398 users and nonusers with HBV, 40,428 users and nonusers with HCV, and 8,661 users and nonusers with dual infection.
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Key Findings
In the matched HBV cohort, the incidence rate of hepatocellular carcinoma for antihistamine users vs nonusers was 198.35 vs 426.03 per 100,000 person-years. In analysis adjusted for age, sex, and comorbidities, risk of hepatocellular carcinoma was significantly lower among antihistamine users (adjusted hazard ratio [HR] = 0.489, 95% CI = 0.455–0.524). A dose-response relationship between antihistamine use and risk of hepatocellular carcinoma was observed, with adjusted hazard ratios of 0.597 (95% CI = 0.530–0.674), 0.528 (95% CI = 0.465–0.600), 0.470 (95% CI = 0.416–0.531), and 0.407 (95% CI = 0.362–0.457) for 28 to 42, 43 to 63, 64 to 119, and ≥ 120 cDDDs vs no antihistamine use.
In the matched HCV cohort, the incidence rate of hepatocellular carcinoma for users vs nonusers was 651.26 vs 1,334.80 per 100,000 person-years. On adjusted analysis, risk of hepatocellular carcinoma was significantly lower among users (adjusted HR = 0.484, 95% CI = 0.450–0.522). A dose-response relationship between antihistamine use and risk of hepatocellular carcinoma was observed, with adjusted hazard ratios of 0.537, 0.518, 0.479, and 0.425 for 28 to 49, 50 to 84, 85 to 168, and ≥ 169 cDDDs.
In the dual-infection cohort, the incidence rate of hepatocellular carcinoma for users vs nonusers was 1,059.31 vs 2,165.81 per 100,000 person-years. On adjusted analysis, risk of hepatocellular carcinoma was significantly reduced among users (adjusted HR = 0.469, 95% CI = 0.416–0.529). As with the other cohorts, a dose-response relationship was observed, with adjusted hazard ratios of 0.588, 0.514, 0.415, and 0.394 for cDDDs of 28 to 49, 50 to 84, 85 to 168, and ≥ 169.
The investigators concluded, “Antihistamine use may reduce the risk for hepatocellular carcinoma among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.”
Chi-Ching Chang, PhD, of the Division of Allergy, Immunology, and Rheumatology, College of Medicine, Taipei Medical University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the Ministry of Science and Technology of the Republic of China and Taipei Medical University Hospital. For full disclosures of the study authors, visit ascopubs.org.
