Use of cyclooxygenase inhibitor and the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nested case‐control study using a nationwide population‐based data

Abstract

The study aimed to investigate the relationship between the use of COX inhibitors and the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB) using a nationwide population‐based data. A nested case‐control study was conducted using the National Health Insurance Service–National Sample Cohort (NHIS‐NSC) from 2002 to 2013 in Korea. We compared the use of COX inhibitors between HCC cases and matched controls by categorizing 5 groups according to the cumulative defined daily dose (cDDD, <28, 28‐90, 91‐180, 181‐360, and >360) adjusting the use of antiviral agents. A total of 4980 patients with CHB were analysed as 996 HCC cases and 3984 matched controls. The number of COX inhibitor users (≥28 cDDD) was 358 patients (36%) and 1814 patients (45%) in the HCC group and control group, respectively. The use of COX inhibitors was significantly associated with a decreased risk of HCC development compared with nonusers (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52‐0.73, P < .001). There was a dose‐dependent inverse relationship between the use of COX inhibitors and the risk of HCC. The adjusted ORs were 0.75 (95% CI: 0.63‐0.90), 0.41 (95% CI: 0.31‐0.56), 0.38 (95% CI: 0.25‐0.57) and 0.49 (95% CI: 0.31‐0.79) for the 28‐90, 91‐180, 181‐360 and >360 cDDDs, respectively (P < .01). In conclusion, the use of COX inhibitors was associated with a reduced risk of HCC in CHB. COX inhibitor may have a chemopreventive role in HCC development in patients with chronic liver disease.

Hepatitis B virus‐related hepatocellular carcinoma in the era of antiviral therapy: The emerging role of non‐viral risk factors

“…The abnormal expression of cyclooxygenase in inflammation implies a potential chemoprevention target of HBV‐related HCC 85 . Research studies have shown an association between the reduced risk of HBV‐associated HCC and the use of a cyclooxygenase inhibitor, such as aspirin 86,87 . These results from clinical studies are consistent with previous findings that platelets facilitate immune‐mediated liver injury by promoting the hepatic accumulation of virus‐specific CD8(+) T cells 88 .…”

Systematic review with meta‐analysis: The effects of non‐steroidal anti‐inflammatory drugs and anti‐platelet therapy on the incidence and recurrence of hepatocellular carcinoma

“…Nine studies (n = 115 124) reported on HCC incidence. [28][29][30][31][32][33][34][35][36] The pooled aHR from seven matched cohort and case-control studies…”

“…The case-control study by Cho et al 33 One three-arm study 36 (n = 840) evaluated the effects of APT and the matched results showed evidence that the use of aspirin or clopidogrel, alone or in combination, reduces the risk of HCC incidence; HR: 0.34, 95% CI: 0.15-0.7.…”

“…Nineteen studies were eligible with 147 283 participants in the final analyses. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] The CONSORT diagram of the search strategy is outlined in Figure 1.…”

“…All studies were conducted in adults with viral hepatitis, alcohol-related liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Of the nineteen studies, eight studies focussed on HBV-infected patients, 28,33,[35][36][37][38]40,46 two studies on HCV-infected patients, 31,32 one study on ALD patients and eight studies with mixed aetiologies. 29,34,39,[41][42][43][44][45] Nine studies were included in HCC incidence analysis and 10 studies were included in recurrence and liver-related mortality analysis.…”