Incidence of Extrahepatic Cancers Among Individuals With Chronic Hepatitis B or C Virus Infection

A Nationwide Cohort Study

Chai Yeong Hong; Dong Hyun Sinn; Danbee Kang; Seung Woon Paik; Eliseo Guallar; Juhee Cho; Geum-Youn Gwak

Disclosures

J Viral Hepat. 2020;27(9):896-903. 

In This Article

Results

The mean (±SD) age of study participants (N = 537 103) was 42.6 (±12.6) years. Of these participants, 272 848 (50.8%) were men. Proportions of participants with chronic HBV infection, chronic HCV and chronic HBV/HCV dual infection were 26 665 (5.0%), 7251 (1.4%) and 2507 (0.5%), respectively. Compared to participants without chronic HBV or HCV infection, participants with chronic HBV or HCV infection were more likely to be male, older and obese and have more comorbidities (Table 1).

During 3 854 130 person-years of follow-up (median follow-up: 8.0 years), 19 089 participants developed cancer (1402 cases of liver cancer and 17 687 cases of extrahepatic cancers). Participants with chronic HBV infection, chronic HCV infection or chronic HBV/HCV dual infection had higher cumulative incidence of cancer of all types and liver cancer than participants without HBV or HCV infection over the entire follow-up period (Figure 1). Cumulative incidence of extrahepatic cancers was also higher in participants with chronic HBV infection, chronic HCV infection or chronic HBV/HCV dual infection.

Figure 1.

Cumulative incidence of cancer according to chronic HBV or HCV infection status. (A) All types of cancer, (B) liver cancer and (C) extrahepatic cancers. Participants who developed chronic HCV infection during follow-up contributed to 'unexposed' group prior to chronic HCV infection, and 'exposed' group from the onset of chronic HCV infection. For instance, a person without HBV infection who newly developed HCV infection at age 40 contributed person-time to the 'No HBV or HCV' group until age 40, and to the 'HCV' group after age 40 in both the Kaplan-Meier analyses and the log-rank tests

After adjusting for sex, BMI, smoking, drinking, income percentile, residential area and comorbidities, HRs for incident cancer of all types were higher in participants with chronic HBV infection (HR: 2.06, 95% CI: 1.97–2.16), chronic HCV (HR: 1.52, 95% CI: 1.36–1.70) or chronic HBV/HCV dual infection (HR: 2.64, 95% CI: 2.29–3.06) compared to participants without HBV or HCV infection (Table 2). For liver cancer, HRs were remarkably higher in participants with chronic HBV infection (HR: 32.05, 95% CI: 28.42–36.14), chronic HCV infection (HR: 9.51, 95% CI: 7.15–12.65) or chronic HBV/HCV dual infection (HR: 46.14, 95% CI: 36.68–58.04). For extrahepatic cancers, HRs were also significantly higher in participants with chronic HBV infection (HR: 1.27, 95% CI: 1.20–1.35), chronic HCV infection (HR: 1.31, 95% CI: 1.16, 1.48) or chronic HBV/HCV dual infection (HR: 1.41, 95% CI: 1.16, 1.72). A positive association between chronic HBV or HCV infection and incident extrahepatic cancer was observed in all subgroups analysed (Figure 2). A stronger association was observed for ever-smokers, ≥light alcohol drinkers and individuals with CCI score 0 among participants with chronic HBV infection, and for males, and individuals with CCI score 0 among participants with chronic HCV infection, respectively.

Figure 2.

Hazard ratios for incident extrahepatic cancer comparing (A) participants with chronic HBV infection, (B) participants with chronic HCV infection and (C) participants with chronic HBV/HCV dual infection compared to participants with no HBV or HCV infection in predefined subgroups at baseline. Adjusted for sex (male or female), BMI (underweight, normal, overweight, obese and unknown), smoking status (never or past, current or unknown), alcohol intake (none, light, moderate, heavy or unknown), income percentile (≤30%, 30< to ≤70% and 70%<), residential area (metropolitan and rural) and Charlson comorbidity index score. Participants who developed chronic HCV infection during follow-up contributed to 'unexposed' group prior to chronic HCV infection, and 'exposed' group from the onset of chronic HCV infection

In participants with chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92–3.15)], gallbladder [1.55 (1.05–2.29)], pancreas [1.52 (1.07–2.15)], stomach [1.39 (1.22–1.58)], lung [1.27 (1.04–1.55)], colorectum [1.21 (1.03–1.42)] and thyroid cancer [1.20 (1.05–1.36)] in fully adjusted model (Table 2). In participants with chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35–79.78)], gallbladder [2.90 (1.62–5.18)], prostate [2.51 (1.65–3.82)] and thyroid cancer [1.46 (1.10–1.93)]. In participants with chronic HBV/HCV dual infection, the cancer risk was higher for kidney cancer [6.21 (2.45–11.080)] and haematologic malignancy [3.01 (1.34–6.75)]. Sensitivity analysis using chronic HBV infection as a time-varying variable showed virtually the same results (Table S1).

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