Table IV.
Association of insulin with incident HCC stratified by time and selected risk factors
| Fasting plasma insulin levels (μU/ml) |
P for trend | |||||
| Factor, group | <2.75 | 2.75–4.10 | 4.11–6.10 | >6.10 | ||
| Follow-up, years | ||||||
| <8 (n = 1082) | HR (95% CI)a | 2.11 (1.17–3.82) | 1 (Ref) | 1.34 (0.69–2.61) | 1.79 (0.91–3.49) | 0.5785 |
| ≥8 (n = 1061) | HR (95% CI)a | 1.33 (0.62–2.88) | 1 (Ref) | 2.32 (1.11–4.85) | 4.15 (2.05–8.39) | <0.0001 |
| Age, years | ||||||
| <50 (n = 806) | HR (95% CI)a | 1.56 (0.83–2.93) | 1 (Ref) | 0.93 (0.45–1.95) | 2.24 (1.17–4.28) | 0.1400 |
| ≥50 (n = 336) | HR (95% CI)a | 2.25 (1.11–4.53) | 1 (Ref) | 2.82 (1.40–5.66) | 3.13 (1.55–6.30) | 0.0436 |
| BMI, kg/m2 | ||||||
| <25 (n = 791) | HR (95% CI)a | 2.07 (1.19–3.59) | 1 (Ref) | 1.95 (1.06–3.60) | 2.22 (1.17–4.23) | 0.6184 |
| ≥25 (n = 351) | HR (95% CI)a | 1.43 (0.55–3.71) | 1 (Ref) | 1.02 (0.44–2.37) | 2.12 (0.97–4.64)b | 0.0306 |
| <23c (n = 455) | HR (95% CI)a | 1.63 (0.83–3.24) | 1 (Ref) | 1.48 (0.65–3.38) | 2.70 (1.17–6.23) | 0.2269 |
| ≥23 (n = 687) | HR (95% CI)a | 2.20 (1.15–4.22) | 1 (Ref) | 1.83 (0.98–3.43) | 2.77 (1.51–5.07) | 0.0394 |
| HBV genotype | ||||||
| C (n = 202) | HR (95% CI)a | 1.28 (0.67–2.45) | 1 (Ref) | 1.10 (0.56–2.19) | 2.28 (1.20–4.34) | 0.0223 |
| B or B + C (n = 923) | HR (95% CI)a | 2.46 (1.20–5.02) | 1 (Ref) | 2.13 (1.01–4.49) | 3.38 (1.63–6.98) | 0.0747 |
| Baseline HBV viral load, log10 copies/mld | ||||||
| <4.39 (n = 666) | HR (95% CI)a | 1.68 (0.63–4.46) | 1 (Ref) | 1.85 (0.65–5.25) | 6.15 (2.48–15.22) | <0.0001 |
| ≥4.39 (n = 476) | HR (95% CI)a | 1.71 (1.00–2.94) | 1 (Ref) | 1.43 (0.82–2.51) | 1.49 (0.84–2.66) | 0.7928 |
| Time trend for HBV viral loade | ||||||
| Sustained | ||||||
| Low (n = 686) | HR (95% CI)a | 3.31 (1.13–9.71) | 1 (Ref) | 1.90 (0.57–6.34) | 5.80 (1.98–17.00) | 0.0337 |
| Sustained | ||||||
| High (n = 366) | HR (95% CI)a | 2.10 (1.13–3.89) | 1 (Ref) | 1.74 (0.93–3.28) | 1.93 (1.02–3.63) | 0.7497 |
| Extremely | ||||||
| High to low (n = 90) | HR (95% CI)a | 0.43 (0.14–1.37) | 1 (Ref) | 0.87 (0.27–2.86) | 0.84 (0.26–2.75) | 0.2363 |
| BCP double mutations | ||||||
| Absence (n = 732) | HR (95% CI)a | 1.74 (0.71–4.27) | 1 (Ref) | 2.85 (1.20–6.78) | 4.12 (1.77–9.60) | 0.0007 |
| Presence (n = 369) | HR (95% CI)a | 1.97 (1.10–3.52) | 1 (Ref) | 1.57 (0.83–2.95) | 2.31 (1.25–4.28) | 0.3359 |
HRs and 95% CIs were adjusted for number of visits, age (continuous), smoking, alcohol consumption and a first-degree family history of HCC.
P = 0.0607.
Asian BMI criterion of overweight (29).
The cutpoint is the threshold of viral load associated with increased risk for HCC in previous studies (3,5). P for heterogeneity of HRs by HBV viral load = 0.0021.
Three patterns of time trend for viral load (‘sustained low’: having a level of 3–4 log10 copies/ml over time; ‘sustained high’: having a level of 5–6 log10 copies/ml over time and ‘extremely high to low’: having a level of 8–9 log10 copies/ml at study entry that declined linearly over time) were defined according to our previous longitudinal viral-load study (6), in which trajectory analysis, a type of latent class analysis which identifies homogeneous groups within a heterogeneous population assumed to contain multiple latent trajectories, was performed with the SAS procedure PROC TRAJ to estimate trajectories of viral load across 16 years of follow-up. P for heterogeneity of HRs by time trends for HBV viral load = 0.0629.