Table 2:
Multivariable Risk of Incident HCC According to Attained BMI1
| BMI Category (kg/m2) | Continuous HR (95% CI)* | P for Trend* | ||||
|---|---|---|---|---|---|---|
|
| ||||||
| Women | ||||||
| Early Adult BMI* | BMI < 19 | BMI 19 to <23 | BMI 23 to <25 | BMI ≥ 25 | -- | -- |
| No. of cases | 23 | 30 | 34 | 11 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.63 (0.79–3.36) | 1.83 (0.85–3.96) | 2.65 (1.02–6.86) | 1.04 (1.02–1.10) | 0.042 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.64 (0.80–3.39) | 1.76 (0.81–3.81) | 2.37 (0.87–5.94) | 1.03 (0.97–1.09) | 0.094 |
| Mid-Life BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 58 | 25 | 8 | 7 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.44 (0.76–2.74) | 1.62 (0.85–3.08) | 1.74 (0.95–3.24) | 1.04 (1.01–1.09) | 0.037 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.40 (0.73–2.65) | 1.47 (0.77–2.83) | 1.70 (0.93–3.00) | 1.03 (1.00–1.08) | 0.042 |
| Updated BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 51 | 25 | 11 | 11 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.98 (1.05–3.71) | 2.05 (0.98–4.26) | 2.31 (1.15–4.66) | 1.09 (1.05–1.12) | 0.030 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.35 (0.64–2.86) | 1.54 (0.73–3.27) | 2.05 (0.92–3.30) | 1.07 (1.03–1.11) | 0.039 |
| Men | ||||||
| Early Adult BMI* | BMI < 19 | BMI 19 to <23 | BMI 23 to <25 | BMI ≥ 25 | -- | -- |
| No. of cases | 7 | 16 | 30 | 7 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 0.76 (0.30–1.91) | 1.28 (0.52–3.15) | 1.87 (0.76–5.53) | 1.07 (1.03–1.13) | 0.020 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 0.80 (0.32–2.01) | 1.36 (0.55–3.36) | 1.76 (0.70–5.27) | 1.07 (1.02–1.13) | 0.087 |
| Mid-Life BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 17 | 21 | 10 | 12 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.41 (0.68–2.92) | 2.28 (1.10–4.73) | 4.68 (2.18–10.03) | 1.06 (1.02–1.12) | <0.0001 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.36 (0.67–2.88) | 2.24 (1.07–4.67) | 4.44 (2.03–9.69) | 1.05 (1.02–1.10) | 0.002 |
| Updated BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 17 | 20 | 13 | 10 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.33 (0.65–2.70) | 2.13 (1.00–4.57) | 4.07 (1.82–9.10) | 1.11 (1.07–1.15) | 0.0003 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.25 (0.61–2.55) | 1.86 (0.61–4.00) | 3.20 (1.30–6.89) | 1.09 (1.04–1.14) | 0.005 |
| Combined Cohort | ||||||
| Early Adult BMI* | BMI < 19 | BMI 19 to <23 | BMI 23 to <25 | BMI ≥ 25 | -- | -- |
| No. of cases | 30 | 46 | 64 | 17 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.18 (0.56–2.47) | 1.57 (0.88–2.83) | 2.24 (1.08–4.66) | 1.06 (1.02–1.10) | 0.009 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.22 (0.61–2.44) | 1.58 (0.88–2.84) | 2.12 (1.02–4.42) | 1.05 (1.02–1.09) | 0.019 |
| Mid-Life BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 75 | 46 | 18 | 19 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.43 (0.88–2.31) | 1.88 (1.16–3.05) | 2.78 (1.16–7.33) | 1.05 (1.03–1.07) | 0.026 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.40 (0.89–2.31) | 1.83 (1.13–2.98) | 2.64 (1.13–7.00) | 1.05 (1.02–1.07) | 0.034 |
| Updated BMI* | BMI <25 | BMI 25 to <30 | BMI 30 to <35 | BMI ≥ 35 | -- | -- |
| No. of cases | 68 | 45 | 24 | 21 | -- | -- |
| Age-adjusted HR (95% CI) | 1 (ref.) | 1.62 (0.85–2.77) | 2.02 (1.13–3.63) | 3.15 (1.40–5.01) | 1.09 (1.07–1.11) | 0.001 |
| Multivariable adjusted HR‡ (95% CI) | 1 (ref.) | 1.30 (0.70–2.76) | 1.80 (0.98–3.27) | 2.69 (1.33–4.68) | 1.08 (1.06–1.10) | 0.004 |
Abbreviations: HCC, hepatocellular carcinoma; BMI, body mass index; HR, hazard ratio; CI, confidence interval; kg, kilogram
P-trend calculated using continuous BMI exposure variables, per each 1 kg/m2 of BMI.
Early adult BMI was defined at age 18 years (among women) or age 21 years (among men). Mid-life BMI was defined at baseline (1980 among women [median age 46 years]; 1986 among men [median age 52 years]). Updated BMI was assessed as a time-updated exposure, every 2 years of follow-up, as outlined in the Methods.
Multivariable Cox proportional hazard regression models were stratified by age (years), and year of questionnaire return, with further adjustment for race (white vs. non-white), alcohol intake (0–4.9, 5–14.9, ≥15 g/day), smoking status (current vs. prior vs. never), type 2 diabetes (yes vs. no), hypertension (yes vs. no), dyslipidemia (yes vs. no), regular aspirin use (≥2 tablets per week vs. no), adherence to a healthy diet, defined by the alternative healthy eating index 2010 (AHEI) without alcohol, and physical activity, in continuous metabolic equivalent task (MET)-hours per week. For analyses of early-adult BMI and mid-life BMI, all covariates were modeled at baseline; for analyses of updated BMI, all covariates (with the exception of race/ethnicity) were updated over each questionnaire cycle and modeled as time-varying covariates. For the combined cohort, results were meta-analyzed.