TABLE 3.
Risk of Incident Cancer With Increasing NAFLD Histological Severity, Compared With Simple Steatosis*
| NAFLD* | ||||
|---|---|---|---|---|
| Types of Incident Cancer, N. | Simple Steatosis N = 5,939 |
NASH Without Fibrosis N = 1,050 |
Noncirrhotic Fibrosis N = 1,400 |
Cirrhosis N = 503 |
| All incident cancers | 1,160 | 187 | 233 | 111 |
| Incidence RD1 (95% CI) | 0 (ref.) | 2.0 (−0.3–4.2) | 3.4 (1.2–5.6) | 12.1 (7.4–16.8) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 4.4 (−1.1–10.0) | 6.7 (0.8–12.5) | 17.3 (5.8–28.9) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.10 (0.94–1.29) | 1.08 (0.93–1.26) | 1.46 (1.19–1.79) |
| HCC | 72 | 16 | 35 | 30 |
| Incidence RD1 (95% CI) | 0 (ref.) | 0.7 (0.0–1.3) | 1.5 (0.8–2.3) | 5.4 (3.3–7.6) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 1.0 (−0.5–2.4) | 3.4 (1.5–5.3) | 10.2 (5.3–15.2) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.61 (0.91–2.84) | 2.45 (1.57–3.84) | 4.95 (3.08–7.97) |
| Non-HCC liver cancers | 16 | 2 | 5 | 2 |
| Incidence RD1 (95% CI) | 0 (ref.) | 0.0 (−0.2–0.2) | 0.2 (−0.1–0.5) | 0.2 (−0.3–0.8) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 0.0 (−0.6–0.5) | 0.1 (−0.5–0.6) | 0.7 (−1.0–2.3) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 0.76 (0.16–3.52) | 1.97 (0.66–5.88) | 1.56 (0.35–7.08) |
| EHSO cancers | 987 | 152 | 175 | 77 |
| Incidence RD1 (95% CI) | 0 (ref.) | 1.0 (−1.0–3.0) | 1.2 (−0.7–3.1) | 6.3 (2.4–10.1) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 3.3 (−1.7–8.4) | 2.9 (−2.2–7.9) | 9.5 (0.0–19.0) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.04 (0.88–1.25) | 0.94 (0.80–1.12) | 1.23 (0.97–1.56) |
| Hematologic cancers | 85 | 17 | 19 | 2 |
| Incidence RD1 (95% CI) | 0 (ref.) | 0.4 (−0.3–1.0) | 0.4 (−0.2–1.0) | −0.5 (−1.1–0.1) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 0.3 (−0.9–1.5) | 1.3 (−0.5–3.0) | −0.7 (−2.4–1.0) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.38 (0.80–2.36) | 1.39 (0.81–2.37) | 0.35 (0.08–1.46) |
*
NAFLD was defined by liver histology. For definitions and algorithm, see the Methods section and Supporting Information.
1
Incidence rates were calculated by dividing the number of cases by PYs; CIs for incidence rates and absolute RDs were approximated by the normal distribution (Methods).
2
20-year absolute risks and absolute risk differences (percentage points) were calculated based on Kaplan-Meier estimates (Methods).
3
The multivariable aHR model accounted for the covariates outlined in Table 2.