TABLE 2.
Risk of Incident Cancer Among Adults With Histologically Confirmed NAFLD and Matched Population Comparators
| Population Comparators N = 39,907 |
NAFLD* | |||||
|---|---|---|---|---|---|---|
| Incident Cancer | All NAFLD N = 8,892 |
Simple Steatosis N = 5,939 |
NASH Without Fibrosis N = 1,050 |
Noncirrhotic Fibrosis N = 1,400 |
Cirrhosis N = 503 |
|
| Overall cancers, N. | 6,733 | 1,691 | 1,160 | 187 | 233 | 111 |
| Incidence rate1 per 1,000 PYs (95% CI) | 10.9 (10.6–11.2) | 13.8 (13.2–14.5) | 12.8 (12.1–13.6) | 14.7 (12.7–17.0) | 16.2 (14.1–18.4) | 24.8 (20.4–29.9) |
| Incidence RD1 (95% CI) | 0 (ref.) | 2.9 (2.2–3.7) | 1.9 (1.1–2.7) | 3.8 (1.7–6.0) | 5.3 (3.2–7.4) | 14.0 (9.3–18.6) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 5.4 (3.7–7.0) | 3.4 (1.6–5.2) | 7.8 (2.5–13.2) | 10.0 (4.4–15.7) | 20.7 (9.3–32.1) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.27 (1.18–1.36) | 1.22 (1.12–1.32) | 1.27 (1.03–1.56) | 1.35 (1.13–1.61) | 1.95 (1.48–2.55) |
| P value3 | NA | <0.001 | <0.001 | 0.024 | 0.001 | <0.001 |
| HCC, N. | 56 | 153 | 72 | 16 | 35 | 30 |
| Incidence rate1 per 1,000 PYs (95% CI) | 0.1 (0.1–0.1) | 1.2 (1.0–1.4) | 0.8 (0.6–1.0) | 1.2 (0.7–1.9) | 2.3 (1.6–3.2) | 6.2 (4.2–8.8) |
| Incidence RD1 (95% CI) | 0 (ref.) | 1.1 (0.9–1.3) | 0.7 (0.5–0.8) | 1.1 (0.5–1.7) | 2.2 (1.4–3.0) | 6.1 (3.9–8.3) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 2.1 (1.7–2.5) | 1.2 (0.8–1.6) | 2.1 (0.7–3.6) | 4.6 (2.7–6.5) | 11.4 (6.5–16.3) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 17.08 (11.56–25.25) | 9.25 (5.63–15.20) | 55.66 (14.43–214.72) | 72.72 (19.20–275.51) | 49.48 (15.71–155.81) |
| P value3 | NA | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
| Non-HCC liver cancers, N. | 82 | 25 | 16 | 2 | 5 | 2 |
| Incidence rate1 per 1,000 PYs (95% CI) | 0.1 (0.1–0.2) | 0.2 (0.1–0.3) | 0.2 (0.1–0.3) | 0.2 (0.0–0.5) | 0.3 (0.1–0.8) | 0.4 (0.1–1.5) |
| Incidence RD1 (95% CI) | 0 (ref.) | 0.1 (0.0–0.2) | 0.0 (0.0–0.1) | 0.02 (−0.2–0.2) | 0.2 (−0.1–0.5) | 0.3 (−0.3–0.9) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 0.1 (0.0–0.3) | 0.1 (−0.1–0.3) | 0.1 (−0.4–0.6) | 0.2 (−0.3–0.7) | 0.8 (−0.8–2.4) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.75 (0.98–3.14) | 1.26 (0.62–2.58) | 3.49 (0.36–34.00) | 4.20 (1.05–16.86) | 3.08 (0.35–27.48) |
| P value3 | NA | 0.062 | 0.535 | 0.261 | 0.048 | 0.175 |
| EHSO cancers, N. | 6,160 | 1,390 | 987 | 152 | 174 | 77 |
| Incidence rate1 per 1,000 PYs (95% CI) | 9.9 (9.7–10.2) | 11.3 (10.7–11.9) | 10.8 (10.2–11.5) | 11.8 (10.0–13.9) | 12.0 (10.3–13.9) | 17.1 (13.5–21.3) |
| Incidence RD1 (95% CI) | 0 (ref.) | 1.4 (0.7–2.0) | 0.9 (0.2–1.6) | 1.9 (0.0–3.8) | 2.0 (0.3–3.8) | 7.1 (3.3–11.0) |
| 20-year absolute risk ifference,2 % (95% CI) | 0 (ref.) | 3.0 (1.5–4.5) | 1.9 (0.2–3.6) | 5.2 (0.4–10.1) | 4.7 (−0.2–9.5) | 11.4 (2.0–20.7) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.12 (1.04–1.20) | 1.11 (1.02–1.22) | 1.11 (0.89–1.39) | 1.05 (0.86–1.28) | 1.41 (1.04–1.91) |
| P value3 | NA | 0.002 | 0.013 | 0.26 | 0.529 | 0.018 |
| Hematologic cancers, N. | 435 | 123 | 85 | 17 | 19 | 2 |
| Incidence rate1 per 1,000 PYs (95% CI) | 0.7 (0.6–0.7) | 1.0 (0.8–1.1) | 0.9 (0.7–1.1) | 1.3 (0.7–2.0) | 1.2 (0.8–1.9) | 0.4 (0.0–1.5) |
| Incidence RD1 (95% CI) | 0 (ref.) | 0.3 (0.1–0.5) | 0.2 (0.0–0.4) | 0.6 (0.0–1.2) | 0.6 (0.0–1.1) | −0.3 (−0.8–0.3) |
| 20-year absolute risk difference,2 % (95% CI) | 0 (ref.) | 0.6 (0.2–1.0) | 0.5 (0.0–0.9) | 0.8 (−0.3–1.9) | 1.8 (0.1–3.5) | −0.3 (−1.9–1.4) |
| Multivariable aHR3 (95% CI) | 1 (ref.) | 1.46 (1.12–1.90) | 1.47 (1.06–2.03) | 1.05 (0.51–2.15) | 1.86 (0.96–3.62) | 1.07 (0.19–5.93) |
| P value3 | NA | 0.004 | 0.014 | 0.874 | 0.083 | 0.652 |
NAFLD was defined by liver histology. For definitions and algorithm, see the Methods section and Supporting Information.
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).
20-year absolute risks and absolute risk differences (percentage points) were calculated based on Kaplan-Meier estimates (Methods).
The multivariable-adjusted model accounted for age at the index date, sex, calendar year, county of residence, cardiovascular disease, diabetes, hypertension, dyslipidemia, obesity, end-stage renal disease, family history of cancer at age <50 years, education (3 groups + missing category), the number of recorded hospital encounters in the year prior to the index biopsy date (or corresponding matching date), and alcohol abuse/misuse defined as a time-varying covariate. All clinical covariates were ascertained from the Patient Register using established ICD codes, and defined by the presence of ≥1 inpatient diagnosis or by the second of ≥2 outpatient diagnoses (as outlined in the Supporting Methods and Supporting Table S3). P values signify the comparison between each NAFLD category and population comparators.
Abbreviations: aHR, adjusted hazard ratio; CI, confidence interval; EHSO, extrahepatic solid organ; HCC, hepatocellular carcinoma; N., number; PYs, person-years; RD, rate difference; ref., referent.