Table 5.
Risk of Hepatocellular Carcinoma in Patients With Autoimmune Hepatitis and Matched General-Population Reference Individuals, Sweden 1969–2016
| Total | Events | Incidence Rate Per 1,000 PY | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AIH | Comparators | AIH | Comparators | AIH | 95% CI | Comparators | 95% CI | |||||||||
| Group | No. | % | No. | % | No. | % | No. | % | HR a | 95% CI | HR b | 95% CI | ||||
| Overall (≥3 months) | 5,268 | 100 | 22,996 | 100 | 178 | 3.4 | 41 | 0.2 | 2.5 | 2.2, 2.9 | 0.1 | 0.1, 0.1 | 32.01 | 20.52, 49.93 | 29.18 | 17.52, 48.61 |
| Sex | ||||||||||||||||
| Female | 3,115 | 59.1 | 13,278 | 57.7 | 73 | 2.3 | 15 | 0.1 | 1.9 | 1.5, 2.3 | 0.1 | 0.0, 0.1 | 31.89 | 15.91, 63.89 | 37.67 | 16.17, 87.74 |
| Male | 2,153 | 40.9 | 9,718 | 42.3 | 105 | 4.9 | 26 | 0.3 | 3.4 | 2.7, 4.0 | 0.1 | 0.1, 0.2 | 32.10 | 18.00, 57.24 | 31.79 | 15.12, 66.83 |
| Age at diagnosis, years | ||||||||||||||||
| 18.0–29.9 | 594 | 11.3 | 2,702 | 11.7 | 8 | 1.3 | 0 | 0.0 | 0.8 | 0.2, 1.3 | 0.0 | 0.0, 0.0 | ||||
| 30.0–39.9 | 722 | 13.7 | 3,242 | 14.1 | 28 | 3.9 | 3 | 0.1 | 2.1 | 1.4, 2.9 | 0.0 | 0.0, 0.1 | 38.57 | 11.68, 127.37 | 185.16 | 6.82, 5024.3 |
| 40.0–49.9 | 909 | 17.3 | 4,146 | 18.0 | 29 | 3.2 | 9 | 0.2 | 1.8 | 1.2, 2.5 | 0.1 | 0.0, 0.2 | 28.72 | 10.05, 82.06 | 58.18 | 11.13, 304.11 |
| 50.0–59.9 | 1,103 | 20.9 | 4,896 | 21.3 | 34 | 3.1 | 11 | 0.2 | 2.2 | 1.5, 2.9 | 0.1 | 0.0, 0.2 | 31.62 | 11.16, 89.60 | 70.95 | 8.09, 622.60 |
| 60.0–69.9 | 1,150 | 21.8 | 4,884 | 21.2 | 49 | 4.3 | 12 | 0.2 | 4.5 | 3.2, 5.8 | 0.2 | 0.1, 0.3 | 23.21 | 10.93, 49.33 | 22.34 | 8.97, 55.64 |
| ≥70.0 | 790 | 15.0 | 3,126 | 13.6 | 30 | 3.8 | 6 | 0.2 | 6.4 | 4.1, 8.6 | 0.2 | 0.0, 0.4 | 36.33 | 11.03, 119.66 | 28.32 | 6.52, 122.97 |
| Age at diagnosis, restricting follow-up to 5 years, years | ||||||||||||||||
| 18.0–29.9 | 594 | 11.3 | 2,702 | 11.7 | 1 | 0.2 | 0 | 0.0 | 0.4 | 0.0, 1.1 | 0.0 | 0.0, 0.0 | ||||
| 30.0–39.9 | 722 | 13.7 | 3,242 | 14.1 | 5 | 0.7 | 0 | 0.0 | 1.5 | 0.2, 2.8 | 0.0 | 0.0, 0.0 | ||||
| 40.0–49.9 | 909 | 17.3 | 4,146 | 18.0 | 7 | 0.8 | 0 | 0.0 | 1.7 | 0.4, 2.9 | 0.0 | 0.0, 0.0 | ||||
| 50.0–59.9 | 1,103 | 20.9 | 4,896 | 21.3 | 6 | 0.5 | 1 | 0.0 | 1.2 | 0.2, 2.2 | 0.0 | 0.0, 0.1 | 23.68 | 2.82, 199.14 | ||
| 60.0–69.9 | 1,150 | 21.8 | 4,884 | 21.2 | 21 | 1.8 | 1 | 0.0 | 4.5 | 2.6, 6.4 | 0.0 | 0.0, 0.1 | ||||
| ≥70.0 | 790 | 15.0 | 3,126 | 13.6 | 27 | 3.4 | 3 | 0.1 | 9.7 | 6.0, 13.3 | 0.2 | 0.0, 0.5 | 34.58 | 10.45, 114.38 | 26.12 | 6.12, 111.45 |
| Year of diagnosis | ||||||||||||||||
| 1969–1986 | 1,831 | 34.8 | 8,494 | 36.9 | 83 | 4.5 | 23 | 0.3 | 2.6 | 2.0, 3.1 | 0.1 | 0.1, 0.2 | 29.15 | 15.49, 54.83 | 23.09 | 11.33, 47.08 |
| 1987–2001 | 1,751 | 33.2 | 7,703 | 33.5 | 76 | 4.3 | 16 | 0.2 | 2.7 | 2.1, 3.3 | 0.1 | 0.1, 0.2 | 31.25 | 16.13, 60.54 | 51.29 | 18.72, 140.58 |
| 2002–2016 | 1,686 | 32.0 | 6,799 | 29.6 | 19 | 1.1 | 2 | 0.0 | 2.0 | 1.1, 2.9 | 0.0 | 0.0, 0.1 | 70.96 | 9.46, 532.03 | ||
| 1997–2016 | 1,871 | 35.5 | 7,572 | 32.9 | 26 | 1.4 | 5 | 0.1 | 2.1 | 1.3, 3.0 | 0.1 | 0.0, 0.2 | 32.31 | 9.74, 107.23 | 78.41 | 8.05, 763.76 |
| Year of diagnosis, restricting follow-up to 5 years | ||||||||||||||||
| 1969–1986 | 1,831 | 34.8 | 8,494 | 36.9 | 29 | 1.6 | 2 | 0.0 | 3.6 | 2.3, 4.9 | 0.0 | 0.0 0.1 | 125.52 | 17.08, 922.16 | 45.68 | 5.41, 386.00 |
| 1987–2001 | 1,751 | 33.2 | 7,703 | 33.5 | 26 | 1.5 | 3 | 0.0 | 3.3 | 2.0, 4.5 | 0.1 | 0.0, 0.2 | 37.49 | 11.32, 124.16 | 67.07 | 6.79, 662.91 |
| 2002–2012 | 1,154 | 21.9 | 4,675 | 20.3 | 10 | 0.9%) | 0 | 0.0 | 1.9 | 0.7, 3.1 | 0.0 | 0.0, 0.0 | ||||
| 1997–2012 | 1,339 | 25.4 | 5,448 | 23.7 | 24 | 1.8 | 5 | 0.1 | 2.2 | 1.3, 3.1 | 0.1 | 0.0, 0.2 | 30.25 | 9.06, 100.94 | 91.49 | 7.38, 1134.14 |
| Country of birth | ||||||||||||||||
| Nordic | 4,962 | 94.2 | 21,570 | 93.8 | 162 | 3.3 | 40 | 0.2 | 2.4 | 2.1, 2.8 | 0.1 | 0.1, 0.1 | 28.90 | 18.30, 45.64 | 25.98 | 15.49, 43.59 |
| Other | 304 | 5.8 | 1,424 | 6.2 | 16 | 5.3 | 1 | 0.1 | 4.3 | 2.2, 6.5 | 0.1 | 0.0, 0.1 | ||||
| Education, years | ||||||||||||||||
| ≤9 | 1,679 | 31.9 | 7,938 | 34.5 | 52 | 3.1 | 21 | 0.3 | 2.1 | 1.5, 2.7 | 0.1 | 0.1, 0.2 | 24.38 | 8.66, 68.63 | 27.42 | 8.22, 91.47 |
| 10–11 | 1,932 | 36.7 | 8,450 | 36.7 | 54 | 2.8 | 13 | 0.2 | 1.9 | 1.4, 2.4 | 0.1 | 0.0, 0.1 | 46.11 | 11.131, 90.98 | 87.97 | 9.47, 816.95 |
| >12 | 1,050 | 19.9 | 5,010 | 21.8 | 34 | 3.2 | 5 | 0.1 | 2.5 | 1.7, 3.4 | 0.1 | 0.0, 0.1 | ||||
| Missing data | 607 | 11.5 | 1,598 | 6.9 | 38 | 6.3 | 2 | 0.1 | 12.7 | 8.7, 16.8 | 0.2 | 0.0, 0.4 | 63.55 | 8.50, 475.26 | 58.15 | 6.99, 483.73 |
| Pathology findings | ||||||||||||||||
| Cirrhosis | 733 | 13.9 | 3,203 | 13.9 | 59 | 8.0 | 5 | 0.2 | 8.1 | 6.0, 10.2 | 0.1 | 0.0, 0.2 | 249.59 | 34.56, 1802.6 | ||
| Fibrosis | 1,110 | 21.1 | 4,622 | 20.1 | 21 | 1.9 | 3 | 0.1 | 2.2 | 1.3, 3.2 | 0.1 | 0.0, 0.1 | 39.86 | 9.30, 170.91 | 65.17 | 4.01, 1059.82 |
| Inflammation, no fibrosis | 1,842 | 35.0 | 8,053 | 35.0 | 54 | 2.9 | 9 | 0.1 | 2.1 | 1.5–2.6 | 0.1 | 0.0–0.1 | 41.95 | 16.73, 105.23 | 121.88 | 19.88, 747.41 |
| Other | 1,583 | 30.0 | 7,118 | 31.0 | 44 | 2.8 | 24 | 0.3 | 1.6 | 1.1, 2.1 | 0.2 | 0.1, 0.2 | 11.93 | 6.51, 21.89 | 14.66 | 6.61, 32.55 |
| Necrosis | 129 | 2.4 | 557 | 2.4 | 2 | 1.6 | 0 | 1.1 | 0.0, 2.6 | 0.0 | 0.0, 0.0 | |||||
| Severity of liver disease | ||||||||||||||||
| Portal hypertension | 263 | 5.0 | 1,130 | 4.9 | 17 | 6.5 | 3 | 0.3 | 8.7 | 4.5, 12.8 | 0.2 | 0.0, 0.4 | 75.43 | 10.02, 567.70 | ||
| Acute/subacute liver failure | 139 | 2.6 | 629 | 2.7 | 9 | 6.5 | 0 | 4.8 | 1.7, 7.9 | 0.0 | 0.0, 0.0 | |||||
| Overlap syndromes | ||||||||||||||||
| PSC | 84 | 1.6 | 362 | 1.6 | 6 | 7.1 | 0 | 9.2 | 1.8, 16.6 | 0.0 | 0.0, 0.0 | |||||
| PBC | 201 | 3.8 | 815 | 3.5 | 8 | 4.0 | 1 | 0.1 | 5.2 | 1.6, 8.8 | 0.1 | 0.0, 0.3 | ||||
| Family history of cancer in 1st degree relative | ||||||||||||||||
| Overall | 1,221 | 23.2 | 5,130 | 22.3 | 35 | 2.9 | 4 | 0.1 | 2.3 | 1.6, 3.1 | 0.1 | 0.0, 0.1 | ||||
| Age ≤50 years | 590 | 11.2 | 2,596 | 11.3 | 20 | 3.4 | 1 | 0.0 | 2.0 | 1.1, 2.8 | 0.0 | 0.0, 0.1 | ||||
| Age >50 years | 631 | 12.0 | 2,534 | 11.0 | 15 | 2.4 | 3 | 0.1 | 3.1 | 1.5, 4.7 | 0.1 | 0.0, 0.3 | ||||
| Comorbid conditions | ||||||||||||||||
| Cardiovascular disease | 680 | 12.9 | 1,201 | 5.2 | 28 | 4.1 | 1 | 0.1 | 5.7 | 3.6, 7.8 | 0.1 | 0.0, 0.3 | ||||
| Diabetes | 519 | 9.9 | 427 | 1.9 | 23 | 4.4 | 0 | 5.4 | 3.2, 7.5 | 0.0 | 0.0, 0.0 | |||||
| End-stage renal disease | 13 | 0.2 | 16 | 0.1 | 0 | 0 | 0.0 | 0.0, 0.0 | 0.0 | 0.0, 0.0 | ||||||
| Other autoimmune diseases | 751 | 14.3 | 319 | 1.4 | 13 | 1.7 | 0 | 1.8 | 0.8, 2.8 | 0.0 | 0.0, 0.0 | |||||
Abbreviations: AIH, autoimmune hepatitis; CI, confidence interval; HR, hazard ratio; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; PY, person-years.
a Conditioned on age, sex, county, and calendar period.
b Conditioned on age, sex, county, and calendar period, and further adjusted for education, country of birth, family history of cancer, baseline medical comorbid conditions (cardiovascular disease, diabetes, end-stage renal disease, and other autoimmune disease), and time-dependent adjustment for alcohol use disorder.