Supplementary Material 3: Time trends in mortality rates (with 95% confidence intervals), per cause of death. The x-axis corresponds to the year of death.

Supplementary Material 1: Details on the multiple imputation

Because adding variables that are not part of the analysis can improve the imputation, we added the following baseline explanatory variables: body mass index (BMI), HIV co-infection, cirrhotic status, diabetes comorbidity, alcohol consumption (light/no drinker if average consumption ≤ 20g/day, moderate drinker if average consumption between 21 and 40g/day, excessive drinker if average consumption > 40g/day, and former drinker if ever drank more than 40g/day but is now a light or moderate drinker). Furthermore, the outcome was also included in the imputation. We ran the model on 20 imputed datasets for each analysis and combined the estimates with Rubin’s rule.

Supplementary Material 2: Comparison between SCCS and SFSO death cause groups

SCCS / SFSO Cardiovascular Liver cancer Liver failure Non−liver cancer Other Unnatural cause Cardiovascular

Liver cancer Liver failure Non−liver cancer

Other Overdose Unnatural cause

Unspecified

9 0 3 0 6 1 0 10

2 34 22 2 6 0 0 13

9 1 34

1 21

0 0 24

3 2 2 33 12 0 0 15

3 0 7 0 14

1 2 29

1 0 1 0 3 5 9 28

Supplementary Material 3: Time trends in mortality rates (with 95% confidence intervals),

per cause of death. The x-axis corresponds to the year of death.

Supplementary Material 4: Hazard ratios from univariable Cox regression models, excluding persons with missing information

A) For all-cause mortality ; B) For cause-specific mortality

Total: 2745 persons All−cause (296 deaths) Sex

Male Female

P < 0.001 1

0.6 (0.47 − 0.77) Age at baseline (yr)

20 40 60

P < 0.001 0.3 (0.16 − 0.58)

1

2.62 (2.03 − 3.38) Treatment status

Never treated Treated with DAA, SVR Treated with DAA, failure

Treated with IFN, SVR Treated with IFN, failure

P < 0.001 1

0.26 (0.06 − 1.04) 0.62 (0.09 − 4.49) 0.42 (0.3 − 0.59) 1.23 (0.96 − 1.58) Fibrosis score

F0, F1 or F2 F3 or F4

P < 0.001 1 3.94 (3.11 − 5) IDU

Never Ever

P = 0.73 1

1.04 (0.83 − 1.31) A)

Total: 2745 persons

Liver failur e (80 deaths,

27%)

Liv er cancer

(61 deaths, 20.6%)

Non−liv er cancer

(47 deaths, 15.9%)

Cardiovascul ar (21 deaths,

7.1%)

Unnatur al cause

(28 deaths,

9.5%)

Sex

Male Fema

le

P = 0.1 6 1 0.72 (0.45 −

1.15)

P = 0.00

6 1 0.42 (0.23 −

0.78)

P = 0.06

1 1 0.53 (0.28 −

1.03)

P = 0.16 1 0.49 (0.18 −

1.33)

P = 0.26 1 0.62 (0.27 −

1.41)

Age at baseline

(yr)

20 40 60

P <

0.0 01 0.1 (0.02 −

0.44) 1 3.02 (1.71 −

5.34)

P <

0.0 01 0.05 (0.01 −

0.41) 1 7.42 (3.03 −

18.16)

P <

0.0 01 0.18 (0.03 −

1.12) 1 3.37 (1.65 −

6.9)

P < 0.001 0.94 (0.07 −

12.25) 1 3.99 (1.43 −

11.13)

P = 0.27 1.21 (0.29 −

4.95) 1 0.47 (0.19 −

1.17)

Treatme nt status

Never treated Treated with

SVR Treated with

failure

P <

0.0 01 1 0.16 (0.06 −

0.42) 1.34 (0.85 −

2.12)

P <

0.0 01 1 0.59 (0.24 −

1.42) 3.39 (1.81 −

6.34)

P = 0.6 7 1 0.76 (0.37 −

1.56) 1.04 (0.52 −

2.06)

P = 0.28 1 0.48 (0.16 −

1.41) 0.51 (0.18 −

1.46)

P = 0.73 1 0.69 (0.27 −

1.73) 0.89 (0.37 −

2.15)

Fibrosis score

F0, F1 or F2 F3 or F4

P <

0.0 01 1 17.18 (8.59 −

34.37)

P <

0.0 01 1 17.17 (7.81 − 37.74)

P = 0.2 8 1 1.38 (0.77 −

2.49)

P = 0.015 1 2.93 (1.23 −

6.96)

P = 0.35 1 1.44 (0.67 −

3.07) B)

IDU

Never Ever

P = 0.6 6 1 0.91 (0.58 −

1.4)

P = 0.04

5 1 0.59 (0.35 −

0.99)

P

= 0.

2 1 1.47 (0.82 −

2.65)

P = 0.014 1 0.28 (0.1 −

0.78)

P = 0.0037

1 4.19 (1.59

− 11.02)

Supplementary Material 5: Hazard ratios from multivariable Cox regression models, excluding persons with missing information (sensitivity analysis)

A) For all-cause mortality ; B) For cause-specific mortality

Total: 2745 persons All−cause (296 deaths) Sex

Male Female

P = 0.001 1

0.65 (0.5 − 0.84) Age at baseline (yr)

20 40 60

P < 0.001 0.43 (0.22 − 0.84)

1

2.81 (2.09 − 3.78) Treatment status

Never treated Treated with DAA, SVR Treated with DAA, failure

Treated with IFN, SVR Treated with IFN, failure

P < 0.001 1

0.13 (0.03 − 0.51) 0.3 (0.04 − 2.17) 0.32 (0.22 − 0.45) 0.76 (0.59 − 0.99) Fibrosis score

F0, F1 or F2 F3 or F4

P < 0.001 1

3.55 (2.75 − 4.58) IDU

Never Ever

P < 0.001 1

1.98 (1.46 − 2.68)

Total: 2745 persons

Liver failur e (80 deaths,

27%)

Liv er cancer

(61 deaths,

20.6%)

Non−liv er cancer

(47 deaths,

15.9%)

Cardiovascul ar (21 deaths,

7.1%)

Unnatur al cause

(28 deaths,

9.5%)

Sex

Male Fema le

P = 0.6 6 1

0.9 (0.55 −

1.45)

P = 0.01

3 1 0.45 (0.24 −

0.84)

P = 0.06

9 1 0.54 (0.27 −

1.05)

P = 0.045 1 0.35 (0.12 −

0.98)

P = 0.53 1 0.77 (0.33 −

1.76)

Age at baseline

(yr)

20 40 60

P = 0.1 2 0.25 (0.06 −

1.15) 1 1.96 (1.03 −

3.72)

P <

0.0 01 0.14 (0.01 −

1.4) 1 5.55 (2.06 −

14.96)

P <

0.0 01 0.15 (0.02 −

1) 1 6.71 (2.92 −

15.39)

P < 0.001 0.85 (0.06 −

12.7) 1 3.87 (1.18 −

12.7)

P = 0.72 1.69 (0.38 −

7.52) 1 0.77 (0.28 −

2.12)

Treatme nt status

Never treated Treated with

SVR Treated with

failure

P <

0.0 01 1 0.09 (0.03 −

0.23) 0.53 (0.33 −

0.86)

P <

0.0 01 1 0.35 (0.14 −

0.86) 1.55 (0.8 −

2.99)

P = 0.6 4 1 0.71 (0.34 −

1.46) 0.88 (0.43 −

1.79)

P = 0.14 1 0.42 (0.14 −

1.28) 0.37 (0.12 −

1.13)

P = 0.74 1 0.7 (0.27 −

1.8) 0.93 (0.37 −

2.38)

Fibrosis score

F0, F1 or F2 F3 or F4

P <

0.0 01 1 18.32 (8.92 −

37.66)

P <

0.0 01 1 11.35 (5.07 −

25.41)

P = 0.8 4 1 1.06 (0.58 −

1.97)

P = 0.076 1 2.27 (0.92 −

5.63)

P = 0.21 1 1.69 (0.74 −

3.83)

IDU

Never Ever

P = 0.5 1 1

1.2 (0.7 −

2.06)

P = 0.1 6 1 1.62 (0.83 −

3.17)

P <

0.0 01 1 4.42 (1.91 −

10.21)

P = 0.88 1 0.9 (0.24 −

3.38)

P = 0.019 1 3.78 (1.24

− 11.51)