Table 3:

Factors associated with the development of HCC in patients with virologically cured HCV and cirrhosis.

Variable	Baseline (N=29,398)		12 months (N=26,648)		24 months (N=21,600)
	HR (95% CI)	P-Value	HR (95% CI)	P-Value	HR (95% CI)	P-Value
Demographics
Sex (Ref: Female)
Male	1.89 (1.37–2.59)	<0.0001	1.93 (2.79–1.33)	0.0005	1.99 (3.13–1.26)	0.0031
Race/ethnicity (Ref: White not Hispanic)
African American	0.78 (0.71–0.86)	<0.0001	0.83 (0.75–0.93)	0.0017	0.85 (0.74–0.98)	0.0206
White Hispanic	0.89 (0.75–1.07)	0.21	0.89 (0.73–1.10)	0.2781	0.91 (0.71–1.18)	0.4813
Other	1.17 (0.93–1.47)	0.18	1.12 (0.86–1.47)	0.4097	1.33 (0.96–1.84)	0.0865
Clinical Characteristics
HCV genotype (Ref: 1a)
1a/1b	0.93 (0.74–1.16)	0.51	0.89 (0.68–1.16)	0.3915	0.96 (0.70–1.32)	0.7978
1b	1.09 (0.98–1.21)	0.10	1.06 (0.94–1.19)	0.3473	0.97 (0.83–1.12)	0.643
2	0.84 (0.71–0.99)	0.04	0.82 (0.67–1.00)	0.0515	0.78 (0.61–1.00)	0.0466
3	1.47 (1.27–1.71)	<0.0001	1.41 (1.18–1.68)	0.0002	1.35 (1.08–1.69)	0.0087
4, 5, or 6	1.01 (0.63–1.61)	0.97	1.66 (0.97–2.82)	0.2066	1.31 (0.74–2.34)	0.3591
Prior HCV treatment	1.08 (1.00–1.17)	0.06	1.07 (0.97–1.18)	0.1567	1.11 (0.99–1.25)	0.0847
FIB-4 baseline (Ref: <1.45)
1.45–3.25	2.01 (1.71–2.37)	<0.0001	N/A	--	N/A	--
>3.25	2.49 (2.11–2.94)	<0.0001	N/A	--	N/A	--
Change in FIB-4* ǂ (Ref: High-High)
(Ref: Low-Low)
High-High	N/A	--	1.75 (1.54–1.99)	<.0001	1.70 (1.45–2.00)	<0.0001
High-Low	N/A	--	1.17 (1.00–1.36)	0.0456	1.40 (1.19–1.65)	<0.0001
Low-High	N/A	--	1.86 (1.50–2.30)	<.0001	1.81 (1.37–2.38)	<0.0001
Years since cirrhosis diagnosis**
1–<2 years	1.41 (1.14–1.74)	0.001	Ref	--	N/A^	--
2–<5 years	1.47 (1.24–1.74)	<0.0001	1.58 (1.30–1.93)	<0.0001	Ref	--
≥ 5 years	1.71 (1.46–2.00)	<0.0001	1.79 (1.49–2.15)	<0.0001	1.34 (1.16–1.55)	<0.0001
Varices	1.73 (1.57–1.91)	<0.0001	1.60 (1.40–1.82)	<0.0001	1.56 (1.34–1.82)	<0.0001
Ascites	NS		1.27 (1.05–1.53)	0.0135	1.33 (1.07–1.66)	0.0106
Baseline albumin, g/dl	0.48 (0.44–0.52)	<0.0001	0.47 (0.41–0.52)	<0.0001	0.49 (0.42–0.57)	<0.0001
Change in albuminǂ, g/dl	N/A	--	0.82 (0.70–0.97)	0.02	0.90 (0.75–1.08)	0.2627
Baseline bilirubin, (log) mg/dl	1.24 (1.15–1.34)	<0.0001	1.30 (1.17–1.45)	<0.0001	1.30 (1.13–1.48)	0.0002
Change in bilirubinǂ, (log) mg/dl	N/A	--	1.20 (1.06–1.36)	0.0033	1.22 (1.06–1.41)	0.0055
Baseline INR ≥2 (Ref: <2)	0.83 (0.58–1.18)	0.30	N/A		N/A	–
Baseline sodium, mEg/l	NS	--	0.99 (0.97–1.01)	0.3078	NS	–
Change in sodiumǂ, mEq/l	N/A	--	1.01 (0.99–1.03)	0.2883	NS	–
Baseline hemoglobin, g/dl	NS	--	1.03 (1.00–1.07)	0.0745	1.05 (1.00–1.09)	0.0387
Change in hemoglobinǂ, g/dl	N/A	--	1.03 (0.99–1.07)	0.1337	1.04 (1.00–1.09)	0.0715
Behavioral Characteristics
Smoking (Ref: Non-smoker)
Current	1.32 (1.16–1.51)	<0.0001	1.22 (1.05–1.41)	0.0084	1.24 (1.04–1.48)	0.019
Former	1.12 (0.97–1.29)	0.12	1.07 (0.91–1.25)	0.4138	1.08 (0.90–1.31)	0.3891

^*Based on first date of elevated FIB-4; Low-Low indicates FIB-4 was <3.25 at both times, High-High indicates FIB-4 was >3.25 at both times, High-Low indicates FIB-4 was >3.25 at baseline and <3.25 at the landmark times, and Low-High indicates FIB-4 was <3.25 at baseline and increased to >3.25 at the landmark times.

^ǂChange variables calculated from baseline to 12 months for the model at 12 month landmark time and from baseline to 24 months for the model at 24 month landmark time.

^**Reference group for years since cirrhosis diagnosis: Baseline ref: <1 year; 12 month ref: 1-<2 years; 24 month ref: 2-<5 years.

NS: Not selected through model building strategy at given landmark time.

N/A: Not considered for in model building strategy at given landmark time.

^{^}: This category is not available at 24 month landmark time.

Abbreviations: HCC-hepatocellular carcinoma; HCV-hepatitis C virus; HR-hazard ratio; CI-confidence interval; Ref-reference group; FIB-4-fibrosis-4 index; INR-international normalized ratio