Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

Figures & data

Table 1 Baseline characteristics of the overall NAFLD cohort and by diabetes status

Baseline patient characteristicsa	Overall NAFLD cohort (N=18,754), n (%)b	No diabetes (N=11,097), n (%)	Type 2 diabetes (N=7,311), n (%)
Age category, years
18–44	5,999 (32.0)	3,970 (35.8)	1,750 (23.9)
45–54	4,562 (24.3)	2,753 (24.8)	1,774 (24.3)
55–64	4,199 (22.4)	2,321 (20.9)	1,859 (25.4)
65–74	2,732 (14.6)	1,396 (12.6)	1,331 (18.2)
75–84	1,039 (5.5)	531 (4.8)	502 (6.9)
85+	223 (1.2)	126 (1.1)	95 (1.3)
Gender
Male	7,211 (38.5)	4,499 (40.5)	2,689 (36.8)
Female	11,543 (61.5)	6,598 (59.5)	4,622 (63.2)
BMI categoryc
Underweight (<18.5 kg/m^2)	58 (0.3)	45 (0.4)	13 (0.2)
Normal (18.5–24.9 kg/m^2)	997 (5.3)	770 (6.9)	217 (3.0)
Overweight (25–29.9 kg/m^2)	2,594 (13.8)	1,809 (16.3)	755 (10.3)
Obese (≥30 kg/m^2)	13,283 (70.8)	7,057 (63.6)	5,936 (81.2)
Unknown/missing	1,822 (9.7)	1,416 (12.8)	390 (5.3)
Baseline comorbiditiesd
Atherosclerosis	2,714 (14.5)	1,133 (10.2)	1,566 (21.4)
Atrial fibrillation	1,007 (5.4)	471 (4.2)	529 (7.2)
Coronary heart disease	3,118 (16.6)	1,348 (12.1)	1,751 (24.0)
Heart failure	1,223 (6.5)	425 (3.8)	789 (10.8)
Hyperlipidemia	9,734 (51.9)	4,820 (43.4)	4,769 (65.2)
Hypertension	9,897 (52.8)	4,699 (42.3)	5,066 (69.3)
Diabetes	7,364 (39.3)	0 (0)	7,311 (100.0)
Baseline medication usee
Biguanides	4,323 (23.1)	0 (0)	4,170 (57.0)
Sulfonylureas/meglitinides	2,070 (11.0)	0 (0)	2,030 (27.8)
Thiazolidinediones	813 (4.3)	0 (0)	803 (11.0)
GLP-1 receptor agonists	232 (1.2)	0 (0)	226 (3.1)
DPP-4 inhibitors	578 (3.1)	0 (0)	571 (7.8)
Insulin	2,013 (10.7)	0 (0)	1,928 (26.4)
Other glucose-lowering treatments	336 (1.8)	0 (0)	328 (4.5)
Lipid-lowering drugs	7,273 (38.8)	3,058 (27.6)	4,124 (56.4)
ARBs and ACE inhibitors	5,518 (29.4)	2,083 (18.8)	3,369 (46.1)

Notes:

a Baseline characteristics are measured from the year prior to and including the index date.

b Patients with gestational and type 1 diabetes are included in the overall NAFLD cohort, but excluded from the no diabetes and type 2 diabetes subgroups.

c If multiple observations during the baseline period are available, BMI is calculated from the height and weight recorded closest to the index date.

d Comorbidities were identified by the presence of at least one diagnosis code during the baseline period.

e Excludes medication prescribed on the index date.

Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers; BMI, body mass index; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; NAFLD, nonalcoholic fatty liver disease.

Table 2 Baseline liver function scores of the overall NAFLD cohort and by diabetes status

Liver function severity scoresa	Overall NAFLD cohort (N=18,754), n (%)	No diabetes (N=11,097), n (%)	Type 2 diabetes (N=7,311), n (%)
AST to Platelet Ratio Index
Number with data available	12,038	7,062	4,746
≤0.5	8,649 (71.8)	5,171 (73.2)	3,297 (69.5)
>0.5 to 1.5	2,721 (22.6)	1,513 (21.4)	1,164 (24.5)
>1.5 (advanced fibrosis/cirrhosis)^Citation6,Citation14	668 (5.5)	378 (5.4)	285 (6.0)
Fibrosis-4
Number with data available	11,988	7,032	4,726
<1.30	7,006 (58.4)	4,299 (61.1)	2,507 (53.0)
1.30 to <3.25	3,713 (31.0)	2,122 (30.2)	1,565 (33.1)
≥3.25 (advanced fibrosis/cirrhosis)^Citation5,Citation17	1,269 (10.6)	611 (8.7)	654 (13.8)
NAFLD Fibrosis Score
Number with data available	10,550	6,000	4,334
<−1.455	3,512 (33.3)	2,888 (48.1)	548 (12.6)
−1.455 to 0.676	4,522 (42.9)	2,480 (41.3)	1,933 (44.6)
>0.676 (advanced fibrosis/cirrhosis)^Citation4	2,516 (23.8)	632 (10.5)	1,853 (42.8)
Model for End-stage Liver Disease
Number with data available	2,203	1,213	961
<10: least severe:	1,461 (66.3)	873 (72.0)	565 (58.8)
10 to <20	583 (26.5)	280 (23.1)	299 (31.1)
20 to <30	152 (6.9)	59 (4.9)	91 (9.5)
≥30: most severe:	7 (0.3)	1 (0.1)	6 (0.6)

Notes:

a For patients with multiple laboratory values during the baseline period, the value selected was closest to or on the index date. Advanced fibrosis/cirrhosis thresholds were identified using references 6, 14, 5, 17, and 4, as indicated in the table.

Abbreviations: AST, aspartate aminotransferase; NAFLD, nonalcoholic fatty liver disease.

Table 3 Disease severity of overall NAFLD cohort and by diabetes status at the index datea

Disease stage within 90 days of index date	All NAFLD cohort (N=18,754), n (%)	No diabetes (N=11,097), n (%)	Type 2 diabetes (N=7,311), n (%)
Uncomplicated NAFLD	13,109 (69.9)	8,672 (78.1)	4,165 (57.0)
Advanced fibrosis	2,198 (11.7)	519 (4.7)	1,635 (22.4)
Cirrhosis	3,337 (17.8)	1,862 (16.8)	1,448 (19.8)
Hepatocellular carcinoma	74 (0.4)	25 (0.2)	47 (0.6)
Liver transplant	36 (0.2)	19 (0.2)	16 (0.2)

Note:

a Time frame for severity indicators was within 90 days of the first qualifying NAFLD diagnosis date.

Abbreviation: NAFLD, nonalcoholic fatty liver disease.

Figure 1 Time to disease progression among patients,^a stratified by diabetes status.

Notes: ^aIncludes patients with index stage of uncomplicated NAFLD, advanced fibrosis, cirrhosis, or hepatocellular carcinoma; patients with an index stage of liver transplant were excluded from progression analyses.
Abbreviations: NAFLD, nonalcoholic fatty liver disease; SD, standard deviation.

Figure 2 Transition rates of disease progression within one year, derived from multistate model.

Notes: Arrows indicate progression from one disease stage to another. Colored circles indicate different disease stages over the NAFLD disease course, and colored arrows indicate progression to the corresponding disease stage.
Abbreviations: HCC, hepatocellular carcinoma; NAFLD, nonalcoholic fatty liver disease.

Table S1 Study sample attrition

Criterion	Number of patients remaining	N (%) excludeda
With diagnosis of NAFLD	30,440	N/A
Earliest activity date in system at least 12 months before index dateb and latest activity date >90 days after index	22,577	7,863 (25.8)
Age ≥18 years at index date	22,203	374 (1.2)
Exclude diagnosis of alcoholism	20,286	1,917 (6.3)
Exclude other diagnoses of interestc	18,754	1,532 (5)

Notes:

a Percentage excluded from the starting total.

b The index date may not be the first NAFLD diagnosis date.

c Patients may have had more than one of the diagnoses listed: Alpha-1 antitrypsin deficiency, hemochromatosis, hepatitis B, hepatitis C, Wilson’s disease.

Abbreviations: N/A, not applicable; NAFLD, nonalcoholic fatty liver disease.

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