Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in cystic fibrosis patients

Table 1 Demographics for all subjects and stratified by modulator (lumacaftor/ivacaftor) use

	All subjects (n = 20)	CFTR modulator (n = 9)	No CFTR modulator (n = 11)	P value
Age at MRI (yr)	22.3 (11.3-39.0)	26.4 (16.3-39.0)	21.9 (11.3-36.1)	0.29
Genotype
F508del/F508del	10	9	1	< 0.01
F508del/other	9	0	9	< 0.01
Other/other	1	0	1	< 0.01
Male sex	16 (80%)	7 (78%)	9 (82%)	1.00
BMI percentile	39 (2-96)	51 (3-77)	23 (2-96)	0.21
% predicted FEV1	77 (33-105)	73 (33-89)	77 (48-105)	0.24
CFRD	12 (60%)	7 (78%)	5 (45%)	0.20
Insulin therapy	10 (50%)	6 (67%)	4 (36%)	0.37

Data presented as median (range) or frequency (percent) as appropriate. BMI (percentile): body mass index percentile adjusted for age; FEV1: forced expiratory volume at 1 s; CFRD: cystic fibrosis related diabetes.

Table 2 Summary of data stratified by presence of steatosis, use of modulator (lumacaftor/ivacaftor), and diabetes status

	Normal Range	All subjects (n = 20)	Steatosis (n = 6)	No Steatosis (n = 14)	P value	CFTR modulator(n = 9)	No CFTR modulator(n = 11)	P value	CFRD (n = 12)	NGT (n = 8)	P value
Hepatic Fat Fraction	--	3.0	9.5	2.4	0.01	2.0	4.1	0.002	2.2	4.9	0.06
		0.0-21.0	6.0-21.0	0-4.1		0.0-6.4	2.7-21		0.0-14.5	2.4-21
Age	--	22.3	16.7	26.0	0.08	26.4	21.9	0.29	28.2	18.0	0.04
		11.3-39.0	13.4-36.1	11.3-39.0		16.3-39.0	11.3-36.1		17.0-39.0	11.3-30.6
Sex (male)	--	16	5	11	1.00	7	9	1.00	8	8	0.12
		80%	83%	78%		78%	82%		67%	100%
BMI	--	21.0	20.5	21.0	0.6	22.4 18.8-25.7	20.0 16.9-32.4	0.05	21.0 18.8-32.4	19.6 16.9-22.4	0.05
		16.9-32.4	16.9-32.4	18.8-25.7
BMI percentile	--	39	50	30	0.77	51	23	0.21	39	37.5	0.62
		2-96	2-96	3-77		3-77	2-96		3-96	2-73
FEV1 %	--	77	86	74.5	0.22	73	77	0.24	63.5	88	0.001
		33-105	62-105	33-97		33-89	48-105		33-105	65-97
CFTR modulator	--	9	1	8	0.16	9	11	--	7	2	0.20
		45%	17%	57%		100%	100%		58%	25%
Hemoglobin A1C (%)	< 5.8	5.8	5.7	6.3	0.30	6.3	5.7	0.21	6.4	5.6	0.002
		5.2-8.2	5.4-6.4	5.2-8.2		5.3-8.2	5.2-7.4		5.4-8.2	5.2-5.7
AST (U/L)	9-39	23	27	23	0.93	20	27	0.39	20	26	0.87
		11-45	11-45	11-42		11-42	11-45		11-42	11-45
ALT (U/L)	10-52	22	24.5	22	0.57	18	29	0.19	18	26	0.46
		10-58	12-58	10-45		10-45	12-58		10-58	14-47
GGT (U/L)	5-64	14	19	13.5	0.10	12	19	0.07	13.5	19	0.30
		9-29	14-25	9-29		9-24	10-29		9-29	11-24
Alk Phos (U/L)	33-120	110	172	90	0.01	66	155	0.01	90	157	0.04
		44-310	146-310	44-234		44-178	103-310		44-178	71-310
Alk Phos SD	-2-2	1.2	3.1	-0.3	0.03	-0.3	1.8	0.07	0.6	1.4	0.65
		-1.5-4.8	-0.6-4.8	-1.5-4.7		-1.5-4.7	-0.6-4.8		-1.5-4.8	-0.6-3.2
Total Bili (µmol/L)	0-20.5	6.8	8.5	5.1	0.47	5.1	8.6	0.003	5.1	8.6	0.06
		3.4-20.5	3.4-15.4	3.4-20.5		3.4-6.8	3.4-20.5		3.4-18.8	5.1-20.5
Triglyceride (mmol/L)	< 1.7	1.02	1.25	0.68	0.07	0.9	1.25	0.79	0.68	1.28	0.15
		0.36-2.55	0.69-2.55	0.36-1.54		0.64-2.55	0.36-2.35		0.64-2.35	0.36-2.55
LDL (mmol/L)	< 3.4	1.7	1.4	1.7	0.05	1.6	1.7	0.53	1.7	1.6	0.71
		0.8-2.4	0.9-1.6	0.8-2.4		0.8-2.2	0.9-2.4		0.9-2.4	0.8-2.0
HDL (mmol/L)	> 1.0	1.03	0.84	1.09	0.02	1.04	0.98	0.31	1.01	1.05	0.73
		0.53-2.03	0.53-1.41	0.91-2.03		0.86-2.03	0.53-1.54		0.53-2.03	0.84-1.53

Data is stratified by steatosis (MRI proton density fat fraction >5%) or no steatosis (MRI proton density fat fraction <5%), use of CFTR modulator lumacaftor/ivacaftor, and diabetes status. Data are presented as median and range. To convert total bilirubin from μmol/L to mg/dL multiply by 0.0585.To convert triglycerides from mmol/L to mg/dL multiply by 88.5. To convert LDL from mmol/L to mg/dL multiply by 38.7. To convert HDL from mmol/L to mg/dL multiply by 38.7. CFRD: cystic fibrosis related diabetes. NGT: normal glucose tolerance; AST: Aspartate transaminase; ALT: Alanine transaminase; GGT: Gamma-glutamyltransferase; LDL: Low density lipoprotein; HDL: High density lipoprotein; BMI: Body mass index.

Table 3 Magnetic resonance imaging proton density fat fraction and biochemistry for all subjects and stratified by modulator (lumacaftor/ivacaftor) status

	Reference range	All subjects, n = 20	CFTR modulator, n = 9	No CFTR modulator, n = 11	P value
PDFF (%)	< 5%	3.0 (0.0-21.0)	2.0 (0.0-6.4)	4.1 (2.7-21.0)	0.002
HbA1C (%)	< 5.8%	5.8 (5.2-8.2)	6.3 (5.3-8.2)	5.7 (5.2-7.4)	0.21
Alk Phos (U/L)	1	110 (44-310)	66 (44-178)	155 (103-310)	0.01
Alk Phos (SD)	-2.0-2.0	1.2 (-1.5-4.8)	-0.3 (-1.5-4.7)	1.8 (-0.6-4.8)	0.07
Total bilirubin (µmol/L)2	0-20.5	6.8 (3.4-20.5)	5.1 (3.4-6.8)	8.6 (3.4-20.5)	0.003
AST (U/L)	9-39	23 (11-45)	20 (11-42)	27 (11-45)	0.39
ALT (U/L)	10-52	22 (10-58)	18 (10-45)	29 (12-58)	0.19
GGT (U/L)	5-64	14 (9-29)	12 (9-24)	19 (10-29)	0.07
Triglyceride (mmol/L)3	< 1.7	1.02 (0.36-2.55)	0.9 (0.64-2.55)	1.25 (0.36-2.35)	0.79

¹Reference range is age dependent;

²To convert from μmol/L to mg/dL multiply by 0.0585;

³To convert to mg/dL multiply by 88.5. Results of magnetic resonance imaging proton density fat fraction and key laboratory parameters for all subjects and stratified by cystic fibrosis transmembrane conductance regulator modulator (lumacaftor/ivacaftor) use. Data presented as median (range) or number (percent) as appropriate. CFTR: Cystic fibrosis transmembrane conductance regulator; PDFF: Proton density fat fraction; AST: Aspartate transaminase; ALT: Alanine transaminase; GGT: Gamma-glutamyltransferase.