Critical flicker frequency improves after alcohol detoxification and is associated with liver stiffness

Table 1 Patient characteristics of the total cohort (n = 108)

	Total (n = 108)		ALD (n = 93)		Non-ALD (n = 15)		P value
	mean	SD	mean	SD	mean	SD
CFF (Hz)	40.5	6.1	41.0	6.1	37.3	5.5	0.0282
Sex (male, %)	74.1		72.0		86.7		0.2343
Age (years)	53.7	13.8	51.5	12.8	67.0	12.7	0.0000
Alcohol consumption (g/day)	120.7	121.7	140.4	121.8	11.5	23.1	0.0001
Pack years	21	26	23	26	10	20	0.1400
HE (1 or 0, %)	11.1		9.7		20.0		0.2418
BMI (kg/m2)	25.8	4.7	25.7	5.1	26.3	2.5	0.7440
Laboratory
AST (U/L)	102	138	100	135	116	164	0.7010
ALT (U/L)	69	84	64	61	102	169	0.1115
GGT (U/L)	286	432	316	458	101	110	0.0850
AP (U/L)	106	55	107	56	103	51	0.8486
Bilirubin total (μmol/L)	34.2	81.6	34.2	86.0	34.4	45.8	0.9934
Quick (%)	96.8	27.6	98.8	26.5	82.0	31.6	0.0470
INR	1.06	0.32	1.03	0.24	1.32	0.62	0.0025
Urea (mmol/L)	5.12	3.74	4.69	3.25	7.89	5.41	0.0024
Creatinine (μmol/L)	77.8	46.0	72.5	41.5	109.6	57.5	0.0036
Sodium (mmol/L)	134.6	17.6	134.4	18.9	135.6	5.0	0.8189
Potassium (mmol/L)	4.1	1.9	4.2	2.0	3.9	0.6	0.6369
Lipase (U/L)	52.7	44.3	52.5	45.9	54.1	31.6	0.9117
PTT (seconds)	36.6	7.2	36.7	7.0	35.5	9.9	0.7658
Hemoglobin (g/L)	145.7	82.9	148.1	88.1	130.2	31.3	0.4555
Hematocrit (%)	39.2	8.3	39.4	8.2	37.9	8.7	0.5219
Erythrocytes (/pL)	4.14	0.79	4.15	0.75	4.11	1.04	0.8534
Leukocytes (/nL)	8.38	4.14	8.52	4.04	7.39	4.86	0.3592
Platelets (/nL)	202	117	215	114	123	114	0.1355
Ferritin (μg/L)	562	712	558	705	586	794	0.9082
CRP (mg/L)	130	251	132	262	121	176	0.8930
Albumin (g/L)	42.1	9.4	42.5	9.6	36.8	2.9	0.4121
Protein total (g/L)	71.9	7.0	72.6	6.5	64.3	8.7	0.0201
Glucose (mmol/L)	6.00	2.65	6.15	2.88	5.54	1.93	0.6388
Triglycerides (mmol/L)	1.83	2.40	1.86	2.46	1.21	0.69	0.7132
Cholesterol (mmol/L)	6.15	2.37	6.24	2.39	4.29	0.77	0.2617
Ultrasound
Spleen size (cm)	10.5	1.5	10.6	1.3	9.8	2.4	0.1235
Steatosis hepatis (0-3)	0.67	0.68	0.71	0.68	0.17	0.41	0.0582
Ascites (1 or 0, %)	23.5		22.1		37.5		0.3335
Signs of cirrhosis (1 or 0, %)	28.2		28.6		25.0		0.8333
Liver stiffness (kPa)	14.78	17.34	14.45	17.50	20.97	15.04	0.5304

CFF: Critical flicker frequency; HE: Hepatic encephalopathy; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AP: Alkaline phosphatase; INR: International normalized ratio; PTT: Partial thromboplastin time; CRP: C-reactive protein; ALD: Alcohol-related liver disease.

Table 2 Spearman correlation coefficient with all patients (alcohol-related liver disease and non-alcohol-related liver disease, n = 108)

Spearman correlation coefficient	CFF, r	P value
Sex (female = 0, male = 1)	0.084	0.387
Age (years)	-0.202	0.036
Alcohol consumption (g/day)	0.122	0.233
Pack years	0.249	0.031
HE (1 or 0)	-0.179	0.064
BMI (kg/m2)	-0.169	0.266
AST (U/L)	-0.095	0.339
ALT (U/L)	0.017	0.866
GGT (U/L)	-0.115	0.258
AP (U/L)	-0.011	0.915
Bilirubin total (μmol/L)	-0.173	0.083
Quick (%)	0.126	0.208
INR	-0.107	0.289
Urea (mmol/L)	-0.065	0.514
Creatinine (μmol/L)	-0.176	0.070
Sodium (mmol/L)	-0.026	0.799
Potassium (mmol/L)	0.259	0.010
Lipase (U/L)	0.063	0.550
PTT (seconds)	0.141	0.434
Hemoglobin (g/L)	0.149	0.129
Hematocrit (%)	0.103	0.294
Erythrocytes (/pL)	0.176	0.073
Leukocytes (/nL)	0.143	0.149
Platelets (/nL)	0.318	0.001
Ferritin (μg/μL)	-0.133	0.254
CRP (mg/L)	-0.025	0.807
Spleen size (cm)	0.000	0.997
Ascites (1 or 0)	-0.176	0.108
Steatosis hepatis (0-3)	0.072	0.537
Cirrhosis (1 or 0)	-0.170	0.116
Liver stiffness (kPa)	-0.263	0.042

CFF: Critical flicker frequency; HE: Hepatic encephalopathy; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AP: Alkaline phosphatase; INR: International normalized ratio; PTT: Partial thromboplastin time; CRP: C-reactive protein.

Table 3 Patient characteristics of the detoxification cohort (n = 57) for patients with critical flicker frequency measurements before and after detoxification (n = 44)

Parameter	Before detox (n = 57)1		Before (n = 44)2		After (n = 44)2		P value
	mean	SD	mean	SD	mean	SD
CFF (Hz)	41.8	5.9	40.7	5.4	43.7	4.7	0.0001
CFF below 39 Hz (%)	34		40		14
Sex (male, %)	70.7		70.5
Age (years)	50.6	12.9	50.4	11.8
Alcohol consumption (g/day)	136.7	120.3	132.2	100.8
Duration of drinking (years)	16.7	9.7	16.8	9.4
Packyears	20.2	20.8	22.1	19.4
HE (1 or 0, %)	5.2		2.3
BMI (kg/m2)	26.7	5.1	26.3	5.8
AST (U/L)	96	139	90	88	73	77	0.0591
ALT (U/L)	71	70	66	49	67	52	0.0379
GGT (U/L)	335	497	371	554	310	419	0.0386
AP (U/L)	105	54	107	54	80	42	0.0001
Bilirubin total (μmol/L)	30.4	97.5	15.4	22.1	10.1	8.6	0.2091
Quick (%)	104.6	19.2	106.6	17.0	106.2	18.2	0.3481
INR	0.98	0.18	0.96	0.14	0.96	0.16	0.5897
Urea (mmol/L)	4.18	2.55	3.50	1.56	4.03	1.42	0.4524
Creatinine (μmol/L)	66.3	28.3	60.1	17.7	75.1	15.9	0.0010
Sodium (mmol/L)	136	15	138	4	139	4	0.0466
Potassium (mmol/L)	4.0	0.5	3.9	0.4	4.0	0.3	0.4057
Lipase (U/L)	47.3	26.7	49.7	28.0	142.3	229.5	0.2654
PTT (seconds)	35.8	5.0	35.3	4.4	36.1	5.1	0.2407
Hemoglobin (g/L)	147	44	141	13	134	18	0.0039
Hematocrit (%)	41.3	8.1	40.3	3.9	38.5	5.2	0.0399
Erythrocytes (/pL)	4.3	0.6	4.3	0.5	4.0	0.6	0.0044
Leukocytes (/nL)	8.0	2.7	7.7	2.7	7.6	2.2	0.2333
Platelets (/nL)	224	87	222	78	210	69	0.3502
Ferritin (μg/L)	470	550	536	605	410	463	0.0527
CRP (mg/L)	75	168	70	171	126	195	0.9390
Alcohol (g/L)	1.05	1.19	1.16	1.24	0.00	0.01	0.0003
Spleen size (cm)	10.3	0.9	10.3	0.8
Ascites (1 or 0, %)	9.1		7.3
Steatosis hepatis (0-3)	0.83	0.71	0.85	0.66
Signs of cirrhosis (1 or 0, %)	18.5		15.0
Liver stiffness (kPa)	12.1	15.8	10.7	14.5	6.5	4.4	0.1015

¹Total.

²Follow-up after detox.

CFF: Critical flicker frequency; HE: Hepatic encephalopathy; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AP: Alkaline phosphatase; INR: International normalized ratio; PTT: Partial thromboplastin time; CRP: C-reactive protein.

Table 4 Spearman correlations for critical flicker frequency before and after alcohol detoxification (n = 44)

Parameter	CFF1 (Hz)			CFF2 (Hz)
	r	P value	n	r	P value	n
CFF1 (Hz)	1.00	< 0.001	44	0.59	< 0.001	44
CFF2 (Hz)	0.59	< 0.001	44	1.00	< 0.001	44
Sex (female = 0, male = 1)	0.08	0.586	44	0.15	0.347	44
Age (years)	-0.13	0.385	44	-0.10	0.518	44
Alcohol consumption (g/day)	0.18	0.263	40	0.06	0.717	40
Pack years	-0.10	0.591	30	0.10	0.606	30
BMI (kg/m2)	-0.55	0.015	19	-0.29	0.223	19
AST (U/L)	-0.10	0.530	44	-0.02	0.936	25
ALT (U/L)	0.03	0.829	44	-0.04	0.845	24
GGT (U/L)	-0.22	0.169	39	-0.03	0.886	24
AP (U/L)	0.01	0.947	44	0.02	0.943	25
Bilirubin total (μmol/L)	-0.13	0.419	42	0.18	0.415	23
Quick (%)	0.23	0.136	44	0.23	0.319	20
INR	-0.25	0.105	43	-0.26	0.274	20
Urea (mmol/L)	-0.10	0.544	43	-0.27	0.233	21
Creatinine (μmol/L)	-0.12	0.426	44	-0.31	0.176	21
Sodium (mmol/L)	0.01	0.971	41	-0.53	0.027	17
Potassium (mmol/L)	0.19	0.243	41	-0.26	0.315	17
Lipase (U/L)	-0.13	0.435	39	0.07	0.867	8
PTT (seconds)	0.12	0.681	14	0.09	0.727	17
Hemoglobin (g/L)	0.15	0.344	44	0.19	0.364	25
Hematocrit (%)	0.12	0.432	44	0.14	0.495	25
Erythrocytes (/pL)	0.25	0.096	44	0.09	0.671	25
Leukocytes (/nL)	0.13	0.415	44	-0.31	0.130	25
Platelets (/nL)	0.48	0.001	44	-0.29	0.163	25
Ferritin (μg/L)	-0.22	0.204	35	0.17	0.571	13
CRP (mg/L)	-0.12	0.466	42	0.18	0.451	20
Alcohol (g/L)	-0.02	0.902	38	-0.02	0.937	20
Spleen size (cm)	0.02	0.883	39	0.20	0.221	39
Ascites (1 or 0)	-0.15	0.361	41	-0.25	0.122	41
Steatosis hepatis (0-3)	0.04	0.823	40	0.09	0.595	40
Cirrhosis (1 or 0)	-0.11	0.469	44	-0.13	0.399	44
Liver stiffness (kPa)	-0.04	0.819	35	0.64	0.033	11

CFF1: Critical flicker frequency before alcohol detoxification; CFF2: Critical flicker frequency after alcohol detoxification; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AP: Alkaline phosphatase; INR: International normalized ratio; PTT: Partial thromboplastin time; CRP: C-reactive protein.