The Predictive Value of Liver Tests for the Presence of Liver Metastases

Figures & data

Table 1. Patient characteristics and biochemical liver test abnormalities in patients with and without lung cancer liver metastases.

Patient characteristics	Patients with liver metastases (n = 80)	Matched controls (n = 69)	p-value
Age (years)	65 (58, 73)	70 (60, 73)	0.235
BMI	23.72 (20.22, 28.48)	25.47 (21.73, 28.92)	0.144
Gender:			0.930
– Male	40 (50.00%)	34 (49.30%)
– Female	40 (50.00%)	35 (50.70%)
Race and ethnicity			0.130
– White	37 (46.30%)	43 (62.30%)
– Black	28 (35.00%)	21 (30.40%)
– Latina	1 (1.30%)	1 (1.40%)
– Asian	11 (13.80%)	2 (2.90%)
– Other	3 (3.80%)	2 (2.90%)
Bone metastases	43 (53.80%)	24 (34.80%)	0.020^†
Prior or current cancer therapy:			0.047^†
– None	43 (53.80%)	24 (34.80%)
– Chemotherapy	17 (21.30%)	13 (18.80%)
– Target or immunotherapy	6 (7.50%)	9 (13.00%)
– Chemo and targeted or immunotherapy	14 (17.50%)	23 (33.30%)
Presenting symptom of liver metastases:
– None	65 (81.25%)
– Abdominal pain	11 (13.75%)
– Weight loss	4 (5.00%)
– Encephalopathy	3 (3.75%)
– Jaundice	1 (1.25%)
– Scleral icterus	1 (1.25%)
AST	34.00 (20.00, 61.50)	20.00 (15.00, 26.00)	<0.001^†
ALT	32.50 (18.50, 54.50)	21.00 (15.00, 27.00)	<0.001^†
ALP	122.50 (89.00, 235.50)	89.00 (75.00, 112.00)	<0.001^†
TB	0.50 (0.30, 0.90)	0.40 (0.30, 0.60)	0.036^†
Elevation above normal range:
– AST	41 (51.20%)	9 (13.00%)	<0.001^†
– ALT	24 (30.00%)	6 (8.70%)	0.001^†
– ALP	44 (55.00%)	16 (23.20%)	<0.001^†
– TB	8 (10.00%)	1 (1.40%)	0.029^†
AST × ULN:			0.284
– >1 to <1.25	8 (19.50%)	4 (50.00%)
– ≥1.25 to <1.5	3 (7.30%)	1 (12.50%)
– ≥1.5 to <2	12 (29.30%)	2 (25.00%)
– ≥2 to <3	7 (17.10%)	1 (12.50%)
– ≥3	11 (26.80%)	0 (0.00%)
ALT × ULN:			0.487
– >1 to <1.25	6 (25.00%)	3 (50.00%)
– ≥1.25 to <1.5	6 (25.00%)	2 (33.30%)
– ≥1.5 to <2	3 (12.50%)	1 (16.70%)
– ≥2 to <3	6 (25.00%)	0 (0.00%)
– ≥3	3 (12.50%)	0 (0.00%)
ALP × ULN:			0.145
– >1 to <1.25	10 (23.30%)	5 (33.30%)
– ≥1.25 to <1.5	10 (23.30%)	5 (33.30%)
– ≥1.5 to <2	4 (9.30%)	3 (20.00%)
– ≥2 to <3	5 (11.60%)	2 (13.30%)
– ≥3	14 (32.60%)	0 (0.00%)

† Statistically significant (p ≤ 0.05).

Statistics presented as median (P25, P75) or frequency (%).

Elevation above normal range defined as AST >33, ALT >49, ALP >117, TB >1.2; Liver tests × ULN, percentage of patients within range of elevation listed out of total number of patients with elevated liver tests.

ULN: Upper limit of normal.

Table 2. Patient characteristics and biochemical liver test abnormalities in patients with and without breast cancer liver metastasis.

Patient characteristics	Patients with liver metastasis (n = 50)	Matched controls (n = 58)	p-value
Age (years)	59 (51, 66)	52 (47, 64)	0.025^†
BMI	28.63 (23.31, 36.11)	28.51 (24.22, 32.15)	0.781
Gender:			0.279
– Male	1 (2.00%)	0 (0.00%)
– Female	49 (98.00%)	58 (100.00%)
Race and ethnicity:			0.005^†
– White	8 (16.00%)	25 (43.10%)
– Black	37 (74.00%)	24 (41.40%)
– Asian	1 (2.00%)	4 (6.90%)
– Other	4 (8.00%)	5 (8.60%)
Bone metastases	38 (76.00%)	10 (17.20%)	<0.001^†
Prior or current cancer therapy:			0.316
– None	4 (8.00%)	13 (22.41%)
– Chemotherapy	12 (24.00%)	10 (17.24%)
– Hormone therapy	8 (16.00%)	5 (8.62%)
– Chemo and hormone therapy	13 (26.00%)	11 (18.97%)
– Chemo & targeted or immunotherapy	3 (6.00%)	7 (12.07%)
– Hormone and targeted or immunotherapy	1 (2.00%)	1 (1.72%)
– Chemo, hormone and targeted or immunotherapy	9 (18.00%)	11 (18.97%)
Presenting symptom of liver metastases:
– None	39 (78.00%)
– Weight loss	2 (4.00%)
– Ascites	1 (2.00%)
– Abdominal pain	8 (16.00%)
– Other	0 (0.00%)
AST	40.50 (25.00, 106.00)	19.00 (15.00, 26.00)	<0.001^†
ALT	30.00 (22.00, 50.00)	21.00 (16.00, 30.00)	<0.001^†
ALP	122.50 (95.00, 211.00)	77.50 (59.00, 113.00)	<0.001^†
TB	0.40 (0.30, 0.80)	0.40 (0.30, 0.50)	0.022^†
Elevation above normal range:
– AST	30 (60.00%)	8 (13.80%)	<0.001^†
– ALT	13 (26.00%)	3 (5.20%)	0.002^†
– ALP	28 (56.00%)	13 (22.40%)	<0.001^†
– TB	7 (14.00%)	2 (3.45%)	0.048^†
AST × ULN:			0.03^†
– >1 to <1.25	5 (16.70%)	4 (50.00%)
– ≥1.25 to <1.5	2 (6.70%)	2 (25.00%)
– ≥1.5 to <2	6 (20.00%)	1 (12.50%)
– ≥2 to <3	4 (13.30%)	1 (12.50%)
– ≥3	13 (43.30%)	0 (0.00%)
ALT × ULN:			0.186
– >1 to <1.25	3 (23.10%)	3 (100.00%)
– ≥1.25 to <1.5	3 (23.10%)	0 (0.00%)
– ≥1.5 to <2	2 (15.40%)	0 (0.00%)
– ≥2 to <3	0 (0.00%)	0 (0.00%)
– ≥3	5 (38.50%)	0 (0.00%)
ALP × ULN:			0.136
– >1 to <1.25	7 (25.00%)	6 (46.20%)
– ≥1.25 to <1.5	3 (10.70%)	4 (30.80%)
– ≥1.5 to <2	6 (21.40%)	2 (15.40%)
– ≥2 to <3	6 (21.40%)	1 (7.70%)
– ≥3	6 (21.40%)	0 (0.00%)

† Statistically significant (p ≤ 0.05).

Statistics presented as median (P25, P75) or frequency (%).

Elevation above normal range defined as AST >33, ALT >49, ALP >117, TB >1.2; Liver tests × ULN, percentage of patients within range of elevation listed out of total number of patients with elevated liver tests.

ULN: Upper limit of normal.

Table 3. Patient characteristics and biochemical liver test abnormalities in patients with and without colorectal cancer liver metastases.

Patient characteristics	Patients with liver metastases (n = 68)	Matched controls (n = 54)	p-value
Age (years)	61 (52, 70)	69 (57, 75)	0.021^†
BMI	26.37 (22.71, 30.64)	26.31 (22.83, 30.97)	0.836
Gender:			0.203
– Male	35 (51.50%)	34 (63.00%)
– Female	33 (48.50%)	20 (37.00%)
Race and ethnicity:			0.564
– White	34 (50.00%)	25 (46.30%)
– Black	25 (36.80%)	18 (33.30%)
– Latina	1 (1.50%)	2 (3.70%)
– Asian	2 (2.90%)	5 (9.30%)
– Other	6 (8.80%)	4 (7.40%)
Bone metastases	5 (7.40%)	1 (1.90%)	0.163
Prior or current cancer therapy:			0.475
– None	46 (67.60%)	38 (70.40%)
– Chemotherapy	13 (19.10%)	10 (18.50%)
– Target or immunotherapy	0 (0.00%)	1 (1.90%)
– Chemo and hormone therapy	0 (0.00%)	1 (1.90%)
– Chemo and targeted or immunotherapy	9 (13.20%)	4 (7.40%)
Presenting symptom of liver metastases:
– Abdominal pain	33 (48.53%)
– Weight loss	23 (33.82%)
– None	19 (27.94%)
– Hematochezia	12 (17.65%)
– Nausea and vomiting	7 (10.29%)
– Jaundice	2 (2.94%)
– Melena	1 (1.47%)
AST	36.00 (20.50, 88.00)	20.50 (14.00, 30.00)	<0.001^†
ALT	26.00 (19.00, 55.50)	23.50 (13.00, 34.00)	0.018^†
ALP	135.00 (87.50, 285.50)	93.50 (72.00, 115.00)	<0.001^†
TB	0.50 (0.40, 0.95)	0.40 (0.30, 0.60)	0.062
Elevation above normal range:
– AST	35 (51.50%)	12 (22.20%)	0.001^†
– ALT	20 (29.40%)	3 (5.60%)	0.001^†
– ALP	38 (55.90%)	13 (24.10%)	<0.001^†
– TB	10 (14.70%)	2 (3.70%)	0.043^†
AST × ULN:			0.039^†
– >1 to <1.25	3 (8.60%)	4 (40.00%)
– ≥1.25 to <1.5	4 (11.40%)	2 (20.00%)
– ≥1.5 to <2	7 (20.00%)	3 (30.00%)
– ≥2 to <3	8 (22.90%)	1 (10.00%)
– ≥3	13 (37.10%)	0 (0.00%)
ALT × ULN:			0.531
– >1 to <1.25	3 (15.00%)	1 (33.30%)
– ≥1.25 to <1.5	5 (25.00%)	0 (0.00%)
– ≥1.5 to <2	5 (25.00%)	1 (33.30%)
– ≥2 to <3	2 (10.00%)	1 (33.30%)
– ≥3	5 (25.00%)	0 (0.00%)
ALP × ULN:			0.001^†
– >1 to <1.25	4 (10.50%)	7 (53.80%)
– ≥1.25 to <1.5	4 (10.50%)	4 (30.80%)
– ≥1.5 to <2	7 (18.40%)	1 (7.70%)
– ≥2 to <3	12 (31.60%)	1 (7.70%)
– ≥3	11 (28.90%)	0 (0.00%)

† Statistically significant (p ≤ 0.05).

Statistics presented as median (P25, P75) or frequency (%).

Elevation above normal range defined as AST >33, ALT >49, ALP >117, TB >1.2; Liver tests × ULN, percentage of patients within range of elevation listed out of total number of patients with elevated liver tests.

ULN: Upper limit of normal.

Table 4. Patient characteristics and biochemical liver test abnormalities in patients with and without melanoma liver metastases.

Patient characteristics	Patients with liver metastases (n = 17)	Matched controls (n = 16)	p-value
Age (years)	62 (56, 71)	62 (48, 71)	0.769
BMI	27.48 (23.89, 30.45)	26.18 (24.96, 33.11)	0.986
Gender:			0.353
– Male	9 (52.90%)	11 (68.80%)
– Female	8 (47.10%)	5 (31.30%)
Race and ethnicity:			0.374
– White	15 (88.20%)	13 (81.30%)
– Black	0 (0.00%)	2 (12.50%)
– Asian	1 (5.90%)	1 (6.30%)
– Other	1 (5.90%)	0 (0.00%)
Bone metastases	6 (35.30%)	0 (0.00%)	0.009^†
Prior or current cancer therapy:			0.504
– None	6 (35.29%)	4 (25.00%)
– Chemotherapy	0 (0.00%)	0 (0.00%)
– Hormone therapy	0 (0.00%)	0 (0.00%)
– Targeted or immunotherapy	11 (64.71%)	11 (68.75%)
– Hormone and targeted or immunotherapy	0 (0.00%)	1 (6.25%)
Presenting symptom of liver metastases:
– None	8 (47.10%)
– Jaundice	1 (5.90%)
– Ascites	1 (5.90%)
– Encephalopathy	2 (11.80%)
– Abdominal pain	5 (29.40%)
– Other	0 (0.00%)
AST	46.00 (33.00, 82.00)	27.50 (23.00, 32.50)	0.006^†
ALT	49.00 (29.00, 86.00)	33.00 (23.50, 37.50)	0.194
ALP	161.00 (116.00, 311.00)	95.50 (70.50, 105.00)	<0.001^†
TB	0.60 (0.30, 1.10)	0.60 (0.35, 0.80)	0.865
Elevation above normal range:
– AST	12 (70.60%)	3 (18.80%)	0.003^†
– ALT	8 (47.10%)	2 (12.50%)	0.031^†
– ALP	12 (70.60%)	3 (18.80%)	0.003^†
– TB	4 (23.53%)	0 (0.00%)	0.038^†
AST × ULN:			0.525
– >1 to <1.25	2 (16.70%)	2 (66.70%)
– ≥1.25 to <1.5	2 (16.70%)	1 (33.30%)
– ≥1.5 to <2	1 (8.30%)	0 (0.00%)
– ≥2 to <3	3 (25.00%)	0 (0.00%)
– ≥3	4 (33.30%)	0 (0.00%)
ALT × ULN:			0.782
– >1 to <1.25	3 (33.30%)	1 (50.00%)
– ≥1.25 to <1.5	1 (11.10%)	0 (0.00%)
– ≥1.5 to <2	1 (11.10%)	1 (50.00%)
– ≥2 to <3	1 (11.10%)	0 (0.00%)
– ≥3	3 (33.30%)	0 (0.00%)
ALP × ULN:			0.437
– >1 to <1.25	2 (16.70%)	2 (66.70%)
– ≥1.25 to <1.5	2 (16.70%)	1 (33.30%)
– ≥1.5 to <2	2 (16.70%)	0 (0.00%)
– ≥2 to <3	2 (16.70%)	0 (0.00%)
– ≥3	4 (33.30%)	0 (0.00%)

† Statistically significant (p ≤ 0.05).

Statistics presented as median (P25, P75) or frequency (%).

Elevation above normal range defined as AST >33, ALT >49, ALP >117, TB >1.2; Liver test × ULN, percentage of patients with elevations within range listed out of total number of patients with elevated liver tests.

ULN: Upper limit of normal.

Table 5. Screening tests for liver metastases.

Liver enzyme elevation	Sensitivity (%)	Specificity (%)	PV+	PV-	AUC
Lung cancer
AST >ULN	51.25	86.96	0.82	0.61	0.69
ALT >ULN	30.00	91.30	0.80	0.53	0.61
ALP >ULN	55.00	76.81	0.73	0.60	0.66
AST ≥1.5 × ULN	73.17	62.50	–	–	0.74
ALT ≥1.5 × ULN	50.00	83.33	–	–	0.72
ALP ≥1.5 × ULN	53.49	66.67	–	–	0.66
Breast cancer
AST >ULN	60.00	86.21	0.79	0.71	0.73
ALT >ULN	26.00	94.00	0.81	0.60	0.60
ALP >ULN	56.00	77.59	0.68	0.67	0.67
AST ≥1.5 × ULN	76.67	75.00	–	–	0.80
ALT ≥1.25 × ULN	76.92	100.00	–	–	0.88
ALP ≥1.5 × ULN	64.29	76.92	–	–	0.73
Colon cancer
AST >ULN	51.47	77.78	0.74	0.56	0.65
ALT >ULN	29.41	94.44	0.87	0.52	0.62
ALP >ULN	55.88	75.93	0.75	0.58	0.66
AST ≥2 × ULN	60.00	90.00	–	–	0.81
ALT ≥1.25 × ULN	85.00	33.33	–	–	0.57
ALP ≥1.5 × ULN	78.95	84.62	–	–	0.86
Melanoma
AST >ULN	70.59	81.25	80.00	0.72	0.76
ALT >ULN	47.06	87.50	80.00	0.61	0.67
ALP >ULN	70.59	81.25	80.00	0.72	0.76
AST ≥1.5 × ULN	66.67	100.00	–	–	0.86
ALT ≥1.25 × ULN	66.67	50.00	–	–	0.67
ALP ≥1.5 × ULN	66.67	100.00	–	–	0.86

ULN range for each liver test: AST >33, ALT >49 and ALP >117.

AUC: Area under the curve; PV+: Positive predictive value; PV-: Negative predictive value; ULN: Upper limit of normal.