Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma

Table 1 Patient characteristics for cirrhotic hepatocellular carcinoma, n (%)

Variable	BMI < 25 kg/m2 (n = 654)	BMI 25.0-29.9 kg/m2 (n = 767)	BMI ≥ 30 kg/m2 (n = 841)	P value
Age (yr)	62.0 ± 8.9	62.6 ± 8.7	62.5 ± 8.4	0.43
Male	522 (79.8)	650 (84.7)	620 (73.7)	< 0.001
Race
White	437 (66.8)	599 (78.6)	697 (83.1)	< 0.001
Black	166 (25.4)	110 (14.4)	98 (11.7)
Hispanic	14 (2.1)	27 (3.5)	31 (3.7)
Asian	24 (3.7)	14 (1.8)	9 (1.1)
Other	13 (2.0)	12 (1.6)	4 (0.48)
Diabetes	144 (22.1)	256 (33.5)	440 (52.3)	< 0.001
Hypertension	325 (49.8)	450 (58.8)	579 (68.8)	< 0.001
Dyslipidemia	127 (19.4)	192 (25.1)	252 (30.0)	< 0.001
Coronary artery disease	105 (16.1)	110 (14.4)	181 (21.5)	< 0.001
Peripheral vascular disease	74 (11.3)	76 (9.9)	83 (9.9)	0.6
ALT (Units/L)	63.0 ± 67.9	64.3 ± 68.8	56.8 ± 112.1	0.19
AST (Units/L)	103.5 ± 147.4	94.3 ± 99.0	90.6 ± 183.2	0.25
Total bilirubin (mg/dL)	2.1 ± 3.0	2.3 ± 3.7	2.2 ± 3.2	0.62
Alkaline phosphatase (Units/L)	161.3 ± 142.8	144.7 ± 108.2	146.6 ± 104.6	0.017
Albumin (g/dL)	3.15 ± 0.67	3.24 ± 0.69	3.16 ± 0.63	0.015
Platelets (k/cumm)	146.9 ± 96.8	122.4 ± 74.5	123.5 ± 76.1	< 0.001
Creatinine (md/dL)	1.03 ± 0.84	1.02 ± 0.63	1.07 ± 0.71	0.37
Sodium (mEq/L)	135.7 ± 4.1	136.6 ± 3.9	136.8 ± 3.8	< 0.001
INR	1.3 ± 0.31	1.3 ± 0.41	1.3 ± 0.39	0.1
MELD-Na score	14.3 ± 5.6	14.0 ± 5.5	14.3 ± 5.4	0.72
Alcohol abuse	342 (53.4)	380 (50.1)	312 (37.8)	< 0.001
Etiology of chronic liver disease
All HCV	465 (71.2)	474 (61.8)	409 (48.6)	< 0.001
HCV with known SVR	158 (34)	183 (38.6)	167 (40.8)	0.07
Alcohol alone	82 (12.5)	106 (13.8)	123 (14.6)	0.51
NAFLD	34 (5.2)	108 (14.1)	230 (27.3)	< 0.001
AIH/PBC/PSC	7 (1.1)	12 (1.6)	14 (1.7)	0.61
HBV	32 (4.9)	35 (4.6)	19 (2.3)	0.01
HC/A1AT	4 (0.61)	7 (0.91)	15 (1.8)	0.08
Child-Pugh classification
Child A	277 (43.0)	328 (43.5)	336 (40.8)	0.58
Child A-B	15 (2.3)	26 (3.4)	25 (3.0)
Child B	263 (40.8)	284 (37.7)	345 (41.9)
Child C	89 (13.8)	116 (15.4)	118 (14.3)
Complications
Ascites	300 (54.1)	383 (49.9)	404 (48.0)	0.31
Encephalopathy	170 (26.0)	252 (32.9)	302 (35.9)	< 0.001
Varices	259 (39.6)	368 (48.0)	427 (50.8)	< 0.001
Portal vein thrombus	148 (22.6)	164 (21.4)	181 (21.5)	0.83

BMI: Body mass index; MELD: Model for end-stage liver disease; HCV: Hepatitis C virus; NAFLD: Non-alcoholic fatty liver disease; AIH: Autoimmune hepatitis; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; HBV: Hepatitis B virus; HC: Hemochromatosis; A1AT: Alpha 1 antitrypsin deficiency; SVR: Sustained virologic response; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio.

Table 2 Tumor, diagnosis, and treatment characteristics for cirrhotic hepatocellular carcinoma, n (%)

Variable	BMI < 25 kg/m², (n = 654)	BMI 25.0-29.9 kg/m², (n = 767)	BMI ≥ 30 kg/m², (n = 841)	P value
Tumor size (cm)	5.1 ± 4.2	4.2 ± 3.0	4.2 ± 3.2	< 0.001
AFP (ng/mL) category
< 20	269 (43.7)	399 (54.8)	417 (51.9)	< 0.001
20-200	125 (20.3)	164 (22.5)	178 (22.1)
> 200	221 (35.9)	165 (22.7)	209 (26.0)
Tumor stage
Single	230 (35.2	331 (43.2)	386 (46.0)	< 0.001
3 tumors < 3 cm	88 (13.5)	97 (12.7)	116 (13.8)
Large multinodular	142 (21.7)	173 (22.6)	153 (18.2)
Vascular invasion or extrahepatic spread	193 (29.6)	165 (21.5)	184 (21.9)
Anatomic stage
Stage I	173 (32.8)	239 (41.0)	293 (43.3)	< 0.001
Stage II	147 (27.9)	169 (29.0)	179 (26.5)
Stage IIIA	36 (6.8)	38 (6.5)	49 (7.2)
Stage IIIB	55 (10.4)	38 (6.5)	65 (9.6)
Stage IIIC + IVA + IVB	116 (22.0)	99 (17.0)	90 (13.3)
Tumor outside of Milan criteria	363 (55.6)	370 (48.3)	397 (47.3)	0.003
Tumor differentiation
Well	70 (27.1)	109 (31.5)	116 (32.6)	0.15
Moderate	128 (49.6)	175 (50.6)	184 (51.7)
Poor	53 (20.6)	59 (17.0)	54 (15.2)
Undifferentiated/anaplastic	7 (2.7)	3 (0.9)	2 (0.5)
How was HCC diagnosed?
Part of screening	236 (45.8)	285 (48.6)	350 (54.8)	0.007
Incidental	120 (23.3)	120 (20.5)	116 (18.2)	0.098
Symptoms work up	246 (47.8)	244 (41.6)	241 (37.7)	0.003
Evidence of screening within 2 years	190 (36.8)	259 (44.0)	334 (52.1)	< 0.001
Liver transplantation	61 (9.3)	134 (17.5)	150 (17.8)	< 0.001
Palliative care/hospice	268 (41.0)	271 (35.3)	265 (31.5)	< 0.001

BMI: Body mass index; AFP: Alpha fetoprotein; HCC: Hepatocellular carcinoma.

Table 3 Multivariable cox regression model of cirrhotic patient and tumor risk factors associated with survival after hepatocellular carcinoma diagnosis

Characteristic	Adjusted HR (95%CI)	P value
Age	1.0 (0.99-1.01)	0.58
Female (Ref.: Male)	0.94 (0.76-1.16)	0.57
Race (Ref.: White)		0.72
Asian	0.98 (0.55-1.76)
Black	0.87 (0.70-1.08)
Hispanic	0.94 (0.57-1.55)
Other	0.81 (0.45-1.45)
BMI classification (kg/m²) (Ref.: BMI < 25)		0.36
BMI 25.0-29.9	0.87 (0.72-1.06)
BMI ≥ 30	0.90 (0.73-1.11)
Diabetes	0.96 (0.81-1.14)	0.64
Alcohol abuse	1.10 (0.90-1.34)	0.35
HCV SVR	0.27 (0.21-0.35)	< 0.0001
Tumor size (cm)	1.08 (1.05-1.12)	< 0.0001
AFP (ng/mL) (Ref.: < 20)		< 0.0001
20-200	1.51 (1.23-1.85)
> 200	1.93 (1.61-2.32)
Tumor within Milan criteria	0.59 (0.48-0.72)	< 0.0001
Liver transplantation	0.10 (0.06-0.16)	< 0.0001
Any method of screening within 2 years before HCC diagnosis (Ref.: No)		0.0634
Yes	1.01 (0.85-1.21)
Unknown	0.79 (0.63-0.99)

BMI: Body mass index; AFP: Alpha fetoprotein; HCC: Hepatocellular carcinoma; HR: Hazard ratios; HCV: Hepatitis C virus; SVR: Sustained virologic response.