Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

Table 1 Comparison of the clinical characteristics of patients with and without hepatocellular carcinoma

Characteristic	no-HCC group (n = 145)	HCC group (n = 121)	P value
Age ≥ 60 yr, n (%)	41 (28.3)	64 (52.9)	< 0.001
Male, n (%)	99 (68.3)	91 (75.2)	0.133
Etiology of liver cirrhosis, n (%)
HBV	101 (60.7)	76 (62.8)	0.363
HBV + alcohol	31 (21.4)	45 (37.2)	0.006
HBV + HEV	1 (0.6)	0 (0.0)	-
HBV + schistosome	1 (0.6)	0 (0.0)	-
Smoking history, n (%)	21 (14.5)	51 (42.1)	< 0.001
Family history of HBV-related HCC, n (%)	10 (6.9)	23 (19.0)	0.004
Medication history
Duration of NA treatment, yr, median (P25, P75)	3.9 (2.1, 5.8)	5.4 (2.3, 6.9)	0.067
LAM resistance, n (%)	18 (12.4)	27 (22.3)	0.021
HBsAg level, IU/L, median (P25, P75)	255.0 (56.0, 678.0)	269.0 (67.0, 656.0)	0.456
HBeAg positive, n (%)	37 (25.5)	21 (17.4)	0.136
HBV DNA negative, n (%)	67 (46.2)	39 (32.2)	0.033
ALB, U/L	36.29 ± 7.98	33.34 ± 6.62	0.002
ALT, U/L, median (P25, P75)	27.00 (18.00, 37.00)	32.00 (21.27, 62.00)	0.006
AST, U/L, median (P25, P75)	33.00 (23.00, 47.00)	44.50 (31.65, 96.85)	< 0.001
GGT, U/L, median (P25, P75)	33.00 (20.00, 46.00)	61.50 (32.75, 160.75)	< 0.001
ALP, U/L, median (P25, P75)	99.00 (73.00, 126.00)	134.50 (92.00, 198.85)	< 0.001
TB, μmol/L, median (P25, P75)	20.41 (13.81, 44.60)	24.46 (16.60, 42.80)	0.192
FBS, mmol/L, median (P25, P75)	5.17 ± 0.68	6.99 ± 1.31	0.025
Ascites, n (%)	33 (20.0)	43 (34.7)	0.022
Child-Pugh class, n (%)
A	81 (55.9)	55 (45.5)	0.001
B	38 (26.2)	26 (21.5)	0.561
C	26 (17.9)	40 (33.1)	0.002
AFP ≥ 20 μg/L, n (%)	14 (9.7)	56 (46.3)	< 0.001
PT s, median (P25, P75)	13.25 (11.80, 14.20)	13.51 (12.41, 15.02)	0.475

AFP: Alpha-fetoprotein; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FBS: Fasting blood sugar; GGT: Glutamyl transpeptidase; HBeAb: Hepatitis B e-antibody; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LAM: Lamivudine; PT: Prothrombin time; SD: Standard deviation; TB: Total bilirubin.

Table 2 Univariate logistic regression analysis of hepatitis B-related cirrhosis progressing to hepatocellular carcinoma in patients treated with nucleos(t)ide analogs

Characteristic	No-HCC group (n = 145)	HCC group (n = 121)	Univariate adjusted HR (95%CI)	P value
Age, yr
≥ 60	40 (27.6)	65 (52.9)	2.664 (1.606-4.418)	0.001
< 60	105 (72.4)	56 (46.3)
HBV + alcohol
Yes	31 (21.4)	45 (37.2)	2.384 (1.271-4.473)	0.007
No
Smoking history
Yes	21 (14.5)	51 (42.1)	4.073 (2.281-7.273)	< 0.001
No
Family history of HBV-related HCC
Yes	10 (6.9)	23 (19.0)	3.546 (1.573-7.998)	0.002
No
LAM resistance
Yes	18 (12.4)	27 (22.3)	2.284 (1.214-4.297)	0.011
No
HBV DNA negative
Yes	67 (46.2)	39 (32.2)	0.559 (0.339-0.922)	0.023
No
ALB (g/L)
< 35	67(46.2)	62(51.2)	1.223 (0.754-1.984)	0.414
≥ 35	78 (53.8)	59 (48.8)
ALT (U/L)
50-100	13 (9.0)	15 (12.4)	1.324 (0.612-2.866)	0.476
> 100	10 (7.0)	14 (11.6)	1.138(0.482-2.688)	0.768
AST (U/L)
40-80	32 (22.1)	24 (19.8)	0.919 (−0.713-0.514)	0.783
> 80	16 (10.3)	31 (29.8)	2.899 (0.436-1.767)	0.002
GGT (U/L)
60-120	15 (10.3)	20 (16.5)	1.853 (0.892-3.847)	0.098
> 120	8 (5.1)	28 (23.1)	5.663 (1.075-2.573)	0.001
ALP (U/L)
125-250	36(24.8)	45 (38.8)	1.609 (−0.062-1.028)	0.073
> 250	6 (1.4)	21 (17.4)	4.865 (0.667-2.993)	0.001
FBG (mmol/L)
≥ 6.16	19 (13.1)	37 (30.6)	3.3179 (0.587-1.902)	0.001
< 6.16
Ascites class
Yes	33 (22.8)	43 (35.5)	0.834 (−0.412-0.060)	0.142
No
Child-Pugh class
A	81 (58.6)	55 (37.9)	0.658 (−0.938-0.064)	0.091
B	38 (26.2)	26 (21.5)	0.671 (−0.981-0.112)	0.165
C	26 (17.9)	40 (33.1)	2.260 (0.247-1.427)	0.005

Data are n (%) or mean ± SD as shown. AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CI: Confidence interval; FBG: Fasting blood glucose; GGT: Glutamyl transpeptidase; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HR: Hazard ratio; LAM: Lamivudine. .

Table 3 Multivariate analysis of factors associated with hepatitis B-related cirrhosis progression to hepatocellular carcinoma in nucleos(t)ide analog-treated patients

Risk factor	β	SE	Wald	P value	OR (95%CI)
Age ≥ 60 yr	1.127	0.390	8.347	0.004	3.089 (1.437-6.631)
Smoking history	1.387	0.397	12.180	< 0.01	4.001 (1.836-8.716)
Family history of HBV-related HCC	1.911	0.860	4.938	< 0.05	6.763 (1.253-36.499)
LAM resistance	1.082	0.456	5.638	0.018	2.949 (1.207-7.208)
HBV DNA negative	-3.479	0.816	19.427	< 0.01	0.026 (0.007-0.139)
FBG ≥ 6.16 mmol/L	1.977	0.339	34.030	< 0.01	7.219 (3.716-14.024)

CI: Confidence interval; FBG: Fasting blood glucose; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LAM: Lamivudine OR: Odds ratio;; SE: Standard error.

Table 4 Comparison of the alpha-fetoprotein level distributions in patients with and without hepatocellular carcinoma, n (%)

AFP (μg/L)	No-HCC group (n = 145)	HCC group (n = 121)	P value
< 20	128 (88.27)	65 (53.72)	< 0.001
20-100	12 (8.27)	14 (11.57)	0.51
100-200	1 (0.69)	2 (2.17)	0.231
200-400	2 (1.38)	3 (2.48)	1
≥ 400	2 (1.38)	37 (30.58)	< 0.001

AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma.