Improvement of improve the two years survival rate of patients with hepatitis B virus-related primary liver cancer after antiviral treatment

doi:10.3877/cma.j.issn.1674-1358.2016.03.011

Abstract

Abstract:

Objective

To investigate the relationship between HBV DNA, antiviral therapy and prognosis of patients with hepatitis B virus-related primary liver cancer (HBV-PLC).

Methods

Total of 632 patients diagnosed as HBV-PLC between January 2008 and December 2012 in Beijing Ditan Hospital, Capital Medical University were analyzed, retrospectively. All the baseline data of the patients were recorded before treatment including the virus index. According to the antiviral therapy or not before diagnosis, all the patients were divided into the antiviral (230 cases) and non-antiviral groups (402 cases). Furthermore, the 402 cases without antiviral therapy were divided into the antiviral (325 cases) and non-antiviral groups (77 cases). The Kaplan-Meier survival analysis was perfomed to compare the overall survival of the patients with HBV-PLC in different groups.

Results

Multivariate Cox analysis showed that tumor number and diameter, the portal vein tumor thrombus, aspertate aminotransferase, gamma glutamyl transpeptidase, alpha fetoprotein, neutrophils/lymphocyte ratio, BCLC staging and HBV DNA levels were the independent risk factors affecting the prognosis of HBV PLC [Exp (β)]: 1.309, 1.734, 1.599, 1.002, 1.001, 1.486, 1.001, 1.486 and 1.282, respectively. The Kaplan-Meier survival analysis showed that the HBV DNA negative group had higher two-year survival rate than HBV DNA positive group (χ² = 7.297, P = 0.007). Stratificationl analysis showed that the survival of rates of HBV DNA < 500 IU/ml group and HBV DNA ≥ 10⁵ IU/ml group were with significant difference (χ² = 6.735, P = 0.009). Compared with non-antiviral therapy before diagnosis, antiviral therapy could significantly increase the two-year survival rate (χ² = 33.792, P = 0.000). Meanwhile, after the antiviral therapy in the observation period after diagnosis could also increase the rate of two-year survival patients with HBV-PLC (χ² = 33.179, P = 0.000).

Conclusions

The HBV DNA level is closely related to the prognosis of patients with HBV-PLC. In addition, antiviral treatment could improve the two-year survival rates of patients with HBV-PLC.

Key words: Hepatitis B virus, Primary liver cancer, Prognosis, Viral load, Antiviral therapy

Xieqiong Ye, Fangyuan Gao, Le Sun, Rui Wang, Jialiang Cheng, Mingfan Geng, Xiaoshu Li, Xianbo Wang. Improvement of improve the two years survival rate of patients with hepatitis B virus-related primary liver cancer after antiviral treatment[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2016, 10(03): 304-310.

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指标		死亡组（317例）	生存组（315例）	统计量	P值
男/女		281/36	251/64	χ² = 9.525	0.002
年龄（岁）		52.6 ± 9.3	55.1 ± 10.0	t =-3.189	0.001
饮酒史		150	95	χ² = 19.599	0.000
HCC家族史		55	42	χ² = 1.962	0.185
肿瘤数量≥ 3个		163	60	χ² = 72.510	0.000
肿瘤直径≥ 5 cm		167	42	χ² = 110.522	0.000
PVTT		170	312	χ² = 180.069	0.000
淋巴结转移		56	131	χ² = 252.045	0.000
ALT（IU/L）		42.2（28.4～71.1）	32.3（22.9～49.3）	Z =-4.630	0.000
AST（IU/L）		59.1（35.9～99.2）	34.5（26.1～54.3）	Z =-8.606	0.000
TBil（μmoI/L）		23.4（15.7～38.7）	16.7（11.9～23.0）	Z =-7.012	0.000
ALB（g/L）		36.0（31.1～40.1）	38.7（33.4～42.7）	Z =-4.699	0.000
GGT（IU/L）		114.4（50.0～197.1）	40.8（24.4～69.3）	Z =-10.948	0.000
Gr（μmoI/L）		65.0（57.3～75.0）	67.4（58.0～77.0）	Z =-1.167	0.243
AFP≥ 400 ng/ml		127	35	χ² = 69.475	0.000
BCLC分期				χ² = 335.348	0.000
	A	45	246
	B	56	63
	C	177	4
	D	39	3
MELD评分		5.9（3.3～9.0）	4.4（1.9～7.0）	Z =-5.211	0.000
NLR		3.19（2.2～4.5）	1.8（1.3～2.3）	Z =-13.042	0.000
HBV DNA≥ 500 IU/ml/<500 IU/ml		186/131	156/159	χ² = 5.329	0.021
HBV DNA（±s，Log₁₀IU/ml）
	500～10⁴	3.52 ± 0.35	3.33 ± 0.35	t = 2.473	0.015
	10⁴～10⁵	4.54 ± 0.26	4.61 ± 0.30	t =-1.203	0.232
	≥ 10⁵	5.98 ± 0.76	5.88 ± 0.62	t = 0.874	0.383
手术切除（例，有/无）		13/304	76/239	χ² = 52.371	0.000
TACE（例，有/无）		207/110	249 /66	χ² = 14.462	0.000
RFA（例，有/无）		72/245	175/140	χ² = 71.582	0.000
PLC确诊前抗病毒者/未抗病毒者		82/235	148/167	χ² = 30.436	0.000

指标		死亡组（317例）	生存组（315例）	统计量	P值
男/女		281/36	251/64	χ² = 9.525	0.002
年龄（岁）		52.6 ± 9.3	55.1 ± 10.0	t =-3.189	0.001
饮酒史		150	95	χ² = 19.599	0.000
HCC家族史		55	42	χ² = 1.962	0.185
肿瘤数量≥ 3个		163	60	χ² = 72.510	0.000
肿瘤直径≥ 5 cm		167	42	χ² = 110.522	0.000
PVTT		170	312	χ² = 180.069	0.000
淋巴结转移		56	131	χ² = 252.045	0.000
ALT（IU/L）		42.2（28.4～71.1）	32.3（22.9～49.3）	Z =-4.630	0.000
AST（IU/L）		59.1（35.9～99.2）	34.5（26.1～54.3）	Z =-8.606	0.000
TBil（μmoI/L）		23.4（15.7～38.7）	16.7（11.9～23.0）	Z =-7.012	0.000
ALB（g/L）		36.0（31.1～40.1）	38.7（33.4～42.7）	Z =-4.699	0.000
GGT（IU/L）		114.4（50.0～197.1）	40.8（24.4～69.3）	Z =-10.948	0.000
Gr（μmoI/L）		65.0（57.3～75.0）	67.4（58.0～77.0）	Z =-1.167	0.243
AFP≥ 400 ng/ml		127	35	χ² = 69.475	0.000
BCLC分期				χ² = 335.348	0.000
	A	45	246
	B	56	63
	C	177	4
	D	39	3
MELD评分		5.9（3.3～9.0）	4.4（1.9～7.0）	Z =-5.211	0.000
NLR		3.19（2.2～4.5）	1.8（1.3～2.3）	Z =-13.042	0.000
HBV DNA≥ 500 IU/ml/<500 IU/ml		186/131	156/159	χ² = 5.329	0.021
HBV DNA（±s，Log₁₀IU/ml）
	500～10⁴	3.52 ± 0.35	3.33 ± 0.35	t = 2.473	0.015
	10⁴～10⁵	4.54 ± 0.26	4.61 ± 0.30	t =-1.203	0.232
	≥ 10⁵	5.98 ± 0.76	5.88 ± 0.62	t = 0.874	0.383
手术切除（例，有/无）		13/304	76/239	χ² = 52.371	0.000
TACE（例，有/无）		207/110	249 /66	χ² = 14.462	0.000
RFA（例，有/无）		72/245	175/140	χ² = 71.582	0.000
PLC确诊前抗病毒者/未抗病毒者		82/235	148/167	χ² = 30.436	0.000

选入变量	回归系数（β）	标准误（S.E.）	Wald统计量（Z）	P值（Sig）	相对危险度Exp（β）	95%CI
性别	0.522	0.177	8.676	0.003	1.685	1.191～2.384
年龄	-0.020	0.006	11.697	0.001	0.980	0.969～0.992
肿瘤数量≥ 3个	1.027	0.113	82.226	0.000	2.792	2.236～3.486
肿瘤直径≥ 5 cm	1.360	0.115	140.345	0.000	3.895	3.110～4.877
PVTT	2.229	0.124	325.560	0.000	9.291	7.293～11.836
淋巴结转移	1.285	0.150	73.071	0.000	3.615	2.693～4.854
AST（IU/L）	0.003	0.000	44.359	0.000	1.003	1.002～1.003
TBil（μmoI/L）	0.007	0.001	54.358	0.000	1.007	1.005～1.009
ALB（g/L）	-0.039	0.008	23.506	0.000	0.961	0.946～0.977
GGT（IU/L）	0.005	0.000	232.363	0.000	1.005	1.004～1.005
Gr（μmoI/L）	0.004	0.002	5.451	0.020	1.004	1.001～1.008
AFP≥ 400 ng/ml	1.146	0.118	94.916	0.000	3.144	2.497～3.959
NLR	0.312	0.022	207.980	0.000	1.366	1.310～1.426
MELD评分	0.076	0.011	49.716	0.000	1.079	1.056～1.102
BCLC分期	1.145	0.057	398.781	0.000	3.143	2.809～3.517
HBV DNA	0.302	0.114	7.000	0.008	1.353	1.081～1.692
确诊前抗病毒	-0.719	1.129	31.311	0.000	0.487	0.379～0.627
确诊后抗病毒	-0.815	0.149	30.036	0.000	0.442	0.331～0.592

选入变量	回归系数（β）	标准误（S.E.）	Wald统计量（Z）	P值（Sig）	相对危险度Exp（β）	95%CI
性别	0.522	0.177	8.676	0.003	1.685	1.191～2.384
年龄	-0.020	0.006	11.697	0.001	0.980	0.969～0.992
肿瘤数量≥ 3个	1.027	0.113	82.226	0.000	2.792	2.236～3.486
肿瘤直径≥ 5 cm	1.360	0.115	140.345	0.000	3.895	3.110～4.877
PVTT	2.229	0.124	325.560	0.000	9.291	7.293～11.836
淋巴结转移	1.285	0.150	73.071	0.000	3.615	2.693～4.854
AST（IU/L）	0.003	0.000	44.359	0.000	1.003	1.002～1.003
TBil（μmoI/L）	0.007	0.001	54.358	0.000	1.007	1.005～1.009
ALB（g/L）	-0.039	0.008	23.506	0.000	0.961	0.946～0.977
GGT（IU/L）	0.005	0.000	232.363	0.000	1.005	1.004～1.005
Gr（μmoI/L）	0.004	0.002	5.451	0.020	1.004	1.001～1.008
AFP≥ 400 ng/ml	1.146	0.118	94.916	0.000	3.144	2.497～3.959
NLR	0.312	0.022	207.980	0.000	1.366	1.310～1.426
MELD评分	0.076	0.011	49.716	0.000	1.079	1.056～1.102
BCLC分期	1.145	0.057	398.781	0.000	3.143	2.809～3.517
HBV DNA	0.302	0.114	7.000	0.008	1.353	1.081～1.692
确诊前抗病毒	-0.719	1.129	31.311	0.000	0.487	0.379～0.627
确诊后抗病毒	-0.815	0.149	30.036	0.000	0.442	0.331～0.592

选入变量	回归系数（β）	标准误（S.E.）	Wald统计量（Z）	P值（Sig）	相对危险度Exp（β）	95%CI
肿瘤数量≥ 3个	0.269	0.119	5.097	0.024	1.309	1.036～1.653
肿瘤直径≥ 5 cm	0.550	0.131	17.609	0.000	1.734	1.341～2.242
PVTT	0.469	0.159	8.704	0.003	1.599	1.171～2.184
AST	0.002	0.001	6.069	0.014	1.002	1.000～1.003
GGT（IU/L）	0.001	0.001	4.544	0.033	1.001	1.000～1.002
AFP ≥ 400 ng/ml	0.396	0.135	8.560	0.003	1.486	1.140～1.938
NLR	0.183	0.027	44.719	0.000	1.200	1.000～1.002
BCLC分期	0.927	0.079	139.102	0.000	2.528	2.167～2.949
HBV DNA	0.248	0.122	4.124	0.042	1.282	1.009～1.629

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