合并高血压病的乙型肝炎肝硬化患者发生肝细胞癌的风险评估：一项基于倾向性匹配评分的回顾性队列研究

doi:10.12122/j.issn.1673-4254.2024.11.22

摘要/Abstract

摘要：

目的阐明慢性乙型肝炎肝硬化（CHB-Cir）患者合并高血压病（EH）时发生肝细胞癌（HCC）的风险及其协同因素，探讨高血压病对慢性乙型肝炎肝硬化患者的影响。方法以2017年1月~2024年1月在新乡医学院第三附属医院感染科随访的经抗病毒治疗的CHB-Cir患者为研究对象，形成CHB-Cir合并EH队列和CHB-Cir 无EH队列，排除随访时间过短及主要数据缺失的病例，将两组队列中的患者进行倾向性匹配评分后构成EH组和无EH组，采用Kaplan-Meier法比较两组HCC累积发生率；以Cox比例风险回归模型分析CHB-Cir合并EH时发生HCC的风险及其协同因素。结果高血压病与肝细胞癌的发生显著相关（HR=1.69，P=0.002），在多因素分析中，男性（HR=1.73，P=0.005）、肝癌家族史（HR=2.23，P<0.001）、甲胎蛋白升高（HR=2.83，P=0.001）、谷胱甘肽还原酶升高（HR=1.53，P=0.046）、高密度脂蛋白降低（HR=1.46，P=0.027）、低密度脂蛋白升高（HR=2.29，P=0.003）与肝细胞癌的发生相关，甘油三酯升高（HR=0.37，P<0.001）为肝细胞癌发生的保护因素。在EH组中，非RASIs药物治疗（HR=2.77，P=0.021）、未治疗/利尿剂治疗（HR=7.18，P<0.001）与肝细胞癌的发生相关。结论高血压病及其特征增加了慢性乙型肝炎肝硬化患者发生肝细胞癌的风险。对这些患者应该强调高血压病控制的重要性。

关键词: 慢性乙型肝炎, 肝硬化, 肝细胞癌, 高血压病, 危险因素

Abstract:

Objective To analyze the factors affecting the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by essential hypertension (EH) and explore the impact of EH on HCC risk in patients with CHB-Cir. Methods This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department, Third Affiliated Hospital of Xinxiang Medical University from January, 2017 to January, 2024. The cases with insufficient follow-up time or missing data were excluded. The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group. The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups, and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk. Results A total of 390 CHB-Cir patients (274 male and 116 female patients) were enrolled in this study, including 195 with EH and 195 without EH. In these patients, EH was significantly correlated with the occurrence of HCC (HR=1.69, P=0.002). Multivariate analysis suggested that the male gender (HR=1.73, P=0.005), a family history of liver cancer (HR=2.23, P<0.001), elevated alpha-fetoprotein (HR=2.83, P=0.001), elevated glutathione reductase (HR=1.53, P=0.046), reduced high-density lipoprotein (HR=1.46, P=0.027), and elevated low-density lipoprotein (HR=2.29, P=0.003) were all significantly correlated with HCC occurrence, while elevated triglycerides (HR=0.37, P<0.001) was a protective factor against HCC. In the EH group, treatment with non-RASIs drugs (HR=2.77, P=0.021) and no treatment/diuretic treatment (HR=7.18, P<0.001) were significantly correlated with HCC occurrence. Conclusion Hypertension increases the risk of HCC in patients with CHB-Cir, suggesting the importance of controlling hypertension in these patients.

Key words: chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, essential hypertension, risk factors

胡嘉伟, 杜芳, 丁璐, 王路翔, 赵巍峰. 合并高血压病的乙型肝炎肝硬化患者发生肝细胞癌的风险评估：一项基于倾向性匹配评分的回顾性队列研究[J]. 南方医科大学学报, 2024, 44(11): 2243-2249.

Jiawei HU, Fang DU, Lu DING, Luxiang WANG, Weifeng ZHAO. Risk assessment of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis and hypertension: a propensity score matching-based retrospective cohort study[J]. Journal of Southern Medical University, 2024, 44(11): 2243-2249.

图/表 6

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Characteristics	EH group (n=195)	Non-EH group (n=195)	P
Age (years)	57 (49-65)	56 (48-65)	0.577
Female (%)	60 (30.8)	56 (28.7)	0.658
Smoking history (%)	78 (40)	70 (35.9)	0.404
Family history of liver cancer (%)	15 (7.7)	24 (12.3)	0.129
Type 2 diabetes (%)	67 (34.4)	65 (33.3)	0.831
Overweight (%)	66 (33.8)	53 (27.2)	0.153
CTP score	7 (5-8)	7 (5-9)	0.064
HBeAg (+)	55 (28.2)	47 (24.1)	0.357
HBV-DNA (IU/mL)	2860 (0-372000)	791 (0-165000)	0.184
AFP (ng/mL)	7.29 (3.07-40.15)	5.57 (2.64-47.60)	0.259
GR (U/L)	82.00 (62.70-109.00)	82.20 (62.90-112.90)	0.739
ALT (U/L)	41 (24-111)	45 (29-77)	0.697
AST (U/L)	45 (29-119)	50 (32-88)	0.944
TC (mmol/L)	3.77 (2.94-4.46)	3.65 (2.91-4.33)	0.468
TG (mmol/L)	1.03 (0.78-1.61)	0.96 (0.71-1.42)	0.115
HDL (mmol/L)	1.09 (0.87-1.37)	1.12 (0.88-1.35)	0.903
LDL (mmol/L)	2.13 (1.50-2.89)	2.03 (1.49-2.63)	0.212
Duration of hypertension (years)
<5	102 (52.3)
>5	93 (47.7)
Hypertension treatment (%)
RASIs	44 (22.6)
Non-RASIs	74 (37.9)
Untreated/diuretic	77 (39.5)

Characteristics	EH group (n=195)	Non-EH group (n=195)	P
Age (years)	57 (49-65)	56 (48-65)	0.577
Female (%)	60 (30.8)	56 (28.7)	0.658
Smoking history (%)	78 (40)	70 (35.9)	0.404
Family history of liver cancer (%)	15 (7.7)	24 (12.3)	0.129
Type 2 diabetes (%)	67 (34.4)	65 (33.3)	0.831
Overweight (%)	66 (33.8)	53 (27.2)	0.153
CTP score	7 (5-8)	7 (5-9)	0.064
HBeAg (+)	55 (28.2)	47 (24.1)	0.357
HBV-DNA (IU/mL)	2860 (0-372000)	791 (0-165000)	0.184
AFP (ng/mL)	7.29 (3.07-40.15)	5.57 (2.64-47.60)	0.259
GR (U/L)	82.00 (62.70-109.00)	82.20 (62.90-112.90)	0.739
ALT (U/L)	41 (24-111)	45 (29-77)	0.697
AST (U/L)	45 (29-119)	50 (32-88)	0.944
TC (mmol/L)	3.77 (2.94-4.46)	3.65 (2.91-4.33)	0.468
TG (mmol/L)	1.03 (0.78-1.61)	0.96 (0.71-1.42)	0.115
HDL (mmol/L)	1.09 (0.87-1.37)	1.12 (0.88-1.35)	0.903
LDL (mmol/L)	2.13 (1.50-2.89)	2.03 (1.49-2.63)	0.212
Duration of hypertension (years)
<5	102 (52.3)
>5	93 (47.7)
Hypertension treatment (%)
RASIs	44 (22.6)
Non-RASIs	74 (37.9)
Untreated/diuretic	77 (39.5)

Variable	HR	95% CI	P
Age >65 years	0.96	0.65-1.38	0.768
Male	1.57	1.09-2.26	0.016
Smoking history	1.05	0.77-1.44	0.761
Family history of liver cancer	1.85	1.20-2.85	0.006
Type 2 diabetes	0.93	0.69-1.29	0.654
Essential hypertension	1.42	1.04-1.94	0.028
Overweight	1.09	0.79-1.51	0.612
CTP score>6	2.00	1.43-2.80	<0.001
HBeAg(+)	0.72	0.50-1.05	0.088
HBV-DNA>20000 IU/mL	0.91	0.66-1.26	0.568
AFP	3.19	2.34-4.36	<0.001
GR	2.01	1.43-2.84	<0.001
ALT	1.20	0.88-1.64	0.241
AST	1.87	1.33-2.64	<0.001
TC	1.06	0.64-1.75	0.829
TG	0.64	0.41-1.00	0.048
HDL	1.52	1.12-2.07	0.008
LDL	1.54	1.05-2.26	0.027

Variable	HR	95% CI	P
Age >65 years	0.96	0.65-1.38	0.768
Male	1.57	1.09-2.26	0.016
Smoking history	1.05	0.77-1.44	0.761
Family history of liver cancer	1.85	1.20-2.85	0.006
Type 2 diabetes	0.93	0.69-1.29	0.654
Essential hypertension	1.42	1.04-1.94	0.028
Overweight	1.09	0.79-1.51	0.612
CTP score>6	2.00	1.43-2.80	<0.001
HBeAg(+)	0.72	0.50-1.05	0.088
HBV-DNA>20000 IU/mL	0.91	0.66-1.26	0.568
AFP	3.19	2.34-4.36	<0.001
GR	2.01	1.43-2.84	<0.001
ALT	1.20	0.88-1.64	0.241
AST	1.87	1.33-2.64	<0.001
TC	1.06	0.64-1.75	0.829
TG	0.64	0.41-1.00	0.048
HDL	1.52	1.12-2.07	0.008
LDL	1.54	1.05-2.26	0.027

Variable	HR	95% CI	P
Male	1.73	1.18-2.54	0.005
Family history of liver cancer	2.23	1.40-3.55	<0.001
Type 2 diabetes	0.74	0.52-1.05	0.093
Essential hypertension	1.69	1.22-2.34	0.002
Overweight	1.13	0.80-1.61	0.47
CTP Score>6	1.38	0.97-1.98	0.077
AFP	2.83	2.04-3.94	0.001
GR	1.53	1.01-2.31	0.046
AST	0.84	0.56-1.25	0.395
TC	0.63	0.31-1.27	0.196
TG	0.37	0.23-0.61	<0.001
HDL	1.46	1.04-2.04	0.027
LDL	2.29	1.33-3.93	0.003