Abstract:

Objective　To investigate the effect of Fufang Biejia Ruangan tablets combined with entecavir for patients with chronic hepatitis B (CHB) and hepatic fibrosis. Methods　A total of 80 patients with CHB and liver fibrosis treated at Zhengzhou Sixth People's Hospital from August 2020 to August 2021 were selected for the randomized controlled trial, and were divided into an observation group and a control group by the random number table method, with 40 cases in each group. Three cases dropped out in the observation group [7.5% (3/40)], and 2 cases in the control group [5.00% (2/40)]. There were 37 cases in the observation group, including 27 males and 10 females; they were (40.34±9.62) years old; the hepatitis B E antigen (HBeAg) positive rate was 62.20% (23/37); the alanine transaminase (ALT) level was (198.52±50.73) U/L; there were 6, 16, 10, and 5 cases of F1-F4 of fibrosis stage, respectively. There were 38 cases in the control group, including 29 males and 9 females; they were (39.58±10.17) years old; the HBeAg positive rate was 22 (57.90%); the ALT level was (193.66±47.79) U/L; there were 7, 14, 12, and 5 cases of F1-F4 of fibrosis stages, respectively. The control group orally took entecavir tablets, 0.5 mg/time, once per day, and the observation group orally took entecavir tablets, 0.5 mg/time, once per day, and Fufang Biejia Ruangan tablets, 2.0 g/time, 3 times/d, for 12 months. The normalcy rates of ALT and negative conversion rates of hepatitis B virus deoxyribonucleic acid (HBV DNA) were compared between the two groups before the treatment and after 6 and 12 months' treatment. The serum markers of liver fibrosis [hyaluronic acid (HA), procollagen type Ⅲ protein (PCⅢ), laminin (LN), and type Ⅳ collagen (CⅣ)] in both groups were determined by chemiluminescence before the treatment and after 6 and 12 months' treatment. The liver stiffness measurernents (LSM) were measured by a transient elastic tester. At the same time, the incidences of adverse reactions in the two groups were analyzed. χ² and t tests and analysis of variance were applied. Results　After 6 and 12 months' treatment, the ALT normalcy rates in both the observation group and the control group were higher than those before the treatment (χ²=75.542 and 71.356; both P<0.05). There were no statistical differences in the ALT normalcy rates after 6 and 12 months' treatment between the two groups (both P>0.05). After 6 and 12 months' treatment, the negative HBV DNA conversion rates in the observation group and the control group were higher than those before the treatment (χ²=71.101 and 73.020; both P<0.05). After 6 and 12 months' treatment, the levels of HA [(103.90±33.78) μg/L vs. (121.53±37.04) μg/L and (86.68±26.72) μg/L vs. (100.61±28.73) μg/L], PCⅢ [(116.73±29.54) μg/L vs. (132.73±32.79) μg/L and (89.21±25.30) μg/L vs. (104.51±28.27) μg/L], LN [(110.72±30.97) μg/L vs. (126.84±33.80) μg/L and (92.50±28.40) μg/L vs. (107.42±30.21) μg/L], and CⅣ [(92.50±32.61) μg/L vs. (109.15±35.34) μg/L and (73.38±23.05) μg/L vs. (86.77±26.85) μg/L] in the observation group were lower than those in the control group (all P<0.05). After 6 and 12 months' treatment, the LSM's in the observation group were significantly lower than those in the control group [(7.27±2.15) kPa vs. (9.84±2.52) kPa and (6.50±1.94) kPa vs. (7.61±2.26) kPa; both P<0.05]. No serious adverse events were observed in all the patients. Conclusion　Fufang Biejia Ruangan tablets combined with entecavir has obvious synergistic effect on reversing liver fibrosis in patients with CHB, and the long-term treatment is beneficial to continuously and stably improve the patients' liver fibrosis and is safe.

Key words:

Hepatic fibrosis caused by chronic hepatitis B, Entecavir, Fufang Biejia Ruangan tablets, Hepatic fibrosis markers, Liver stiffness measurement value

摘要：

目的　探讨复方鳖甲软肝片联合恩替卡韦治疗慢性乙型肝炎（chronic hepatitis B，CHB）肝纤维化患者的效果。方法　选取2020年8月至2021年8月郑州市第六人民医院收治的80例CHB肝纤维化患者进行随机对照试验。采用随机数字表法将其分为观察组和对照组，每组40例。观察组脱落3例［7.5%（3/40）］，对照组脱落2例［5.00%（2/40）］。观察组37例，男27例，女10例，年龄（40.34±9.62）岁，乙型肝炎E抗原（hepatitis B E antigen，HBeAg）阳性率23（62.20%），丙氨酸氨基转移酶（alanine transaminase，ALT）（198.52±50.73）U/L；纤维化分期F1～F4分别有6例、16例、10例、5例。对照组38例，男29例，女9例，年龄（39.58±10.17）岁，HBeAg阳性率22（57.90%），ALT（193.66±47.79）U/L，纤维化分期F1～F4分别有7例、14例、12例、5例。对照组口服恩替卡韦片，0.5 mg/次，1次/d治疗；观察组则在此基础上口服复方鳖甲软肝片治疗，2.0 g/次，3次/d；两组均治疗12个月。比较两组治疗前和治疗6、12个月时ALT复常率和乙型肝炎病毒脱氧核糖核酸（hepatitis B virus deoxyribonucleic acid，HBV DNA）转阴率；治疗前及治疗6、12个月时采用化学发光法测定两组患者血清肝纤维化标志物［透明质酸（hyaluronic acid，HA）、Ⅲ型前胶原（procollagen type Ⅲ protein，PCⅢ）、层黏连蛋白（laminin，LN）、Ⅳ型胶原（Ⅳ collagen，CⅣ）］水平，并运用肝脏瞬时弹性探测仪测量其肝硬度测定值（liver stiffness measurements，LSM）；同时统计两组不良反应发生情况。采用χ²检验、t检验和方差分析。结果　治疗6、12个月时，观察组和对照组ALT复常率均高于治疗前（χ²=75.542、71.356，均P<0.05）；治疗6、12个月时，两组ALT复常率对比，差异均无统计学意义（均P>0.05）。治疗6、12个月时，观察组和对照组HBV DNA转阴率均高于治疗前（χ²=71.101、73.020，均P<0.05）。治疗6、12个月时，观察组HA［（103.90±33.78）μg/L比（121.53±37.04）μg/L、（86.68±26.72）μg/L比（100.61±28.73）μg/L］、PCⅢ［（116.73±29.54）μg/L比（132.73±32.79）μg/L、（89.21±25.30）μg/L比（104.51±28.27）μg/L］、LN［（110.72±30.97）μg/L比（126.84±33.89）μg/L、（92.50±28.40）μg/L比（107.42±30.21）μg/L］、CⅣ［（92.50±32.61）μg/L比（109.15±35.34）μg/L、（73.38±23.05）μg/L比（86.77±26.85）μg/L］均低于对照组（均P<0.05）；治疗6、12个月时，观察组LSM均低于对照组［（7.27±2.15）kPa比（9.84±2.52）kPa、（6.50±1.94）kPa比（7.61±2.26）kPa，均P<0.05］。所有患者均未见严重不良反应。结论　复方鳖甲软肝片联合恩替卡韦在逆转CHB患者肝纤维化上具有明显的协同效应，且长期治疗有利于持续稳定地改善患者肝纤维化，且安全性好。

关键词:

慢性乙型肝炎肝纤维化, 恩替卡韦, 复方鳖甲软肝片, 肝纤维化标志物, 肝硬度测定值