Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality. Early diagnosis and timely intervention in the precancerous stage can effectively reduce the incidence of HCC, which is of great significance for its prevention and treatment. Modern medical treatment of precancerous lesions of HCC has problems such as difficulties to grasp the timing of intervention and single treatment method, traditional Chinese medicine (TCM) may be a simple and effective new approach to prevent and treat precancerous lesion of HCC.

To observe the clinical efficacy and safety of Qizhuhuaji formula in the treatment of precancerous lesion of HCC (liver-depression and spleen-deficiency, phlegm and blood stasis syndrome) .

Patients with precancerous lesion of HCC who met the TCM syndrome type "liver-depression and spleen-deficiency, phlegm and blood stasis syndrome" admitted in the hepatology clinic of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Weihai Hospital of Traditional Chinese Medicine and Taian Hospital of Traditional Chinese Medicine from October 2019 to March 2020 were included as the study subjects. General information (gender, age, history of HBV-related cirrhosis, family history of HCC, history of alcohol consumption for more than 10 years), the TCM syndrome score, liver function indicators [alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) ], tumor marker indexes [alpha-fetoprotein (AFP), alpha-fetoprotein variants-L3 (AFP-L3), des-γ-carboxy-prothrombin (DCP) ], imaging indexes (lesion type, lesion nature, lesion length diameter), safety indexes and adverse reactions were collected. The 64 patients who met the inclusion criteria and completed the study were divided into the observation group (n=34) and the control group (n=30) using the random number tables. The patients in the control group were treated with conventional therapy such as antiviral, anti-inflammatory and liver-protective therapy; the observation group was treated with conventional therapy combined with Qizhuhuaji formula. The treatment course was 48 weeks, and the follow-up period was 48 weeks after drug withdrawal. The incidence of HCC and complications in the treatment cycle and follow-up period of the two group were observed, and the differences in the improvement indexes of TCM syndrome (TCM syndrome scores, total effective rate), liver function indicators, tumor marker indexes, imaging indexes (lesion length diameter, lesion stability rate, lesion improvement rate), and safety index (safety rate) between the two groups before and after treatment.

After treatment, the TCM syndrome scores, ALT, AST, TBIL, GGT, ALP, and AFP-L3 were lower than those before treatment in both groups, and the ALB level was higher than that before treatment (P<0.05) ; the DCP value and lesion length-diameter of patients in the observation group were lower than those before treatment (P<0.05) ; the comparison results between the two groups showed that the TCM syndrome scores, AST, and ALP values in the observation group were lower than those in the control group, and the ALB value was higher than that in the control group (P<0.05). The total effective rate of TCM syndrome in the observation group (91.2%) was higher than that in the control group (63.3%) at the end of the treatment cycle (P<0.05) ; there was no statistically significant differences (P>0.05) in the rates of lesion improvement (35.3%) and lesion stability (50.0%) in the observation group compared with the control group (20.0%, 43.3%). There was no statistically significant difference in the incidence of HCC between the observation group (8.8%) and the control group (16.7%) at the end of the follow-up period (P>0.05) ; the incidence of complications (8.8%) in the observation group was lower than that of the control group (30.0%) (P<0.05). Regarding the safety indexes, 2 cases in the observation group showed mild adverse reactions and 3 cases in the control group showed mild adverse reactions, no abnormal safety indexes were observed in both groups, there was no statistically significant difference (P>0.05) in the safety rate between the observation group (94.1%) and the control group (90.0%) .

The treatment of precancerous lesions of HCC (liver depression and spleen deficiency, phlegm and blood stasis syndrome) with Qizhuhuaji formula has better clinical efficacy and higher safety in improving TCM syndrome, improving liver function, shrinking lesion nodules, reducing the incidence of long-term HCC and complications of liver cirrhosis.

肝细胞癌（HCC）存在发病率高、死亡率高的特点，在癌前病变阶段进行早期诊断及时干预可有效降低HCC的发生率，对其防治具有显著意义。现代医学对于HCC癌前病变的治疗存在干预时机难以把握、治疗手段单一等问题，中医药防治HCC癌前病变或许是一种简单有效的新途径。

观察芪术化积方治疗HCC癌前病变（肝郁脾虚、痰瘀互结证）的临床疗效及安全性。

纳入2019年10月—2020年3月在山东中医药大学附属医院、威海市中医院、泰安市中医院肝病科门诊就医且符合中医证型"肝郁脾虚、痰瘀互结证"的HCC癌前病变初诊患者为研究对象。收集患者的一般资料[性别、年龄、乙型病毒性肝炎（HBV）后肝硬化史、HCC家族史、10年以上饮酒史]，患者的中医证候积分、肝功能指标[丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、白蛋白（ALB）、谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP）]、肿瘤标志物指标[甲胎蛋白（AFP）、甲胎蛋白异质体（AFP-L3）、异常凝血酶原（DCP）]、影像学指标（病灶类型、病灶性质、病灶长径）、安全性指标、不良反应。采用随机数字表法将符合纳入标准且完成研究的64例患者分为观察组（n=34）和对照组（n=30），对照组予以抗病毒、抗炎保肝等常规治疗；观察组予以常规治疗联合芪术化积方治疗。疗程为48周，停药后随访48周，观察两组患者治疗周期及随访周期中HCC发生率及并发症的发生情况，比较两组患者治疗前后中医证候改善指标（中医证候积分、总有效率）、肝功能指标、肿瘤标志物指标、影像学指标（病灶长径、病灶稳定率、病灶改善率）、安全性指标（安全率）的差异。

治疗后两组中医证候积分、ALT、AST、TBIL、GGT、ALP、AFP-L3均低于治疗前，ALB水平高于治疗前（P<0.05）；观察组患者治疗后的DCP值、病灶长径均低于治疗前（P<0.05）。组间比较结果显示，观察组中医证候积分、AST、ALP水平低于对照组，ALB水平高于对照组（P<0.05）。治疗周期结束后观察组的中医证候总有效率（91.2%）高于对照组（63.3%）（P<0.05）；观察组病灶改善率（35.3%）和病灶稳定率（50.0%）与对照组（20.0%，43.3%）比较，差异无统计学意义（P>0.05）。随访周期结束后观察组HCC发生率（8.8%）与对照组（16.7%）比较，差异无统计学意义（P>0.05）；并发症发生率（8.8%）低于对照组（30.0%）（P<0.05）。安全性指标方面，观察组2例出现轻度不良反应，对照组3例出现轻度不良反应，两组均未出现安全性指标异常，观察组安全率（94.1%）与对照组（90.0%）比较，差异无统计学意义（P>0.05）。

芪术化积方治疗HCC癌前病变（肝郁脾虚、痰瘀互结证），在改善中医证候、改善肝功能、缩小病灶结节、降低远期HCC发生率及减少肝硬化并发症等方面有较好的临床疗效及安全性。