Objective:To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma(HCC) using early treatment by Compound Phyllanthus Urinaria L.(CPUL) on patients with preneoplastic hepatitis B virus(HBV)-associated HCC.Methods:A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins(five up-regulated genes URG4,URG7,URG11,URG12 and URG19,and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software.Fifty-two patients were in the treatment group and 50 patients were in the control group.CPUL was used in the treatment group for 3 years,while the control group did not receive any treatment.The changes in HBV-DNA level,number of antibodies,and hepatocarcinogenesis occurred were observed.Patients who did not develop HCC were followed up for another 2 years.Results:HBV-DNA levels decreased >2log in 22.2%(10/45) of patients in the treatment group in contrast to only 5.0%(2/40) of patients in the control group(P=0.0228).The number of antibodies that were tested positive in the treatment group(1.08± 1.01)was significantly lower compared with the control group(2.11 ±1.12) after 24 months of drug treatment(P<0.01).Both the positive rates of anti-URG11(33/52) and anti-URG19(31/52) were over 60%at baseline in the two groups,and were decreased to 48.1%(25/52) and 46.2%(24/52) respectively at 36 months of drug treatment,while the rates increased to 68.0%(34/50) and 66.0%(33/50) respectively(P=0.0417,P=0.0436) in the control group.The positive rate of anti-DRG2 was increased to 55.8%(29/52) at 36 months of drug treatment,while in the control group was decreased to 36.0%(18/50,P=0.0452).Among the 102 patients who developed HCC,2 were in the treatment group and 9 were in the control group,meaning that a significant difference between the two groups(P=0.0212).In11 patients who developed HCC,anti-URG11 and anti-URG19 were always positive,while anti-DRG2 was negative.Pat