Clinical Observation And Study Of Traditional Chinese Medicine “#1 Chinese Herbal Prescription For Hepatopathy” For 30 Patients Who Are Resistant To Nucleoside (Nucleotide) Analogues

Objective: The purpose of this study is to investigate the clinical efficacy and safety of the combined treatment of traditional Chinese and western medicine for the hepatitis B virus(HBV) patients who are resistant to nucleoside(nucleotide) analogues.Method: A sample of 59 chronic hepatitis B patients were selected from the outpatient and inpatient departments of Hubei Provincial Hospital of Traditional Chinese Medicine for this clinical observation and study. All of these patients have been treated with the nucleoside(nucleotide) analogues for more than a year, and all of their HBV-DNA levels are higher than 1.0×103IU/ml. The sample consists of 50 patients with the B gene of HBV and 9 patients with the C gene of HBV.It is normal that the patients are first resistant to one medicine and then become resistant to another one or more when the doctor changes the prescription hoping to see better results as the former one does not really work any longer. Under such circumstance and among the sample, 4 patients are resistant to Entecavir; 30 patients are resistant to both Lamivudine and Entecavir; 7 patients are resistant to Adefovir and Entercavir; 10 patients are resistant to Telbivudine and Entercavir; and 8 patients are resistant to Lamivudine, Adefovir and Entercavir regardless how the doctor changes the prescriptions. In compliance with the principle of informed consent, these patients were divided into two groups based on gender, age and the time of seeking medical care. Group 1 with 30 patients was given the combined treatment of traditional Chinese and western medicine. The prescription includes the Entercavir made by Sino-American Shanghai Squibb Pharmaceuticals Ltd.(0.5mg/d), the Adefovir Dipivoxil Tablets made by Tianjin Institute of Pharmaceutical Research(TIPR) LLC(10mg/d), the necessary supplementary treatment and the “#1 Chinese Herbal Prescription for Hepatopathy” developed by professor Mr. Shen Zhongyuan(1 package/d). Group 2 with 29 patients was given the western medicine treatment only that includes the Entercavir made by Sino-American Shanghai Squibb Pharmaceuticals Ltd.(0.5mg/d), the Adefovir Dipivoxil Tablets made by Tianjin Institute of Pharmaceutical Research(TIPR) LLC(10mg/d), and necessary supplementary treatment. The gender, age, family history, course of disease, modern medical diagnosis, Traditional Chinese Medicine(TCM) symptom integral before Chinese medical treatment, ALT, AST, ALP, GGT, ALB, etc. were analyzed and compared between the two groups of patients. The routine blood parameters, routine urinalysis, stool routine, electrocardiography(ECG), renal function and side effects of the medicine were carefully observed for the patients to evaluate the efficacy and safety of the treatment.Results: 1. Comparison of HBe Ag negative conversion rate of the two groups after half year treatment: Group 1 that under the combined treatment with “#1 Chinese Herbal Prescription for Hepatopathy” had a much higher negative conversion rate of 55.33% whereas Group 2 had it at 20.00%. The difference is statistically and clinically significant(P<0.05), which means that the “#1 Chinese Herbal Prescription for Hepatopathy” can increase the HBe Ag negative conversion rate for the patients who are resistant to Entercavir. 2. Comparison of HBV-DNA level changing rate of the two groups after half year treatment: The rate that the HBV-DNA levels changed completely for Group 1 that under the combined treatment with “#1 Chinese Herbal Prescription for Hepatopathy” was 90.00% while for Group 2, it was 62.06%. The difference is statistically and clinically significant(P<0.05), which indicates that the “#1 Chinese Herbal Prescription for Hepatopathy” can help change the HBV-DNA level of the patients who are resistant to Entercavir.3. Comparison of overall clinical efficacy of the two groups after half year treatment: The clinical efficacy for Group 1 that under combined treatment with “#1 Chinese Herbal Prescription for Hepatopathy” was 90.0% and for Group 2, the rate was 68.97%. The difference is statistically and clinically significant(P<0.05), which demonstrates that the overall clinical efficacy of Group 1 is better than that of Group 2.4. Comparison of the total integral of TCM symptoms of the two groups: ○1the difference before and after the treatment for Group 1 was statistically significant – the results got much better after the treatment; the difference before and after the treatment for Group 2 was statistically significant – the results improved after the treatment; ○3 After the different treatments, the difference of the clinical efficacy between Group 1 and Group 2 was statistically significant – Group 1 that under combined treatment with “#1 Chinese Herbal Prescription for Hepatopathy” had much more remarkable improvements.5. Comparison of main Chinese-medicine clinical symptoms of the two groups: Both groups showed improvements in lack of strength, loss of appetite, discomforter in liver, abnormal emotions, abdominal distention, dry and bitter mouth, hepatosplenomegaly, loose and jaundice. But the improvements showed in Group 1 were superior to Group 2, and difference was statistically significant(P<0.05).6. Comparison of liver functions of the two groups after different treatments:○1the difference of ALT(P<0.05) and AST(P<0.05) before and after the treatment for Group 1 was statistically significant – the results were much better after the treatment; ○2 the difference of ALT(P<0.05) and AST(P<0.05) before and after the treatment for Group 2 was statistically significant – the results were better after the treatment; ○3After the different treatments, the difference of ALT(P<0.05) and AST(P<0.05) testing results between Group 1 and Group 2 was statistically significant – Group 1 that under combined treatment with “#1 Chinese Herbal Prescription for Hepatopathy” had much more remarkable improvements in the testing results. But for the ALP(P>0.05), GGT(P>0.05), ALB(P>0.05) and TBi L(P>0.05), the improvement differences between the two groups of patients were not statistically significant.Conclusion: The study shows that adding traditional Chinese herbal medicine that is for enhancing the immune system to resist the pathogen into the western medicine – Entercavir and Adefovir based prescription has a certain clinical efficacy to the patients who are resistant to nucleoside(nucleotide) analogues. The combined treatment can increase the HBe Ag negative conversion rate and improve the HBV-DNA level of the patients as well as relief the clinical symptoms and signs. Yet the clinical safety worth further researching and promoting.