Clinical Study On Haizhu Yigan Jiawei Formular In Treating Chronic Hepatitis B With Spleen Deficiency And Phlegm-dampness Combined With Non-alcoholic Fatty Liver Disease

Background:Chronic Hepatitis B（CHB）is one of the most prevalent infectious diseases in the world,and is closely related to the occurrence of cirrhosis,primary liver cancer and other diseases.China is a big country of hepatitis B,with about 90million hepatitis B virus carriers,and about 300,000 people die of cirrhosis and liver cancer related to CHB every year^[1].The goal of treatment for CHB is to inhibit HBV replication to the maximum extent,reduce the liver histological damage,delay and reduce the incidence of serious complications such as cirrhosis and liver cancer,and improve the quality of life and prolong the survival time of patients.The most important treatment means is antiviral therapy,followed by liver protection,anti-inflammatory,anti-oxidation,anti-liver fibrosis and immunological regulation.Traditional Chinese medicine is not as effective as western medicine in antiviral,but it plays a significant role in improving symptoms,fighting liver fibrosis,controlling and delaying the progression of disease.Clinical anti-HBV drugs mainly include nucleos（t）ide analogues（NAs）and Interferon（IFN）.The recommended first-line NAS drugs include entecavir,tenofovir and propofol tenofovir.In recent years,the incidence of fatty liver has been increasing year by year,and has become the largest chronic liver disease in China.At present,the treatment of non-alcoholic fatty liver disease（NAFLD）mainly focuses on weight loss,prevention and treatment of complications.For non-alcoholic steatohepatitis,NASH)has not been recommended for liver protection and enzyme lowering.In the process of clinical practice,we found that many patients with CHB complicated with NAFLD,the superposition of the two damage factors can further increase the incidence of liver fibrosis,cirrhosis and even liver cancer.Hepatitis,cirrhosis and liver cancer are known as the"trilogy"of chronic liver diseases.Traditional Chinese medicine has a good effect in improving clinical symptoms,fighting liver fibrosis,controlling and delaying the progression of diseases.Traditional Chinese medicine has a long history of development,and the understanding of CHB is also developing and changing.The team of Professor Sheng Guoguang from Hubei Provincial Hospital of Traditional Chinese Medicine has long been committed to the research on the treatment of chronic liver diseases with traditional Chinese medicine.During the"Seventh Five-Year Plan"period,our hospital undertook the scientific and technological research topic"Research on the treatment of chronic active hepatitis B and liver fibrosis with traditional Chinese medicine".In cooperation with many organizations across the country,Chinese medicine prescriptions were used to treat CHB,and it was discovered that detoxification was the key to CHB treatment,and it was proposed that the pathogenesis of CHB in Chinese medicine is caused by damp-heat toxins.During the"Eighth Five-Year Plan"period,we started with detoxification and studied the anti-HBV efficacy of Phyllanthus vulgaris preparations,and verified the role of heat-clearing and detoxifying methods in the treatment of CHB.CHB is persistent and difficult to heal,which is similar to the characteristics of TCM"phlegm"cases.CHB is difficult to heal for a long time,and the toxic and phlegm are intertwined,which leads to liver failure and qi and blood stagnation.As a result,during the"Ninth Five-Year Plan"period,Professor Sheng Guoguang’s team proposed that the etiology and pathogenesis of CHB was"poisonous phlegm and blood stasis",and established The treatment method of"detoxification,phlegm,and blood stasis"was developed and applied in clinical practice.The academic thought of treating chronic liver disease from the spleen also has guiding significance in the contemporary treatment of CHB.In clinical practice,Professor Sheng Guoguang’s team found that fatigue is the most common symptom of patients with chronic liver disease,and is often accompanied by gastrointestinal symptoms such as nausea and vomiting,oiliness,abdominal distension,diarrhea,loose stools,etc.The Haizhu Yigan Decoction is added with Pseudoginseng,Lycium barbarum and other products that strengthen the body and strengthen the qi,have a better effect on improving the symptoms and liver function indicators of patients with liver disease.Based on this,during the"Tenth Five-Year Period",Professor Sheng Guoguang further proposed the pathogenesis characteristics of chronic hepatitis B with"toxicity,phlegm,blood stasis,and deficiency".He started with strengthening the spleen and adding two flavors of Radix Ginseng and Chinese wolfberry on the basis of Haizhu Yigan Decoction.The medicinal materials form the Haizhu Yigan Jiawei Formular.A large number of preliminary and clinical studies have confirmed that Haizhu Yigan Jiawei Formular can improve liver function in multiple ways and has a significant effect on improving the quality of life of patients with chronic hepatitis B.According to traditional Chinese medicine,the incidence of CHB combined with NAFLD is mainly related to liver,spleen and kidney,Qi deficiency,Qi stagnation,phlegm turbidity,water dampness and blood stasis are the main pathological factors.In clinical practice,we found that patients with CHB complicated with NAFLD often had fatigue,nausea,vomiting,oil disgust,diarrhea and other symptoms.Therefore,it was proposed that dampness accumulation of spleen deficiency and dampness of phlegm were the internal basis of the disease,and the clinical treatment achieved a good effect by invigorating spleen and eliminating phlegm.Based on the above,Haizhu Yigan Jiawei Formular combined with Enticavir was used in this study to treat CHB patients with spleen deficiency and dampness type CHB combined with NAFLD,and observe the changes in clinical symptoms,biochemical indicators,HBV DNA and fatty liver degree.Purpose:This study uses Haizhu Yigan Jiawei Formular combined with entecavir to treat patients with spleen deficiency and dampness CHB combined with NAFLD,and observe the clinical symptoms and biochemical indicators of the patients The changes of HBV DNA and fatty liver degree are expected to provide reference basis for clinical treatment of CHB combined with NAFLD.Method:A total of 48 patients with spleen deficiency phlegm-dampness type CHB complicated with NAFLD were collected from the liver disease outpatient and inpatient departments of Hubei Hospital of Traditional Chinese Medicine from October 2018 to October 2020.They were divided into 2 groups,26 cases in the treatment group,and22 cases in the control group.The control group was treated with Entecavir Dispersible Tablets and conventional liver-protecting treatment,and the treatment group was treated with Entecavir Dispersible Tablets,conventional liver-protecting treatment and Haizhu Yigan Jiawei Formular,and the medication was adjusted according to the symptoms of the patients.The two groups received treatment for 3 months,and compared the clinical symptoms,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,serum triglycerides（TG）,liver fat CAP values of the patients before and after treatment.HBV DNA quantification,full set quantification of hepatitis B,liver color Doppler ultrasound changes.Result:1.Comparison of liver function indexes before and after treatment:ALT levels of patients in the treatment group were significantly reduced after treatment（P<0.05）,and AST levels were significantly reduced（P<0.05）;ALT levels of patients in the control group were significantly reduced after treatment（P<0.05）,AST level was significantly reduced（P<0.05）;Compared with the control group,the ALT level in the treatment group was significantly lower than the control group（P<0.05）after treatment,and the AST level was significantly lower than the control group（P<0.05）.The results show that entecavir and liver-protecting treatment and combined treatment with Haizhu Yigan Jiawei Formular can improve the liver function of patients with spleen-deficiency and damp-resistance CHB combined with NAFLD,and the liver function improvement of the combined Chinese medicine group is better.2.Comparison of TG levels before and after treatment:The TG level of patients in the treatment group was significantly reduced after treatment（P<0.05）,and the TG level of patients in the control group was significantly reduced after treatment（P<0.05）;compared with the control group,the treatment group was treated After the TG level was higher than the control group,the difference was not statistically significant（P>0.05）.The results show that entecavir and liver-protecting treatment and on this basis combined with Haizhu Yigan Jiawei Formular can improve the serum TG of patients with spleen-deficiency dampness type CHB combined with NAFLD,but the combination of traditional Chinese medicine treatment and simple entecavir anti-virus+liver-protection Compared with the treatment plan,there is no obvious advantage in improving the serum TG level.3.Comparison of CAP levels before and after treatment:The CAP level of patients in the treatment group decreased after treatment（P<0.05）,and the CAP level of patients in the control group decreased after treatment（P<0.05）;compared with the control group,the CAP level in the treatment group after treatment The level was higher than that of the control group,and the difference was not statistically significant（P>0.05）.The above results show that,compared with the treatment plan of combined Haizhu Yigan Jiawei Formular with entecavir and liver protection treatment,both of them have a positive effect on the CAP level of patients with spleen-deficiency and damp-resistance CHB combined with NAFLD,but combined with traditional Chinese medicine Compared with the pure entecavir antiviral+liver protection treatment,the treatment has no obvious advantage in improving CAP.4.Comparison of serum HBV DNA transformation before and after treatment:There was no statistically significant difference in HBV DNA transformation（P>0.05）.The results showed that compared with the treatment plan of the combination of antiviral and liver protection,the combination of traditional Chinese medicine has no obvious effect on improving the efficacy of antiviral therapy in patients.5.Comparison of TCM syndrome scores before and after treatment:Compared within the group,the TCM symptom scores of the two groups of patients after treatment were lower than those before treatment,and the difference was statistically significant（P<0.05）;Comparison between groups:TCM symptom scores of the treatment group after treatment Significantly lower than before treatment,the difference was statistically significant（P<0.05）.The results show that the combined treatment with traditional Chinese medicine has a significant positive effect on the improvement of patients’symptoms of traditional Chinese medicine.6.Comparison of curative effect:the total effective rate is95.83%in the treatment group and 87.50%in the control group.There is a statistically significant difference in the total effective rate between the treatment group and the control group（P<0.05）.Combined use of traditional Chinese medicine has significant advantages in improving the condition of CHB patients with spleen deficiency and dampness resistance combined with NAFLD.Conclusion:Haizhu Yigan Jiawei Decoction combined with entecavir and liver protection treatment can improve the liver function and CAP level of patients with spleen deficiency and dampness CHB combined with NAFLD.It has a good effect on improving the symptoms of traditional Chinese medicine,but it has no significant effect on the rate of HBV DNA negative conversion.