Clinical Effects Of Compound Fuzheng Huyu Capsule/Tablet Combined With Entecavir In Patients With Chronic Hepatitis B With Hepatic Fibrosis

Background:Hepatic fibrosis is a necessary stage of chronic hepatitis B(CHB)progress to cirrhosis and has been proved to be reversible.Studies emphasized the anti-fibrosis therapy lead to clinical benefit such as suppression of viral replication and reduction of liver inflammation in treating CHB,but lack of drugs affect directly.Chinese herbal formula(CHF),is used to delay and restrain the process of liver fibrosis by regulating multiple pathways and targets.However,pure CHF lack of effective inhibition of HBV virus and cannot solve the problem from the root cause,so combination with antiviral drugs may be a better treatment to exert anti-fibrosis effects for CHB patients.Objective: To assess the clinical efficacy and long-term follow-up of Fuzheng Huayu(FZHY)capsules/tablets combined with entecavir in treating CHB with fibrosis and its mechanism,provide reliable basis for clinical medication.Methods : 80 CHB patients who met the inclusive criteria and signed consent were enrolled during November 2016 to November 2017 in the Southwest Medical University Affiliated Hospital outpatient and ward,randomly assigned to the combination(40 patients)and single(40 patients)group,and respectively received FZHY combined with entecavir or entecavir alone for 48 weeks;Changes of clinical symptoms(fatigue,anorexia,abdominal distension,hypochondriac pain),Hepatitis B Virus-DNA(HBV-DNA),liver function(ALT,AST),the width of abdominal B-mode portal vein,the liver stiffness measurement(LSM)was detected by Fibroscan,serological indicators of liver fibrosis(HA,LN,PIIIP,C-IV)and numerical variation of TGF-?1,PDGF,TIMP-1,MMP2 before and after treatment were detected and compared between groups.To observe therapeutic effect and safety of FZHY combined with entecavir on patients with CHB fibrosis.Results:(1)Clinical symptoms improvement:The symptoms,such as fatigue,insufficiency,abdominal distension and hypochondriac pain,etc.,were significantly improved after treatment(P<0.001)and no difference was found between groups(P>0.05).(2)Virological response: HBV-DNA of two groups was obviously lower than before treatment(P<0.001)with insignificant difference of descent degree between the group(4.35±0.40 vs 4.45±0.49,p=0.754).(3)Biochemical response:The level of ALT and AST in each groups changed obviously(P<0.001),However,the falling range of combination group was significantly lower than the single group(P<0.001).(4)Imaging aspect,the abdominal B-mode portal vein width of combination group improved significantly(P<0.001)while the changes in the single group were meaningless(p>0.05).Group comparison showed the index of combination group improved more obviously,the descent degree between was statisticallysignificant(5.40±0.55 mm vs 1.45±0.29 mm,P<0.001).(5)FibroScan comparison:The FibroScan value of combination group decreased significantly(P<0.001)and more obviously(10.47±0.70 Kpa vs 1.64±0.90 Kpa,P<0.001),while changes in single group was meaningless(p>0.05).(6)Hepatic fibrosis serological index(HA,LN,PIIIP,C-IV): Contents of index were decreased remarkable after treatment in two groups(p<0.05)and the level of combination group changed more obviously(p<0.05).(7)liver fibrosis related factors:The levels of TGF-?1,PDGF and TIMP-1 in two groups decreased significantly(p<0.05)and changes in combination group more obviously(p<0.05).the serum content of MMP2 in combination group was improved(p<0.05),while this index showed meaningless change in single group(p=0.664).Group comparison showed the drop of combination group was more obviously than single group(p<0.001).(8)Adverse reaction:1 cases of headache,1 cases of vertigo and 1 cases of nausea were found in combination group,while 2 nausea,1 headache and 1 vertigo in single group.There was no statistical difference in the incidence of adverse reactions among the groups(P=0.692>0.05).Conclusions:1.Fuzheng Huayu capsule / tablet combined with entecavir can achieve effective anti-virus and anti-inflammatory treatment,and to some extent,reverse the progress of liver fibrosis,delay the disease and improve the clinical symptoms,deserve to be widely used and promoted in clinic because of reliableefficacy and safety.2.The combination treatment can downgrade PDGF and TGF-?1 to inhibit the formation of extracellular matrix ECM,reduce the expression of TIMP-1 to promote the degradation of ECM,as a result to relieve liver fibrosis.