Real World Efficacy Of DAAs In The Treatment Of Patients With Chronic HCV Infection

Purpose:Hepatitis C virus infection is a world-widely important medical problem that needs to be solved urgently.The asymptomatic period after HCV infection is very long,so it is usually difficult to attract patients’attention before cirrhosis and HCC appear.In the past,there are fewer options for chronic HCV infection therapy.There are certain limitations in the applicable population and adverse actions which affect the prognosis of patients.Direct acting Antiviral Agents which have a wider scope of application and higher effectiveness,have been widely used worldwide after they are marketed.However,the drugs were launched late in China,and real-world researches are still insufficient.There are certain hidden dangers in clinical application due to lack of relevant research data.The purpose of this study is to enrich clinical research data by exploring the safety and effectiveness of a variety of DAAs to provide diagnosis and treatment basis for clinical decision-making.Methods:From January 2018 to June 2020,Patients who met the following conditions would be included in the study group:First of all,the enrolled patients need to meet the time condition.These patients should be treated at Hepatobiliary and Pancreatic Department of the Second Hospital in Jilin University between 2018.1-2020.6.Second,these patients need to be diagnosed with chronic hepatitis C,with or without cirrhosis.Finally,these patients need to voluntarily receive DAAs treatment and follow their doctors’advice.Combining the specific conditions of the patients and the situations of DAAs already on the market at that time,different DAAs were used for antiviral treatment.The treatment plans for patients with GT1 were:Elbasvir 50mg,Grazoprevir 100mg,1 tablet/day,oral,12 weeks,Merck&Co;Ledipasvir90mg Sofosbuvir 400mg±RBV,the dosage of RBV combined with patients’weight(For those weighing less than 75 kg,1000 mg once per day;for those weighing more than 75 kg,1200 mg once per day),oral,12 weeks,Gilead Sciences;Sofosbuvir 400mg,Velpatasvir 100mg±RBV,1 tablet/day,oral,12weeks,Gilead Sciences;Daclatasvirin 60mg(1 time/day)+Asunaprevir 100mg(2 times/day),24 weeks,Bristol-Myers Squibb;Obiparil mixture(2 tablets/time,1 time/day)+Dasabuvir 250mg(1 tablet/time,2 times/day)(This program is referred to 3D program),oral,12 weeks,Abb Vie.The treatment plan for GT2patients are:Ledipasvir 90mg/day,Sofosbuvir 400mg/day,±RBV,oral,12weeks;Sofosbuvir 400mg,Velpatasvir 100mg±RBV,1 tablet/day,oral,12weeks.Treatment plan for GT3 patients:Sofosbuvir 400mg,Velpatasvir100mg±RBV,1 tablet/day,oral,12 weeks.Treatment plan for GT1b+2a patients:Velpatasvir 100mg±RBV,1 tablet/day,oral,12 weeks.Treatment plan for unknown GT patients:Sofosbuvir 400mg/day,Velpatasvir 100mg/day±RBV,oral,12 weeks.Antiviral programs for patients with compensated liver cirrhosis:Ledipasvir 90mg/day+Sofosbuvir 400mg/day+RBV,oral,12weeks;Sofosbuvir 400mg/day,Velpatasvir 100mg/day,oral,12 weeks;Antiviral programs for patients with decompensated liver cirrhosis:Sofosbuvir400mg/day,Velpatasvir 100mg/day+RBV,oral,12 weeks;Daclatasvirin 60mg(1 time/day)+Asunaprevir 100mg(2 times/day),24 weeks.Detect the patients’GT before DAAs treatment,and use statistical methods to compare the patients’HCVRNA,liver function index,LSM,blood function index,coagulation function index,and kidney function index before and after treatment.Meanwhile,we observe the virological response rate of different patients treated with DAAs at different periods to evaluate the effectiveness and safety of DAAs.Results:(1)Our study included 104 patients.There were 49 male patients and 55female patients.The age was 50.98±10.91 years old,and the HCV RNA quantitative was 3.25(19.20,45.62)×10~5IU/ml.There were 56 cases of genotype 1b,42 cases of genotype 2a,2 cases of genotype 3a,1 case of 1b+2a genotype,and 3 cases of unknown genotype,accounting for 53.8%,40.4%,1.9%,1.0%,and 2.9%,respectively.(2)The virological response of DAAs in patients with different genotypes:Sofosbuvir+velpatasvir±RBV group of patients with different genotypes:The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT1b were respectively 91.7%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT2a were respectively 92.5%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT3a were respectively 50%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT1b+2a were respectively 100%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with unknown GT were respectively 100%、100%、100%、100%.The virological response of patients with different GTs in the ledipasvir+sofosbuvir±ribavirin group:The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT1b were respectively 87.1%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with GT2a were respectively 100%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with genotype 1b in the elbasvir grazoprevir group were respectively 75%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with genotype 1b in Daclatasvir+Asunaprevir group were respectively 75%、100%、75%、75%.The incidence of RVR、ETVR、SVR12、SVR24 in the 3D method group genotype 1b patients were 100%、100%、100%、100%.(3)The virological response of patients with different stages of DAAs treatment:The virological response of Sofosbuvir+velpatasvir±RBV group patients with different stages:the overall incidence of RVR,ETVR,SVR12,SVR24 of patients in this group were 91.4%,100%,100%,100%.The incidence rate of RVR,ETVR,SVR12,SVR24 in patients with CHC were93.5%,100%,100%,100%.The incidence of RVR,ETVR,SVR12,SVR24 in patients with compensatory cirrhosis were 92.9%,100%,100%,100%.The incidence of RVR,ETVR,SVR12,SVR24 in patients with decompensated liver cirrhosis were 84.6%,100%,100%,100%;Comparison of the virological response of patients with cirrhosis and non-cirrhosis in the sofosbuvir+velpatasvir±RBV group:HCVRNA in the non-cirrhotic group before treatment was 3.14×10~6(4.37×10~5,7.43×10~6)IU/ml and the HCVRNA in the cirrhosis group was 5.40×10~5(5.52×10~4,2.74×10~6)IU/ml.The Z value between the two groups was-2.475,and the P value was 0.013.The results of the study showed that both groups had high incidence,and there was no statistical difference between two groups.Virus response of patients with different stages in the ledipasvir+sofosbuvir±RBV group:The total incidence of RVR、ETVR、SVR12、SVR24 of patients in this group were 87.9%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with CHC were 90.9%、100%、100%、100%.The incidence of RVR、ETVR、SVR12、SVR24 in patients with compensatory cirrhosis were 81.8%,100%,100%,100%.The results in the cirrhotic group and non-cirrhotic group of Ledipasvir Sofosbuvir±RBV both showed high viral response.There is no difference in statistical comparison(P>0.05).The virological response of patients in the elbasvir grazoprevir group at different stages:the incidence of RVR,ETVR,SVR12,and SVR24 in patients with chronic hepatitis C in the elbasvir grazoprevir group were 75%,100%,100%,100%.The virological response of patients with different stages in asunaprevir+daclatasvirin group:the incidence of RVR,ETVR,SVR12,and SVR24 in patients with CHC in the asunaprevir+daclatasvirin group were 100%,100%、100%、100%;The incidence of RVR、ETVR、SVR12、SVR24 in patients with decompensated liver cirrhosis and HCC in asunaprevir daclatasvirin group were 0%、100%、0%、0%.The virological response of patients with different stages in the 3D plan group:The incidence of RVR、ETVR、SVR12、SVR24 in patients with CHC in the 3D plan group were 100%,100%,100%,100%.(4)After treatment with DAAs,the liver function of patients showed highly improvement.The amount of transaminase after therapy were decreased.Statistical analysis showed that there were significant differences in transaminase before and after DAAs therapy(P<0.01).The patients’LSM were highly lower than before,which have statistical significance(P<0.01).There were no obvious statistical significance in red blood cells,platelets,prothrombin time,activated partial thromboplastin time,β2microglobulin,glomerular filtration rate,and creatinine before and after therapy.Statistical analysis showed that there was no statistical significance in the above indices after DAAs thearpy(P>0.05).(5)Of the 104 patients included in this study,7 patients had adverse reactions during the medication period,accounting for 7.7%of the total.Three patients had abdominal distension while taking DAAs drugs.And two of them reported that taking DAAs before meals would affect appetite.One patient had fatigue,another had pulsatile headache,and one patient had a temporary increase in blood pressure after taking the drug.One patient had postoperative hemorrhage due to the same use of rivaroxaban while taking Sofosbuvir and Velpatasvir.During treatment,one hepatitis B carrier developed hepatitis B virus HBV DNA increased to 8.28×10~2IU/ml.His ALT increased to 55U/L and AST increased to 67U/L.After 2 weeks of treatment with entecavir(1 tablet per day),HBVDNA was lower than 100IU/ml.None of the adverse reactions described above affect patients’normal completion of the DAAs treatment course,and the adverse reactions disappeared within 1 week of the patients’withdrawal.Conclusion:(1)DAAs drugs are very effective in treating patients with chronic HCV infection.Most patients with chronic hepatitis C and patients with liver cirrhosis can obtain long-term stable virological response..(2)After DAAs treatment,patients’liver function has been significantly improved.The liver stiffness value has been highly reduced,and the prognosis is good.(3)DAAs have few adverse drug reactions.They are very safe and have no obvious impact on the blood system,coagulation function and renal function.