Preliminary Study On Clinical Effectiveness Of DAA In Patients With Chronic Hepatitis C

Section 1 Preliminary study on Clinical effectiveness of DAA in patients with chronic hepatitis C: a real-world cohort based on Chinese Han population[Background] According to a survey released by the WHO,more than 70 million people worldwide was infected with HCV in 2015,and new infections reached 1.75 million.HCV infection has become a global public health concern.Since the occult nature,about 80% of infected people live with the virus and become chronic,and the self-restricted clearance rate is low.With the introduction of direct-acting antiviral(DAA),treatment options for patients with chronic hepatitis C(CHC)have undergone tremendous changes,greatly improving the efficiency and safety of CHC patients.However,due to policy and economic reasons,DAA had not been officially approved for listing in China in April 2017.There is no research on the effectiveness and safety of DAA patients in China in the real world.[Methods] A total of 474 patients with HCV infection were enrolled in this research.All patients were treated for 12 or 24 weeks with DAA regimens under the guidance of a physician.Informations of viral load biochemical test data,adverse events and the number of hepatocellular carcinoma(HCC)were collected at baseline,12 weeks of treatment,the end of treatment,and 24 weeks after treatment,respectively.The virological and chemical response rates,the incidence of adverse reactions,and the occurrence and recurrence rates of HCC were taken into consideration to evaluate the effectiveness and safety of DAA.[Results] Patients enrolled into the study were divided into four groups according to the DAA regimens,including 174 patients treated with sofosbuvir(SOF)combined with daclatasvir(DCV),28 patients receiving the treatment of SOF plus interferon(IFN)and ribavirin(RBV),64 people who received SOF combined with ledipasvir(LED),and 208 people treated with SOF combined with velpatasvir(VEL).91.38%(350/383)patients obtained rapid virological response(RVR).Patients treated with SOF plus VEL had the highest RVR rate of 95.98%(167/174),sofosbuvir combined with interferon and Ribavirin obtained the lowest RVR rate of 85.19%(23/27);99.14%(245/247)of patients obtained sustained virological response(SVR).Except for the regimen of SOF combined with IFN and RBV,the SVR rates of the other three regimens exceeded 99%.After DAA treatment,the liver function indicators and alpha-fetoprotein level were significantly improved,the ALT conversion rate reached 89.2%.The adverse effect rate was low,only 11 of 474 patients had general adverse reactions and no serious adverse effects.Seven patients had a progression to HCC with the occurrence density of 1.56/100 person-years.[Conclusion] In our research of Chinese Han HCV population treated with DAA regimens,patients achieved high SVR rate,low incidence of adverse reactions and no serious adverse reactions.The incidence of HCC was low,which needs further monitoring.Section 2 The development of hepatocellular carcinoma in HCV infected patients treated with DAA: A comprehensive analysis[Background] It has been proved by many researchers that hepatitis C virus(HCV)eradication after IFN based treatment can reduce the risk of hepatocarcinogenesis.However,there were some arguments about whether the treatment of direct-acting antivirals(DAA)boosts the development of hepatocellular carcinoma(HCC).We systematically review this crucial topic by combining all the relevant articles to calculate the pooled HCC density after DAA.[Methods] Studies reporting the recurrence or occurrence in chronic hepatitis C patients received DAA regimens were selected from two-retrieval library screening.Data on baseline and outcomes were extracted independently by two observers.Primary outcomes were incidence density of HCC.Pooled estimates of HCC occurrence and recurrence rate per 100 person years(py)were undertaken by random effects meta-analysis.[Results] Twenty-one studies with twenty-six cohorts,embracing 67350 patients,were enrolled in this study and divided into two groups(HCC occurrence and HCC recurrence).In the pooled analysis,HCC developed at a rate of 3.30 /100 py(95%CI: 2.31-4.71)among patients without a history of HCC compared with 18.12 /100 py(95%CI: 11.13-29.50)among patients existed.Furthermore,HCC occurrence rate following DAA-induced SVR was 1.90/100py(95%CI: 1.33-2.72),however,the rate in patients without SVR was 8.99/100py(95%CI: 5.96 – 13.57).HCV cured after DAA therapy could induce a reduction of 87% in the risk of HCC occurrence compared with non-responders.The similar result could be found at HCC recurrence by a reduction of 79%.[Conclusion] There is no strong evidence for an increased risk of HCC occurrence or recurrence in patients treated by DAA.There was significantly declined in the incidence of HCC occurrence after SVR.