The Efficacy Of Direct-Acting Antiviral Agents In Real World And The Diseases Progression And Clinical Outcomes Of Chronic Hepatitis C With Anti-Viral Treatments

BackgroundHepatitis C virus(HCV)infection,a global public health problem,an estimated 71 million people worldwide become infected,with the risk of making progress towards cirrhosis,hepatocellular carcinoma,death and multiple extrahepatic diseases besides,arise from the pantropic HCV.China is a high-incidence area with a high disease burden.There are two antiviral options for chronic HCV infection recommended by the Chinese guidelines for the present:(1)pegylated interferons plus ribavirin(PR)regimen;and(2)direct-acting antiviral agents(DAA).Comparing with the longer course of treatment,more serious adverse reactions,lower tolerance and poorer efficacy of PR regimen,DAA is the first-line antiviral option recommended by the latest authoritative international guidelines with the safety and efficacy having been confirmed by a great quantity of clinical studies since its coming on the scene.The limited data of short-term efficacy of DAA in real world in China due to the late marketing of the agents,first approved by European Union in 2011,especially in 2017,approved in mainland China,however,previous long-term observational studies with patients treated by PR regimen from 1998 having shown the reducing the incidence of HCC,delaying the progression of liver fibrosis,partial reversing liver cirrhosis after HCV erasion are absent in DAA in real world to research the long-term disease progression and clinical outcomes,especially based on Chinese and even East Asian patients,including but not limited to long-term antiviral efficacy,liver-related serious adverse events,all-cause death events,extrahepatic diseases,even though the efficacy and safety of DAA demonstrated in Chinese phase Ⅲ clinical trials.We originally studied three issues based on a prospective real-world cohort of our center in these studies:1)description of real-world short-term efficacy of DAA in a single center in the east of China;2)prospective description of real-world short-tomedium-term diseases progression and clinical outcomes after HCV erasion by DAA in a single center in China’s east;3)prospective exploration of predictors of progression of liver diseases and occurrence of HCC at short-to-medium-term follow-up after HCV erasion by DAA in a single center in eastern China.MethodsIn these studies,based on a prospective real-world cohort of patients with chronic hepatitis C in our enter,collecting the patient’s medical history and treatment plan,besides the blood routine,liver blood tests,HCV RNA(COBAS(?) TaqMan HCV test),alpha fetoprotein,blood lipids,fasting blood glucose,fasting insulin,abdominal ultrasound,FibroScan(?),adverse events(including death,hepatocellular carcinoma,surgery,etc.),complication,combined medications,etc.every 0.5 years,we retrospectively analyzed the SVR12 rate of DAA in Chinese patients and predictors of non-SVR12 by Logistic regression in PART A,prospective describe the rate of delayed relapse and clinical outcomes of liver blood tests,liver fibrosis,adverse events,metabolic markers,etc.at 1.0-to-1.5-year(average 1.28-year)follow-up after HCV erasion by DAA in PART B,and prospective analyze predictors of diseases progression and occurrence of HCC at short-to-medium-term follow-up after HCV erasion by DAA by logistic regression and Cox regression at a follow-up of 1.0-to-1.5-year(average 1.28-year)in PART C.ResultsIn real world,the overall SVR12 rate of DAA in Chinese patients was 97.0%(95%CI 95.0%-98.7%),and predictors of non-SVR12 including HCV GT3b[p<0.001,OR 136.000(95%CI 15.152-1220.702)]and HBV/HIV co-infection[p<0.001,OR 90.667(95%CI 7.200-1141.709)].At the 1.0-to-1.5-year follow-up after HCV erasion by DAA,the delayed relapse rate was<0.6%,the liver diseases were stable,no death,severe decompensation events or cirrhosis related surgical events occured,the rate of occurrence of HCC was 4.5%,the rate of progression of fibrosis was 8.4%,and the metabolic changes were TCho,LDL-C and HDL-C improved within 0.5 years and stable afterwards,insulin resistance increased within 0.5 years without improvement subsequently,and fatty infiltration of liver gradually aggravated.Predictors of the progression of liver fibrosis within 1.0-to-1.5 years were FibroScan(?)-E 7.4 kPa<E≤9.5 kPa[p=0.004,OR 15.208(95%CI 2.417-95.694)],PLT<140×109/L[p=0.012,OR 17.824(95%CI 1.870-169.846)]and history of drinking[p=0.045,OR 33.523(95%CI 1.088-1033.267)],and hepatocellular carcinoma were FibroScan(?)-E>9.5kPa[p=0.008,HR 21.791(95%CI 2.271-209.114)],LDL-C≥3.4mmol/L[p=0.007,HR 10.011(95%CI 1.892-52.975)]and elevated ALT[p=0.037,HR 5.337 95%CI 1.11125.647)].ConclusionsDAA is very effective in Chinese patients with HCV infection in real world,and at a short-to-medium follow-up after HCV erasion by DAA,stabilization of liver diseases,occurrence rate of hepatocellular carcinoma of 4.5%,improvement of blood liquids,aggravation in insulin resistance and gradually aggravation of fatty infiltration in liver being observed,with predictors of progression of liver fibrosis including mild liver fibrosis,low platelet count and history of drinking,and predictors of occurrence of hepatocellular carcinoma encompassing advanced fibrosis and cirrhosis,abnormal LDL-C and elevated ALT.