Follow-up Study Of Disease Progression In Patients With Chronic Hepatitis C Treated With Antiviral Therapy

Chronic hepatitis C(CHC)is one of the global public health problems caused by hepatitis C virus(HCV)infection that seriously endangers human health.The goal of HCV antiviral therapy is to eliminate the virus and achieve sustained virologic response(SVR).The ultimate goal is to improve survival,reduce or eliminate HCV-related liver damage,reverse liver fibrosis,prevent progression to cirrhosis,decompensated cirrhosis,liver failure or hepatocellular carcinoma(HCC),and improve the long-term survival and quality of life.Direct-acting antivirals(DAAs)have greatly reformed antiviral therapy,being on the market for a short period of time,and lacking of the longterm follow-up studies in China.However,it is unclear whether the impact of SVR with either interferon(IFN)regimens or DAAs on event-free survival(EFS)of liver-related events or death.[Objectives] Based on the real-world data of antiviral therapy for Chinese Han population with chronic hepatitis C,we understand the EFS post-treatment,and explore the association between SVR and EFS,and provide a theoretical basis for guiding the rational use of DAAs therapy.[Methods] All patients with chronic HCV infection who initiated treatment at the outpatient and inpatient department of an infectious disease department in Jurong People’s hospital affiliated to Jiangsu University(Zhenjiang,Jiangsu)from January 2009 to December 2019 with known treatment outcome(SVR or Non-SVR)were included.In order to control the severity of the disease,refer to the hepatitis C prevention and treatment guidelines(2015 Edition)to determine whether interferon contraindications(IFN-Eligible or IFN-Ineligible).Outcome events were liver-related events(decompensation and hepatocellular carcinoma),and mortality.[Results] A total of 1241 patients with chronic hepatitis C on antiviral therapy were enrolled.The annual incidence of liver-related events or death was 1.47%;the five-year EFS was 95.37% for IFN-Eligible and 89.65% for IFN-Ineligible.In 662 IFN-Eligible patients,332 DAAs and 330 IFN.SVR was 97.9% with DAAs vs.55.8% with IFN(P<0.0001).SVR was associated with improved EFS with an adjusted hazard ratio(HR)of 0.16(95% confidence interval [CI]: 0.05–0.48,P=0.001).Using inverse probability of treatment weighting to match SVR in IFN-eligible,there was no statistical significance of EFS between DAAs and IFN(HR=0.70,95%CI: 0.14-3.37,P=0.652).[Conclusion] The higher 5-year EFS in IFN-Eligible than IFN-Ineligible posttreatment in Jiangsu.Among similar severity of liver disease,SVR is more commonly achieved with DAAs and confers a similar EFS benefit as in those treated with IFN.Among patients treated with either IFN or DAAs regimens,in contrast to Non-SVR,an increase of EFS in SVR.The widespread availability of pan-genotypic combination DAAs regimens has provided new era in HCV infection.DAAs is highly effective,well-tolerated,and relatively short duration.These beneficial effects of antiviral therapy for HCV have been clearly demonstrated in patients who achieve SVR,whereby liver-related and allcause mortality are significantly reduced.However,HCV recurrence risk persists after virus eradication with DAAs,particularly in patients with ongoing high-risk behaviors.Currently,there are limited data that recurrence occurs post-SVR.Furthermore,there are less data available regarding long-term durability of SVR.[Objectives] We conducted a systematic analysis in order to assess the risk of HCV recurrence in chronic HCV infection after successful DAAs-based treatment.[Methods] A search was conducted for manuscripts published between January 2011 and December 2020 reporting HCV recurrence(late relapse or reinfection)rates.Identified publications were then divided into three different groups according to risk factor for HCV reinfection: low-risk,high-risk and human immunodeficiency virus(HIV)coinfection population.The primary HCV recurrence rate was estimated by using events divided by the person-years of follow-up(PYFU).Results were pooled using a random-effects model and used to calculate 5-year recurrence risk.HCV recurrence was defined as confirmed detectable HCV RNA following documented SVR with DAAs therapy.[Results] In the 15 studies of HCV mono-infected low-risk patients(n=14950),the pooled recurrence rate was 0.98/1000 PYFU(95%CI: 0.18-2.23,I2=61%),with a corresponding 5-year recurrence risk of 0.49%(95%CI: 0.09%-1.11%).In contrast,in the 17 studies of HCV mono-infected high-risk patients(n=7693),the pooled recurrence rate was 19.06/1000 PYFU(95%CI: 9.34-31.63,I2=87%),with a corresponding 5-year recurrence risk of 9.17%(95%CI: 2.55%-14.85%).In the eight studies of HIV/HCV co-infected patients(n=3568),the pooled recurrence rate was 24.72/1000 PYFU(95%CI: 3.27-61.04,I2=94%),leading to a 5-year recurrence risk of 11.76%(95%CI: 1.62%-27.01%).The higher pooled estimates of recurrence in the high-risk HCV mono-infected and HIV/HCV co-infected populations were driven by an increase in reinfection rather than late relapse.[Conclusion] The HCV recurrence risk after achieving SVR with all-oral DAAs therapy is low and the risk of HCV recurrence in high-risk and HIV/HCV coinfected populations was driven by an increase in reinfection rather than late relapse.