Ten-year Follow-up Outcomes And Predictive Factors Analysis Of Patients With Chronic Hepatitis C After Getting Sustained Virological Response To Pegylated Interferon And Ribavirin Therapy

Backgrounds and aimsChronic hepatitis C(CHC)is caused by hepatitis virus C(HCV)infection at least six months ago.According to the data from the World Health Organization(WHO),the HCV infection rate is about 3%worldwide,and it is estimated that people,who were infected with HCV,approximate 180 million.Moreover,there are about 35000 new infections with HCV each year.CHC is global epidemic,which can lead to chronic necro-inflammation and fibrosis of the liver,and some patients may develop liver cirrhosis and hepatocellular carcinoma(HCC).Within the next two decades,the mortality associated with HCV infection(liver failure or HCC)will continue to increase,which would bring a great harm to patient's health and life.Thus,CHC has become a serious social and public health problem.Antiviral therapy with pegylated interferon-?(PEG-IFN-?)plus ribavirin is the standard treatment of chronic hepatitis C,and the ultimate aim of antiviral therapy is to prevent progression to liver cirrhosis,HCC or death from chronic liver disease and to improve the quality of life for patients.It can be considered as a clinical recovery if a patient achieved a sustained virological response(SVR,defined as serum negative HCV RNA 24 weeks after the end of antiviral therapy using the TaqMan method),but a virological relapse is usually found in some patients during subsequent follow-up.Thus,SVR is only a surrogate for the ultimate aim of CHC patients.Recently,although the near-term benefits of SVR have been well established in CHC patients treated with PEG-IFN-? plus ribavirin,little is known regarding the long-term clinical,biochemical,virological and histological outcomes after SVR,which determined whether the ultimate aim of antiviral therapy can realize or not,but these ideal endpoints of antiviral therapy generally take years or decades to reach,and a few of existing long-term follow-up studies had some limitations because of fewer population,shorter follow-up period,different therapeutic regimen,no histological assessment or fewer tissue specimen.So,it is imperative to perform a more long-term clinical,biochemical,virological and histological assessment on a large patient population to more exactly draw the outline of long-term follow-up outcomes of CHC patients after getting SVR.MethodsThus,we conducted a prospective cohort study in five medical centers in China from January 2002 to December 2015.In this study,325 patients who achieved SVR after combination treatment with PEG-IFN-? and ribavirin were enrolled between 2002 and 2004 with an average follow-up period of ten years.All patients underwent consistent clinical,biochemical and virological evaluation every six months,and patients with pretherapy Ishak fibrosis score ?2 were invited to accept a second liver biopsy at the last follow-up.Liver biopsy specimens were blindly evaluated using Ishak's scoring system.We also analyzed the factors that could were associated with virological relapse with multiple logistic regression model.ResultsAt the end of follow-up,five(1.5%)patients developed decompensated liver cirrhosis,and one patient(0.3%)with pretherapy cirrhosis was diagnosed with HCC.Five patients died,but only two of them died from liver-related diseases----HCC and complications of liver cirrhosis,respectively.305 patients(94%)had normal serum ALT and AST levels during the entire period of follow-up.Twenty-seven patients(8%)had conclusive evidence of virological relapse.117 patients accepted the second liver biopsy,and among the 117 patients with paired pretherapy and long-term follow-up biopsies,ninety-six(82%)had a decreased fibrosis score;ninety-nine(85%)had a decrease in combined inflammation score;thirty-seven(32%)had normal or nearly normal livers on long-term follow-up biopsy.ConclusionsThe SVR achieved with PEG-IFN-a and RBV combination therapy is very durable,while late virological relapse may still occur in some patients.The clinical outcomes for CHC patients who obtain SVR are excellent,although the patients with cirrhosis are still at a low risk of hepatocellular carcinoma.Multiple logistic regression analysis indicates the independent factors associated with virological relapse were age,genotype,histological fibrosis,and presence of RVE or EVR.