Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure

Abstract

Summary Background A sustained viral response (SVR) after interferon‐based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work‐up with highly sensitive HCV RNA detection, and the determination of immune responses. Aim To determine clinical, histological, virological and immunological markers 5–20 years after SVR. Methods In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV‐specific T‐cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3‐specific antibodies and virus neutralisation. Results Liver disease regressed significantly in all patients, and 51 were HCV RNA‐negative in all tissues tested. There was an inverse association between liver disease, HCV‐specific T‐cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5–9 years after SVR. All three had HCV‐specific T cells and NS3 antibodies, but no cross‐neutralising antibodies. Conclusions Our combined data confirm that a SVR corresponds to a long‐term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

The accuracy and cost‐effectiveness of hepatitis C core antigen assay in the monitoring of anti‐viral therapy in patients with chronic hepatitis C genotype 4

“…Detection of HCV RNA in blood by qualitative and quantitative HCV‐PCR testing is the currently accepted ‘gold standard’ for diagnosis of active HCV infection and monitoring response to therapy given that sustained virological response was shown to correspond to a long‐term clinical cure . However, HCV‐PCR is a costly, time consuming procedures that require highly skilled technicians and well‐equipped laboratories that may be lacking in many resource‐limited countries .…”

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

“…HCV genotype 1 is the most common genotype and the most difficult to treat with interferon‐based therapy . Successful therapy has been equated with cure; it improves survival and quality of life …”

Long‐term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry

“…Second, although decent in the first few years after the transplantation, the survival of lung transplant patients with HCV deteriorates with time, and having HCV infection is a predictor of shorter time to death after the transplantation. Thus, aggressive management of HCV infection in pre‐ and post‐transplant patients is warranted …”

“…Thus, aggressive management of HCV infection in pre-and post-transplant patients is warranted. 17,18 An important limitation of the study is the availability HCV serology rather than HCV RNA positivity in the SRTR database. It is important to note, that for the U.S. general population, until the era of DAA which has not started until a few years ago, approximately 75% of seropositive individuals were also viremic.…”