No evidence of occult hepatitis C or E virus infections in liver‐transplant patients with sustained virological response after therapy with direct acting agents

Abstract

Background and Aims: It has been recently suggested that occult hepatitis C virus (HCV) infection and hepatitis E virus (HEV) reactivation might occur after direct acting antiviral agent-induced (DAA-induced) sustained virological response (SVR). The aim of our study was to identify occult HCV and HEV infection in a cohort of organ transplant patients who had achieved SVR and had persistent elevation in liver-enzyme levels. Patients and Method: Sixty-six liver and/or kidney transplant patients were treated with DAAs. All but one achieved SVR12. Twenty-nine (8-39) months post-SVR12, 8 of the 65 patients (12.3%) who achieved SVR12 had persistently elevated liver enzyme levels. In 1 patient, this was related to hepatitis B virus reactivation. In the 7 remaining patients, blood samples (n = 7), liver biopsies (n = 4), and peripheral blood mononuclear cells (PBMCs) (n = 7) were collected simultaneously in order to identify occult HCV or HEV infection.Results: Hepatitis C virus RNA and HEV RNA were not detected in serum, liver tissues, or PBMCs. No HEV reactivation was observed after HCV clearance in patients who had anti-HEV IgG. Conclusion:Our study suggests that there is no occult HCV or HEV infection in transplant patients after successful treatment of HCV infection with DAAs, even in patients with a persistent elevation of liver enzyme levels. However, due to the small number of patients included in our study, this finding should be confirmed in a larger cohort. K E Y W O R D Sdirect acting antiviral agents, hepatitis C virus, hepatitis E virus, kidney transplantation, liver transplantation, occult infection, ribavirin

Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus

“…The existing studies differ significantly in reporting the prevalence of occult infection. Some authors detect no or very rare cases of OCI, concluding that the clinical significance of this infection is negligible, and questioning the necessity to test for the presence of residual HCV-RNA [105][106][107][108]. Others find a relatively high percentage of OCI [5,53,103].…”

“…Differences in criteria of initial patient selection can greatly impede the comparison of OCI prevalence reported by different authors. In some studies, only those patients who have persistently elevated liver enzymes are selected for analysis among the initially enrolled individuals [34,108]. However, as this parameter cannot be regarded as a reliable marker for occult infection [5], the true OCI prevalence in the initial, unselected group of patients, can be underestimated.…”

“…Immunosuppression in OCI and CHC Another important variable in the selection of patients is the presence of immunosuppressive therapy. Some authors argue that if patients had OCI before transplantation or oncological treatment, immunosuppression applied afterward would lead to a robust HCV replication [108,110,111]. Indeed, enhanced HCV replication was observed in CHC patients treated with systemic chemotherapy or immunosuppressive therapy [112][113][114][115][116].…”

Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience

“…The mortality and morbidity of kidney transplant patients positive for HCV are higher than those of non-HCV infected individuals. 16 Although use of DAAs as a new therapeutic regimen has resulted in considerable improvement in management of CHD patients, 17 there are some recent findings on the observation of OCI in those who have developed sustained virologic response after DAA treatment. 18,19 The global reported prevalence of OCI in CHD patients is extremely variable with a range between zero and 45%, 20 which seems to have been affected by the regional epidemiology of HCV as well as access to new treatments.…”