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Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents for Recurrent Infection After Liver Transplantation
Elmasry S, et al .
Gastroenterology 2017 ; 152 :550-3.

Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum.
We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct acting antiviral (DAA) agents for recurrent HCV infection after liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection after liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12).
In >10% of the patients who achieved SVR12 (n = 14), serum levels of aminotransferases did not normalize during or after DAA therapy, or they normalized transiently but then increased sharply after DAA therapy. Of these 14 patients, 9 were assessed for occult HCV infection by reverse transcription quantitative polymerase chain reaction. This analysis revealed that 55% of these patients (n = 5) had an occult infection, with the detection of negative strand viral genome, indicating viral replication.
These findings indicate the presence of occult HCV infection in some patients with abnormal levels of serum aminotransferases, despite SVR12 to DAAs for HCV infection after liver transplantation

Expert's Commentary

« The clinical significance of occult hepatitis C infection (OCI), defined by the presence of HCV RNA in liver tissue or peripheral blood mononuclear cells (PBMC) in the absence of serum HCV RNA,  remains a topic of debate. Elmasry et al detected OCI in 5 patients who achieved SVR after liver transplantation, but had elevated ALT levels and factors associated with HCV chronicity, such as non-CC IL28B genotype. OCI has been detected in patients who achieved SVR in different ways: spontaneously, induced by interferon treatment, or Induced by direct-acting antivirals. Therefore, it seems that the manner in which the virus is cleared does not have an impact on the presence of OCI. Determination of HCV RNA in liver tissue requires sophisticated, sensitive methods that are not available in all laboratories. In addition, data about persistent detection of HCV RNA in PBMCs in patients with treatment-induced SVR are conflicting, as some studies have found genomic and antigenomic HCV RNA in PBMCs, and it is difficult to perform repeated invasive liver biopsies, particularly in patients with normal ALT levels. Nonetheless, it may be even more important to detect OCI In patients with normal ALT than in immunosuppressed patients. »

Pr Maria Butti,
Hospital General Universitari Valle Hebron, Barcelona