When to Search for Occult Infection After Eradication of Hepatitis C?

Abstract

Dear Editors:We read with great interest the article by Elmasry et al on the detection of occult hepatitis C virus (HCV) infection (OCI) in patients with abnormal levels of serum aminotransferases despite a sustained virologic response (SVR), after treatment with direct-acting antiviral (DAA) agents for HCV reinfection, after liver transplantation. 1 OCI is characterized by 2 immune-viral/clinically distinct forms. The first is characterized by anti-HCV positivity but undetectable HCV-RNA in serum, and normal levels of serum aminotransferases. Individuals with this form have been labelled as having "secondary OCI" and are characterized by the presence of HCV-RNA in peripheral blood mononuclear cells and in the liver. They have a residual persistent HCV infection despite spontaneous or therapy-induced SVR.2 The second form is characterized by negativity for both anti-HCV and HCV-RNA in serum, although still displaying elevated levels of serum aminotransferases. 3,4 The reason that HCV-RNA is not detectable in the serum of OCI patients is unknown. It has been proposed that the number of circulating viral particles is too low to be detected by conventional molecular techniques.5 Although several authors have described this new form of infection with emerging implications in different clinical scenarios, 6 few data are available in the setting of liver transplantation.The results from Elmasry et al are very interesting. The authors found that 5 of 9 subjects with SVR, who were also biochemical nonresponders, had OCI. Consequently, they proposed that this group should receive an additional course of antiviral therapy.1 Considering that at the moment the prevalence of patients with OCI remains unclear, the proposal to treat patients who, after antiviral therapy, still have abnormal liver function tests and OCI, needs to be studied further. We think that the search for OCI and its treatment should also be justified in patients treated for HCV before liver transplantation 7 who maintain abnormal liver function tests despite achieving a SVR. This could limit the risk of viral recurrence after surgery. LAURA DE MARCO Conflicts of interestThe authors disclose no conflicts. Among the 9 patients in whom serum alanine aminotransferase (ALT) levels did not normalize despite a sustained virologic response (SVR) 12 weeks after therapy with direct-acting antiviral (DAA) agents for posttransplant recurrent hepatitis C virus (HCV) infection, positive-and negative-strand HCV-RNA were detected in 5 patients (55%): 4 (44%) in liver tissue, 2 (22%) in peripheral blood monocytes, and 1 in both. Notably, all 5 patients with the occult HCV infection (OCI) had the unfavorable (TT) genotype for rs12979860 near the interleukin-28B gene. The authors proposed that further investigations in subjects with normal ALT are necessary to determine whether OCI can cause the abnormal ALT levels. We obtained liver biopsy specimens from 25 patients (mean age, 63 ± 11 years; 9 men and 16 women) without a history of liver transplantation or the use of im...