Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents

Abstract

We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection.

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C

“…Our study here suggested that rapid viral suppression by IFN-free DAAs may depress cytotoxic inflammatory cells, thus leading to a state of temporal relative immunosuppression due to immune reconstitution, not only to transformed cells as shown in this study, but also to cells co-infected with viruses such as hepatitis B virus (HBV) or herpes viruses, as increased reactivations of these viruses have been reported in patients who undergo IFN-free DAA treatment[48, 49]. However, in this study, successful HCV eradication (leading to SVR or not) was still an optimistic predictor of HCC development (Table 3).…”

Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals

“…Rapid decline of HCV viral load by DAAs was experimentally or clinically associated with restored HCV-specific, often exhausted, CD8+ T cell function, memory T cell re-differentiation and lymphocyte deactivation, and normalized NK cell function [45–48], all of which may indicate a quick loss of anti-HCV immune responses. Interestingly, reactivation of other co-infected viruses, such as herpes virus, was observed after DAA-based anti-HCV therapy [49], suggesting simultaneous loss of bystander immune response to the viruses and possibly to neoplastic cells, which may lead to higher HCC recurrence after DAA treatment. On the other hand, complete remission of follicular lymphoma after DAA-based therapy was reported, suggesting that the influence of DAA-based SVR on cancer may vary according to cancer types and biological/clinical contexts [50].…”

Early emergence of opportunistic infections after starting direct‐acting antiviral drugs in HIV/HCV‐coinfected patients

“…There is no clear reason for the episodes of immunodepression‐related infections and reactivations that we found in HIV‐infected patients with suppressed HIV replication. It has been speculated that transient changes in immune status after HCV clearance with DAA combinations might increase the likelihood of VZV reactivations in HIV seronegative patients . Supporting this, a down‐regulation of intrahepatic interferon‐stimulated genes has been found after the resolution of HCV infection with sofosbuvir plus RBV .…”

“…However, it is not known whether some benefits of SVR to PegIFN/RBV on non‐hepatic outcomes might be extrapolated to DAA. On the contrary, some clinical events, such as HCC, herpes virus and hepatitis B virus reactivations, have been suggested to be related with the use of DAA combinations …”

“…Specifically, for herpes virus infections, a potentially high frequency of varicella‐zoster virus (VZV) reactivations was reported after all‐oral DAA regimens in HIV seronegative patients . It is not known whether DAA use in HIV/HCV coinfection may be associated with a greater likelihood of those infections.…”