HBV Reactivation a Serious Adverse Effect of DAAs in the Treatment of HCV

A kidney transplant patient treated with direct-acting antivirals (DAAs) for a chronic hepatitis C virus (HCV) infection showed reactivation of the hepatitis B virus (HBV), which proved fatal. The authors of the report recommend a call to action for including HBV testing as part of the patient’s work-up in transplant recipients who are on immunosuppressants, especially in the context of abnormal liver tests.

There are 4 classes of DAAs that target different proteins in the HCV virus:

• NS3/4A protease inhibitors: block the viral protease, which inhibits survival and replication in the host cell (galexos, grazoprevir, sunvepra)
• NS5B polymerase inhibitors: inhibit replication in the liver by binding viral RNA (sofosbuvir)
• NS5A inhibitors: prevent viral replication and infection process (daclatasvir, elbasvir, ledipasvir, ombitasvir)
• Non-nucleoside NS5B polymerase inhibitors: inhibit viral replication (dasabuvir)

Of these, the discovery of second-generation DAAs revolutionized the treatment landscape of HCV and introduced a potential for a cure. However, according to the new study published in the International Journal of Infectious Diseases, there are certain complications associated with these treatments that may be associated with patient comorbidities.

The authors of the report describe a 48-year-old male kidney transplant recipient with a chronic HCV infection who was treatment-naïve. On immunosuppressants (tacrolimus, mycophenolate mofetil, and prednisone), he developed end-stage renal disease and was evaluated for a third transplant. Following a panel of metabolic and liver-function tests, the patient was started on a combination of 2 DAAs: grazoprevir (100 mg/day) and elbasvir (50 mg/day) for 12 weeks.

Following a reduction in the dose of tacrolimus in the first few weeks, HCV-RNA was below the limit of detection (LOD) 6-weeks after DAA treatment was initiated. However, the patients had persistent elevated aminotransferase levels that were significant even till week 9. The patient was subsequently taken off of grazoprevir, which is known to cause liver toxicity and treated with valganciclovir for a cytomegaloviral load that was detected.

When the patient was readmitted to the hospital with fever and jaundice 2 months later, the HCV-RNA remained below LOD but the HBsAg antigen was detected, indicative of infection with HBV. A subsequent retrospective analysis of frozen serum samples found both HBsAg and HBV-DNA before DAA treatment was initiated, but the biomarkers peaked within a few weeks of treatment initiation.

The patient was started on entecavir for the HBV, but that did not prevent his liver deterioration and subsequent death a month later.

“This is a case of severe hepatitis B reactivation during anti-HCV therapy with grazoprevir and elbasvir,” the authors wrote, adding that a septic shock associated with profound immunosuppression may have had a significant role to play in the patient’s deterioration. They further highlight the need to test for HBV in immunosuppressed patients with the hope that earlier diagnosis and can help alter untoward outcomes.

Reference

Sastre L, Ruiz P, Costa J, Forns X. Severe hepatitis B reactivation during direct-acting antiviral treatment in “the absence” of hepatitis B surface antigen. Int J Infect Dis. 2018;pii: S1201-9712(18)34593-4. doi: 10.1016/j.ijid.2018.11.014.