Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma

Abstract

BackgroundImmunotherapy with immune checkpoint inhibitor (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC). However, whether ICIs would have the risk of hepatitis B virus (HBV) reactivation and the necessary of nucleos(t)ide analogs (NUCs) prophylaxis are still unclear. We aimed to investigate the role of NUCs prophylaxis in HBV-infected patients who underwent ICIs treatment.MethodsThe study was a retrospective prospective design to review and follow-up consecutive 62 patients with chronic hepatitis B or resolved HBV infection who had received ICIs treatment for the unresectable HCC. Of them, 60 patients with documented baseline serum HBV DNA value were classified into three categories according to the baseline HBV viral load and the status of antiviral therapy before ICI treatment. The clinical status, including tumor response, viral kinetics and liver function, was recorded and investigated.ResultsNo HBV reactivation occurred in the 35 patients with HBV DNA ≤100 IU/mL on NUCs therapy. Of the 19 patients with HBV DNA >100 IU/mL who started NUCs simultaneously with ICI treatment, none encountered HBV reactivation during the immunotherapy. Of the six HBV patients without NUCs treatment, three had a greater than 1 log decrease in HBV viral load, and one maintained his serum HBV DNA in undetectable status during ICI treatment. Eventually, one out of six experienced HBV reactivation after 9 weeks of ICI treatment.ConclusionNo patients on antiviral therapy developed HBV reactivation, and one out of six not receiving antiviral therapy had HBV reactivation. HBV viral load higher than 100 IU/mL is safe and not a contraindication for ICI treatment for HCC, if NUCs can be coadministrated.

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

“…One out of six patients who did not receive NUCs treatment experienced HBV reactivation and was controlled by tenofovir treatment soon, no HBVrelated liver failure occurred. 40 Accordingly, HBV surface antigen (HBsAg), HBV core antibody (HBcAb), HBV surface antibody (HBsAb), and HCV antibody should be tested before ICI therapy. HBV DNA and quantitative HCV RNA levels and genotype should be obtained if HBsAg, HBcAb or HCV antibody are positive.…”

Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients

“…There was no increased incidence of major safety issues such as HBV reactivation during ICIs treatment. In a study of 60 CHB-HCC patients, no patients on antiviral therapy (regardless of HBV viral load at baseline) developed HBV reactivation, and one out of six not receiving Nucs had HBV reactivation [ 159 ]. In another large cohort of 397 patients, HBV reactivation only occurred in 2 HBsAg-positive patients (<1%) [ 160 ].…”

Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

“… 22 A recent publication has also found that treatment with anti-PD-1 antibodies with simultaneous treatment with antiviral drugs is safe and precludes viral reactivation. 23 Indeed, general guidelines for immunosuppressed patients recommend antiviral prophylaxis for patients with occult HBV infection (HBsAg-negative, anti-HBc-positive, with detectable HBV DNA), 24 although the risk of reactivation is very low, 25 26 and that periodic monitoring of alanine aminotransferase levels, HBsAg and HBV DNA should be performed, with antiviral therapy deferred until confirmation of viral reactivation (seroconversion to HBsAg-positive or detectable HBV DNA). The most frequent antiviral drugs used for HBV are nucleoside or nucleotide analogs (NUCs), such as entecavir, tenofovir disoproxil or tenofovir alafenamide.…”