Comparison of HBV Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing ICI and Concurrent Antiviral Prophylaxis: a Prospective Observational Study

Study Overview
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Brief Summary
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Immune checkpoint inhibitor (ICI), including programmed cell death protein-1 (PD-1) inhibitor or programmed cell death-Ligand 1 (PD-L1) inhibitor , is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of ICI in patients with a high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and ICI.

Official Title
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Comparison of Hepatitis B Virus Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing Immune Checkpoint Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: ICI
* Drug: Antiviral Prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL) Seropositive for hepatitis B surface antigen (HBsAg) Received concurrent antiviral prophylaxis and at least one cycle of ICI treatment. Prior use of antiviral therapy was allowed Adherence to antiviral therapy A life expectancy of 3 months or more An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 Exclusion Criteria: other positive viral markers, including IgM antibodies to hepatitis A virus, the hepatitis C virus viral load, IgG antibodies to hepatitis D virus, IgM antibodies to hepatitis E virus Antibodies to human immunodeficiency virus, A lack of HBV DNA and liver function testing before the first immunotherapy and during the follow-up period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| high HBV-DNA group<br>patients with HBV-DNA >500 IU/ml | Drug: ICI<br>* Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)<br>Drug: Antiviral Prophylaxis<br>* Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir<br>|
| low HBV-DNA group<br>patients with HBV-DNA≤500 IU/ml | Drug: ICI<br>* Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)<br>Drug: Antiviral Prophylaxis<br>* Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV Reactivation rate | HBV Reactivation rate was defined as one of the following according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidelines: (i) a ≥2 log (100-fold) increase in HBV DNA compared to the baseline level, (ii) HBV DNA ≥3 log (1,000) IU/mL in a patient with previously undetectable level (since HBV DNA levels fluctuate) | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV-associated hepatitis | HBV-associated hepatitis was defined as HBV Reactivation plus an ALT increase to ≥3 times the baseline level and >100 U/L according to the AASLD 2018 Hepatitis B Guidance | 2 months | 
| PD-1 inhibitor disruption due to hepatitis | PD-1 inhibitor disruption due to hepatitis was defined as either premature termination or a delay of at least 7 days between PD-1 inhibitor cycles because of hepatitis. | 2 months | 
| overall survival |  | 12 months | 
| adverse event |  | 30 Days after ICI |