Patients receiving immunosuppressive therapy are being put at risk of severe hepatitis flares and liver failure because they are not being tested for hepatitis B infection prior to starting therapy, a South Australian study shows.
Although screening is recommended in guidelines to avoid reactivation of hepatitis B infection by immunomodulator drugs, only about half of patients taking rituximab (Mabthera) had adequate hepatitis testing, an audit by Adelaide clinicians found.
The lack of adherence to screening protocols suggested a lack of awareness of screening guidelines by rheumatologists, they said.
In a review of 438 patients starting rituximab at six hospital in South Australia, the researchers from Flinders Medical Centre found that 48% failed to receive the recommended HBV screening.
Given the risk of reactivation of hepatitis B, current guidelines state that all patients starting rituximab therapy should be screened for infection, with tests that include hepatitis B surface antigen (HBsAg ) and hepatitis B core antibody (HBcAb).
However, one in five patients starting rituximab had neither hepatitis B surface antigen nor hepatitis B core antibody performed, and 119 (27%) had only hepatitis B surface antigen performed.
The lack of adherence was a concern because the study also showed that 5% of patients (20 of the 438) treated with rituximab were at risk because they were either HBsAg or HBcAb positive.
There were five cases of current hepatitis B infection among the study patients, of whom one developed hepatitis B virus reactivation 16 months after staring rituximab. There were no cases leading to acute liver failure, transplantation or death.
Writing in the Internal Medicine Journal, the study authors, from the Liver Transplant Unit at Flinders Medical Centre, said reactivation of hepatitis B was uncommon, but when it did occur it could have serious consequences including fulminant liver failure and death.
The absolute risk for hepatitis B reactivation was 25% for chronically infected patients (HBsAg positive) and 3% for resolved infection (HBsAg negative and anti-HBc positive), they noted.
The researchers said rheumatologists were less frequent users of rituximab than haematologists, with consequent lower awareness of risks and the need for HBV screening, they added.
“Informal feedback suggested that there was a poor understanding of anti-HBc which was frequently confused with anti-HCV antibody,” they noted.
Adherence to testing protocols was better among haematologists, perhaps because they were more familiar with the use of rituximab as part of widely-used R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) for haematological malignancies, the study authors said.
“It is also possible that the [hepatitis B screening] protocol itself contributed to poor adherence for rheumatologists as the first line of the protocol describes screening requirements for chemotherapy patients rather than also identifying rituximab use as a biological agent,” the researchers said.
The findings showed a need for better clinician education on rituximab protocols and perhaps a re-design of the system to prevent hospital pharmacies supplying rituximab to a patient without documentation of HBsAg and anti-HBc results, they suggested.