Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases.
The emergence of tumor necrosis factor-α (TNF-α)-targeted therapies as a key therapeutic option for patients with rheumatic, digestive, and dermatologic autoimmune diseases has been associated with increasing reports of liver damage in patients with hepatitis B virus (HBV) infection. We studied the current evidence on the use of anti-TNF agents in patients with HBV through a systematic analysis of cases reported in the MEDLINE and EMBASE databases using the MeSH term "hepatitis B virus" combined with the terms "infliximab," "etanercept," "adalimumab," "certolizumab," "golimumab," and "anti-TNF agents," and summarize the results here. We analyzed 257 patients with positive HBV markers who received anti-TNF therapy (255 identified in the search strategy and 2 new cases), 89 HBsAg+ carriers, and 168 anti-HBc+ persons. HBV reactivation was reported in 35 (39%) HBsAg+ carriers. The percentage of reactivation was higher in patients previously treated with immunosuppressive agents (96% vs. 70%, p=0.033) and lower in those who received antiviral prophylaxis (23% vs. 62%, p=0.003). Acute liver failure was reported in 5 patients, 4 of whom died. Infliximab was associated with a higher rate of induced liver disease (raised transaminase levels, clinical signs, viral reactivation, and acute liver failure) compared with etanercept. In anti-HBc+ persons, reactivation was reported in 9 (5%) cases, including 1 patient who died due to fulminant liver failure.In summary, our search of the current evidence identified 257 reported HBV+ patients treated with anti-TNF agents, with a significant percentage of liver damage in HBsAg+ carriers, including raised transaminase levels (42%), signs and symptoms of liver disease (16%), reappearance of serum HBV-DNA (39%), and death related to liver failure (5%). The rate of reactivation in anti-HBc+ persons was 7-fold lower than in HBsAg+ carriers. The increasing number of reported cases of HBV reactivation following TNF-targeted therapies and the associated morbidity and mortality demand specific preventive strategies.
From Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, Department of Autoimmune Diseases (RP-A, CD-L, PB-Z, MP-d-L, SR, AB, MR-C), Department of Internal Medicine, ICMiD (XB), and Liver Unit, Ciberehd, IDIBAPS (J-MS-T, XF), Hospital Clínic, Barcelona; Department of Internal Medicine (RP-A, MP-d-L), Hospital do Meixoeiro, Vigo; Department of Internal Medicine, Collagenosis and Pulmonary Hypertension Unit (FG-H), Hospital Virgen del Rocío, Sevilla; and Department of Gastroenterology and Hepatology (LL-R), Hospital Xeral-Calde, Lugo, Spain.
Roberto
R
Pérez-Alvarez
Cándido
C
Díaz-Lagares
Francisco
F
García-Hernández
Leopoldo
L
Lopez-Roses
Pilar
P
Brito-Zerón
Marta
M
Pérez-de-Lis
Soledad
S
Retamozo
Albert
A
Bové
Xavier
X
Bosch
Jose-Maria
JM
Sanchez-Tapias
Xavier
X
Forns
Manuel
M
Ramos-Casals
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000068800:Etanercept; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept