Subfulminant hepatitis B after infliximab in Crohn’s disease: Need for HBV-screening

Abstract

Infections are a major adverse effect during the treatment with anti-TNF-alpha. While exclusion of any bacterial infection and screening for tuberculosis are mandatory before initiating a therapy with anti-TNF-alpha-antibodies, there are no guidelines whether to screen for or how to deal with chronic viral infections such as hepatitis B. In this case report, we have described a patient with Crohn's disease who developed subfulminant hepatitis B after the fourth infusion of infliximab due to an unrecognized HBs-antigen carrier state. He recovered completely after lamivudine therapy was started, but this severe adverse event could have been prevented if screening for HBV and pre-emptive therapy with lamivudine would have been started prior to infliximab. We therefore strongly argue in favor of extended screening recommendations for infectious diseases including viral infections before considering a therapy with infliximab.

Tumor necrosis factor alpha inhibits the suppressive effect of regulatory T cells on the hepatitis B virus–specific immune response

“…Neutralization of the TNF receptor during therapy with infliximab for Crohn's disease resulted in (re)activation of HBV among chronic HBV carriers. 31,32 Infliximab has been shown to restore the suppressive capacity of Treg. 19,33 PBMCs from patients with an acute HBV infection produce more TNF-␣ compared with PBMCs from patients with a chronic HBV infection, and a previous study by Van der Molen et al showed that the total amount of TNF-␣ produced by isolated myeloid-derived DC from patients with a chronic HBV infection was decreased compared with myeloidderived DC from healthy controls.…”

Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease

“…[25][26][27][28][29][30] Table 3 presents a summary of studies reporting reactivation of HBV after infliximab, specifically in patients with IBD (CD in all cases). 7,[31][32][33][34][35][36][37][38] Cases of reactivation after treatment with infliximab have been described in occult carriers of HBV who are negative for HBsAg and positive for anti-HBc antibody 37 (see occult HBV infection, below). Reactivation of HBV infection in HBsAg carriers occurred as soon as after the HBsAg, hepatitis B surface antigen.…”

Risk of Infections of Biological Therapies with Accent on Inflammatory Bowel Disease

“…Among patients who have received immunosuppressants, the rate of liver dysfunction was higher among HBsAg-positive patients than among HBsAgnegative ones (166). HBV reactivation in IBD patients treated with IFX is described in several patients in Table 4 (167)(168)(169)(170)(171)(172)(173)(174).…”

“…Symptoms of HBV reactivation can include fever, malaise, fatigue, nausea, loss of appetite, weight loss, weakness, dyspepsia, and joint and/or abdominal pain (169,(171)(172)(173). Hepatic manifestations are the predominant symptoms, including hepatitis or jaundice with elevated AST, ALT, alkaline phosphatase (ALP), γ-glutamyl transpeptidase and total bilirubin.…”

“…Two of these patients were found to be HBV carriers based on markers of HBV infection in serum collected at previous visits (169,171). Archival serum was not available in a third patient (172), while results are not described in the fourth (173).…”