Chronic hepatitis E in a patient treated with rituximab and mycophenolate mofetil for Sjögren’s syndrome

Rheumatology key message HEV infection should be considered in case of unexplained hepatitis in immunosuppressed patients treated for systemic autoimmune diseases. We describe the case of a 65-year-old woman affected by SS and severe cryoglobulinaemic vasculitis since 2002. At disease onset she was treated with steroid boluses, plasmapheresis and oral CYC. Unfortunately, due to persistent skin ulcerations, severe multineuropathy and transverse myelitis, in the ensuing years the patient received several other immunosuppressants such as ciclosporin and AZA. Since 2010, rituximab cycles (2 g every 6 months) along with daily MMF (2 g/day) have been administered, leading to clinical remission. Liver enzymes findings correlated to immunosuppressive treatment and ribavirin course The figure shows the trend of liver enzymes from January 2013 through October 2015 and its relation to immunosuppressive treatment and ribavirin course. RTX: rituximab course; AST: aspartate aminotransferase; ALT: alanine aminotransferase. To our knowledge, this is the first report of chronic HEV infection in an immunocompromised patient treated with rituximab and MMF for a systemic autoimmune disease. Cases of acute hepatitis E in patients with inflammatory arthritis [4–7] and chronic evolution of HEV infection in an immunocompetent patient affected by SLE have been published [8], but reported either spontaneous viral clearance or successful antiviral treatment. As in most of the cases reported in Western countries, a foodborne infection is the likely cause of HEV hepatitis in our patient. Whether the first observation of transaminase elevation corresponds to a primary infection or to the reactivation of occult hepatitis E is questionable; nevertheless, the patient reached the most pronounced immunosuppression with the association of rituximab and MMF, right before the onset of overt hepatitis. Supposedly the depletion of B cells and the impairment of T cell function determined by the combined treatment was crucial not only for the absence of the primary immune response, but also for the persistence of HEV infection. Indeed, the diagnosis of acute and chronic hepatitis E in immunosuppressed patients may be challenging due to the lack of an effective antibody response or, conversely, to the high prevalence of HEV antibodies in the general population [3]. A PCR analysis to detect viral RNA should therefore be included in the workup of unexplained hepatitis in these patients. Moreover, beyond the possibility of spontaneous viral clearance after discontinuation of treatment [6, 7], in immunosuppressed patients HEV replication may persist despite a standard course of ribavirin, and re-treatment should be considered whenever possible to prevent disease progression [2]. Whether high-risk patients affected by autoimmune systemic diseases should be routinely screened before undergoing immunosuppressive treatment is debatable. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: A.G. has received research grants from Roche. All other authors have declared no conflicts of interest. Supplementary data are available at Rheumatology Online.