Outcome of Hepatitis E Virus Infection in Patients With Inflammatory Arthritides Treated With Immunosuppressants: A French Retrospective Multicenter Study

The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs.All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire.From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2–20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3–55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed.Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure.Hepatitis E virus (HEV) infection is ubiquitous and is due to a small nonenveloped virus with a positive-sense, single-stranded RNA genome. The virus was discovered in the 1980s. Four major genotypes representing a single serotype have been recognized: HEV1 and HEV2 are restricted to humans and transmitted via contaminated water in developing countries; HEV3 and HEV4 infect humans, pigs, and other mammalian species and are responsible for sporadic cases of autochthonous HEV infection in Western countries. In this setting, HEV infection causes acute disease, mainly in middle-aged and older men. Such an infection might be mistaken for drug-induced liver injury.¹ Acute HEV infection might range in severity from subclinical to fulminant, in particular in the risk group of pregnant women, whose death rate in the course of HEV infection could approach 15% to 20%.^2,3 However, in the rest of the population and in immunosuppressed patients,⁴ acute HEV infection is usually asymptomatic. Thus, in a French study of kidney transplant recipients, acute HEV infection was asymptomatic in 14 of 16 patients (87.5%).⁵ Some extrahepatic manifestations of HEV infection were reported. Kamar et al⁶ reported neurologic disorders among 126 patients with HEV infection: inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Hematological disorders, notably acute immune thrombocytopenia,⁷ were also reported.Recent efforts to develop and standardize the HEV serology led to data showing increasingly recognized cases of HEV infection. HEV infection might correspond to about 10% of cases of non-A–D acute viral hepatitis in Western countries among nontravelers.⁸Another feature of HEV is its ability to cause chronic infection, defined as a persistent infection lasting >6 months, usually in severely immunocompromised patients.⁹ In 3 well-known circumstances of immunodeficiency—AIDS, kidney or liver transplantation, and haematological malignancies—HEV infection can develop into chronic infection.^10,11 In liver transplant recipients,¹² chronic infection with HEV can result in HEV-related cirrhosis.¹³ However, little is known about the incidence and severity of acute and chronic HEV infection in patients with inflammatory rheumatic diseases. We therefore addressed this issue of HEV infection in patients receiving treatment for inflammatory arthritides.