Hepatitis E infection in a patient with rheumatoid arthritis treated with leflunomide: A case report with emphasis on geoepidemiology

Abstract

Rationale: Hepatitis E is an infectious disease due to inflammation of the liver caused by hepatitis E virus (HEV) and represents one of the most common causes of acute hepatitis and jaundice in the world. Although data of hepatitis E infection in patients with rheumatoid arthritis (RA) are accumulating, little is known on the course of HEV infection. We reported, for the 1st time, a case of patient with RA with hepatitis E that developed during leflunomide therapy in combination with low-dose steroids.

Patient concerns: We present a 39-year-old woman, affected by RA and treated with leflunomide, reported diffuse itching and persistent fatigue laboratory data revealed elevated liver enzyme levels.

Diagnosis: Positivity for anti-HEV IgM and IgG was observed. HEV-RNA of the genotype 3 was detected, indicating acute E hepatitis.

Interventions and outcomes: Leflunomide was stopped and restarted 5 months after the initial diagnosis at the same dosage, with a close clinical and laboratory follow-up. The virus was eradicated from the serum without chronic transformation. The patient is alive and well 7 months after the initial diagnosis.

Lessons: To our knowledge, this report is the 1st case of acute E hepatitis in a patient with RA developed during leflunomide therapy in combination with low-dose steroids. Moreover, geoepidemiology of infection is important, due to the fact that Abruzzo, a central region of Italy, has the highest HEV seroprevalence in general population, related to the zoonotic transmission of the infection from domestic and wild animals. Our case highlighted that immunosuppressive therapy, and in particular leflunomide, could be safely reintroduced after the resolution of the infection and the clearance of the virus. Further studies are needed to evaluate potential advantages in serologic testing for HEV infection as a part of the routine workup done to patients with rheumatic diseases and selected for immunosuppressive therapy.

Figure 1

Course of liver enzymes and disease activity, considering HEV infection and immunosuppressive treatment for rheumatoid arthritis. ALT = alanine aminotransferase, AST = aspartate aminotransferase, DAS28-CRP = disease activity score 28-C-reactive protein, ENT = entecavir, HEV = hepatits E virus, LEF = leflunomide, PDN = prednisone, γ-GT = gamma-glutamyl-transferase.