Chronic Hepatitis E Virus Infection: Successful Virologic Response to Pegylated Interferon-α Therapy FREE

Background: Acute hepatitis E virus (HEV) infection is usually followed by complete recovery, but some cases of chronic HEV infection have been reported.

Objective: To report a case of chronic HEV infection in an immunocompromised patient with no history of immunosuppressive therapy or HIV infection.

Case Report: Clinicians diagnosed hairy cell leukemia in a man aged 57 years in 2007. He was never treated because the disease was indolent with only moderate thrombocytopenia (platelet count, 85 × 10⁹ cells/L). We saw him in November 2008 for elevated liver enzyme levels (alanine aminotransferase, 135 IU/L; aspartate aminotransferase, 80 IU/L; and γ-glutamyltransferase, 311 IU/L). We ruled out all other causes of acute and chronic liver disease and detected HEV RNA in the patient's serum and stools. Test results for anti-HEV IgG and IgM were positive (Adaltis, Ingen, France), and the HEV genotype was 3c. We performed a liver biopsy in December 2008 and found mild lobular hepatitis without fibrosis. The leukocyte count was 4.3 × 10⁹ cells/L, and the hairy cell leukocyte count was 0.45 × 10⁹ cells/L. The CD4⁺ cell count was normal (0.582 × 10⁹ cells/L). We detected no monocytes in the peripheral blood. After 1-year follow-up without therapy, we started the patient on a 3-month course of pegylated interferon-α2b, 1 µg/kg of body weight per week (Figure). The serum HEV RNA concentration decreased from 5.6 log₁₀ copies/mL at baseline to 2.4 log₁₀ copies/mL by week 2, and the patient achieved a complete virologic response by week 4 (Figure). At week 7, liver enzyme levels remained within the normal range, and we could not detect HEV RNA in stools (lower limit of detection, 200 copies/g). We stopped antiviral treatment in November 2009 and could not detect serum HEV RNA after 5 months (lower limit of detection, 200 copies/mL) (Figure).

Discussion: We have reported elsewhere (1) that HEV infection can evolve into chronic hepatitis E in organ transplant recipients receiving immunosuppressive drugs. Two other cases (2 - 3) of prolonged HEV infection have been reported: 1 in a patient with lymphoma being treated with rituximab (2), and another in an immunocompromised patient with HIV infection (3). The lymphocyte and CD4⁺ cell counts were lower than normal in our transplant recipients (1) and in the patient with HIV (3), and they were not reported for the patient with lymphoma (2). Hairy cell leukemia is an indolent chronic B-cell lymphoproliferative disease with a good long-term prognosis, and its main complication is infection (4). We chose to treat this patient with pegylated interferon-α2b for several reasons. We have reported (1) that immunosuppressive drugs are associated with progression to severe liver fibrosis in chronic HEV infection, so we treated this patient's chronic HEV infection with pegylated interferon-α2b before using immunosuppressive drugs for leukemia. Also, interferon-α was the first effective treatment for chronic hepatitis B and C infections, and we have reported elsewhere (5) that pegylated interferon-α has antiviral effects in liver transplant recipients with chronic HEV infection. In addition, pegylated interferon-α is used to treat hairy cell leukemia and has no substantial adverse effects (4). In our patient, a short, 3-month course of pegylated interferon-α2b was associated with clearance of HEV without relapse. Although pegylated interferon-α2b might have affected the leukemia, which in turn might have led to improved immune function, we believe that pegylated interferon-α2b had a direct antiviral effect against the HEV infection because of the rapid decrease in serum viral RNA after only 2 weeks of treatment without a change in monocyte or lymphocyte levels.

Conclusion: To our knowledge, this is the first report that chronic HEV infection may occur in an immunocompromised patient without a history of immunosuppressive therapy or HIV infection. In addition, we suggest that pegylated interferon-α is an effective treatment for chronic HEV infection.

Laurent Alric, MD, PhD

Delphine Bonnet, MD

Guy Laurent, MD, PhD

Nassim Kamar, MD, PhD

Jacques Izopet, PharmD, PhD

Toulouse University Hospital

31059 Toulouse, France