We read with interest the article by Grewal et al., which describes a case of chronic genotype-3 hepatitis E virus (HEV) infection that occurred in a patient with systemic lupus erythematosus and was successfully treated by ribavirin. The authors claimed that the patient was immunocompetent. However, the presented data are not sufficient to consider the patient as being immunocompetent.
Indeed, to date, chronic genotype-3 HEV infection has been only observed in immunosuppressed patients, i.e., transplant patients, hematological patients that have received chemotherapy, or patients infected with the human immunodeficiency virus (HIV). In solid-organ transplant patients, the use of tacrolimus, a potent immunosuppressant agent that targets T-cells, a low CD4-positive and CD3-positive cell counts, and a low anti-HEV-specific T-cell response were associated with the development of chronic HEV infection.[3-5] In HIV-positive patients, chronic HEV infection has been only observed in patients who have a CD4-positive cell count of <200/mm3.2,6 These data suggest that HEV occurred in a patient who was already heavily immunosuppressed.
In the case report by Grewal et al., the patient had a history of an autoimmune disease that had been treated nearly 40 years before the hepatitis episode with hydroxychloroquine and steroids. Since that time, the patient had been considered to be in remission. As mentioned by the authors, the history of lupus may have predisposed her to the development of a chronic infection. Furthermore, when the patient presented with elevated liver-enzyme levels, she was given azathioprine and steroids for 7 months. By 2 years later, because of persisting elevated liver-enzyme levels and progressive liver fibrosis, she received further treatment with oral steroids and azathioprine. However, the duration of this second course of immunosuppressants is not mentioned. Before claiming that this patient who received several courses of immunosuppressive therapy is immunocompetent, the authors should provide more details about her immunological status, i.e., total lymphocyte count, CD4-, CD8-, and CD3-positive cell counts, as well as her anti-HEV specific T-cell response. If the patient is really immunocompetent, this case report suggests that being immunosuppressed is not the only factor responsible for the chronic HEV infection. This has major implications for understanding the mechanisms of HEV persistence.
In summary, in the absence of additional immunological data, the case report by Grewal et al. describes an immunocompromised patient with chronic HEV infection who had a history of being treated for lupus and had received immunosuppressive drugs for an undiagnosed HEV infection, which was suspected to be autoimmune hepatitis.
Nassim Kamar, M.D., Ph.D.1-3
Jacques Izopet, Pharm.D., Ph.D.2-4
1Department of Nephrology and Organ Transplantation
3Université Paul Sabatier
4Department of Virology