American Society of Hematology

Figure 2

$Figure 2. Courses of hepatitis E infection in all 8 individual patients. (A) HEV RNA persisted, although HEV-IgM and HEV-IgG seroconversion occurred under immunosuppressive therapy. This patient died of therapy refractory progressive gastrointestinal GVHD with concurrent chronic HEV infection. (B) Acute ALT abnormalities arose during HEV infection. This patient was mistakenly diagnosed as hepatic GVHD, and immunosuppression was intensified multiple times because of persisting liver enzyme abnormalities. This patient cleared HEV with stopping all immunosuppression, after the diagnosis of HEV infection in this study. (C) This patient developed primary graft failure of a 8/8 human leucocyte antigen (HLA)-matched unrelated donor graft after reduced-intensity conditioning with rabbit antithymocyte globulin, fludarabine, and a single donor fraction of 2 gray total body irradiation. HEV RNA was present after second alloHSCT. This patient cleared infection after HEV-IgM and HEV-IgG seroconversion, supported by reduction of immunosuppressive therapy. (D) This patient developed graft failure of a 7/8 HLA-matched unrelated donor graft after reduced-intensity conditioning with rabbit antithymocyte globulin, fludarabine, and a single fraction of 2 gray total body irradiation. Patient’s disease relapsed 3 months after graft failure. Reinduction therapy was started with alemtuzumab (ALEM), and a second alloHSCT was prepared. However, because of recurrent infections, this patient was not able to complete treatment. Patient died shortly after his second cycle of alemtuzumab because of complications of meningitis and secondary sepsis with E coli. Of note, patient’s CSF samples tested positive for HEV. (E) Secondary graft failure occurred 3 months after the first alloHSCT. The second alloHSCT was complicated by multiple respiratory viral and bacterial infections, which eventually led to respiratory failure and death. (F) This patient was diagnosed as hepatic GVHD, and immunosuppression was introduced in August 2010. Patient cleared HEV after cessation of all immunosuppression, following the diagnosis of HEV infection. (G) HEV RNA was detectable at time of alloHSCT, and viral load increased under immunosuppressive therapy until patient died because of a respiratory viral infection. This patient showed HEV-IgM in 1 sample (black bar) and no HEV-IgG seroconversion. (H) HEV reactivation occurred after initial undetectable HEV RNA without seroconversion. After reduction of immunosuppressive therapy and addition of ribavirin (RIBA), the patient seroconverted and cleared HEV. The ALT upper limit of normal is 33 U/L and 44 U/L for females and males, respectively. The HEV RNA lower limit of detection is 143 (2.16 log) IU/mL.$

Courses of hepatitis E infection in all 8 individual patients. (A) HEV RNA persisted, although HEV-IgM and HEV-IgG seroconversion occurred under immunosuppressive therapy. This patient died of therapy refractory progressive gastrointestinal GVHD with concurrent chronic HEV infection. (B) Acute ALT abnormalities arose during HEV infection. This patient was mistakenly diagnosed as hepatic GVHD, and immunosuppression was intensified multiple times because of persisting liver enzyme abnormalities. This patient cleared HEV with stopping all immunosuppression, after the diagnosis of HEV infection in this study. (C) This patient developed primary graft failure of a 8/8 human leucocyte antigen (HLA)-matched unrelated donor graft after reduced-intensity conditioning with rabbit antithymocyte globulin, fludarabine, and a single donor fraction of 2 gray total body irradiation. HEV RNA was present after second alloHSCT. This patient cleared infection after HEV-IgM and HEV-IgG seroconversion, supported by reduction of immunosuppressive therapy. (D) This patient developed graft failure of a 7/8 HLA-matched unrelated donor graft after reduced-intensity conditioning with rabbit antithymocyte globulin, fludarabine, and a single fraction of 2 gray total body irradiation. Patient’s disease relapsed 3 months after graft failure. Reinduction therapy was started with alemtuzumab (ALEM), and a second alloHSCT was prepared. However, because of recurrent infections, this patient was not able to complete treatment. Patient died shortly after his second cycle of alemtuzumab because of complications of meningitis and secondary sepsis with E coli. Of note, patient’s CSF samples tested positive for HEV. (E) Secondary graft failure occurred 3 months after the first alloHSCT. The second alloHSCT was complicated by multiple respiratory viral and bacterial infections, which eventually led to respiratory failure and death. (F) This patient was diagnosed as hepatic GVHD, and immunosuppression was introduced in August 2010. Patient cleared HEV after cessation of all immunosuppression, following the diagnosis of HEV infection. (G) HEV RNA was detectable at time of alloHSCT, and viral load increased under immunosuppressive therapy until patient died because of a respiratory viral infection. This patient showed HEV-IgM in 1 sample (black bar) and no HEV-IgG seroconversion. (H) HEV reactivation occurred after initial undetectable HEV RNA without seroconversion. After reduction of immunosuppressive therapy and addition of ribavirin (RIBA), the patient seroconverted and cleared HEV. The ALT upper limit of normal is 33 U/L and 44 U/L for females and males, respectively. The HEV RNA lower limit of detection is 143 (2.16 log) IU/mL.

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