Chronic hepatitis E in lung transplant recipients

Chronic courses of hepatitis E virus (HEV) infections have been described in various groups of immunosuppressed patients. We identified a particular high seroprevalence of anti-HEV in heart transplanted patients (Pischke et al., Am J Transplant 2012). However, the relevance of HEV infections in lung transplant recipients (Lu-TR) is unknown. We therefore studied in a first phase sera of 95 Lu-TR (including 44 patients with strongly [2 times ULN] elevated transaminases) for the presence of serological and virological markers of HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. Anti-HEV seroprevalence rate was compared to previously published data obtained for 537 healthy individuals (employees and blood donors), tested by the same assay. Subsequently, a prospective HEV screening of Lu-TR was initiated (second phase) which is still ongoing.

Results: Anti-HEV antibodies were detected in 5 of the 95 lung transplant recipients (5.3%) which was slightly higher than in healthy controls (2%, 11/537; p=0.07). Three Lu-TR were chronically infected with HEV. All of three patients had clinical evidence of advanced liver disease with significant biochemical activity (peak ALT levels of 89, 215 and 270 IU/ml respectively). We identified two additional Lu-TR with chronic hepatitis E during the second phase of prospective screening (peak ALT 359 and 318 IU/ml).

One Lu-TR died after development of multi-organ failure under the condition of liver cirrhosis before the diagnosis of hepatitis has been established (retrospective screening, phase I). Ribavirin therapy was initiated in the four remaining Lu-TR according to renal function and hemoglobine levels (400–1200mg/d for 5 months). Two patients cleared the infection with a sustained virological response; one patient is still under treatment. The fourth patient died from from graft failure which was not considered to be associated with ribavirin therapy.

Conclusion:

Chronic hepatitis E may explain elevated liver enzymes in some Lu-TR. Lung transplant recipients may develop chronic HEV infections which can cause end-stage liver cirrhosis and death. Lu-TR with elevated liver transaminases should be tested for HEV RNA. Ribavirin is an efficient treatment option for Lu-TR with persistent HEV infections.