In Europe, the dynamics of endemic hepatitis E virus (HEV) infection remain enigmatic. We studied the presence of silent HEV infection among Dutch blood donors. Using donations collected throughout the
Hepatitis E virus (HEV) infection is known to run a self-limited course. Recently, chronic hepatitis E has been described in several immunosuppressed patients after solid organ transplantation. The prevalence of HEV infection after transplantation, however, is unknown. We studied HEV parameters [HEV RNA, HEV immunoglobulin M (IgM), and HEV immunoglobulin G (IgG) by enzyme-linked immunosorbent assay and confirmatory immunoblotting] in a cohort of 285 adult liver transplant recipients. The most recent freeze-stored sera were investigated, and if they were positive, a retrospective analysis was performed. Samples from 274 patients (96.1%) tested negative for all HEV parameters. This included a patient described earlier as having experienced an episode of chronic HEV hepatitis in the past. One patient was found positive for HEV RNA without HEV antibodies. She presently suffers from chronic HEV hepatitis and has also been described before. Sera from 9 patients tested positive for HEV IgG without HEV IgM or HEV RNA. Six of these 9 patients (2.1% of the total) were found to have HEV IgG antibodies in retrospect related to an HEV infection at some time pre-transplant as they also tested positive in a pretransplant serum sample. One of these 9 patients suffered in retrospect from a chronic HEV infection with mild hepatitis between 2 and 5 years after liver transplantation on the basis of the course of HEV RNA, IgM, and IgG, aminotransferases, and liver histology. Overall, the prevalence of acquired HEV hepatitis after liver transplantation was 1% in this cohort. We conclude that liver transplant recipients have a risk for chronic HEV infection, but the prevalence is low.
Hepatitis E virus (HEV) infections are known to run a self-limiting course. Recently, chronic hepatitis E has been described in immunosuppressed patients after solid-organ transplantation. Besides the general recommendation to lower the immunosuppressive medication in these patients, there is currently no specific treatment. We here describe the successful use of pegylated interferon alpha-2b in the treatment of 2 liver transplant recipients who suffered a chronic HEV infection for 9 years (case A) or 9 months (case B). After 4 weeks of therapy, a 2-log decrease (case A) and a 3-log decrease (case B) in the viral load were observed. In case A, who received treatment for 1 year, serum viral RNA became undetectable from week 20 onward, and serum liver enzymes normalized completely. In case B, interferon was discontinued at week 16 because of a lack of a further decline in the viral load. However, 4 weeks after the cessation of therapy, viral RNA was no longer detectable in the serum, and this was probably related to a further decline in the immunosuppressive medication. Liver tests normalized completely. In both cases, no relapse has been noted so far. We conclude that pegylated interferon alpha-2b may be useful in the treatment of chronic HEV infections in patients in whom the reduction of the immunosuppressive medication alone is not sufficient. Enterically transmitted human hepatitis E virus (HEV) has long been known as a major cause of acute hepatitis E in developing countries, with occasional travelrelated cases in developed countries.
Background
Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response.
Methods
Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months.
Results
After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event.
Conclusions
This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.
This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.
We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.
Classic human polyomaviruses (JC and BK viruses) become pathogenic when reactivating from latency. For the rare skin disease trichodysplasia spinulosa, we show that manifestations of the causative polyomavirus (TSPyV) occur during primary infection of the immunosuppressed host. High TSPyV loads in blood and cerebrospinal fluid, sometimes coinciding with cerebral lesions and neuroendocrine symptoms, marked the acute phase of trichodysplasia spinulosa, whereas initiation and maturation of TSPyV seroresponses occurred in the convalescent phase. TSPyV genomes lacked the rearrangements typical for reactivating polyomaviruses. These findings demonstrate the clinical importance of primary infection with this rapidly expanding group of human viruses and explain the rarity of some novel polyomavirus-associated diseases.
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