Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial.

BACKGROUND: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). OBJECTIVE: To determine whether MARS improves survival in ALF. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705). SETTING: 16 French liver transplantation centers. PATIENTS: 102 patients with ALF. INTERVENTION: Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. MEASUREMENTS: 6-month survival and secondary end points, including adverse events. RESULTS: 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. LIMITATION: The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. CONCLUSION: This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. PRIMARY FUNDING SOURCE: Assistance Publique-Hôpitaux de Paris.

From RNA to quasispecies: a DNA polymerase with proofreading activity is highly recommended for accurate assessment of viral diversity.

RNA viruses are characterized by their high rates of genetic variation. Their genetic diversity is generally studied by reverse transcription (RT) followed by polymerase chain reaction (PCR) amplification and nucleotide (nt) sequence determination. The misinterpretation of viral diversity due to copy errors introduced by the enzymes used in this two-step protocol has not yet been assessed systematically. In order to investigate the impact of such errors, we sought to bypass the intrinsic viral heterogeneity by starting from a homogeneous cDNA template. With this in mind, the hepatitis C virus (HCV) 5' non-coding region (5'NCR) was amplified either by PCR starting from a homopolymeric cDNA template or by RT-PCR starting from the in vitro RNA transcript derived from the same original cDNA template. Amplicons were cloned and the 17-20 individual clones were sequenced in each assay. Different quasispecies patterns were obtained with various commercially available DNA polymerases, resulting in different computed error rates. The non-proofreading Taq DNA polymerase provided the highest error rate which was seven times higher than that obtained with the most reliable of the proofreading polymerases tested. We, therefore, emphasize that the misleading interpretation of the observed heterogeneity for a given viral sample could be due to ignorance of the fidelity of the polymerase used for viral genome amplification, and thus that proofreading DNA polymerases should be preferred for the investigation of natural genetic diversity of RNA viruses.

Borna disease virus RNA in immunocompromised patients in southwestern France.

Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range. Human infections, although controversial, have been described in Europe, Asia, and the United States. The present study investigated the existence of BDV infections in immunocompromised human beings, namely, 82 human immunodeficiency virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40 RNAs were detected in peripheral white blood cells with reverse transcription-nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the two groups of patients. BDV p24 RNAs were identified in only one of those. BDV RNA was detected in the absence of any neuropsychiatrical illness, suggesting that BDV infections may occur in asymptomatic carriers. The severity and particularity of cellular immunosuppression could explain the significantly increased detection of BDV RNA in HIV-infected patients.