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Objective Viral infections are often suspected to cause pediatric acute liver failure (PALF) but large-scale studies have not been performed. We analyzed results of viral testing among non-acetaminophen (non APAP) PALF study participants. Methods Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either Causative Viruses (CV) or Associated Viruses (AV). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included “Viral”, “Indeterminate” and “Other”. Results Of 860 participants, 820 had at least one test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among “Viral” [66/80 (82.5%)], “Indeterminate” [52/420 (12.4%)] and “Other” [48/320 (15.0%)] diagnoses. CV accounted for 81/166 (48.8%) positive tests. Herpes Simplex Virus (HSV) was positive in 39/335 (11.6%) who were tested: 26/103 (25.2%) and 13/232 (5.6%) among infants 0 - 6 months and over 6 months, respectively. HSV was not tested in 61.0% and 53% of the over-all cohort and those 0 - 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Conclusions Viral testing in PALF occurs frequently but is often incomplete. Evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

A study to determine the reproducibility of histopathological findings and diagnoses of rejection was carried out on a series of 42 liver allograft needle biopsy specimens by five pathologists practicing at four liver transplant centers. Pathologists from each of the four centers read each slide independently on two different occasions and were asked to assess 12 histopathological features and render a diagnosis. For all histological variables, the intrarater agreement was higher than the interrater agreement. Moderate to excellent agreement occurred among the pathologists about all histological variables thought to be important in establishing the diagnosis of acute rejection (i.e., portal tract inflammation, subendothelial inflammation and bile duct damage). Other variables such as lobular disarray, bile duct proliferation and particularly arteritis, however, were only fairly or poorly reproducible. Surprisingly, the diagnosis of acute rejection was more reproducible than the individual histopathological findings that were thought to be the basis for the diagnosis. The agreement for the diagnosis of chronic rejection, however, varied according to observer. We noted that relatively inexperienced observers within this group had some difficulties agreeing with more experienced observers in establishing a diagnosis of chronic rejection. These findings demonstrate that the histopathological diagnosis of acute cellular liver allograft rejection is highly reproducible within a group of experienced pathologists and that this diagnosis can be pooled in a common data base with confidence.

In order to determine risk factors associated with the development of AIDS-associated lymphoma (AIDS-NHL) in individuals with haemophilia, we undertook a case-control study of 25 patients with AIDS-NHL identified prospectively in the multicentre Hemophilia Malignancy Study (HMS) and 100 haemophilia controls with AIDS matched 1:4 by age and date of AIDS diagnosis. Clinical, laboratory and lifestyle characteristics and blood product usage during the 2 years before seroconversion and AIDS or AIDS-NHL diagnosis were compared between cases and controls. AIDS-NHL cases had higher haemoglobin, platelets, %CD4 and white blood count, with the latter approaching significance, 5700 microL-1 vs. 4000 microL-1, P = 0.063. The proportion of cases receiving anti-retroviral treatment prior to diagnosis was similar to that of AIDS-controls, 72% vs. 86%, but a significantly lower proportion of cases had been treated with intravenous pentamidine, 4% vs. 26%, P = 0.048. There were no differences between cases and controls in prevalence of antibody to hepatitis B or hepatitis C, HIV-related symptoms, lifestyle characteristics, or in the type or amount of blood product usage. Thus, clinical, lifestyle characteristics, antiviral drug treatment and blood product usage appear to have little, if any, effect on the development of AIDS lymphoma in HIV(+) patients with haemophilia.