Faculty Bibliography

Background: In the Foscarnet-Ganciclovir Cytomegalovirus (CMV) Retinitis Trial, time to first progression of newly diagnosed CMV retinitis was similar in the 2 treatment groups but was shorter when assessed by grading of fundus photographs at a central reading center than when assessed at the participating clinical centers. This report describes the extent and causes of this disagreement and considers the implications of the findings for clinical practice and future research. Methods: Clinical findings and photographic gradings were compared for extent and activity of retinitis at baseline and during follow-up. In selected cases of disagreement, the photographs and summaries of gradings and clinical findings were reviewed concurrently to determine the cause of disagreement. Results: Movement of the border of retinitis was observed sooner and activity of the border was considered to have increased more often at the reading center than at the clinical centers. Disagreements on time to first progression were more frequent when degree of border movement was small (odds ratios [ORs] for several comparisons ranged from 1.7 to 5.2), when border activity was judged to have decreased or remained the same since the preceding visit (OR, 2.0-193), and when retinitis at baseline did not involve zone 1 (the area within 1 disc diameter of the disc or within 2 disc diameters of the center of the macula [OR, 1.4-3.6]). There were 2 important causes of disagreement between clinical center and reading center. First, difficulty was encountered clinically in recognizing retinitis border movement in the absence of an obvious increase in border activity. Second, the reading center used a threshold for border movement small enough to be crossed by an initial expansion of retinitis borders occurring within 2 to 5 weeks of enrollment in some patients who were responding favorably to treatment (in that retinitis was becoming inactive and showed no further progression for many weeks). Conclusions: Comparisons of photographs from the current visit with those from several previous visits may increase clinicians' abilities to detect progression promptly. The use of additional outcome measures by reading centers, such as border movement of 1500 pm or more and change in area of retina involved by retinitis, may provide more accurate and useful comparisons of treatments. In making such comparisons, centralized photographic grading has the advantages of greater reproducibility and lesser risk of observer bias

Recurrence of hepatitis C is a significant problem after liver transplantation. This prospective study was done to assess the rate of recurrence and discuss two possible treatment modalities that have been successful in avoiding retransplantation. Twenty-one patients underwent orthotopic liver transplantation for hepatitis C at a metropolitan medical center over a 34-month period. The mean follow-up interval was 13.4 +/- 2.2 months (range 5-28 months). The patients were routinely evaluated with clinic visits and liver function tests, specifically total bilirubin, serum glutamic-oxaloacetic transaminase, and gamma-glutamyl transpeptidase. If values were elevated, the patient was admitted to the hospital for liver biopsy. Ten of the 21 patients demonstrated recurrence on biopsy. Two of 10 patients required no therapy. Interferon A was initiated in the remaining eight. Three of the eight patients had no significant response to interferon and were given intravenous ribavirin under an experimental protocol. Two of these three showed significant improvement in liver function values. The third died of chronic rejection. The incidence of recurrent hepatitis C after liver transplantation is significant. Many centers have had to resort to retransplantation. Our results show that with early detection and aggressive treatment with interferon and ribavirin, hepatitis C can be controlled and retransplantation may be avoided

Patients infected with human immunodeficiency virus (HIV) are at risk for a variety of liver diseases. We undertook a retrospective study of 501 HIV-seropositive patients to assess the yield of percutaneous liver biopsy. The most common indications for liver biopsy were liver test abnormalities (89.5%), fever for 2 weeks (71.9%), and hepatomegaly (52.0%). The most common biopsy-derived diagnosis was Mycobacterium avium complex (MAC), seen in 87 (17.4%) biopsies. Mycobacterium tuberculosis was found in 13 biopsies (2.6%). In 28 biopsies (5.6%) mycobacteria was seen, but speciation of the organism was not possible. Chronic active viral hepatitis was seen in 60 biopsies (12.0%). Opportunistic hepatic infection from other organisms was found in 14 biopsies (2.8%). The most common neoplasm was lymphoma, which was seen in 12 biopsies (2.4%). MAC infection of the liver was associated with elevated alkaline phosphatase (p = 0.01). Among patients with fever for 2 weeks after an extensive negative workup including bone marrow biopsy, 58.2% had a diagnosis by liver biopsy. Overall, 64.3% of liver biopsies yielded a histopathological diagnosis, 45.7% of which were potentially treatable. We could not evaluate whether liver biopsy had a positive effect on patient outcome and survival, nor did we attempt to prove that liver biopsy resulted in a change in treatment or a change in preprocedure clinical diagnosis. Thus, questions about the efficacy of liver biopsy cannot be answered. Liver biopsy may be a helpful diagnostic tool in HIV-positive patients with fever, liver test abnormalities or hepatomegaly

To examine whether the prolonged survival seen in patients treated with foscarnet compared with those treated with ganciclovir was due to a direct effect on human immunodeficiency virus (HIV) replication, HIV p24 antigen was measured. Of 71 receiving foscarnet, 54% were p24 antigen-positive at enrollment (vs. 44% of 79 receiving ganciclovir). By immune complex-dissociated (ICD) p24 antigen analysis, 87% and 78%, respectively, were positive. After 1 month of treatment, there was a significant decline in standard (mean decline, 10.1 pg/mL) and ICD (mean, 39.6 pg/mL) p24 antigen in both groups (P = .0001). Mortality was greater in those who were ICD p24 antigen-positive than in those -negative at baseline (P = .03) and in subjects with an increase in ICD p24 antigen than in those with a decline (P = .09). Thus, each drug had a suppressive effect on circulating p24 antigen, which was predictive of improved survival. The inhibitory effect on CMV replication may have a beneficial effect on limiting HIV replication

The clinical importance of gastrointestinal disorders among patients with acquired immunodeficiency syndrome (AIDS) is enormous. Estimates of gastrointestinal complaints among AIDS patients range from 30% to 90%. Many of these patients may be chronically ill and have multiple simultaneous opportunistic pathogens and neoplasms. The diagnosis and management of serious gastrointestinal complications that often occur in the setting of chronic illness represent major challenges in the care of patients with AIDS