Faculty Bibliography

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

Background: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial compared the use of either ganciclovir or foscarnet for the initial treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We previously reported that patients treated with foscarnet lived longer but were more likely to have their treatment switched, the latter suggesting foscarnet may not have been as well tolerated as ganciclovir. This study compared the morbidity and toxic reactions reported during the trial. Methods: Two hundred thirty-four patients with the acquired immunodeficiency syndrome and preciously untreated cytomegalovirus retinitis at 11 university centers were randomly assigned to receive intravenously either foscarnet (n = 107) or ganciclovir (n = 127). Medical histories, laboratory tests, and drug treatment histories during the first 6 months of treatment were analyzed. Results: Neutropenia was more common in patients assigned to ganciclovir than to foscarnet (34% vs 14%; P = .001). Patients assigned to foscarnet reported more infusion-related symptoms (58% vs 24%; P < .001) and, in male patients, more genitourinary symptoms (36% vs 16%; P > .001); they also experienced a trend toward more nephrotoxic effects (13% vs 6%; P = .082) and electrolyte abnormalities. The incidence of seizures was similar in both groups (foscarnet, 12%; ganciclovir, 9%; P = .511). Patients assigned to foscarnet were more likely to be switched to the alternative treatment (foscarnet to ganciclovir, 46%; ganciclovir to foscarnet, 11%, P < .001), and most of this excess was attributable to toxic reactions. In 88% of cases in which treatment was snitched as a result of toxic reactions and in which follow-up data were available, the toxic reaction resolved after the switch. No permanent disability or death resulted from toxic reactions. Conclusions: Compared with ganciclovir, the use of foscarnet was more frequently limited by the occurrence of toxic reactions. However, these toxic reactions rarely had long-term sequelae. In light of the previously reported survival benefit seen in patients treated with foscarnet, these data support the use of foscarnet for the initial treatment of cytomegalovirus retinitis

Esophageal disease is a significant cause of morbidity among patients with the acquired immunodeficiency syndrome (AIDS). Many organisms have been implicated in the pathogenesis of dysphagia and odynophagia. We describe a unique presentation of actinomyces esophageal infection in two homosexual male patients with AIDS and biopsy proven CMV esophagitis. After failure of esophagitis to resolve with ganciclovir or foscarnet therapy, the patients underwent repeat endoscopy and were subsequently found to have a secondary infection of the ulcers by Actinomyces. Treatment with intravenous penicillin G resulted in symptomatic and histopathological resolution of esophageal disease. This appears to be the first report of Actinomyces infection of esophageal ulcers in AIDS patients, possibly a commonly overlooked diagnosis