Faculty Bibliography

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

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

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

To determine the efficacy and safety of albendazole for treatment of intestinal microsporidosis due to Enterocytozoon bieneusi, 29 patients with AIDS were studied. All had chronic diarrhea, weight loss, and evidence of malabsorption. After 1 month of treatment with albendazole (400 mg orally twice a day), the mean number of bowel movements decreased from 7.0 to 3.8 stools/day (P < .0001) and the mean weight gain was 0.56 kg (P = .259). Albendazole at this dose did not clear E. bieneusi on follow-up small-bowel biopsies, but ultrastructural studies revealed an apparent decrease in parasite burden in 2 patients and an increased proportion of dividing plasmodia in 5 patients. There were no significant adverse events associated with this dose of albendazole. A formal double-blind placebo-controlled study using higher doses has recently been approved and will soon be underway (AIDS Clinical Trial Group protocol 207)

To determine the pharmacokinetics (pk) as well as evaluate the safety and efficacy of foscarnet (FOS) treatment at a dose of 90 mg/kg IV q12h in upper and lower gastrointestinal (GI) cytomegalovirus (CMV) infection 10 patients with the Acquired Immunodeficiency Syndrome (AIDS) were studied. Plasma FOS concentrations were measured by ion-pair reversed-phase liquid chromatography on days 1 and 20. Safety was evaluated by monitoring clinical/laboratory variables and adverse events. Efficacy was measured by histopathological examination of biopsies and endoscopic grading which were performed at baseline, week 3 and week 6. If resolution occurred at week 3, FOS was discontinued. Five patients with upper GI CMV disease and 5 with lower GI CMV disease were enrolled into study. Median age was 43.5 years and median CD4 count was 26.5 cells/mm3. On day 1, mean peak and trough plasma FOS levels were 621 +/- 130 and 37 +/- 20 micromolar, while on day 20, levels were 687 +/- 141 and 48 +/- 14 micromolar, respectively. FOS was discontinued in 1 patient after he developed hypokalemia and an increased serum creatinine. Another patient's 24 hour creatinine clearance decreased below 50 mg/ml after three weeks, but he completed therapy. Mild edema was noted in 2/10 patients (20%), but resolved. Eight of 10 patients (80%) required 6 weeks for full resolution. Nine of 10 patients (90%) responded histopathologically (P=.0067) and 9/10 (90%) responded endoscopically (P=.0004). In conclusion, the peak concentrations of twice daily administration of FOS were higher than those necessary to inhibit CMV. There was no difference in the pk between days 1 and 20. This regimen appears to be safe and effective in the treatment of gastrointestinal CMV disease in AIDS patients

Cytomegalovirus (CMV) is a common cause of diarrhea in patients infected with the human immunodeficiency virus (HIV). Infection with this entity is typically regarded as an effect of severe immunosuppression, only seen in AIDS patients when their CD4+ count is below 100 cells/mm3, and usually below 50 cells/mm3. We report two cases of HIV seropositive patients without a history of prior opportunistic infections, both with CD4+ counts over 500 cells/mm3 (510, and 664) documented on two separate occasions. Each patient presented with diarrhea and fever. One also had cramping abdominal pain, and the other hematochezia. Examination of stool samples for enteric bacterial pathogens, ova and parasites, acid fast bacilli, fungi, and assay for Clostridium difficile toxin failed to reveal an etiology. On sigmoidoscopy, the colonic mucosa of each appeared erythematous and inflamed. Biopsies of mucosa showed characteristic CMV inclusions and inflammation, diagnostic for CMV colitis. Both patients underwent induction with ganciclovir, which resulted in clinical endoscopic improvement. Post treatment biopsies showed no evidence of CMV. These patients illustrate the remarkable variability of CMV infection in patients infected with HIV. In patients with CD4+ counts above 500 who present with diarrhea of unknown etiology, CMV must remain a consideration

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied