Granulomatous hepatitis in a patient with chronic hepatitis C treated with interferon-alpha.

Common adverse effects of IFN-alpha include flulike symptoms, headache, irritability, and bone marrow suppression. Hepatic side effects are unusual except in patients with pretreatment autoimmune hepatitis. Granuloma formation in the liver as a result of IFN-alpha therapy has never been reported. We described a 48-year-old female with chronic hepatitis C infection who developed granulomatous hepatitis following treatment with IFN-alpha. The granulomatous inflammation resolved after discontinuation of IFN-alpha treatment. Possible mechanisms for this unusual occurrence are discussed.

Intrahepatic cholestasis due to systemic mastocytosis: a case report and review of literature.

A 35-yr-old female presented with symptoms of obstructive jaundice. Liver biopsy, bone marrow aspiration, and biopsy revealed systemic mastocytosis and acute myeloid leukemia. The liver biopsy specimen showed infiltration of mast cells within portal tracts with periductal and portal edema, irregularity of interlobular duct epithelium, and centrizonal cholestasis. Endoscopic retrograde cholangiography was normal. Following chemotherapy treatment with idarubicin and cytarabine for seven days for AML, the bilirubin levels continued to increase for two weeks and then decreased, reaching normal levels in two months. Infiltration of mast cells in the liver leads to hepatomegaly, liver function abnormality and rarely portal hypertension. Intrahepatic cholestasis due to systemic mastocytosis has never been reported. We report a rare case of systemic mastocytosis causing intrahepatic cholestasis that resolved with remission of AML following chemotherapy.

Candida albicans osteomyelitis in a liver transplant recipient: a case report and review of the literature.

A 51-year-old man developed fever and back pain 2 months after orthotopic liver transplantation for end-stage liver disease secondary to chronic hepatitis C infection. CT scan demonstrated destructive lesions in T12 suggestive of osteomyelitis. Aspiration biopsy of the vertebra revealed granulomatous inflammation and yeast forms; culture yielded Candida albicans. The patient improved with intravenous amphotericin B and 5-fluorocytosine and did not require surgical intervention. Candida osteomyelitis is a rare condition and to our knowledge it has not been reported before in liver transplant recipients. Awareness of this potential complication may shorten the delay in making the definitive diagnosis, which in turn may increase the likelihood of a response without sequela.

Mode of food intake reduction in Lewis rats with indomethacin-induced ulcerative ileitis.

The mechanism of anorexia in inflammatory bowel disease is poorly understood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Crohn's disease. The anorexia of indomethacin-induced ulcerative ileitis was compared with that of the well-known anorexia of total parenteral nutrition (TPN). Forty-five female Lewis rats were randomized to four groups: Control, Indomethacin, Indomethacin + TPN, and TPN. Feeding indices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) were assayed in plasma, mononuclear cell culture, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primarily via reduction in meal number (MN, 54%; p < 0.05) and, to a lesser extent, meal size (MZ, 35%; p < 0.05). In comparison, in the Indomethacin group SFI decreased (74%; p < 0.05) primarily via reduction in MZ (67%, p < 0.05); MN also decreased but to a lesser extent (27%; p < 0.05). In the Indomethacin + TPN group, SFI decreased (55%; p > 0.05) primarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slightly (19%; p < 0.05). Only in the Indomethacin group were IL-1 alpha and TNF-alpha detected in the mononuclear cell culture and plasma, respectively. In the Indomethacin group, an inverse correlation existed between MZ and TNF-alpha (p < 0.05). In the Indomethacin group, IL-1 alpha, PGE2, and LTB4 concentrations did not correlate with feeding indices. SFI reduction in this model was mediated primarily via a decrease in MZ. TNF-alpha is proposed to mediate this effect and TPN was shown to overcome the effect on MZ.

Intravenous nucleosides and a nucleotide promote healing of small bowel ulcers in experimental enterocolitis.

Our aim was to evaluate the possible beneficial effect of intravenous nucleosides and a nucleotide in healing small bowel ulceration in a rat model of enterocolitis. Fourteen Lewis female rats were randomized into total parenteral nutrition (TPN, N = 7) and TPN + nucleosides and a nucleotide (NS/NT, N = 7) groups. After adaptation, two doses of indomethacin (7.5 mg/kg) were administered subcutaneously 24 hr apart to each animal in both groups. Concomitant with the first dose of indomethacin, TPN or TPN + NS/NT were infused for four days. The TPN and TPN + NS/NT were isocaloric and isonitrogenous. At the end of four days, total ulcer length in the entire small bowel was measured. The mucosa surrounding ulcers was studied by optical microscopy. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA). Ileal crypt and villus lengths were measured with an eyepiece micrometer, crypt-villus ratios were calculated, and crypt mitotic index and percentage of PCNA-labeled cells determined to assess cellular proliferation. Total ulcer length decreased significantly in the TPN + NS/NT group compared to the TPN group (42 vs 76 mm). In the TPN + NS/NT versus TPN group, the ileal mucosa surrounding ulcers showed significantly greater crypt length (21%) and there was increased crypt-villus ratio (0.53 vs 0.39), crypt mitotic index (1.2 vs 0.9), and PCNA labeling (43% vs 30%). We conclude that in rats with indomethacin-induced enterocolitis, administration of TPN + NS/NT for four days resulted in significant healing of small bowel ulcers, as indicated by decreased ulcer length. This effect of NS/NT appears to relate, in part, to increased cell proliferation, evidenced by increased crypt length, crypt-villus ratio, mitotic index, and PCNA labeling.

Warfarin and reduced central venous thrombosis in home total parenteral nutrition patients.

Central venous thrombosis is a potentially life-threatening complication in patients on long-term home total parenteral nutrition (HTPN). Lack of venous access due to recurrent thromboses can prevent delivery of life-saving nutritional support. The long-term anticoagulation management to prevent thromboses in patients with central venous catheters for HTPN has not been well established. We have reviewed the role of warfarin in reducing the incidence of thromboses and its safety in our HTPN patients. Ninety consecutive HTPN patients were studied retrospectively. Twenty-two thromboses occurred during 1312 patient-mo in 53 HTPN patients on minidose warfarin. A minidose of warfarin is defined as 1-2 mg and does not prolong the prothrombin time. Seven thromboses occurred over 619 mo in 18 patients on a therapeutic dose of warfarin (minidose compared to therapeutic dose, p > 0.05). A therapeutic dose of warfarin is a dose that increases the prothrombin time to 1.2-1.5 times that of control. Twelve patients who had 18 thromboses in 323 patient-mo while on minidose warfarin were subsequently converted to therapeutic warfarin. The incidence of thromboses decreased to 2 in 369 patient-mo (p < 0.005). There were no hemorrhagic complications in the minidose warfarin group and four nonfatal hemorrhagic complications in the therapeutic dose warfarin group (p > 0.05). A therapeutic dose of warfarin is effective in reducing the incidence of thromboses in patients who experience central venous thrombosis despite minidose warfarin with a minimal increase in hemorrhagic complications.

Nutrition and metabolic management of AIDS during acute illness.

Diarrhea, sepsis, and malnutrition in the AIDS population are common. Some authors have predicted length of survival based on malnutrition biomarkers alone (degree of weight loss at presentation and serum albumin). Similarly, the hypothesis that malnutrition creates a vicious cycle that potentiates susceptibility to opportunistic infections may be valid. Consideration should be given to combining aggressive enteral and parenteral support with metabolic support in the acute phase of illness and between bouts of infections to facilitate patient care and to restore lean tissue. A skilled nutritional support service can deliver needed metabolic support along with nutritional support to these patients. In this case, we focused on the challenges of treating a new patient with significant malnutrition associated with AIDS of unknown duration; untreated gastrointestinal pathogens associated with substantial acid-base, electrolyte, and micronutrient deficiency; and systemic sepsis.