Jpn. J. Infect. Dis., 62, 59-60, 2009
Short Communication
Cryptococcal Liver Abscess: a Case Report of Successful Treatment with Amphotericin-B and Literature Review Po-Yu Liu1,2, Youngsen Yang3, and Zhi-Yuan Shi1,4* 1
Section of Infectious Diseases and 3Section of Hematology-Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; 2Central Taiwan University of Science and Technology, Taichung; and 4National Yang-Ming University, Taipei, Taiwan (Received April 25, 2008. Accepted November 10, 2008)
SUMMARY: Cryptococcus neoformans usually involves the central nervous system and the respiratory tract. We report a case of disseminated cryptococcosis with a liver abscess and meningoencephalitis in a patient with myelodysplastic syndrome. Computed tomography of the abdomen showed a 3-cm low-attenuated lesion in the left lobe of liver. Cultures from specimens of blood, the liver abscess, and the cerebrospinal fluid all yielded C. neoformans. The cryptococcal antigen titers for the serum and cerebral fluid were both 1:32. The patient was successfully treated with 1,335 mg of amphotericin-B followed by fluconazole. Most cryptococcal liver infections present as hepatitis, cholangitis, or microabscesses. A 72-year-old female was admitted to hospital due to fever, headache, and poor appetite for 1 day before admission. The patient had a history of myelodysplastic syndrome with splenomegaly, and splenectomy had been performed 1 month prior to admission. On examination, the patient’s temperature was 38°C. Mild tenderness was found on deep palpation of the right upper abdominal quadrant. The patient had no meningeal signs. The leukocyte count was 18,260/μl with 26% neutrophils, 16% lymphocytes, 43% monocytes, 2% eosinophils, 2% basophils, 7% band neutrophils, and 3% myelocytes. The hemoglobin level was 7.8 g/dl, and the platelet count was 80,000/μl. The patient’s aspartate aminotransferase level was 61 IU/l, alanine aminotransferase was 66 IU/l, alkaline phosphatase was 191 IU/l, and the total bilirubin was 0.4 mg/dl. The antibody test for human immunodeficiency virus (HIV) was negative. Chest x-ray revealed small bilateral pleural effusions, which had been present in the computed tomography (CT) image captured 1 month prior to admission for the present liver condition. No other chest abnormalities were detected. Ultrasonographic examination of the liver disclosed a hypoechoic lesion with sepatation in the left hepatic lobe (Fig. 1B). A contrast-enhanced CT scan of the abdomen revealed a 3-cm low-attenuated lesion in the left lobe of the liver adjacent to the portal vein, and generalized high-attenuated abnormalities in the liver parenchyma and mild widening of the periportal space (Fig. 1A). Ultrasound-guided percutaneous drainage was performed to treat the liver abscess. The cryptococcal antigen titer of the serum was 1:32. CT of the brain revealed no abnormal enhanced lesions in the brain parenchyma. The analysis of the cerebrospinal fluid revealed a leukocyte count of 209/μl with 94% lymphocytes, an erythrocyte count of 6/μl, a protein level of 204 mg/dl, and a glucose level of 59 mg/dl. The cryptococcal antigen titer of the cerebrospinal fluid was 1:32. Cultures from specimens of blood, the abscess, and the
Fig. 1A. Abdominal CT scan with contrast enhancement. A 3-cm irregular abscess involving the left hepatic lobe is revealed.
Fig. 1B. Ultrasonography of the liver showed a hypoechoic lesion with sepatation in the left hepatic lobe.
cerebrospinal fluid all yielded Cryptococcus neoformans. Amphotericin B treatment at a dose of 0.6 mg/kg/day was initiated. The patient’s clinical condition improved after treatment. Ultrasonography of the liver performed 4 weeks after the initiation of treatment showed a reduction in the size of the liver abscess. Ultimately, the patient received a cumulative dose of 1,335 mg of amphotericin B after 7-week treatment, and the Cryptococcus antigen titer of the cerebrospinal fluid decreased to 1:2. The patient was discharged from the
*Corresponding author: Mailing address: Section of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, No. 160, Sec. 3, Chung-Kang Rd., Taichung, Taiwan, R.O.C. 40705. Tel: +886-4-23592525-3083, Fax: +8864-23559016, E-mail:
[email protected] 59
patients post-heart transplantation. In our patient, the risk factors for developing cryptococcosis included myelodysplastic syndrome, splenectomy, and corticosteroid therapy. Most cryptococcal liver infections present as hepatitis, cholangitis, or microabscesses. The CT scan findings of cryptococcal liver abscess in the present case were indistinguishable from those of pyogenic liver abscess. Reports of cryptococcal liver infection are too rare to elucidate characteristic clinical manifestations or features of radiological images. Hence, for immunocompromised hosts with hepatitis and cholangitis of unknown cause, an elevated serum cryptococcal antigen titer or a positive C. neoformans culture from other sources warrant the inclusion of cryptococcal liver infection in the differential diagnosis. Liver biopsy can provide a definitive diagnosis of cryptococcal liver infection, and the survival rate can potentially be improved by early diagnosis and the administration of antifungal agents.
hospital, and was treated with fluconazole at a dosage of 200 mg daily for 7 weeks. Bone marrow biopsy performed during hospitalization showed myelodysplastic syndrome with a leukemoid reaction. The patient elected not to receive additional chemotherapy in order to avoid the side effects of such treatment. Two months later, the patient died of cerebral infarction in the emergency department. Cryptococcal infections usually involve the central nervous system and respiratory tract. Depending on the patients’ immune status, cryptococcal infection can either be localized or disseminate to other organs via hematogenous spread. Previous studies report rates of hepatic cryptococcosis ranging from 1 to 13% of AIDS patients, as determined by autopsy or liver biopsy (1,2). Cryptococcal liver infection is rare in nonHIV-infected patients, and only 13 patients have been reported in 11 references; 10 of the 13 patients were males aged 7 to 73 years. The clinical manifestations of these cases were as follows: hepatic failure (two patients) (3); hepatitis (three patients) (4-6); diffuse microabscesses of the liver (two patients) (7); cirrhosis (one patient) (8); four cases of obstructive jaundice due to either cholangitis (three patients) (9-11) or cholecystitis (one patient) (12); and acute abdominal pain (one patient) (13). C. neoformans was isolated from the clinical specimens of eight patients, including specimens from abscesses, bile, blood, bone marrow, cerebrospinal fluid, gastric lavage, liver, lymph nodes, sputum, urine, and skin. It was clearly demonstrated that all eight patients with positive cultures had disseminated cryptococcal infection involving multiple organs. Six of the 13 patients were examined for serum cryptococcal antigen, and five of these tests yielded positive results. The serum cryptococcal antigen titer ranged from 1:8 to 1:65,532. The pathological findings from the liver biopsy included granulomatous changes (seven patients); necrosis (two patients); hepatitis (one patient); and cholangitis (one patient). The morphology of C. neoformans was demonstrated by periodic acid-schiff, Gomori’s methenamine silver, or Gridley’s fungus stains. Two of the 13 patients received no antifungal therapy, as the diagnosis of cryptococcal infection was made by autopsy after death. Therapy was not mentioned in the case of one patient. Nine of the 10 patients who received antifungal therapy survived. Four patients were treated with amphotericin B and flucytosine, two were treated with amphotericin B, one was treated with amphotericin B and then oral fluconazole, one was treated with fluconazole and one was treated with amphotericin B and flucytosine for 20 days and then oral fluconazole. Liver abscesses are usually caused by Enterobacteriaceae (such as Escherichia coli and Klebsiella pneumoniae) and Entamoeba histolytica. K. pneumoniae has emerged as the leading pathogen causative of liver abscesses in Taiwan (14). In a study of 80 cases of pyogenic liver abscess, 64 (80%) patients had a solitary abscess with predominant localization in the right lobe, and 16 (20%) had multiple abscesses, 10 of which showed unilobar involvement (15). Candida albicans is the most common pathogen found in fungal liver abscesses, and it usually occurs in patients with leukemia or lymphoma who have been treated by chemotherapy (16,17). Diffuse microabscesses are the most common feature of hepatic candidiasis (18). Cryptococcal liver infections tend to occur in compromised hosts such as those with rheumatoid arthritis, hyperimmunoglobulin M syndrome, Hodgkin’s disease, and
REFERENCES 1. Wilkins, M.J., Lindley, R., Dourakis, S.P., et al. (1991): Surgical pathology of the liver in HIV infection. Histopathology, 18, 459-464. 2. Piratvisuth, T., Siripaitoon, P., Sriplug, H., et al. (1999): Findings and benefit of liver biopsies in 46 patients infected with human immunodeficiency virus. J. Gastroenterol. Hepatol., 14, 146-149. 3. Sabesin, S.M., Fallon, H.J. and Andriole, V.T. (1963): Hepatic failure as a manifestation of cryptococcosis. Arch. Intern. Med., 111, 661-669. 4. Utili, R., Tripodi, M.F., Ragone, E., et al. (2004): Hepatic cryptococcosis in a heart transplant recipient. Transpl. Infect. Dis., 6, 33-36. 5. Gollan, J.L., Davidson, G.P., Anderson, K., et al. (1972): Visceral cryptococcosis without central nervous system or pulmonary involvement: presentation as hepatitis. Med. J. Aust., 1, 469-471. 6. Lin, J.I., Kabir, M.A., Tseng, H.C., et al. (1999): Hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis. J. Clin. Gastroenterol., 28, 273-275. 7. Kim, D.Y., Kim, Y., Baek, S.Y., et al. (2003): Simultaneous thoracic and abdominal presentation of disseminated cryptococcosis in two patients without HIV infection. Am. J. Roentgenol., 181, 1055-1057. 8. Goenka, M.K., Mehta, S., Yachha, S.K., et al. (1995): Hepatic involvement culminating in cirrhosis in a child with disseminated cryptococcosis. J. Clin. Gastroenterol., 20, 57-60. 9. Lefton, H.B., Farmer, R.G., Buchwald, R., et al. (1974): Cryptococcal hepatitis mimicking primary sclerosing cholangitis. A case report. Gastroenterology, 67, 511-515. 10. Kim, J.S., Choi, B.I., Han, M.C. (1994): Cryptococcal cholangiohepatitis with intraductal cryptococcoma. Am. J. Roentgenol., 163, 995-996. 11. Nara, S., Sano, T., Ojima, H., et al. (2008): Liver cryptococcosis manifesting as obstructive jaundice in a young immunocompetent man: report of a case. Surg. Today, 38, 271-274. 12. Das, B.C., Haynes, I., Weaver, R.M., et al. (1983): Primary hepatic cryptococcosis. Br. Med. J., 287, 464. 13. Procknow, J.J., Benfield, J.R., Rippon, J.W., et al. (1965): Cryptococcal hepatitis presenting as a surgical emergency. First isolation of Cryptococcus neoformans from point source in Chicago. JAMA, 191, 269274. 14. Lau, Y.J., Hu, B.S., Wu, W.L., et al. (2000): Identification of a major cluster of Klebsiella pneumoniae isolates from patients with liver abscess in Taiwan. J. Clin. Microbiol., 38, 412-414. 15. Wong, W.M., Wong, B.C., Hui, C.K., et al. (2002): Pyogenic liver abscess: retrospective analysis of 80 cases over a 10-year period. J. Gastroenterol. Hepatol., 17, 1001-1007. 16. Halvorsen, R.A., Korobkin, M., Foster, W.L., et al. (1984): The variable CT appearance of hepatic abscesses. Am. J. Roentgenol., 142, 941946. 17. Fitzgerald, E.J. and Coblentz, C. (1988): Fungal microabscesses in immuno-suppressed patients-CT appearances. Can. Assoc. Radiol. J., 39, 10-12. 18. Mathieu, D., Vasile, N., Fagniez, P.L., et al. (1985): Dynamic CT features of hepatic abscesses. Radiology, 154, 749-752.
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