Evaluation of the hepatobiliary system in patients with paracoccidioidomycosis treated with cotrimoxazole or itraconazole

A prospective study was performed in 200 paracoccidioidomycosis (PCM) patients, 51 presenting the acute/subacute form (AF) and 149 the chronic form (CF), submitted to the evaluation of the hepatobiliary system at admission and during the follow-up treatment with cotrimoxazole (CMX) or itraconazole (ITC). This study aimed to better evaluate the involvement of the hepatobiliary system in PCM and the effect of these antifungal compounds on this system. Serum levels of direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were evaluated. At admission, all the variables showed changes with elevated values ranging from 6.2% for TB to 32.6% for GGT. After treatment, the incidence of elevated serum levels ranged from 3.6% for DB to 27.5% for ALT. The course of the alterations during the treatment showed regression to normal values in CMX-treated patients and persistence in ITC-treated patients but without the need to discontinue the therapy. Our findings contribute to the knowledge of the hepatobiliary involvement by Paracoccidioides sp. and to a safe follow-up of PCM patients under treatment.

[1]  R. P. Mendes The Gamut of Clinical Manifestations , 2018 .

[2]  K. Sikaris,et al.  The de ritis ratio: the test of time. , 2013, The Clinical biochemist. Reviews.

[3]  K. Clements,et al.  The Likelihood of Extinction of Iconic and Dominant Herbivores and Detritivores of Coral Reefs: The Parrotfishes and Surgeonfishes , 2012, PloS one.

[4]  M. Felipe,et al.  Genus Paracoccidioides: Species Recognition and Biogeographic Aspects , 2012, PloS one.

[5]  Z. Zakaria,et al.  Effects of Cytochrome P450 Inhibitors on Itraconazole and Fluconazole Induced Cytotoxicity in Hepatocytes , 2009, Journal of toxicology.

[6]  Augusto Hasiak Santo,et al.  Tendência da mortalidade relacionada à paracoccidioidomicose, Estado de São Paulo, Brasil, 1985 a 2005: estudo usando causas múltiplas de morte , 2008 .

[7]  A. H. Santo [Paracoccidioidomycosis-related mortality trend, state of São Paulo, Brazil: a study using multiple causes of death]. , 2008, Revista panamericana de salud publica = Pan American journal of public health.

[8]  F. Queiroz-Telles,et al.  An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  H. M. Khairi,et al.  Involvement of Phenobarbital and SKF 525A in the Hepatotoxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats , 2006, Drug and chemical toxicology.

[10]  K. Brass Observaciones sobre la Anatomía Patológica, Patogénesis y Evolución de la Paracoccidioidomicosis , 1969, Mycopathologia et mycologia applicata.

[11]  Christopher Lawrence Pathology , 1911, The Lancet.

[12]  M. Sulaiman,et al.  Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study , 2004, Human & experimental toxicology.

[13]  B. Barraviera,et al.  Evaluation of acetylator phenotype, renal function and serum sulfadiazine levels in patients with paracoccidioidomycosis treated with cotrimazine (a combination of sulfadiazine and trimethoprim) , 1989, Mycopathologia.

[14]  B. Wanke,et al.  Paracoccidioidomycosis mortality in Brazil (1980-1995). , 2002, Cadernos de saude publica.

[15]  G. Benard,et al.  Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis. , 2002, Medical mycology.

[16]  D. Acosta,et al.  N-deacetyl ketoconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. , 1997, Toxicology.

[17]  M. Franco,et al.  Host-parasite relationship in paracoccidioidomycosis. , 1995, Current topics in medical mycology.

[18]  R. M. Tucker,et al.  Adverse events associated with itraconazole in 189 patients on chronic therapy. , 1990, The Journal of antimicrobial chemotherapy.

[19]  C. Bénichou Criteria of drug-induced liver disorders. Report of an international consensus meeting. , 1990, Journal of hepatology.

[20]  W. Maddrey,et al.  Intrahepatic cholestasis and phospholipidosis associated with the use of trimethoprim‐sulfamethoxazole , 1990, Hepatology.

[21]  Á. Restrepo,et al.  Treatment of paracoccidioidomycosis with itraconazole. , 1990, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[22]  K. Hostetler,et al.  In vitro inhibition of lysosomal phospholipase A1 of rat lung by amiodarone and desethylamiodarone. , 1988, Biochimica et biophysica acta.

[23]  A. Zauber,et al.  Hematologic data of healthy very old people. , 1988, JAMA.

[24]  Zauber Np,et al.  Hematologic data of healthy very old people. , 1987 .

[25]  M. Franco,et al.  Host-parasite relationships in paracoccidioidomycosis. , 1987, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[26]  Á. Restrepo,et al.  Itraconazole in the treatment of paracoccidioidomycosis: a preliminary report. , 1987, Reviews of infectious diseases.

[27]  R. Negroni,et al.  Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans. , 1987, Reviews of infectious diseases.

[28]  A. R. Tanner Hepatic cholestasis induced by trimethoprim. , 1986, British medical journal.

[29]  D. Grant,et al.  Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. , 1986, Annals of internal medicine.

[30]  K. Hostetler,et al.  Chloroquine-induced phospholipid fatty liver. Measurement of drug and lipid concentrations in rat liver lysosomes. , 1985, The Journal of biological chemistry.

[31]  J. Horák,et al.  Severe liver injuries due to sulfamethoxazole-trimethoprim and sulfamethoxydiazine. , 1984, Hepato-Gastroenterology.

[32]  W. Dull,et al.  Trimethoprim-Sulfamethoxazole-Induced Cholestatic Hepatitis: Inadvertent Rechallenge. , 1984, Archives of internal medicine.

[33]  M. Døssing,et al.  Drug-induced liver disease in Denmark. An analysis of 572 cases of hepatotoxicity reported to the Danish Board of Adverse Reactions to Drugs. , 1982, Scandinavian journal of gastroenterology.

[34]  M. Ardiaca,et al.  Trimethoprim-sulfamethoxazole-induced cholestasis. , 1981, The American journal of gastroenterology.

[35]  D. Ransohoff,et al.  Terminal hepatic failure following a small dose of sulfamethoxazole-trimethoprim. , 1981, Gastroenterology.

[36]  L. Young,et al.  Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia. , 1980, Annals of internal medicine.

[37]  L. Levine,et al.  Trimethoprim-sulfamethoxazole-induced intrahepatic cholestasis. , 1980, Annals of internal medicine.

[38]  T. Vree,et al.  Pharmacokinetics of N1-Acetyl- and N4-Acetylsulphamethoxazole in Man , 1979, Clinical pharmacokinetics.

[39]  H. Gelboin,et al.  The Ah locus: genetic regulation of the metabolism of carcinogens, drugs, and other environmental chemicals by cytochrome P-450-mediated monooxygenases. , 1979, CRC critical reviews in biochemistry.

[40]  F. Teixeira,et al.  Morphological patterns of the liver in South American blastomycosis , 1978, Histopathology.

[41]  C. Colucci,et al.  Hepatic Necrosis and Trimethoprim-Sulfamethoxazole , 1975 .

[42]  W. Brumfitt,et al.  Trimethoprim-sulfamethoxazole in the treatment of bacteriuria in women. , 1973, The Journal of infectious diseases.

[43]  K. Brass [Observations on the pathologic anatomy, pathogenesis, and evolution of paracoccidioidomycosis]. , 1969, Mycopathologia et Mycologia Applicata.

[44]  K. Salfelder,et al.  Paracoccidioidomycosis. Anatomic study with complete autopsies. , 1969, Virchows Archiv. A, Pathology. Pathologische Anatomie.

[45]  T. de Brito,et al.  [Liver biopsy in South American blastomycosis]. , 1968, Revista do Instituto de Medicina Tropical de Sao Paulo.

[46]  H. Zimmerman,et al.  Sulfonamide hepatic injury. Review of the literature and report of a case due to sulfamethoxazole. , 1967, The New England journal of medicine.

[47]  L. Böttiger,et al.  Normal erythrocyte sedimentation rate and age. , 1967, British medical journal.

[48]  Á. Campana,et al.  [HEPATIC COMA IN SOUTH AMERICA BLASTOMYCOSIS]. , 1964, Revista da Associação Médica Brasileira.