Drug-induced hepatotoxicity.

Clinical spectrum of X-linked hyper-IgM syndrome

Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing antimicrosporidial drugs. Furthermore, molecular techniques are being developed for diagnostic purposes, taxonomic classification, and analysis of phylogenetic relationships of microsporidia.

Human microsporidial infections.

Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. These risk factors modify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell death, activation of an adaptive immune response and a failure to adapt, with progression to overt liver injury. Idiosyncratic DILI is a relative rare hepatic disorder but can be severe and, in some cases, fatal, presenting with a variety of phenotypes, which mimic other hepatic diseases. The diagnosis of DILI relies on the exclusion of other aetiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients with cancer.

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Drug-induced liver injury

After assessment of tumor histology, the next important factor to consider in the selection of a chemotherapy regime is organ function. Patients who are to receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate, and which drug doses should be modified. Following therapy abnormalities of liver function tests may be due to the therapy rather than to progressive disease, and this distinction is of critical importance. Furthermore, not all abnormalities in liver function are due to the tumor or its treatment, and other processes, such as hepatitis, must be kept in mind. This article reviews the hepatic toxicity of chemotherapeutic agents, and suggests dose modifications based upon liver function abnormalities. Emphasis is placed on agents known to be hepatotoxic, and those agents with hepatic metabolism. The Oncologist 2001;6:162-176

Hepatotoxicity of Chemotherapy

Background and study aims Gastric outlet obstruction is a late event in the natural history of biliopancreatic tumours. Metallic self-expanding stents inserted under endoscopic and fluoroscopic guidance can be used for palliation. The aim of this study was to evaluate the feasibility, efficacy, and complications of endoscopic duodenal stenting in patients with malignant gastric outlet obstruction. Patients and methods Between August 1998 and November 2001, 63 patients (31 women, 32 men; mean age 73 +/- 12) presenting with clinical symptoms of duodenal obstruction underwent endoscopic stenting with large metallic prostheses. Complications and clinical outcome were assessed both retrospectively and prospectively. Results Of the patients, 58 needed one duodenal stent and two overlapping stents were required in five patients. Stenting was immediately successful in 60/63 patients (95%). At the time of the duodenal procedure, 25 previously inserted biliary stents were still patent; biliary stenting was attempted during the same procedure in 18 patients; and 20 patients had no biliary stricture. There was no procedure-related mortality. There were complications in 30 % of patients: 13 stent obstructions, 4 stent migrations and 2 duodenal perforations (treated surgically). For 44 patients (70%) there were no minor or major digestive problem during their remaining lifetime. An exclusively peroral diet was possible in 58 patients (92%), but was considered satisfactory (solid or soft) in 46/63 patients (73%). Of the patients, 53 (84 %) died between 1 and 64 weeks after the duodenal stenting (median survival 7 weeks). Conclusions Endoscopic stenting for the palliation of malignant gastric outlet obstruction is feasible and well-tolerated in most patients. Most dysfunctions can be managed endoscopically.

Endoscopic palliation of malignant gastric outlet obstruction using self-expandable metallic stents: results of a multicenter study.

Etoposide (VP 16-213) induced hepatitis. Report of three cases following standard-dose treatments.

AIDS-related cholangitis: Diagnostic features and course in 15 patients

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Endoscopic palliation of malignant gastric outlet obstruction using self-expandable metallic stents: results of a multicenter study.

Etoposide (VP 16-213) induced hepatitis. Report of three cases following standard-dose treatments.

AIDS-related cholangitis: Diagnostic features and course in 15 patients