Fatal subacute liver failure after repeated administration of sevoflurane anaesthesia.

Sevoflurane is a widely used halogenated inhalation anaesthetic. In comparison with other similar anaesthetics, it is not metabolized to potentially hepatotoxic trifluoroacetylated proteins. In this case report, we present a 66-year-old woman with breast carcinoma, who underwent sevoflurane general anaesthesia twice in 25 days. Soon after the second elective surgical procedure, jaundice and marked elevations in serum transaminases developed. The patient died 66 days thereafter. Autopsy results denied evidence of major cardiovascular abnormality, and histological examination confirmed massive liver cell necrosis with no feature of chronic liver injury. Sevoflurane anaesthesia was imputed as the cause after exclusion of other possible aetiological agents. Besides, coexistent malignant tumours found in the patient could have modulated the immunological response to the applied anaesthetic followed by fatal consequences.

Cyclooxygenase-2 expression determines neo-angiogenesis in gallbladder carcinomas.

Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.

Does end-stage kidney failure influence hepatitis C progression in hemodialysis patients?

BACKGROUND/AIMS: The influence of end-stage kidney failure on the progression of liver disease in patients infected with hepatitis C virus and treated with hemodialysis is still controversial. METHODOLOGY: Liver histology of 154 hepatitis C virus infected non-uremic patients was compared with liver histology of 13 hepatitis C virus infected uremic patients treated with hemodialysis. RESULTS: In either group of altogether 167 patients, no normal liver histology was found. Each patient had at least a low-grade lobular and/or portal inflammation. However, statistically significant differences were observed between hepatitis C virus infected uremic and non-uremic patients in the extent of intralobular changes, portal inflammation, and degree of fibrosis. CONCLUSIONS: Non-uremic hepatitis C virus infected patients appear to have more active and progressive liver disease than hepatitis C virus infected patients on hemodialysis. Regular follow-up of uremic patients, associated with earlier detection of hepatitis C virus infection, so as suggested uremia-associated impaired immunoreactivity and increased levels of hepatocyte growth factor described recently, might be implicated in a more favorable course of hepatitis C virus infection in uremic patients. In addition, due to the absence of normal liver histology in either group of hepatitis C virus infected patients, we propose liver biopsy to be mandatory in all these patients, provided that no contraindications exist clinically.

Efficacy of chronic hepatitis C therapy with interferon alpha (IFN-alpha) in Slovenia.

BACKGROUND/AIMS: Eighty Slovene patients with chronic hepatitis C were included in a prospective study conducted in the period 1997-1998 with the purpose to establish the efficacy of interferon alpha therapy. The average age of the patients was 39 years. In more than half of the patients (52%) the mode and time of onset of the infection were unknown. Two thirds of the patients were males. The plasma viral load exceeded 2 x 10(6) copies/mL in only three patients and in more than half of the cases (54%) HCV genotype 1b was present. METHODOLOGY: The 18-month treatment with 3 MU interferon alpha three times a week was concluded in 53 patients and, after doubling the initial dose of interferon alpha from 3 MU to 6 MU, in 5 patients. In 11 patients, the treatment was discontinued prematurely, after six months, due to therapeutic failure (despite doubling the initial dose of interferon alpha Eleven patients withdrew from the treatment: six of them due to side effects and five due to personal reasons. RESULTS: Complete response to therapy with disappearance of HCV from the blood was observed in 34 patients (49%), while in 24 the response to therapy was partial, i.e., the biochemical tests showed normalization of values but viremia persisted. There was a significant relation between the therapeutic response and those patients with the genotype 3 (p = 0.01). After three months of follow-up, complete therapeutic response was still observed in 19 patients (28%), most of them with genotype 3. Despite persistent viremia there was no progression of liver inflammation in eight partial responders, as evidenced by liver rebiopsy. Thus, it was confirmed that treatment is justified in these patients. CONCLUSIONS: During the continuation of the follow-up period we shall record further course of the disease and make an attempt in a subsequent study to improve the efficacy of the treatment by introducing a combination of interferon alpha and ribavirin into therapy.