Paracetamol-induced liver toxicity after intravenous administration.
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Acetaminophen↗
Biomedical subjects
Y Horsmans
Publications and source records attributed to Y Horsmans.
Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event.
Radiation-induced liver disease is recorded as a form of veno-occlusive disease. Its pathogenesis remains unclear even if the initial injury likely occurs in the endothelial cells of central veins. The aim of our study was to investigate liver morphological features in relation to alpha-isoform of smooth muscle actin expression in hepatic stellate cells in six patients treated by localized radiotherapy on the biliopancreatic area. Within the month after completion of treatment, an activation of hepatic stellate cells strictly confined to irradiated areas and coinciding with congestive changes was observed. At a later stage, collagen deposition gradually increased, replacing the congestive and destroyed areas. This new fibrotic tissue also contained numerous alpha-smooth muscle positive cells. Our data suggest that early hepatic stellate cells activation coinciding with congestive changes plays an important role in radiation liver injury and ensuing fibrosis.
Actins↗
The monoethylglycinexylidide test does not correctly evaluate lidocaine metabolism after ischemic liver injury in the rat.
Although the monoethylglycinexylidide (MEGX) test defined as a single determination of MEGX plasma concentration after lidocaine injection has been proposed as a liver function test, some discrepancies appeared in assessing the quality of liver donor for transplantation as well as the severity of liver disease. The present study used a severe ischemia-reperfusion liver injury (IRI) in rat to evaluate the various factors able to influence the level of MEGX. The metabolism of lidocaine was studied on microsomes isolated from intact rats and from rats submitted to this liver injury. A significant reduction of the various pathways transforming lidocaine but also MEGX was demonstrated. Lidocaine inhibited the MEGX transformation both in intact and injured liver microsomes. In vivo, plasma MEGX concentrations, determined by high-performance liquid chromatography (HPLC), were lower in IRI than in controls up to 80 minutes after lidocaine injection but not later. By contrast, using the usual commercial fluorescence polarization immunoassay (FPIA), MEGX concentrations were paradoxically higher in IRI than in controls. Moreover, MEGX values obtained using FPIA were threefold higher in controls and ninefold higher in IRI than with HPLC. It was shown that these differences were related to the detection by FPIA of free and mainly of conjugated hydroxy-MEGX that accumulated in plasma from rats submitted to an IRI. These data emphasize the complexity of factors influencing the appearance and disappearance of MEGX because of delayed MEGX formation with liver injury but also to inhibition of its further metabolization. The choice of the sampling time for MEGX determination is critical and has to be optimized in every type of liver injury. Moreover, a specific technique, such as HPLC, will avoid cross-reactivity with other metabolites, which may be particularly abundant when the biliary excretion is impaired.
Animals↗
Hepatobiliary cystadenocarcinoma without ovarian stroma and normal CA 19-9 levels. Unusually prolonged evolution.
Hepatobiliary cystadenoma and cystadenocarcinoma are rare tumors of the liver. The differential diagnosis of cystadenoma includes other cystic neoplasms, nonneoplastic cysts, and even on some occasions parasitic liver involvement. It has been suggested that elevated serum level of the tumor marker CA 19-9 may be of value in distinguishing between cystadenoma with ovarian stroma and hydatid disease. We report the unique case of a male patient with a hepatobiliary cystadenocarcinoma without ovarian stroma of prolonged evolution characterized by a normal CA 19-9 serum level, low cyst fluid CA 19-9, and a very weak CA 19-9 expression on cyst epithelium.
Aged↗
Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy.
BACKGROUND: Therapeutic trials suggest that lactulose is an effective treatment of acute and chronic encephalopathy in cirrhotic patients. AIM AND METHODS: As it is likely that portal-systemic shunting and hepatocellular dysfunction are associated with some degree of neurological dysfunction, 14 patients with cirrhosis and documented portal-systemic shunting, but without detectable encephalopathy, were randomized to treatment with either lactulose 20 g t.d.s., or lactose 20 g t.d.s. as placebo, for a 15-day period. Monitoring included manually administered and computer-based psychometric testing, the results of which were correlated with a battery of biochemical and functional parameters. RESULTS: There was no correlation between biochemical or functional parameters and psychometric testing. There was a close correlation between the time required to complete the number connection test and both the number of errors and the duration of errors at sinusoid testing. Lactulose therapy resulted in a significant improvement, assessed by the number connection test and the race track test. CONCLUSION: Our data suggest that lactulose therapy might improve subclinical hepatic encephalopathy in patients with cirrhosis and portal-systemic shunting.
Female↗
Adult polycystic liver disease: is fenestration the most adequate operation for long-term management?
OBJECTIVE: The aim of this study was to evaluate the immediate and long-term results in a retrospective series of patients with highly symptomatic adult polycystic liver disease (APLD) treated by extensive fenestration techniques. A classification of APLD was developed as a stratification scheme to help surgeons conceptualize which operation to offer to patients with APLD. SUMMARY BACKGROUND DATA: Treatment options for APLD remain controversial, with partisans of fenestration techniques or combined liver resection-fenestration. METHODS: Clinical symptoms, performance status, liver volume measurement by computed tomography (CT), and morbidity were recorded before surgery and after surgery. Adult polycystic liver disease was classified according to the number, size, and location of liver cysts and the amount of remaining liver parenchyma. Follow-up was obtained by clinical and CT examinations in all patients. RESULTS: Ten patients with highly symptomatic APLD were operated on using an extensive fenestration technique (by laparotomy in 8 patients and by laparoscopy in 2 patients, 1 of whom conversion to laparotomy was required). The mean preoperative liver volume was 7761 cm3. There was no mortality. Postoperative morbidity occurred in 50%, mainly from biliary complications, requiring reintervention in two cases. Massive intraoperative hemorrhage occurred in one patient. During a mean follow-up time of 71 months (range, 17 to 239 months), all patients were improved clinically according to their estimated performance status. The mean postoperative liver volume was 4596 cm3, which represents a mean liver volume reduction rate of 43%. However, in type III APLD, despite absence of clinical symptoms, a significant increase in liver volume was observed in 40% of the patients. CONCLUSIONS: Extensive fenestration is effective in relieving symptoms in patients with APLD. Hemorrhage and biliary complications are possible consequences of such an aggressive attempt to reduce liver volume. The procedure can be performed laparoscopically in type I APLD. A longer follow-up period is mandatory in type II APLD, to confirm the usefulness of the fenestration procedure. In type III APLD, significant disease progression was observed in 40% of the patients during long-term follow-up. Fenestration may not be the most appropriate operation for long-term management of all types of APLD.
Adult↗
Acute lobular hepatitis as the first manifestation of recurrent autoimmune hepatitis after orthotopic liver transplantation.
Recurrence of autoimmune hepatitis after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in a 43-year-old man. Diagnosis was based on biological, serological and morphological data, as well as on a complete biological recovery following steroid resumption. Recurrence was observed only 4 months after transplantation, when an abrupt increase in liver function tests was observed in association with a mainly lobular hepatitis in liver biopsy. Such a histological appearance has been previously described in the case of recurrence after immunosuppressive treatment weaning in non-transplanted patients. In contrast, this histological feature has not been reported in the rare transplanted patients in whom such recurrence has been observed. Thereafter, the evolution of the disease in our patient remained slow, likely dampened by the administration of cyclosporine and azathioprine. Morphological features are detailed, and importance of immunosuppressive therapy in patients transplanted for end-stage autoimmune hepatitis is emphasized.
Acute Disease↗
Detection and segmental location of malignant hepatic tumors: comparison of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging.
OBJECTIVE: The aim of our prospective study was to compare the values of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging for the detection and segmental location of malignant hepatic tumors. SUBJECTS AND METHODS: Eighteen patients underwent ferumoxides-enhanced T2 weighted spin-echo and steady-state gradient-echo imaging before surgery. Intraoperative sonography was used as the reference examination and showed 28 malignant tumors involving 39 of the 144 hepatic segments. The MR images were reviewed independently by two observers who recorded the number of tumors and their segmental location. The results of the segmental location were subjected to receiver-operating-characteristic analysis. Tumor-liver, vessel-liver, and tumor-vessel contrast-to-noise ratios were calculated. RESULTS: Detection on the gradient-echo images did not differ significantly from that on the T2-weighted spin-echo MR images (observers A and B detected 23 and 24 tumors, respectively, on the gradient-echo images; the two observers each detected 22 tumors on the T2-weighted spin-echo images). Segmental localization was significantly better on the gradient-echo images than on the T2-weighted spin-echo images (mean area under the receiver-operating-characteristic curve: 0.974 versus 0.895 for observer A and 0.962 versus 0.906 for observer B, p = .024). The highest contrast-to-noise ratios for vessel to liver and tumor to vessel were obtained on the gradient-echo images and the highest tumor-liver contrast-to-noise ratio was obtained on the T2-weighted spin-echo images. CONCLUSION: In our study, ferumoxides-enhanced gradient-echo imaging was as accurate as T2-weighted spin-echo imaging for revealing malignant hepatic tumors and was superior for showing their segmental location.
Contrast Media↗
14C-Propoxyphene demethylation in the rat. An example of differences between liver and intestinal drug-presystemic metabolism.
Presystemic metabolism is believed to occur mainly in the liver with some minor intestinal participation. The aim of this study was to investigate the respective part of each of these two organs in the metabolism of the analgesic d-propoxyphene (DP). Pharmacological doses of DP were given in the duodenum (ID), the portal vein (IP), and the femoral vein (IV) of male Wistar rats. A tracer dose of 14C-DP was also administered either in IV, IP, or ID as well as in hepatectomized rats or rats with bile duct diversion. In vitro demethylation occurring in liver and intestinal microsomes was also studied. Absolute DP bioavailability obtained after oral administration was two times higher than that observed after portal administration (48.9% vs. 23.2%, respectively), an result opposite (i.e. a lower bioavailability) of that expected on the basis of the existence of a liver enzyme saturation phenomenon. The 14CO2 cumulative excretion after 14C-DP administration was significantly lower after IV or ID administration than after injection in the portal vein as a bolus or within 20 min. The biliary excretion of the labeled compound varied in the opposite direction, being greater after IV or ID than after IP administration, suggesting that the metabolism of DP in the liver is influenced by an extrahepatic transformation. This most likely occurs in the gut since the production of 14CO2 after IV administration was similar to that after ID administration. This transformation did not prohibit DP detection in the systemic blood but was sufficient to increase the part eliminated with bile and to decrease the part demethylated into NP. Demethylation mainly occurs in the liver since the production of 14CO2 was nearly abolished in hepatectomized rats. Furthermore, microsomes of hepatic but not of intestinal origin were able to demethylate DP. Our data suggest that the transformation of DP occurring in gut after oral administration is responsible for changes in the hepatic metabolism of the drug.
Analgesics, Opioid↗
Phenytoin hydroxylation in a healthy Caucasian population: bimodal distribution of hydroxyphenytoin urinary excretion.
The phenytoin hydroxylation index was studied in 122 unrelated Caucasian volunteers. Following a 100 mg oral dose of phenytoin, phenytoin and hydroxyphenytoin were measured in urine from 0-32 hr after administration. As phenytoin was not found in all urine collections, a phenytoin hydroxylation index was expressed as follows: Phenytoin hydroxylation index = amount of phenytoin administered/0-32 hr urinary output of hydroxyphenytoin. Phenytoin hydroxylation index values appear to be bimodally distributed, 92% of the population showing a mean (+/- S.E.M.) value of 0.639 +/- 0.099 and 8% a mean (+/- S.E.M.) value of 1.001 +/- 0.180 (log10 values). These results are in favour of the existence of a phenytoin genetic polymorphism. Since misuse of urinary metabolite excretion data in drug metabolism studies is a well-known phenomenon, our data emphasize the need for future population studies on phenytoin pharmacokinetics as well as on CYP2C9 genotyping before concluding about existence of a phenytoin genetic polymorphism.
Administration, Oral↗
Pruritus associated with cholestatic liver disease.
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Beverages↗
Fast determination of low-level cytochrome P-450 1A1 activity by high-performance liquid chromatography with fluorescence or visible absorbance detection.
A method to determine the activity of the cytochrome P-450 1A1 enzyme, by measuring 7-ethoxyresorufin-O-deethylase (EROD) activity using high-performance liquid chromatography (HPLC) with fluorescence or with visible absorbance detection of resorufin, is described. The lowest quantifiable activity (0.2 pmol/mg min) is obtained by incubation of 0.3 mg of human duodenal microsomal proteins using HPLC fluorescence detection. Using HPLC with visible absorbance detection, sensivity was ten times lower. However, the equipment for this last method is available in most laboratories. The use of both HPLC assays allows determination of the low EROD activity level in samples of small size, such as two or three human duodenal biopsies obtained by routine endoscopy. These methods will be a useful tool to study the role of drug intestinal metabolism by cytochrome P-450 1A1.
Animals↗
Tamoxifen-induced steatohepatitis.
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Aged↗
Pharmacodynamic activity of lipoprotein lipase and hepatic lipase, and pharmacokinetic parameters measured in normolipidaemic subjects receiving ciprofibrate (100 or 200 mg/day) or micronised fenofibrate (200 mg/day) therapy for 23 days.
The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were investigated after 23 days of ciprofibrate (100 mg or 200 mg) therapy or fenofibrate (200 mg) therapy. In a double-blind, double-placebo, cross-over study, three groups of six healthy volunteers received either 100 mg ciprofibrate/day followed by 200 mg fenofibrate 'high bioavailability' (HB)/day, or vice versa (group A), 200 mg ciprofibrate HB/day followed by 200 mg fenofibrate HB/day, or vice versa (group B), or 100 mg ciprofibrate/day followed by 200 mg ciprofibrate/day, or vice versa (group C). Fasting plasma lipid levels and safety parameters were evaluated before and after treatment. One hundred milligrams ciprofibrate/day therapy was found to be approximately as effective as 200 mg fenofibrate HB/day therapy in altering the lipid profile. The highest activation of LPL was obtained after treatment with 200 mg ciprofibrate/day. A modest, but statistically significant, increase in HL activity was found after 100 or 200 mg ciprofibrate treatment. Investigation of the pharmacokinetics of ciprofibrate and fenofibric acid revealed a shorter time to reach peak plasma levels, but a longer elimination half life for the ciprofibrate preparations in comparison with fenofibrate. A dose of 200 mg ciprofibrate/day is more effective than 100 mg ciprofibrate/day at increasing LPL and HL activity; however, 200 mg ciprofibrate/day is also associated with a potential detrimental change in safety parameters. Two hundred milligrams fenofibrate HB/day therapy may represent an alternative therapy to 100 mg ciprofibrate/day for hyperlipidaemic patients.
Adult↗
Fenoterol-induced hepatitis in a pregnant woman: a case report.
The case of a pregnant woman in whom hepatitis developed after administration of high-dose fenoterol during the third trimester of a second pregnancy is described.
Adult↗
Somatostatin receptor imaging in cholangiocarcinoma.
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Bile Duct Neoplasms↗
Watermelon stomach. An unusual cause of recurrent upper GI tract bleeding in the uraemic patient: efficient treatment with oestrogen-progesterone therapy.
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Angiodysplasia↗
Serum and cystic fluid CA 19-9 determinations as a diagnostic help in liver cysts of uncertain nature.
The distinction between hepatobiliary cystadenoma or cystadenocarcinoma and simple hepatic cyst complicated by intracystic hemorrhage may prove difficult to determine on the sole basis of clinical and radiological features because of the presence of intracystic structures and septations well-demonstrated by ultrasound examination in both situations. We investigated four patients with various types of hepatic cysts, in whom diagnostic difficulties led to further investigations. In this small group, CA 19-9 serum levels were abnormal only in the two patients with cystadenoma or cystadenocarcinoma. Cystic fluid CA 19-9 values were also five times higher in cystadenoma and cystadenocarcinoma than in other benign lesions. Our data thus suggest that the determination of serum and cyst fluid CA 19-9 may be of help in distinguishing between hemorrhagic simple cyst and cystadenoma or cystadenocarcinoma.
Aged↗