Late hypersensitivity to omeprazole and other proton pump inhibitors.

A 63 year-old woman presented with a persistent, red, papular, itching skin eruption localised on the face, right shoulder and the right upper member. The evolution was longer than ten years with a permanent progressive diffuse facial burning sensation and unaesthetic aspect despite topical antibiotic and anti-inflammatory treatments. The clinical and the histological diagnosis corresponded to prurigo. She was treated by omeprazole for gastric reflux since more than ten years, and she had a viral C hepatitis. The relationship between prurigo and omeprazole was evidenced by the complete resolution of symptoms after the drug's interruption and the recurrence after the omeprazole re-introduction. The immediate and late skin tests were negative for the tested drugs. Clinical cross-reactivity was observed with pantoprazole and lansoprazole; this suggested a late hypersensitivity to drugs of the proton pump inhibitors class. To our knowledge, it is the first case of prurigo induced by these drugs.

Abdominal ultrasonography by the hepato-gastroenterologist: problems, demands, solutions.

This document analyzes the reasons for organizing an abdominal ultrasound training for Belgian trainees in hepatogastroenterology. The hepatogastroenterology speciality should implement, together with the radiology speciality and the national scientific and professional associations, the minimum training requirements which are proposed by the European Board of Gastroenterology and Hepatology and the European Federation of Societies for Ultrasound in Medicine and Biology. Trainees in hepatogastroenterology should acquire the same theoretical and practical training as radiologists, they should be taught and supervised by competent instructors and have their expertise evaluated.

Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction?

The case of a patient under tibolone therapy for two years who developed a mixed-type liver injury with prolonged cholestasis and features of the vanishing bile duct syndrome following a ten weeks treatment with St. John wort (Hypericum Perforatum) infusions is reported. In the absence of evidence of a potential role for concomitant medication i.e. hydroxychloroquine sulfate to play a role in the clinical, biochemical and morphological picture, an interaction between the herbal preparation and tibolone was suspected as the likely cause of liver damage.

Severe acute cholestatic hepatitis with prolonged cholestasis and bile-duct injury following atorvastatin therapy: a case report.

We report the case of a patient who exhibited severe acute hepatitis with symptomatic cholestasis for more than 3 months and bile duct injury following the prescription of atorvastatin. After withdrawal the drug, the patient's wellbeing slowly improves and biological features normalize in 4 months. Therapy aimed at treating severe liver steatosis and hypercholesterolemia. Atorvastatin is a highly effective 3-hydroxy-3 methylglutamyl- coenzyme A reductase (statin) used to lower low-density lipoprotein. Reported frequent adverse events of the medication include nausea, depression, myalgia, abdominal pain and abnormal liver function tests. Although abnormal liver function tests is not an uncommon side effect of the medication, more serious liver injury is rare. In a recent literature review, about ten cases of serious hepatotoxicity have been documented. In the typical presentation, the duration of exposure prior to hepatic toxicity is variable. Liver injury is generally of the mixed type. A prolonged cholestasis for more than 3 months has been seldom reported. Morphological changes includes canalicular cholestasis, feathery degeneration but no cholangiolitis nor cholangitis under the form of cytological and inflammatory changes at the level of interlobular bile ducts. This case report provides further evidence that among statins, atorvastatin may be implicated in drug-induced liver injury and indicates for the first time that such liver injury may be followed by prolonged cholestasis and interlobular bile duct injury. Atorvastatin has thus to be added to the list of medication potentially responsible for bile duct injury.

Propylthiouracyl-induced severe liver toxicity: an indication for alanine aminotransferase monitoring?

Propylthiouracyl (PTU)-related liver toxicity is likely to occur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced subacute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the underestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotransferase monitoring, at least during the first six months of therapy.

Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption.

UNLABELLED: Hypervitaminosis A-related liver toxicity may be severe and may even lead to cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells (HSC), which are prone to becoming activated and acquiring a myofibroblast-like phenotype, producing large amounts of extracellular matrix. AIMS: In order to assess the relationship between vitamin A intake, HSC activation and fibrosis, we studied nine liver biopsies from patients belonging to a well-characterized series of 41 patients with vitamin A hepatotoxicity. METHODS: Fibrosis was underlined by Sirius-red staining, whereas activated HSC were immunohistochemically identified using an antibody against alpha smooth muscle actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal and total activated HSC was quantified by the point-counting method. RESULTS: Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to severe architectural distortion. There was a significant positive correlation between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A (P=0.004). CONCLUSION: The close correlation between the severity of perisinusoidal fibrosis and the daily dose of the retinol intake suggests the existence of a dose-effect relationship.

Genes and metals: a deadly combination.

Wilson's disease is an autosomal recessive disease of copper metabolism, with an estimated prevalence of 1:30000. The most common presentations of WD are liver disease and neurological disturbance. For many years the diagnosis was based on the results of several clinical and biochemical tests, for which several limitations had been reported. In recent years the developments of new techniques in genetic and molecular biology have provided useful tools in the diagnosis of Wilson's disease. However, the presence of several mutations and the fact that most patients are compound heterozygote means that the problem is not completely resolved. Chelators and zinc salts have been largely used in the treatment of WD patients with a favorable outcome, but the debate continues as to the agents of first choice. Liver transplantation is a cure for patients with decompensated liver disease but its effect on the neurological outcome is still not clear.

Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

Intragastric distribution of a standardized meal in health and functional dyspepsia: correlation with specific symptoms.

In functional dyspepsia, abnormal intragastric distribution of a test meal has been identified but has never been correlated to any symptom pattern. The aim of this study was to compare the intragastric distribution of a meal between functional dyspepsia patients and controls, and to correlate distribution with symptom patterns, using scintigraphic gastric emptying studies. In forty patients with functional dyspepsia and 29 healthy volunteers, scintigraphic planar images were obtained immediately after ingestion of a mixed radiolabelled test meal and every 20 min for 2 h. The images of the stomach were divided into proximal and distal compartments. The mean intragastric distribution was similar in patients and controls. Over the whole test, 18 (45%) and 20 (50%) patients had a distal redistribution of the solid and liquid phase of the meal, respectively, while proximal retention of these phases was found in 13 (33%) and 9 (23%) patients. Early satiety was associated with early distal redistribution of the liquid phase and fullness was associated with late proximal retention. This study shows similar intragastric distribution of a test meal in health and functional dyspepsia. Within the patient group, an association between abnormal intragastric distribution patterns and symptom profiles was found, which might be related to different pathophysiological mechanisms.

Chronic lymphocytic leukemia with portal hypertension and without liver involvement: a case report underlining the roles of increased spleno-portal blood flow and "protective" sinusoidal vasoconstriction.

We report the case of a 72-year-old woman with well-controlled chronic lymphocytic leukemia (CLL) and splenomegaly who developed portal hypertension with bleeding oesophageal varices in the absence of liver fibrosis or regenerative nodular hyperplasia at surgical wedge liver biopsy. The hepatic venous pressure gradient (HVPG) was elevated and splenectomy resulted in both its normalisation and the regression of oesophageal varices. This case shows the potential for an increased spleno-poral flow to generate severe portal hypertension likely through a "protective" sinusoidal vasoconstriction.

Non-tumoral elevation of alpha-fetoprotein (AFP): a 10 year follow-up in two subjects.

Elevation of serum alpha-fetoprotein (AFP) in the absence of any liver disease or malignancy, likely of genetic origin, is an uncommon observation which may be the source of diagnostic difficulties in routine clinical practice, especially in cases without available familial data. Animal studies suggest that the anomaly may be related to a mutation located in a regulatory gene different from that mapped for AFP. The transmission pattern of the defect is unknown with a strong suggestion for an autosomal dominant inheritance. We report the cases of two patients in whom a stable elevation of unknown origin of the tumoral marker for up to 10 years, has been observed in the absence of any detectable liver and/or malignancy and in whom the lack of familial data was the source of diagnostic difficulties.

Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus.

BACKGROUND/AIMS: Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS: We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS: Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS: This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.

Perception of changes in wall tension of the proximal stomach in humans.

BACKGROUND: Hypersensitivity to distension of the stomach is a frequent finding in functional dyspepsia. During gastric distension studies both wall tension and elongation are increased. AIM: We wished to distinguish changes in wall tension from changes in elongation in the genesis of perception of mechanical stimuli originating from the proximal stomach in healthy subjects. SUBJECTS AND METHODS: Twenty six volunteers were studied using gastric barostat and antroduodenal manometry. In 14 subjects, stepwise isobaric and isovolumetric distensions were performed before and during erythromycin infusion. In all volunteers, on a separate occasion, phasic contractions of the proximal stomach were detected as intraballoon pressure increases during fixed volume inflation. These contractions were matched with perception changes during two 10 minute periods, before and during administration of erythromycin. RESULTS: Erythromycin significantly lowered the perception and discomfort thresholds during stepwise gastric distension. During fixed volume inflation, erythromycin increased the number and amplitude of fundic contractions and enhanced their perception from 51.1 (7.4)% to 64.0 (4.7)%. The proportion of perception score increases coinciding with fundic contractions increased from 47.3 (0.7)% to 81.5 (0.5)%. The amplitude of correctly identified isolated fundic pressure waves was higher compared with non-identified waves. CONCLUSIONS: These results support the hypothesis that changes in gastric wall tension may be involved in the genesis of symptoms originating from the stomach.

The surgical management of congenital liver cysts.

BACKGROUND: Most series that report the results of surgical treatment for congenital liver cysts focus more on the technical aspects of the operation than on the late outcome of these patients. In this paper, we emphasize the importance of appropriate patient selection and adequate surgical technique for successful long-term outcome. METHODS: Twenty-four consecutive patients with congenital liver cysts were selected for surgical treatment. According to our own classification, 13 patients had simple liver cysts, nine had multicystic liver disease, and two had type I polycystic liver disease. All of these patients were treated by the fenestration technique. An open approach was used for five patients (group 1) treated between 1984 and 1990. In 19 patients (group 2) treated since 1991, a laparoscopic approach was used. The incidence of complicated liver cysts was 40% in group 1 and 68% in group 2. RESULTS: There were no treatment-related deaths in this series. The mean postoperative hospital stay was significantly shorter for patients who underwent successful laparoscopic fenestration (p < 0.05). In the open group (group 1), there were no postoperative complications, and all patients were alive and free of symptoms during a mean follow-up of 130 months, without any sign of cyst recurrence. In the laparoscopic group (group 2), four patients were converted to open surgery. One of these patients had an inaccessible posterior cyst; another had bile within the cystic cavity. A further two cases had complicated liver cysts with an uncertain diagnosis between congenital and neoplastic cysts. Four patients (21%) developed peri- or postoperative complications. During a mean follow-up time of 38.5 months, none of the patients with simple liver cysts incurred late symptoms or signs of cyst recurrence. In the six patients with multicystic liver disease, one developed disease-related cyst progression (17%) and required reoperation. One of the two patients with type I polycystic liver disease (50%) developed asymptomatic disease-related cyst progression. CONCLUSIONS: When patients are carefully selected and a proper surgical technique is employed, excellent long-term results with a low morbidity rate can be achieved in patients with congenital liver cysts. Patients with multicystic liver disease or type I polycystic liver disease are more prone to late cyst recurrence. A tailored approach is thus indicated for patients with congenital liver cystic disease. However, the laparoscopic approach appears to be the gold standard for the treatment of highly symptomatic or complicated simple liver cysts.

[Chronic arterial mesenteric ischemia: Doppler color ultrasonography demonstration of collateral flow]. / Ischémie mésentérique chronique d'origine artérielle: mise en évidence de réseaux de vicariance par échographie Doppler couleur.

Two cases of atypical mesenteric ischemia where color Doppler US demonstration of the underlying arterial abnormality and collateral supply was possible are presented. Significant stenosis of the celiac axis and thrombosis of the SMA were clearly depicted, along with the presence of collateral arterial supply. Endovascular treatment was successful in both cases. These cases confirm the possibility of detecting collateral flow at Doppler imaging in patients with mesenteric ischemia, both for diagnosis of mesenteric ischemia and endovascular treatment planning.

Drug and toxin-induced bile duct disorders.

Various drugs of toxins have been implicated in the development of a particular form of liver damage predominantly involving the bile ducts. Such liver toxicity is often associated with a clinical picture of prolonged cholestasis and may even evolve in rare instances, into the full picture of the vanishing bile duct syndrome, eventually complicated with biliary cirrhosis. Drug and toxins potentially responsible for bile duct injury are reviewed as well as the characteristics of its clinical presentation. The pathophysiologic aspects of the syndrome are also reviewed including recent data, which are strongly in favor of the role of a genetic predisposition.

Disposable versus reusable biopsy forceps: a prospective cost evaluation.

BACKGROUND: There is growing advocacy for the use of disposable medical accessories to reduce the risks of infection transmission. Their purchase costs can, however, be considered as prohibitive in an endoscopy unit operating under a cost-containment program. We therefore compared the costs of reusable and disposable biopsy forceps. METHODS: From October 1995 to September 1997, biopsies were obtained in 7740 sessions. The evaluation of costs included purchase prices, repairs, cleaning (chemicals, equipment, technician time) and autoclaving costs in a centralized sterilization unit. For comparison, the lowest purchase price for disposable biopsy forceps was $26.90 in 1997. RESULTS: A mean of 12 new reusable forceps were purchased every year for a total purchase price of $5460. A total of 315 biopsy sessions were performed per forceps (mean time life of 3 years per forceps, including 3 repairs). Yearly repair cost was $3308, equipment $1002, chemicals $3250, central sterilization $8333, and technician salary $4373. Total cost was $25,726 and cost per biopsy session was $6.65. CONCLUSIONS: Total purchase and reprocessing costs for reusable biopsy forceps were 25% of those of disposable devices. The use of disposable biopsy forceps would have led to a yearly extra cost of $78,377 in the operation of our endoscopy unit.