Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A.

We have studied the relative contributions of monomeric (m-) and polymeric IgA (p-IgA) and of IgA1 and IgA2 to total serum IgA in healthy adults and patients with liver disease (LD) or with other diseases and high serum IgA. Serum concentration of total secretory component (SC) was also determined. In addition, fractional catabolic rates (FCR) and synthetic rates for both m- and p-IgA were measured in nine controls and nine cirrhotics. Our results support four main conclusions: (a) In healthy adults, intravascular p-IgA contributes to only 4-22% (mean 12%) of serum IgA, because its FCR and synthetic rate are approximately two times higher and four times smaller, respectively, than those of intravascular m-IgA. (b) in LD, biliary obstruction does not result in a significant increase in serum p-IgA unlike in rats and rabbits, indicating that in humans the SC-dependent biliary transport of p-IgA plays a much less significant role in selective removal of p-IgA from plasma than in rats and rabbits. (c) In contrast to biliary obstruction, parenchymal LD results in a significant and preferential increase in serum p-IgA, which in cirrhotics correlates with a selective reduction of the p-IgA-FCR. This supports a role for the human liver in selective removal of p-IgA from plasma, but another mechanism than the SC-dependent biliary transport should be considered. (d) Total SC, p-IgA, and IgA2 in serum are unlinked parameters, not necessarily reflecting mucosal events. A marked increase in serum SC occurs almost selectively in LD. Although a shift to IgA2 is suggested in Crohn's disease and alcoholic cirrhosis, a shift to IgA1 frequently associated to a shift to p-IgA occurs in chronic active LD, primary Sicca, and connective tissue diseases.

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.

Short report: interferon-alpha decreases 14C-aminopyrine breath test values in patients with chronic hepatitis C.

OBJECTIVE: To investigate the effect of interferon-alpha on cytochrome P-450 dependent microsomal function. METHODS: The 14C-aminopyrine breath test was performed before, during and after a standard dose of interferon-alpha (3,000,000 units three times per week) was administered for at least six months (nine patients with chronic hepatitis C). RESULTS: Mean aminopyrine breath test values obtained during therapy were significantly lower than either pre- or post-treatment, the degree of reduction varying widely between individuals. Pre- and post-treatment aminopyrine breath test values did not differ significantly. CONCLUSION: Interferon therapy is associated with a significant and transient inhibition of cytochrome P-450 activity, which should be taken into account when prescribing concurrent therapy with drugs metabolized by this pathway.

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.

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.

Is early enteral nutrition in acute pancreatitis dangerous? About 20 patients fed by an endoscopically placed nasogastrojejunal tube.

Bowel rest during treatment of acute pancreatitis deprives the gut of nutrients and affects its structure and function. Enteral feeding is usually performed late in the course of acute pancreatitis and therefore cannot prevent intestinal barrier dysfunction and possible bacterial translocation. To assess the effect of early enteral nutrition we performed a prospective study on 21 patients (11 males/10 females) presenting with severe acute pancreatitis (13 biliary, 6 alcoholic, and 2 miscellaneous). Severity was established by a mean Ranson score of 3.57. All but one patient could be fed through a double-lumen nasogastrojejunal tube within 60 h after admission. No significant complication of the technique was observed. We conclude that early jejunal feeding can be used safely in severe acute pancreatitis. Further comparative studies are necessary to demonstrate any superiority to total parenteral nutrition.

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.

The arthritis of hemochromatosis. A review of 25 cases with special reference to chondrocalcinosis, and a comparison with patients with primary hyperparathyroidism and controls.

Twenty-five cases of hemochromatosis established on histological grounds were reviewed in order to study their articular complaints. Symptoms relating to articular damage were the first signs of the disease in about one quarter of the cases. More than half of the patients (n = 14) exhibited inflammatory arthritis, usually of the hands and knees. The arthritis was chronic in all the patients. Acute arthritis of the joints of the hands and feet appeared in the course of the disease in two patients. Chondrocalcinosis was present in 20% of cases with X-rays of joints (n = 20). The classical subchondral arthropathy was observed in the metacarpophalangeal joints in 35% of the patients. In two patients chondrocalcinosis and subchondral arthropathy were both present. These data are compared with those of 66 patients suffering from primary hyperparathyroidism and of 229 controls with rheumatic complaints. The severity of the arthropathy in hemochromatosis is stressed.

Abnormal methylation capacity in human liver cirrhosis.

To investigate the influence of liver cirrhosis on the capacity of methylation, the urinary excretion of the methylated forms of arsenic was measured by atomic absorption spectrometry after the administration of a small dose of inorganic arsenic. The study was carried out in 13 normal controls, 18 patients with various clinical conditions, but without evidence of parenchymal liver disease, and 38 with cirrhosis of varied aetiology and severity. In normal controls, the percentage of arsenic excreted as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) averaged 12.3 +/- 2.8% and 23.3 +/- 6.4%, respectively, and was not significantly different from that obtained in disease controls. The presence of liver cirrhosis did not affect the percentage of the injected dose excreted within 24 h. However, cirrhotic patients excreted significantly less MMA (4.7 +/- 3.3, p less than 0.001) and more DMA (40.4 +/- 16.6%, p less than 0.001). The amount of MMA correlated with the 14C aminopyrine breath test (r = 0.43) and was invariably lower than the normal range in patients with severe liver disease. These findings indicate that liver cirrhosis is associated with profound abnormalities of the methylation pathway, which might have potential consequences in the metabolism of endogenous amines and xenobiotics.

Potentiation of carbon-tetrachloride hepato-nephrotoxicity by phenobarbital in man, a case report.

A 47 year-old male epileptic who had been treated for eight years with variable doses of phenobarbital and valproate was hospitalized in the intensive care unit with the following clinical and biological features: coma grade 2, metabolic acidosis, acute renal and hepatic failure. The recent clinical history revealed that he had been using CCl4 to clean paintings for the last three days in a confined atmosphere. Upon admission, the recent absorption of CCl4 was confirmed by the detection of the solvent in blood and adipose tissue. Cellular lipoperoxidation was suggested by the presence of an increased concentration of pentane in expired air. Evidence of microsomal enzyme induction was provided by the relative preservation of aminopyrine demethylation as indicated by the 14C-aminopyrine breath test and also by the morphological evidence of endoplasmic reticulum proliferation at liver biopsy. Supportive therapy, repeated haemodialysis and administration of antioxidant drugs resulted in a complete recovery. The unusual severity of CCl4-induced liver and renal injury observed in this case is best explained by the induction of CCl4 microsomal activation due to phenobarbital therapy.

Bilateral transient visual obscurations with headaches during alpha-II interferon therapy: a case report.

A 40 year-old woman receiving alpha interferon therapy for chronic active hepatitis C presented transient bilateral visual obscurations with associated visual field defects and headaches, with elevated cryoglobulin levels. These manifestations mimicked the clinical picture of migraine and were associated with worsening of previous moderate Raynaud's syndrome and diffuse paraventricular lesions of the white matter seen in cerebral MRI. Bilateral posterior cerebral transient ischemic episodes rather than an anterior visual pathway lesion were thought to be responsible for the clinical symptoms though the exact role of interferon in these vasospastic-like disorders remains speculative. Their possible relationship with increased cryoglobulinemia is uncertain. We suggest that Raynaud's phenomenon may have a predisposing role for these manifestations.

Human fascioliasis: cure by mebendazole? A case report.

We report a case of invasive human Fasciola hepatica infection in which, for the first time, a successful treatment with high doses of mebendazole (4 g/day for 3 weeks) was achieved. This therapy resulted in a prompt and prolonged normalization of eosinophil counts, liver enzymes abnormalities and specific serological tests together with the disappearance of liver necrosis indicating the eradication of liver flukes. The efficacy of mebendazole in the treatment of fascioliasis must be confirmed by further studies.

[Severe hepatitis with encephalopathy induced by acetylsalicylic acid in a case of lupus erythematosus disseminatus]. / Hépatite grave avec encéphalopathie imputable à l'acide acétylsalicylique dans un cas de lupus érythémateux disséminé.

The observation of a 62 year-old woman who had been suffering from arthritis for several years and in whom treatment with high doses of acetylsalicylic acid resulted in severe acute hepatitis is reported. Clinical and serological findings led to the diagnosis of systemic lupus erythematosus complicated by acute drug induced hepatitis.

[Vascular gastric anomalies, CREST syndrome and primary biliary cirrhosis: efficacy of ethinyl estradiol-norethisterone combination]. / Anomalies vasculaires gastriques, CREST syndrome et cirrhose biliaire primitive: efficacité de l'association éthinyloestradiol-noréthistérone.

Vascular gastric lesions are a rare cause of chronic gastric bleeding. We report the case of a 70-year old woman with primary biliary cirrhosis, CREST syndrome and vascular gastric lesions corresponding to watermelon stomach. Oestrogen-progesterone treatment successfully controlled recurrent blood loss.

[Fulminant or sub-fulminant hepatocellular failure caused by metastatic invasiveness of the liver: an other cause of hypoxic hepatitis?]. / Insuffisance hépatocellulaire fulminante ou subfulminante secondaire à une infiltration métastatique du foie: une autre cause d'hépatite hypoxique?

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

[Role of liver transplantation in the treatment of metastatic disease of the liver]. / Place de la transplantation hépatique dans le traitement des affections métastatiques du foie.

The authors report their experience of liver transplantation for metastatic tumor in 6 patients. Although good palliation can be offered with prolonged survival in some patients, secondaries of the liver remain the poorest indication for liver transplantation. A prospective multicentric study would be needed to evaluate the usefulness of post-transplantation chemotherapy.

[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.

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.