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Background: It has been suggested that the major metabolic block in the methionine catabolic pathway in cirrhotics exists at the level of the enzyme S-adenosylmethionine synthetase because in previous studies using conventional amino-acid analyzers, no intermediates of transmethylation/transsulfuration were found to accumulate in plasma downstream of S-adenosylmethionine synthesis. We therefore measured serum concentration intermediates of methionine transmethylation/transsulfuration using an improved gas chromatography/mass spectrometry technique. Methods: Serum concentrations of methionine, homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, 2-methylcitric acid and α-aminobutyric acid were determined by gas chromatography/mass spectrometry in 108 consecutive patients with liver cirrhosis at Child stages A (mild cirrhosis, n = 27) and B/C (severe cirrhosis, n = 81), 18 outpatients with non-cirrhotic liver disease, and 55 healthy individuals. Results: Serum levels of methionine, N,N-dimethylglycine, N-methylglycine, cystathionine, and homocysteine were significantly higher in patients at Child stages B/C compared with those of healthy controls (P < 0.01), and they were also significantly higher than in patients with non-cirrhotic liver disease (P < 0.01 and P < 0.05 for homocysteine, respectively). They also correlated with the Child-Pugh score (P < 0.01). Homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, and 2-methylcitric acid correlated with serum creatinine. The mean cystathionine concentration was significantly higher in patients with creatinine ≥1.4 mg/dl than in patients with normal creatinine values (P < 0.01). However, the differences between cirrhotics and healthy controls were still significant after correcting for creatinine. Conclusions: Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction. [ABSTRACT FROM AUTHOR]

Background: Increased serum nitrite/nitrate (NOx) levels, the stable metabolites of nitric oxide (NO), have been reported in patients with cirrhosis. NOx levels, however, are influenced not only by endogenous NO synthesis but also by urinary NOx excretion and dietary intake. We attempted to elucidate factors that influence NOx levels independently of endogenous NO production and to determine the conditions under which NOx levels reflect endogenous production in patients with cirrhosis and healthy controls. Methods: NOx serum concentrations and urinary NOx excretion were determined by means of the Griess reaction in relation to Child-Pugh score, kidney function, fasting state, and after exposure to tap water. Results: Multifactor regression analysis showed inulin clearance (P = 0.0074) and Child-Pugh score (P = 0.0001) to be independent factors predicting NOx levels in patients with cirrhosis. NOx serum levels correlated negatively with the inulin clearance (P < 0.0001), which deteriorated with progessive loss of liver function. NOx levels decreased by about 30% within a 24-h fasting period. After 24 h fasting urinary NOx excretion was not significantly increased in patients with advanced cirrhosis. Conclusions: NOx serum levels, taken as a surrogate for endogenous NO formation, have to be viewed with caution in patients with cirrhosis because they often have impaired kidney function. However, in steady-state conditions after an adequate fasting period NOx levels might be good prognostic markers in patients with cirrhosis since they reflect two possible sequelae of liver insufficiency-namely, increased NO formation and impaired kidney function. [ABSTRACT FROM AUTHOR]

A 55-year-old woman with suspected hilar cholangiocarcinoma presented with jaundice and dilated intrahepatic bile ducts owing to high-grade hepatic duct confluence stenosis. The suspected tumour and the entire extrahepatic bile duct system were resected and Roux-en-Y hepaticojejunostomy was performed. Histological investigations showed perihepatic fibrosis but no signs of malignancy. One year later the patient developed bilateral hydronephrosis caused by ureteral obstruction. Since the patient had a gynaecological history of widespread inflammation, she was referred for transabdominal operative ureterolysis combined with hysterectomy and adnexectomy. Histological investigations as well as fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) findings were compatible with retroperitoneal fibrosis (Ormond's disease). Treatment with tamoxifen was initiated. To the best of our knowledge, only a few cases of intraperitoneal fibroses mimicking cholangiocarcinoma followed by the typical symptoms of retroperitoneal Ormond's disease have been reported.

Objective: To examine the relationship of both the unstimulated and the postprandial portal blood flow (PVF) to the time of day and to determine its intra-individual reproducibility over time in patients with liver cirrhosis., Material and Methods: In 24 cirrhotic patients, 27 PVF measurements were performed during 24 h on day 0 and day 7 using Doppler ultrasound. Three standard liquid meals were given orally. On day 7, the baseline hepatic venous pressure gradient (HVPG) was also measured., Results: Circadian area under the time curve of PVF was highly reproducible within individuals (r=0.959, p<0.001). It did not correlate with HVPG. Cosinor analysis showed a significant circadian rhythm of PVF (acrophase at 11:44 and amplitude of 9.44%). Maximal postprandial increase in PVF was significantly higher in the morning than at noon or in the evening., Conclusions: PVF is subject to a circadian rhythm and postprandial portal hyperemia shows a diurnal variability. Both are highly reproducible.

An 18-year-old long-term Norwegian resident of Somali origin was submitted to hospital with bloody diarrhoea, fever, weight loss and abdominal pain. On initial colonoscopy, colitis with segmental appearance was seen. Apart from a single polymerase chain reaction (PCR) from gastric aspirate staining, PCR and culture for acid-fast bacilli revealed negative results from the multiple samples taken including sputum, gastric fluid, stool, urine and intestinal mucosa. On physical examination and CT scan, there was no evidence of ascites, lymph node enlargement or pathologic pulmonary findings. Although the diagnosis was uncertain, tuberculostatic therapy was initiated. As the conformational testing of the PCR and the microbiological work-up remained negative and the patient's condition did not improve, tuberculostatic treatment was stopped and Crohn's disease was stated as the most likely diagnosis. Although the patient improved clinically under therapy with prednisolone, newly appearing fistulas deriving from the ascending colon were noted on follow-up. Thus tuberculostatic treatment was restarted. However, signs of an acute abdomen appeared and laparotomy was performed, thereby revealing a peritoneal spread of nodules. Resection of the ileum and ascending colon was performed. Diagnosis of intestinal tuberculosis with peritoneal spread was made by histology from resected bowel specimens showing caseating granulomas and a positive PCR result. The patient's condition improved after resection of the highly inflamed bowel segments and tuberculostatic therapy. Our case report shows the difficulty of proving intestinal tuberculosis by microbiological testing, macroscopic features on colonoscopy, histology, imaging such as CT scan and by empirical therapy. Therefore, in cases of colonic inflammation, where intestinal tuberculosis is an important differential diagnosis, a more aggressive diagnostic approach such as explorative laparoscopy should be considered.

Background: It has been suggested that the major metabolic block in the methionine catabolic pathway in cirrhotics exists at the level of the enzyme S-adenosylmethionine synthetase because in previous studies using conventional amino-acid analyzers, no intermediates of transmethylation/transsulfuration were found to accumulate in plasma downstream of S-adenosylmethionine synthesis. We therefore measured serum concentration intermediates of methionine transmethylation/transsulfuration using an improved gas chromatography/mass spectrometry technique., Methods: Serum concentrations of methionine, homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, 2-methylcitric acid and alpha-aminobutyric acid were determined by gas chromatography/mass spectrometry in 108 consecutive patients with liver cirrhosis at Child stages A (mild cirrhosis, n = 27) and B/C (severe cirrhosis, n = 81), 18 outpatients with non-cirrhotic liver disease, and 55 healthy individuals., Results: Serum levels of methionine, N,N-dimethylglycine, N-methylglycine, cystathionine, and homocysteine were significantly higher in patients at Child stages B/C compared with those of healthy controls (P < 0.01), and they were also significantly higher than in patients with non-cirrhotic liver disease (P < 0.01 and P < 0.05 for homocysteine, respectively). They also correlated with the Child-Pugh score (P < 0.01). Homocysteine, cystathionine, N,N-dimethylglycine, N-methylglycine, methylmalonic acid, and 2-methylcitric acid correlated with serum creatinine. The mean cystathionine concentration was significantly higher in patients with creatinine > or = 1.4 mg/dl than in patients with normal creatinine values (P < 0.01). However, the differences between cirrhotics and healthy controls were still significant after correcting for creatinine., Conclusions: Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction.