Claudia Sama

Enzymatic determination of cholesterol in bile

Abstract A simple, sensitive and rapid method for measuring the cholesterol concentration in bile is described. The method is based on the combination of an enzymatic technique and spectrophotometry. In the present study the results obtained with this method are compared with those obtained by the standard Liebermann-Burchard reaction on the same samples and are found to be in close agreement.

High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

Background: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. Methods: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. Results: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a “probable autoimmune hepatitis” (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). Conclusions: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.

Pulmonary complications of liver transplantation: radiological appearance and statistical evaluation of risk factors in 300 cases.

Abstract. The aim of this study was to evaluate the incidence, radiographic appearance, time of onset, outcome and risk factors of non-infectious and infectious pulmonary complications following liver transplantation. Chest X-ray features of 300 consecutive patients who had undergone 333 liver transplants over an 11-year period were analysed: the type of pulmonary complication, the infecting pathogens and the mean time of their occurrence are described. The main risk factors for lung infections were quantified through univariate and multivariate statistical analysis. Non-infectious pulmonary abnormalities (atelectasis and/or pleural effusion: 86.7 %) and pulmonary oedema (44.7 %) appeared during the first postoperative week. Infectious pneumonia was observed in 13.7 %, with a mortality of 36.6 %. Bacterial and viral pneumonia made up the bulk of infections (63.4 and 29.3 %, respectively) followed by fungal infiltrates (24.4 %). A fairly good correlation between radiological chest X-ray pattern, time of onset and the cultured microorganisms has been observed in all cases. In multivariate analysis, persistent non-infectious abnormalities and pulmonary oedema were identified as the major independent predictors of posttransplant pneumonia, followed by prolonged assisted mechanical ventilation and traditional caval anastomosis. A “pneumonia-risk score” was calculated: low-risk score ( < 2.25) predicts 2.7 % of probability of the onset of infections compared with 28.7 % of high-risk ( > 3.30) population. The “pneumonia-risk score” identifies a specific group of patients in whom closer radiographic monitoring is recommended. In addition, a highly significant correlation (p < 0.001) was observed between pneumonia-risk score and the expected survival, thus confirming pulmonary infections as a major cause of death in OLT recipients.

Enterohepatic circulation of bile acids after cholecystectomy.

Bile acid metabolism was investigated in 10 patients after cholecystectomy, 10 gallstone patients, and 10 control subjects. Diurnal variations of serum levels of cholic and chenodeoxycholic acid conjugates were not abolished by cholecystectomy. Cholic acid pool size was significantly reduced in cholecystectomised patients and the fractional turnover rate and the rate of intestinal degradation of bile acid showed a significant increase. In cholecystectomised patients fasting bile was supersaturated in cholesterol, though less than in gallstone patients, but, in both, feeding resulted in improvement of cholesterol solubility in bile. These data suggest that after cholecystectomy the small intestine alone acts as a pump in regulating the dynamics of the enterohepatic circulation of bile acids and that the improvement of cholesterol solubility in bile is due to a more rapid circulation of the bile acid pool in fasting cholecystectomised patients.

Bile acid malabsorption and bile acid diarrhea in intestinal resection.

Bile acid fecal excretion and dihydroxy bile acid concentration in the fecal water of patients with large (N=6) and small (N=8) ileal resection, colectomy (N=5), and healthy controls (N=10) have been studied in order to evaluate the degree of bile acid malabsorption and the occurrence of bile acid diarrhea in intestinal resections of different extent. Bile acid malabsorption was severe in large ileal resections, mild in small ones, and slight in colectomy. The fecal pH seems to be a limiting factor in the occurrence of a bile acid diarrhea, playing a critical role in determining the dihydroxy bile acid solubility in the fecal water. These results seem to suggest that the bile acids may induce water secretion in the colon not only in small but also in large ileal resections.

Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case control study

Sleep disturbance and excessive daytime sleepiness have been reported in patients with hepatic cirrhosis. The objective of this study was to evaluate daytime somnolence and sleep complaints in a group of 178 patients with cirrhosis compared to a control group. Sleep features and excessive daytime sleepiness were evaluated by the Basic Nordic Sleep Questionnaire (BNSQ) and the Epworth Sleepiness Scale (ESS). We collected clinical and laboratory data, neurological assessment and EEG recordings in cirrhotic patients. Patients with cirrhosis complained of more daytime sleepiness (p<0.005), sleeping badly at least three times a week (p<0.005), difficulties falling asleep (p<0.01) and frequent nocturnal awakening (p<0.005) than controls. We found a poor correlation between sleep disorders and clinical or laboratory parameters. Our results confirm previous literature reports suggesting a high prevalence of sleep disturbance in patients with cirrhosis. Insomnia and daytime sleepiness are the main complaints. Sleep disorders are probably a multifactorial phenomenon.

Clinical trial: peg-interferon alfa-2b and ribavirin for the treatment of genotype-1 hepatitis C recurrence after liver transplantation

Background  Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates.

Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

UNLABELLED Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. METHODS This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. RESULTS A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). CONCLUSION Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib.

Effect of ursodeoxycholic acid administration on biliary lipid composition and bile acid kinetics in cholesterol gallstone patients

The effect of ursodeoxycholic acid (UDCA) on bile lipid composition and bile acid kinetics was evaluated in seven cholesterol gallstone patients following one month of UDCA administration (12 mg/kg/day). UDCA administration induces a significant reduction in the cholesterol saturation index (SI). After UDCA treatment, UDCA becomes the predominant biliary bile acid while chenodeoxycholic, cholic, and deoxycholic acid are significantly reduced. UDCA pool significantly increases, and chenodeoxycholic, cholic, and total bile acid pools significantly decrease. The reduction in bile lithogenicity during UDCA administration suggests that UDCA may be useful for cholesterol gallstone treatment in man.

Serum Pancreatic Enzyme Concentrations in Chronic Viral Liver Diseases

Serum amylase and lipase concentrations weredetermined in 78 patients with chronic liver diseases[26 chronic active hepatitis (CAH) and 52 livercirrhosis] and in 15 healthy subjects. Pancreaticisoamylase concentrations and macroamylase complexes wereassayed in hyperamylasemic sera. Serum amylase levelswere abnormally elevated in 27 patients (35%; 22 livercirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 livercirrhosis, 1 CAH). In 9 of the 27 hyperamylasemicpatients, the hyperamylasemia was of pancreatic type.Macroamylasemic complexes were not detected inhyperamylasemic sera. Patients with liver cirrhosis had serumlevels of amylase and lipase significantly higher thanboth the healthy subjects and the patients with CAH,while no significant differences were found in serum levels of these enzymes in patients with CAH ascompared to the healthy subjects. A decreased livermetabolism of serum amylase and lipase in patients withchronic infective liver disease, especially in those having liver cirrhosis, may lead to anaccumulation of these enzymes in the blood.