morphine and Liver-Diseases

The article reviews advances in gastrointestinal aspects of cystic fibrosis (CF) published in the literature over the past year, and highlights new and interesting research.. Animal models can be used to understand the pathophysiology of gastrointestinal complications in CF. The CF mouse is useful for studying distal intestinal obstruction, dysmotility and dysbiosis, and the CF pig model has helped us better understand meconium ileus and pancreatic and hepatobiliary secretory problems. Studies in humans help elucidate the evolution of pancreatic insufficiency, how reflux may lead to lung disease, problems with intestinal dysmotility, mechanisms leading to pancreatitis and the increased prevalence of gastrointestinal cancer. Biomarkers are shedding light on CF-related liver disease. Rectal biopsies can help in diagnosis and in studying new drugs for CF.. Gastrointestinal complications of CF are likely to be seen with increasing frequency as patients with CF lead longer lives. CF animal models and modern research techniques are providing new insights into extrapulmonary complications. CF clinicians should be familiar with diagnosis and management of common gastrointestinal complications and should build bridges with specialists so that referrals can be made when needed.

Topics: Animals; Cystic Fibrosis; Digestive System Diseases; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Humans; Ileus; Intestinal Obstruction; Liver Diseases; Meconium; Mice; Pancreatic Diseases; Prognosis; Rectum; Swine

A subcapsular hematoma of the liver is often found during autopsy in stillborn infants rather than clinically. It is usually asymptomatic unless ruptured; thus, the diagnosis is often delayed or missed. Rupture of a subcapsular hematoma in a premature neonate causes massive intraabdominal hemorrhage, which is associated with high mortality. Thus, early recognition and treatment to avoid rupture are imperative. We describe a case of life-threatening hemorrhage from a subcapsular hematoma of the liver during emergent laparotomy for mechanical obstruction in an 860 g premature neonate and discuss the appropriate preoperative preparation and anesthetic management for this case.

Topics: Blood Loss, Surgical; Emergencies; Fatal Outcome; Heart Arrest; Hematoma; Hemostasis, Surgical; Humans; Infant, Extremely Low Birth Weight; Infant, Extremely Premature; Infant, Newborn; Intestinal Obstruction; Intestine, Small; Intraoperative Complications; Laparotomy; Liver Diseases; Male; Meconium; Rupture, Spontaneous

The aim of the present article was to determine the prevalence of liver involvement in Hispanic patients with cystic fibrosis (CF) and identify associations with age and severity of liver involvement.. We used 1994-2005 Epidemiologic Study of CF data to compare abnormal liver findings between Hispanic and non-Hispanic white patients with CF.. Of 30,727 patients with CF, 5015 had liver involvement. Of 1957 Hispanic patients, 20.8% had liver involvement compared with 16.0% of 28,770 non-Hispanic white patients (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.23-1.54). This higher prevalence of liver involvement persisted after adjusting for demographics and meconium ileus and was especially high in the first year of life (adjusted OR 3.14, 95% CI 2.27-4.35). Ten percent of infants with only elevated liver enzymes progressed to more severe liver disease.. The Hispanic population with CF has more liver involvement (both elevated liver enzymes and clinical liver disease) than the non-Hispanic white population with CF, especially during the first year of life.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cystic Fibrosis; Female; Hispanic or Latino; Humans; Ileus; Infant; Infant, Newborn; Liver; Liver Diseases; Male; Meconium; Middle Aged; North America; Odds Ratio; Prevalence; White People; Young Adult

Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF.

Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genes, Modifier; Genetic Linkage; Genetic Markers; Genome-Wide Association Study; Homozygote; Humans; Liver Diseases; Lung Diseases; Mannose-Binding Lectins; Meconium; Mutation; Phenotype

Cystic Fibrosis (CF) is a common autosomal recessive disease that affects multiple organs. The lack of an animal model with manifestations like those typically found in humans has slowed understanding of its pathogenesis. Therefore, because of the similarities between human and swine anatomy, biochemistry, physiology, size, and genetics, we chose to develop a porcine model of CF. We used homologous recombination in primary cultures of porcine fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced CFTR-/- pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic destruction, early focal biliary cirrhosis, and gall bladder abnormalities that were very similar to those observed in humans with CF. At birth, there were no abnormalities in the airway epithelium or submucosal glands and no evidence of inflammation, consistent with findings in the newborn human. We hope that this porcine model will help elucidate the pathogenesis of CF and thereby lead to the development of new mechanism-based therapies.

Topics: Animals; Animals, Genetically Modified; Animals, Newborn; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Gallbladder Diseases; Gene Targeting; Humans; Ileus; Infant, Newborn; Liver Diseases; Meconium; Models, Biological; Mutation; Pancreatic Diseases; Phenotype; Respiratory System; Species Specificity; Swine

Information concerning long-term operative outcomes in patients with cystic fibrosis (CF) is relatively sparse in the operative literature.. A retrospective review of CF patients with operative conditions was performed (1972-2004) at a tertiary children's hospital to analyze outcomes including long-term morbidity and survival.. A total of 226 patients with CF presented with an operative diagnosis (113 men, 113 women). A total of 422 operations were performed in 213 patients (94%). The mean age at operation was 4.1 +/- 6.2 years (range, 1 d to 26 y) and 109 were neonates. Fifteen of 42 (36%) babies with simple meconium ileus (MI) were treated nonoperatively with hypertonic enemas, 27 of 42 and all 45 patients with complicated MI required operation, including 15 with jejunoileal atresia (17%). Seventeen of 27 (63%) patients with meconium ileus equivalent had MI as neonates; 7 of 27 (26%) required operation. Eight of 9 (89%) with fibrosing colonopathy required operation. Organ transplantation was required in 21 patients. Follow-up evaluation was possible in 204 of 213 (96%) patients. The duration of follow-up evaluation was 14.9 +/- 8.5 years (range, 2 mo to 35 y). Operative morbidity was 11% at 1 year, 2% at 2 to 4 years, 1% at 5 to 10 years, and less than 1% at more than 10 years. There were 24 deaths (11%); 22 followed CF-related pulmonary complications and included 8 of 16 (50%) children with pneumothorax.. Long-term survival in CF patients has improved significantly (89%), with many surviving into the fourth decade. MI may predispose to late complications including meconium ileus equivalent and fibrosing colonopathy. Pneumothorax in CF patients is an ominous predictor of mortality. Children with CF are living longer and are good candidates for operation, but require long-term follow-up evaluation because of ongoing exocrine dysfunction.

Topics: Abdomen; Adolescent; Adult; Bile Duct Diseases; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Ileus; Infant; Infant, Newborn; Intestinal Diseases; Intussusception; Liver Diseases; Male; Meconium; Pneumothorax; Postoperative Complications; Retrospective Studies; Survival Analysis; Thoracic Surgical Procedures; Treatment Outcome

To describe the prevalence of liver disease in a cohort of 241 cystic fibrosis (CF) patients.. 241 CF patients were followed-up every 3 months with clinical and biological assessment, and every year with ultrasonography of the liver. The presence of liver disease was studied using a multivariate Cox's regression analysis including variables such as history of meconium ileus, pulmonary function, pancreatic insufficiency and CFTR gene mutations.. The prevalence of liver disease was 18, 29, and 41% after 2, 5 and 12 years, respectively, and did not increase thereafter. In multivariate analysis, the probability of liver disease was independently associated with history of meconium ileus (P = 0.001) and pancreatic insufficiency (P = 0.004). CFTR mutations and severity of pulmonary disease were not associated with liver disease. Cirrhosis occurred in 19 (7.8%) patients at a median age of 10 years, and liver transplantation was required in five patients.. This study shows that CF related-liver disease occurs mainly in the first decade of life with a prevalence of 41% of patients at 12 years of age. A history of meconium ileus and pancreatic insufficiency are predictive of liver disease. Preventive treatment with ursodesoxycholic acid could be considered in patients with meconium ileus.

Topics: Adolescent; Age Distribution; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; Disease Progression; Exocrine Pancreatic Insufficiency; Female; Humans; Ileus; Incidence; Infant; Liver Diseases; Longitudinal Studies; Male; Meconium; Prevalence; Prognosis; Survival Analysis

Cystic fibrosis (CF), the most common lethal autosomal recessive disease in white populations, is characterized by dysfunctional chloride ion transport across epithelial surfaces. Although recurrent pulmonary infections and pulmonary insufficiency are the principal causes of morbidity and death, gastrointestinal symptoms commonly precede the pulmonary findings and may suggest the diagnosis in infants and young children. The protean gastrointestinal manifestations of CF result primarily from abnormally viscous luminal secretions within hollow viscera and the ducts of solid organs. Bowel obstruction may be present at birth due to meconium ileus or meconium plug syndrome. Complications of meconium ileus include volvulus, small bowel atresia, perforation, and meconium peritonitis with abdominal calcifications. Older children with CF may present with bowel obstruction due to distal intestinal obstruction syndrome or colonic stricture, and tenacious intestinal residue may serve as a lead point for intussusception or cause recurrent rectal prolapse. Radiologic studies often demonstrate thickened intestinal mucosal folds in older children and uncommonly show colonic pneumatosis, peptic esophageal stricture due to gastroesophageal reflux, and duodenal ulcer. Appendicitis due to inspissated secretions is uncommon. Obstruction of ducts and ductules produces exocrine pancreatic insufficiency, pancreatitis, cholestasis, cholelithiasis, and cirrhosis with portal hypertension. On imaging studies, the pancreas is commonly small and largely replaced by fat, sometimes displays calcifications, and is rarely replaced by macrocysts. Radiologic features of hepatobiliary disease include an enlarged radiolucent liver from steatosis, gallstones, a shrunken nodular liver, splenomegaly, and portosystemic collateral vessels. With the improved survival of CF patients, an increased risk for developing gastrointestinal carcinomas has been established, many occurring as early as the 3rd decade.

Topics: Adult; Biliary Tract Diseases; Child; Cystic Fibrosis; Digestive System Diseases; Gastrointestinal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Liver Diseases; Meconium; Pancreatic Diseases; Tomography, X-Ray Computed; Ultrasonography

Topics: Adolescent; Child; Child, Preschool; Comorbidity; Cystic Fibrosis; Female; Humans; Incidence; Intestinal Obstruction; Liver Diseases; Liver Function Tests; Male; Meconium; Prevalence; Sweden

We report on a patient with atresia of the colon transversum and a large meconium pseudocyst adherent to the liver. Sonography additionally revealed multiple cystic structures due to intrahepatic meconium masses. Surgical evacuation of the meconium pseudocyst resulted in massive diffuse hemorrhage from the liver which could not be stopped. The child died intraoperatively due to hemorrhagic shock. Histologically the intrahepatic meconium masses were surrounded by various degrees of necrosis and hemorrhage without a well-defined capsule of fibrous granulation tissue.

Topics: Colonic Diseases; Cysts; Fatal Outcome; Humans; Infant, Newborn; Intestinal Perforation; Liver Diseases; Male; Meconium; Peritonitis; Ultrasonography

We prospectively screened for liver disease patients with cystic fibrosis who were more than 3 years of age and who were followed at the cystic fibrosis center of the University of Milan. From January 1991 to December 1992, we screened 189 patients; clinical, biochemical, and echographic abnormalities suggestive of overt liver disease were present in 34 (18%). To define risk factors for the development of liver disease associated with cystic fibrosis, we evaluated the possible role of specific mutations of the CFTR (cystic fibrosis transmembrane regulator) gene and of different clinical and demographic characteristics (sex, pancreatic status, meconium ileus or its equivalent) through a comparison of patients with cystic fibrosis and overt liver disease (n = 34) and those without liver disease (n = 155). Genetic analysis failed to reveal any significant difference in the allele frequencies of defined (delta F508, 1717-1G-A, G542X, N1303K, W1282X, R553X) and undefined mutations of the CFTR gene in the two groups of patients; genotype frequencies were also not significantly different. Pancreatic insufficiency was present in all patients with liver disease and in 87.3% of those without liver disease. A male predominance was found in the group with liver disease. The frequency of meconium ileus or its equivalent was significantly higher in patients with cystic fibrosis and liver disease (35.3%) than in patients without liver disease (12.3%) (p = 0.0025). In the 31 patients with a history of meconium ileus or its equivalent, the following hepatic abnormalities occurred more frequently than in the 155 patients with cystic fibrosis who did not have meconium ileus: hepatomegaly, biochemical abnormalities, heterogeneous echographic pattern of the liver, and microgallbladder. Twenty-four patients with a history of meconium ileus or its equivalent underwent hepatobiliary scintigraphy (with technetium-labeled iminodiacetic acid derivatives), which showed morphologic abnormalities suggestive of impaired biliary drainage in 21 patients and abnormalities in function in 11. The risk of acquiring liver disease was increased almost fourfold in patients with a history of meconium ileus or its equivalent, in comparison with patients who had cystic fibrosis but were unaffected by these complications (odds ratio, 3.9043; 95% confidence interval, 1.666 to 9.149). We conclude that patients with cystic fibrosis and meconium ileus or its equivalent may benefit from prophylactic tre

Topics: Adolescent; Child; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Genotype; Humans; Intestinal Obstruction; Liver Diseases; Male; Meconium; Mutation; Prospective Studies; Risk Factors; Sex Factors

Topics: Adolescent; Adult; Ascites; Bile Duct Diseases; Cecal Diseases; Child; Child, Preschool; Colonic Diseases; Cystic Fibrosis; Duodenal Diseases; Gallbladder Diseases; Gastrointestinal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Intestine, Small; Intussusception; Jaundice, Neonatal; Liver Diseases; Male; Meconium; Peritonitis; Prenatal Diagnosis; Tomography, X-Ray Computed; Ultrasonography

Topics: Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Intestinal Perforation; Liver Diseases; Meconium; Megacolon; Peritonitis; Pseudomonas Infections; Radiography; Sepsis

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Protein Disorders; Bronchopneumonia; Child; Cystic Fibrosis; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diagnosis; Diagnosis, Differential; Diet; Diet Therapy; Electrolytes; Exercise Therapy; Gastroenterology; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Liver Diseases; Meconium; Pancreatic Extracts; Sweat