PubMed Health⌕ Search

Biomedical subjects

Joel E Lavine

Publications and source records attributed to Joel E Lavine.

17 recordsLinked to original sources
PubMed2006

Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group.

OBJECTIVES: To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors. STUDY DESIGN: A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained > or = 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ. RESULTS: The cause of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy. CONCLUSIONS: Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.

Adolescent↗
PubMed2006

Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research.

Although population prevalence is very difficult to establish, nonalcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the preadolescent and adolescent age groups. There seems to be an increase in the prevalence of NAFLD, likely related to the dramatic rise in the incidence of obesity during the past 3 decades. Despite an increase in public awareness, overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed by health care providers. Accurate diagnosis and staging of nonalcoholic steatohepatitis (NASH) requires liver biopsy. The development of noninvasive surrogate markers and the advancements in imaging technology will aid in the screening of large populations at risk for NAFLD. Two distinct histological patterns of NASH have been identified in the pediatric population, and discrete clinical and demographic features are observed in children with these 2 patterns. The propensity for NASH to develop in obese, insulin-resistant pubertal boys of Hispanic ethnicity or a non-Hispanic white race may provide clues to the pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet to be defined, but most biopsies in this age group demonstrate some degree of fibrosis. In addition, cirrhosis can be observed in children as young as 10 years. While the optimal treatment of pediatric NAFLD has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is underway as part of the NASH clinical research network.

Adolescent↗
PubMed2006

Prevalence of fatty liver in children and adolescents.

OBJECTIVE: Fatty liver disease is diagnosed increasingly in children, but the prevalence remains unknown. We sought to determine the prevalence of pediatric fatty liver as diagnosed by histology in a population-based sample. METHODS: We conducted a retrospective review of 742 children between the ages of 2 and 19 years who had an autopsy performed by a county medical examiner from 1993 to 2003. Fatty liver was defined as > or = 5% of hepatocytes containing macrovesicular fat. RESULTS: Fatty liver was present in 13% of subjects. For children and adolescents age 2 to 19 years, the prevalence of fatty liver adjusted for age, gender, race, and ethnicity is estimated to be 9.6%. Fatty liver prevalence increases with age, ranging from 0.7% for ages 2 to 4 up to 17.3% for ages 15 to 19 years. Fatty liver prevalence differs significantly by race and ethnicity (Asian: 10.2%; black: 1.5%; Hispanic: 11.8%; white: 8.6%). The highest rate of fatty liver was seen in obese children (38%). CONCLUSIONS: Fatty liver is the most common liver abnormality in children age 2 to 19 years. The presence of macrovesicular hepatic steatosis in approximately 1 of every 10 children has important ramifications for the long-term health of children and young adults. The influence of the risk factors identified should be taken into consideration in the development of protocols designed to screen at-risk children and adolescents.

Adolescent↗
PubMed2005

Histopathology of pediatric nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common in children and adolescents. However, standard histological criteria for pediatric NAFLD and NASH are undeveloped. We reviewed consecutive patients ages 2 to 18 years with biopsy-proven NAFLD diagnosed between 1997 and 2003. Biopsies were evaluated by two pathologists for individual features of steatohepatitis. Agglomerative hierarchical cluster analysis demonstrated two different forms of steatohepatitis. Type 1 was characterized by steatosis, ballooning degeneration, and perisinusoidal fibrosis; type 2 was characterized by steatosis, portal inflammation, and portal fibrosis. The study included 100 children with NAFLD. Simple steatosis was present in 16% of subjects, and advanced fibrosis was present in 8%. Type 1 NASH was present in 17% of subjects, and type 2 NASH was present in 51%. Boys were significantly (P < .01) more likely to have type 2 NASH and less likely to have type 1 NASH than girls. The NASH type differed significantly (P < .001) by race and ethnicity. Type 1 NASH was more common in white children, whereas type 2 NASH was more common in children of Asian, Native American, and Hispanic ethnicity. In cases of advanced fibrosis, the pattern was generally that of type 2 NASH. In conclusion, type 1 and type 2 NASH are distinct subtypes of pediatric NAFLD, and type 2 is the most common pattern in children. NASH subtypes should be considered when interpreting liver biopsies and planning studies of the pathophysiology, genetics, natural history, or response to treatment in pediatric NAFLD.

Adolescent↗
PubMed2005

Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents.

OBJECTIVES: Fatty liver is a common cause of liver disease in children. However, the epidemiology of pediatric fatty liver is limited to single-center case series of nonalcoholic fatty liver disease (NAFLD). Obesity and insulin resistance are major established risk factors for NAFLD. The role of gender, race, and ethnicity on the prevalence of fatty liver in obese children is unknown. METHODS: We recruited obese 12th-grade participants from the Child and Adolescent Trial for Cardiovascular Health in California, Louisiana, Minnesota, and Texas. Serum samples were collected at school when the participants were well. Alanine aminotransferase (ALT) was measured by kinetic enzymatic assay, and ALT >40 U/L was defined as abnormal. Causes of abnormal ALT other than NAFLD were excluded by serum testing. RESULTS: A total of 127 obese students (73 female, 54 male) had a mean BMI of 35.2 kg/m2. Unexplained ALT elevation was present in 23% of participants overall. The mean ALT for participants with normal values was 28 U/L and for participants with an abnormal ALT was 56 U/L. Abnormal ALT was significantly more prevalent in boys (44%) than in girls (7%). The prevalence of abnormal ALT differed significantly by race and ethnicity (Hispanic: 36%; white: 22%; black: 14%). Serum ALT value was significantly predicted by the combination of gender, race/ethnicity, and BMI. After controlling for gender and BMI, Hispanic ethnicity significantly predicted greater ALT than black race. CONCLUSIONS: In a national, school-based sample of obese adolescents, boys were 6 times more likely than girls to have an unexplained elevated ALT. Given that participants were well and causes of chronic liver disease were excluded, we speculate that obese adolescent boys have an increased prevalence of fatty liver compared with obese adolescent girls. This population-based study also supports the hypothesis that NAFLD is more common in Hispanic adolescents. These findings have implications for both disease screening and studies of fatty liver pathophysiology.

Adolescent↗
PubMed2004

Esophagogastric disconnection following failed fundoplication for the treatment of gastroesophageal reflux disease (GERD) in children with severe neurological impairment.

This report describes our experience with esophagogastric disconnection and Roux-en-Y esophagojejunostomy for the treatment of gastroesophageal reflux disease (GERD) in seven neurologically impaired children as a second antireflux operation following failed Nissen fundoplication. After a mean follow-up of 3 years, three children (43%) were completely or almost completely symptom-free and had improved nutritional status. Early complications occurred in three patients (43%): small bowel obstruction, wound infection, and necrosis of the Roux-en-Y loop. Three patients (43%) presented long-term complications: jejunoesophageal bile reflux and bile reflux with gastric irritation. Two patients required reoperation (28%), and two deaths occurred in the postoperative period (28%). In three previous reports in the surgical literature, severe postoperative complications occurred in 0-44%, requiring reoperation in 0-22% of the patients, and the mortality rate was 0-11%. Esophagogastric disconnection for the treatment of GERD in neurologically impaired children is associated with major complications and should be considered after more conservative procedures fail.

Adolescent↗
PubMed2004

Nonalcoholic fatty liver disease in the pediatric population.

Nonalcoholic fatty liver disease (NAFLD) covers the spectrum of features found in liver laden with macrovesicular fat and variable degrees of inflammation, cell injury, and fibrosis. By definition, NAFLD excludes those with significant ingestion of alcohol or alternative potential cause of steatohepatitis. NAFLD develops with rare exception in children who are obese. Given the rapid rise in prevalence of obesity in children globally, NAFLD is now recognized as the most common cause of liver disease in pediatrics. In obese individuals, Hispanic ethnicity and male gender appear to increase risk. Recent studies suggest that insulin resistance and oxidative stress are important in pathogenesis. Treatment trials are underway to determine if reduction of insulin resistance or oxidative stress will favorably affect outcome. This review summarizes what is known about pediatric nonalcoholic steatohepatitis in terms of prevalence, demographics, clinical presentation, histology,pathogenesis, and treatment. Important differences between pediatric and adult fatty liver disease are highlighted.

Adolescent↗
PubMed2004

Gastrointestinal complications of mitochondrial disease.

The clinical presentation of mitochondrial disease can involve a number of organ systems which are seemingly unrelated. Gastrointestinal manifestations are often an early presentation of mitochondrial disorders. Dysphagia, feeding difficulties, gastroesophageal reflux, dysmotility with delayed gastric emptying, intestinal pseudo-obstruction, diarrhea and pancreatic exocrine insufficiency are amongst the major complications. Neuromuscular dysfunction affecting peristalsis is a common pathophysiologic mechanism causing many of these symptoms and treatment is primarily supportive.

Journal Article↗
PubMed2004

Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn's disease.

We describe 2 cases of autosomal recessive chronic granulomatous disease (CGD) in 2 sisters presenting with a picture consistent with inflammatory bowel disease. The index case is a 10-year-old girl with a history of refractory Crohn's colitis treated with aggressive immunosuppressive therapy whose course subsequently was complicated by central nervous system aspergillosis. Additional evaluation showed a diagnosis of CGD, an underlying immunodeficiency in which phagocytes fail to produce microbicidal reactive oxygen intermediates because of inherited defects in the reduced form of nicotinamide-adenine phosphate dinucleotide (NADPH) oxidase. The diagnosis of a typically X-linked inherited disease in our female patient suggested that she had 1 of the 3 less common autosomal recessive forms of the disease. This was confirmed by studies showing the absence of the p47(phox) subunit of NADPH oxidase in her neutrophils and the presence of a homozygous dinucleotide deletion in the neutrophil cytosolic factor 1 gene that encodes p47(phox). Additional analyses of members of the patient's immediate family showed the same homozygous mutation in 2 siblings, 1 of whom also developed chronic colitis consistent with a diagnosis of Crohn's disease. These 2 cases emphasize the importance of high clinical suspicion for an alternative diagnosis of immune deficiency in the setting of presumed inflammatory bowel disease and opportunistic infection.

Adolescent↗
PubMed2003

Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease.

OBJECTIVE: To describe the clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in children, including insulin resistance, and to test for correlation with liver pathology. STUDY DESIGN: A retrospective review of children with biopsy-proven NAFLD at Children's Hospital San Diego from 1999 to 2002. Liver biopsy specimens were independently reviewed by two pathologists. RESULTS: Children with NAFLD (n=43) were mostly male (70%), Hispanic American (53%) and obese (88%). The criteria for insulin resistance were met by 95% of subjects. Steatosis was predicted by the combination of quantitative insulin sensitivity check index, age, and ethnicity (P<.0001). Portal inflammation was predicted by the combination of ALT and fasting insulin (P=.0009). Perisinusoidal fibrosis was predicted by the combination of AST, fasting insulin, and BMI Z score (P<.0001). Portal fibrosis was predicted by the combination of right upper quadrant pain and homeostasis model assessment of insulin resistance (P=.0028). CONCLUSIONS: We identified significant predictors of liver pathology in children with NAFLD. Children being evaluated for NAFLD should be screened for insulin resistance, which is nearly universal and correlates with liver histology.

Alanine Transaminase↗
PubMed2002

Drugs and the liver: advances in metabolism, toxicity, and therapeutics.

Biotransformation of drugs is one of the major functions of liver. Hepatic drug metabolism develops early in organogenesis and continues in postnatal life through puberty. Genetic and developmental studies on hepatic drug metabolism show that immaturity, polymorphisms, and altered balance of different hepatic enzymatic activities affect pharmacologic inactivation and alter the risk of toxic effects of drugs on the hepatic parenchyma. Although drug-induced liver disease is less common in children, several reports of hepatotoxicity are published every year. Furthermore, the increasing use of nonregulated remedies (eg, herbal preparations or recreational drugs) increases the risk of unpredictable and potentially severe reactions. Many significant advances in the treatment of hepatic diseases have been achieved recently. However, differences in clinical features, natural history, and response to treatment between children and adults require evaluation of new therapeutic options in focused pediatric clinical trials.

Adolescent↗
PubMedDate not supplied

Pyruvate carboxylase deficiency--insights from liver transplantation.

Pyruvate carboxylase deficiency, complex form, presents in early infancy with lethal metabolic acidosis, resulting from ketoacidosis and lactic acidemia. Renal tubular acidosis, hyperammonemia, and citrullinemia complete the picture. In an infant with this disease, large amounts of glucose ameliorated the ketoacidosis, but worsened the lactic acidosis. Orthotopic hepatic transplantation completely reversed the ketoacidosis and the renal tubular abnormality and ameliorated the lactic acidemia. Concentrations of glutamine in cerebrospinal fluid were low and did not improve with liver transplantation.

Acidosis, Renal Tubular↗
PubMedDate not supplied

Fatty liver: imaging patterns and pitfalls.

Fat accumulation is one of the most common abnormalities of the liver depicted on cross-sectional images. Common patterns include diffuse fat accumulation, diffuse fat accumulation with focal sparing, and focal fat accumulation in an otherwise normal liver. Unusual patterns that may cause diagnostic confusion by mimicking neoplastic, inflammatory, or vascular conditions include multinodular and perivascular accumulation. All of these patterns involve the heterogeneous or nonuniform distribution of fat. To help prevent diagnostic errors and guide appropriate work-up and management, radiologists should be aware of the different patterns of fat accumulation in the liver, especially as they are depicted at ultrasonography, computed tomography, and magnetic resonance imaging. In addition, knowledge of the risk factors and the pathophysiologic, histologic, and epidemiologic features of fat accumulation may be useful for avoiding diagnostic pitfalls and planning an appropriate work-up in difficult cases.

Diagnosis, Differential↗