Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin.

Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

Protein-losing enteropathy and hypoalbuminemia in AIDS.

OBJECTIVE: To assess the contribution of protein-losing enteropathy to AIDS-associated hypoalbuminemia. DESIGN: Prospective assessment of patients with AIDS. SETTING: An urban county hospital (Los Angeles & University of Southern California Medical Center. USA). PATIENTS: Four groups of patients with AIDS were studied: (1) patients with normal serum albumin (> or = 3.9 g/dl) and normal bowel habits; (2) patients with normal serum albumin and diarrhea (> or = four loose or watery stools per day for > or = 2 weeks); (3) patients with hypoalbuminemia (< or = 3.0 g/dl) and normal bowel habits; and (4) patients with hypoalbuminemia and diarrhea. MAIN OUTCOME MEASURE: Fecal alpha 1-antitrypsin concentration was used as a measure of protein loss in the gut. RESULTS: Patients with hypoalbuminemia had a significantly higher mean fecal alpha 1-antitrypsin concentration than those with normal albumin (10.8 +/- 3.0 mg/g dry stool versus 2.4 +/- 0.4 mg/g dry stool; P < or = 0.001). Although mean fecal alpha 1-antitrypsin concentrations were similar in patients with and without diarrhea in the normal albumin group, patients with hypoalbuminemia and diarrhea had significantly higher levels of fecal alpha 1-antitrypsin than those with hypoalbuminemia and normal bowel habits (17.3 +/- 5.8 mg/g dry stool versus 4.6 +/- 1.0 mg/g dry stool; P = 0.009). Twelve out of 36 (33%) patients with normal albumin had elevation of fecal alpha 1-antitrypsin compared with 33 (70%) of 47 patients with hypoalbuminemia (P < or = 0.001). Linear regression analysis showed a significant negative correlation between serum albumin and fecal alpha 1-antitrypsin concentration (r = -0.38; P < or = 0.001). Fecal alpha 1-antitrypsin was significantly higher in patients with mucosal disease visualized at upper endoscopy or flexible sigmoidoscopy than in those without gross abnormalities (13.5 +/- 5.8 mg/g dry stool versus 2.4 +/- 0.7 mg/g dry stool; P = 0.005). CONCLUSION: Protein-losing enteropathy is common in patients with AIDS and may contribute to the development of hypoalbuminemia in these patients.

Lactose malabsorption among adult Indians of the Great Basin and American Southwest.

The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.

Hyperammonemia associated with perinatal asphyxia.

Twelve infants with severe perinatal asphyxia were found to have elevated blood ammonia levels (302 to 960 microgram/100 ml). In the seven survivors, hyperammonemia was associated with CNS irritability, hyperthermia, hypertension, and wide neonatal heart rate oscillations. Follow-up examinations revealed severe neurologic dysfunction in five of seven infants. CNS depression, hyperthermia, hypertension, and a nonreactive, fixed heart rate characterized the infants that died. These findings suggest a clinical entity secondary to perinatal asphyxia whose signs and symptoms may be related to hyperammonemia.

Perinatal transmitted acute icteric hepatitis B in infants born to hepatitis B surface antigen-positive and anti-hepatitis Be-positive carrier mothers.

Three infants born to mothers who were hepatitis B surface antigen (HBsAg) positive and had antibody to hepatitis Be antigen (anti-HBe), developed acute icteric hepatitis B within three months of birth. All three infants clinically recovered and developed circulating anti-HBs. Contrary to previous studies, these three cases indicate that mother-infant transmission of the hepatitis B virus (HBV) does occur in infants born to HBsAg-positive, HBe-Ag-negative carrier mothers, and these infants may develop severe acute icteric hepatitis. Therefore, immunoprophylaxis in such newborns may be indicated.

Septo-optic dysplasia: recognition of causes of false-positive hepatobiliary scintigraphy in neonatal jaundice.

Septo-optic dysplasia (SOD), an unusual clinical syndrome associated with intrahepatic cholestasis, is a cause of false-positive hepatobiliary scintigraphy in patients with neonatal jaundice. Use of the criterion of absence of [99mTc]IDA activity in the gastrointestinal tract by 24 hr, as well as application of the more recently used criterion of normal hepatic extraction, failed to differentiate patients with biliary atresia from those with SOD. Septo-optic dysplasia has clinical and scintigraphic features unique from other causes of conjugated hyperbilirubinemia. Identification of the patients with SOD, in a group of 44 infants being evaluated for neonatal jaundice, improved the overall specificity of hepatobiliary scintigraphy in neonatal jaundice from 65% to 79% and accuracy in identification of patients with biliary atresia from 82% to 90%. Recognition of SOD is important to prevent unnecessary surgical exploration of these patients.

Partial peritoneal alimentation in an infant.

We provided partial peritoneal alimentation to a 1.69-kg 11-month-old premature infant who had no available central venous access, depleted peripheral venous access, and gastrointestinal dysfunction. A cuffed silastic catheter was surgically inserted into the suprahepatic space. An alimentation solution was continuously infused into the peritoneum for 28 days to supplement peripheral venous and nasogastric alimentation and contributed 42 +/- 15% of total calories daily. Weight gain was achieved, but complications included hypoglycemia, hypophosphatemia, intravascular dehydration, catheter site leakage, ascites, and hydrocele. At autopsy 11 months later, lipid accumulation was present in the upper peritoneum and the hilar regions of the lungs secondary to preexisting lymphatic obstruction. Partial peritoneal alimentation may be feasible when other access routes are inadequate, but lymphatic obstruction is a contraindication to the peritoneal administration of lipid emulsions.

Calorie and protein requirements of pediatric patients with acute nonlymphocytic leukemia.

The calorie and protein requirements wer studied in 6 pediatric patients with acute nonlymphocytic leukemia treated in a laminar air flow unit. Calorie and protein requirements were estimated from anthropometric data. Mean total caloric requirement for weight maintenance was 136% of estimated basal metabolic rate, which is much lower than the RDA for healthy children. The mean protein requirement was 108% RDA. Provision of intravenous nutrients depressed oral intake. Infection had a deleterious effect on visceral protein status as determined by serum albumin.

Use of Hickman right atrial catheter in pediatric oncology patients.

Eighteen pediatric oncology inpatients had 21 Hickman right atrial catheters placed for total venous access; 16 patients received parenteral nutrition. Mean duration of catheterization was 43 +/- 29 (SD) days. Four catheters had to be removed for infection or clotting. The catheter-related sepsis rate was 10%. Serious catheter-related complications were no more frequent in this population than in patients receiving only parenteral nutrition via Broviac or pediatric Broviac catheters.

Hyperammonemia in neonates receiving intravenous nutrition.

Inadequate arginine intake has been suggested as an etiology for hyperammonemia in neonates on parenteral nutrition. We randomized 26 nonasphyxiated neonates to receive amino acid solutions containing either 3.6 or 10.4% of total nitrogen as arginine when intravenous nutrition (IVN) therapy was initiated. Neonates in both amino acid solution study groups were observed to have significantly elevated blood ammonia (BA) concentrations during IVN (p less than 0.01) as compared to pre-IVN levels. Blood ammonia concentrations tended to be higher in infants receiving the 3.6% arginine amino acid solution. Septic infants were at particular risk for hyperammonemia as compared to nonseptic patients (p less than 0.025). Other clinical parameters including birth weight, gestational age, oxygen requirements, enteral nutritional intake, congenital anomalies, and heart disease did not appear to be related to BA concentration.

Food faddism in pediatrics.

An understanding of the nutritional requirements of healthy, growing infants and children is required to guide parents in appropriate feeding practices which are consistent with their chosen life styles. Among the several prevalent types of food faddism are some that are not harmful or can beneficial, such as breast-feeding, others than can be of long-term benefit but that have limitations in infants and children, and others that can affect infants and children adversely. Those wishing to feed their children unconventional diets should have such diets carefully evaluated to avoid deficiencies of essential nutrients.

Cholestasis in infancy and childhood.

Many disorders are capable of producing cholestasis in infancy. Primary hepatobiliary diseases and systemic infectious, toxic, and metabolic insults may present clinically as conjugated hyperbilirubinemia. A careful, organized diagnostic evaluation allows early identification of potentially treatable lesions. Recent success in the surgical management of biliary atresia, previously a uniformly fatal disorder, has emphasized the need for early diagnosis. Medical management of the complications of chronic cholestasis remains a major challenge. Liver transplantation currently offers the only chance for long-term survival for infants with progressive cirrhosis.

Iatrogenic kwashiorkor in infants.

Four children experienced kwashiorkor six weeks to six months following the introduction of a low-protein, high-fat, nondairy creamer into their diets. In all cases, the milk substitute eventually became their sole nutritional source and resulted in hypoproteinemia, edema, and hepatic abnormalities. All patients had been given the milk substitute in an attempt to control suspected milk protein sensitivity. Only one of the four patients was subsequently shown to have cow's milk sensitivity. All had complete resolution of symptoms within six weeks following institution of a nutritionally adequate diet.

Cholestasis in infancy.

It is imperative that serum bilirubin fractionation be performed in any infant whose jaundice is prolonged to identify the infant who has cholestasis. Conjugated hyperbilirubinemia always is pathologic, and a well-organized and expedient diagnostic evaluation should be undertaken to identify those conditions that are treatable medically or surgically if they are recognized early. The complications of prolonged cholestasis need to be recognized and the appropriate medical therapy instituted to allow patients to maximize their growth potential, avoid the problems of nutrient deficiencies, and maintain a reasonable quality of life. Hepatic transplantation now offers the opportunity for long-term survival for infants whose liver disorders previously were fatal.

Screening laboratory tests for Crohn's disease.

The prevalence of abnormal values of initial screening laboratory tests was assessed for 24 children who eventually proved to have Crohn's disease. The screening tests included in this analysis were fecal alpha 1-antitrypsin (FA) concentration, erythrocyte sedimentation rate (ESR), total leukocyte count, serum albumin level, hemoglobin concentration, and qualitative testing of stool for the presence of blood. Of the 24 patients, 21 had abnormal FA values, 17 had anemia, 19 had an increased ESR, 14 had hypoalbuminemia, rectal bleeding was found in 8, and none had leukocytosis. All 24 patients had at least one abnormal screening test value; the most frequently abnormal result was the FA concentration. Pediatric patients without elevated FA values, anemia, a high ESR, bloody stools, or hypoalbuminemia are unlikely to have active Crohn's disease.

Hepatobiliary scintigraphy and the string test in the evaluation of neonatal cholestasis.

We evaluated [99mTc]diisopropylphenyl-carbamoylmethylimidodiacetic acid ([99mTc]DISIDA) cholescintigraphy with measurement of duodenal fluid radioactivity collected by the string test in patients with neonatal cholestasis. Twenty-six infants with prolonged jaundice and acholic stools were studied prospectively. Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and alpha 1-antitrypsin deficiency liver disease. All infants except the biliary atresia patients and four of the neonatal hepatitis patients revealed bowel activity on scan 6 h after tracer administration. At 24 h, three of these latter patients with neonatal hepatitis and two of the patients with biliary atresia revealed bowel activity. String radioactive counts for neonatal hepatitis ranged from 99,574 to 967,205 cpm (374,504 +/- 232,210 cpm; mean +/- SD) and for biliary atresia from 8,342 to 370,346 cpm (117,149 +/- 98,698 cpm; mean +/- SD). While neither test alone was capable of correctly differentiating among all patients, those patients with biliary atresia had either a negative hepatobiliary scan at 24 h or string radioactive count below 197,007 cpm. Disparity between the hepatobiliary scan and the string radioactive counts mandates further diagnostic investigation. These data suggest that simultaneous administration of the string test with hepatobiliary scintigraphy is advantageous in the evaluation of infants with cholestatic jaundice.

Intractable diarrhoea of infancy.

The intractable diarrhoea syndrome of infancy continues to be a major diagnostic and therapeutic challenge to the paediatrician and paediatric gastroenterologist. A carefully organized, staged approach to diagnosis will provide the best method of identifying those infants in whom a specific aetiology exists and for whom specific therapy is often available. Regardless of aetiology, however, the early use of appropriate nutritional support will not only reduce morbidity and mortality in these infants, but will prevent the development of many of the secondary consequences of malnutrition. The physician must compulsively pay attention to the details of daily management and provide an organized approach to diagnosis and treatment in order to improve the outcome of infants with intractable diarrhoea.

Random fecal alpha-1-antitrypsin concentration in children with gastrointestinal disease.

Random fecal alpha-1-antitrypsin concentration was measured in children with various gastrointestinal diseases and in normal subjects. One hundred fifteen subjects were evaluated: controls (39); chronic inflammatory bowel disease (20); chronic diarrhea (18); acute gastroenteritis (17); allergic gastroenteropathy (5); chronic pancreatic exocrine insufficiency (4); acute gastrointestinal bleeding (4); nonspecific colitis (4); celiac disease (3); and intestinal lymphangiectasia (1). Mean fecal-alpha-1-antitrypsin for the controls was 0.98 mg/g lyophilized stool. All children with celiac disease, allergic gastroenteropathy, lymphangiectasia, nonspecific colitis, acute gastrointestinal bleeding, and 19 of 20 patients with active chronic inflammatory bowel disease had fecal alpha-1-antitrypsin concentrations greater than 2.6 mg/g stool (mean of the controls + 2 SD). These disorders have all been previously documented to cause protein-losing enteropathy by 51Cr-labeled albumin excretion tests. The other study patients had normal fecal alpha-1-antitrypsin excretion when compared with controls. Serial fecal antitrypsin concentrations paralleled disease activity and clinical response to therapy. The results suggest that random fecal antitrypsin concentration is a valuable screening test for mucosal disorders associated with abnormal transmucosal serum protein loss.