Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Multichannel Intraluminal Impedance and pH Monitoring are Complementary Methods in the Diagnosis of Gastroesophageal Reflux Disease in Children.

OBJECTIVE: Gastroesophageal reflux is considered to be a disease when reflux of gastric contents causes troublesome symptoms in infants and children. The aim of this study was to compare the diagnostic value of the multichannel intraluminal impedance monitoring and only pH monitoring in the diagnosis of gastroesophageal reflux disease in infants and children. MATERIALS AND METHODS: This prospective cross-sectional study consisted of pediatric patients aged between 1 month and 18 years old with symptoms suggestive of gastroesophageal reflux disease. Patients were divided into 2 groups as younger than 24 months (group 1) and older than 24 months (group 2). Twentyfour hours multichannel intraluminal impedance-pH monitoring was performed on the patients. RESULTS: This study included 50 pediatric patients. The mean age of the patients was 5.35 ± 4.92 years. In group 1, total reflux events were fewer than group 2 (P = .03) by pH monitoring. In group 1, the number of non-acid reflux events was higher than in group 2 and in group 2, the number of acidic reflux events was higher than group 1 (P = .04). Reflux was detected by multichannel intraluminal impedance-pH monitoring in 13 (40%) of 32 patients who were assessed as negative by pH monitoring. CONCLUSION: It was concluded that more reliable results were obtained when the 2 methods were used together in this study.

Turkish Translation, Validation, and Reliability Analysis of Pediatric Eosinophilic Esophagitis Symptom Severity Module Version 2.0.

The Paediatric Eosinophilic Esophagitis Symptom Severity Modules Version 2.0 (T-PEESv2.0) was developed in English as a valid, reliable questionnaire for follow up. This work aimed to develop a Turkish version of T-PEESv2.0 via translation and cultural adaptation and then to test its validation and reliability. Methods: The PEESv2.0 was translated into Turkish by standardized procedural steps completed in cooperation with the Mapi Research Trust. The final version of the questionnaire was submitted to eosinophilic oesophagitis patients or their parents at 2 times point separated by 1 week. An age-matched control group was used to test the discriminant validity. Construct validity was tested using the Wilcoxon test, and internal consistency was tested using Cronbach's alpha. Test-retest reliability was measured with Cohen's kappa and intraclass correlation coefficient. Results: One hundred twenty-eight participants (70 patients, 58 parents) were enrolled. Fifty-eight (39.1%) of them completed T-PEESv2.0-parent by proxy and 70 (54.7%) were T-PEESv2.0. The Cronbach's alpha coefficient and intraclass correlation coefficient for test-retest reliability were >0.70 for both questionnaires and for all domain (frequency and severity) and total scores. For discriminant validity analysis, subscale (frequency and domain) and total scores of the patient group were compared with those of the control group. The subscale and total scores were significantly different between the groups (P < 0.05). Conclusion: T-PEESv2.0 appeared to be valid and reliable, ready to be introduced as a clinical and research tool for the assessment of patients with eosinophilic oesophagitis.

The Assessment of the Quality of Life in Children with Chronic Liver Disease.

BACKGROUND: Improvement in the quality of life (QoL) of patients with chronic diseases is as important as medical care. This study aimed to evaluate the QoL of children with chronic liver diseases and to determine related factors. METHODS: For this study, 101 children with chronic liver disease, 100 healthy controls, and their parents were included. The Pediatric Quality of Life Scale (PedsQL) was used to evaluate health-related QoL; higher scores indicate better QoL. Patients were evaluated before and after initiation of treatment and being educated about their illness. RESULTS: The mean patient age was 12.9 ± 3.9 years. Total PedsQL scores of the patients and the healthy control group were 38.6 ± 18.9 and 55.4 ± 14.3, respectively (P = .01). The scores of the parents of the patient and control groups were 35.4 ± 14.2 and 54.0 ± 16.9, respectively (P = .02). Patient and parent scores were positively correlated. Significantly higher scores were found in the 5-10 age group compared to the 10-15 and 15-18 age groups in the psychosocial score category. An increase in the QoL scores of patients who were started on medication other than steroid treatment was observed in the sixth month of treatment (35.8 ± 13.4 vs. 33.6 ± 8.9, P = .01, respectively). CONCLUSION: Both children with chronic liver diseases and their parents have a perceived lower QoL than healthy peers. The effect of chronic liver disease on psychosocial health is more pronounced in children older than 10 years. The quality of life is inversely proportional to the severity of the disease. It was observed that primary or symptomatic treatments have a positive impact on the perception of QoL, with the exception of steroid treatment.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Liver Involvement in Congenital Hypopituitarism.

OBJECTIVE: Cholestatic jaundice in early infancy is a complex diagnostic challenge. Cholestasis caused by endocrine disease is rare and poorly recognized. The aim of this paper is to report patients with liver dysfunctions resulting from hypopituitarism. METHODS: Six patients with liver dysfunction diagnosed as hypopituitarism were studied and followed up at Uludag University Faculty of Medicine. RESULTS: The median age of the patients at first presentation was 2.5 mo. Three patients were diagnosed with congenital hypopituitarism at the first visit, and the other three were diagnosed during follow-up. Serum aminotransferase levels were very high in two patients and only moderately elevated in the others. Combined adrenal, thyroid, and growth hormone deficiencies were diagnosed in two patients, while remaining 4 patients had various combinations of adrenal, thyroid, and growth hormone deficiencies. Liver function abnormalities resolved between 10 d and 2 mo follow-up after hormone replacement therapy. CONCLUSIONS: Abnormal liver biochemical test results due to hormonal deficiencies in infants should be considered in the differential diagnosis by pediatricians. Hormone replacement therapy is the basis of treatment.

Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient?

Çekiç S, Özgür T, Karali Y, Özkan T, Kiliç SS. Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient? Turk J Pediatr 2019; 61: 937-940. The loss of inflammatory regulation resulting from the absence of B-lymphocytes leads to a risk for autoimmune and autoinflammatory complications. There is no data on the use of Vedolizumab in patients with X-linked agammaglobulinemia (XLA) as well as children with another primary immunodeficiency (PID) diseases. A 4-year-old boy was admitted to our clinic with a history of recurrent respiratory tract infections. He was diagnosed with XLA based on extremely low immunoglobulins, very low level of B cells, genetic mutation of BTK gene, and family history. At the age of 8, he suffered from intermittent fever attacks, abdominal pain, weakness, oral aft, and weight loss. His clinical and laboratory features were consistent with inflammatory bowel disease. Histopathological examination of the biopsy material obtained from terminal ileum, colon and cecum showed Crohn`s disease. Initially, he was treated with prednisolone and infliximab. Because of the lack of response, infliximab treatment was switched to adalimumab. Terminal ileum was resected to relieve obstruction complication. Although he had been treated with adalimumab, a significant improvement was not observed. Vedolizumab (Entyvio™), a humanized monoclonal antibody α4ß7 integrin-receptor antagonist, was commenced. After treatment with vedolizumab, his fever and abdominal pain attacks reduced, his total daily calorie intake increased and weight gain improved. He began to walk again and continued his school education properly. No side effects were observed in 18 months. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect were seen during the treatment.

Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels.

BACKGROUND: Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. MATERIALS AND METHODS: A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin-like growth factor-1 levels. RESULTS: H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 ± 2.26 vs 9.53 ± 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori-seropositive children (-0.33 ± 1.08 vs 0.04 ± 1.26, p = .044 and 0.13 ± 0.92 vs 0.23 ± 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 ± 753.0 vs 2808.3 ± 911.4 pg/mL, p = .06; 470 ± 176 vs 521 ± 179 ng/mL, p = .32, respectively). CONCLUSIONS: Children infected with H. pylori are prone to short stature. This effect seems to be independent of neuroendocrine hormones.

Mannose-binding lectin gene polymorphism and chronic hepatitis B infection in children.

BACKGROUND/AIMS: Mannose-binding lectin (MBL) is a member of innate immune system that activates complement system through lectin pathway. MBL deficiency is associated with susceptibility to infectious diseases. In this study, the relation between MBL gene polymorphism and chronic hepatitis B infection in children is evaluated. PATIENTS AND METHODS: The study included 67 children with chronic hepatitis B and 99 healthy controls. The hepatitis B patients were divided into immuntolerant, chronic inactive, and treatment groups according to their laboratory findings. MBL gene codon 52, 54, and 57 polymorphisms were studied with polymerase chain reaction in all patients and controls. The associations of MBL gene polymorphism with clinical, laboratory, and histopathologic findings were evaluated. RESULTS: Homozygous codon 54 polymorphism of MBL was found significantly higher in chronic hepatitis B patients than controls. Rate of the polymorphism was similar in all groups and, responsive and nonresponsive patients in the treatment group. CONCLUSIONS: The hepatitis B patients who are homozygous for codon 54 of MBL are prone to develop chronic infection. Longitudinal studies with larger groups are needed.

The diagnostic value of endoscopic narrow band imaging in helicobacter pylori gastritis in children.

BACKGROUND/AIMS: In this study we aimed to investigate the sensitivity and specificity of Narrow Band Imaging (NBI) in H. pylori gastritis and compare them with those of rapid urease test and urea breath test. MATERIALS AND METHODS: A hundred sixty-five children who admitted to Uludag University Pediatric Gastroenterology Unit between October 2009-March 2011 with upper gastrointestinal symptoms were consecutively enrolled. During the endoscopy procedure gastric corporeal, antral and fundal images were obtained, afterwards the same areas were visualized with narrow band imaging and images were recorded again. RESULTS: The study included 68 (41.2%) boys and 97(58.8%) girls. The mean age of the patients were 11.88±4.55. Tissue culture positivity and/or histopathological staining for H. pylori was determined in 56 (33.9%) patients (Group 1) and the other patients (n:109, 43.6%) didn't have an evidence of H. pylori infection (Group 2). Narrow band images have supported H. pylori infection in 56.4%. The sensitivity of narrow band images for determining H. pylori infection was 92.86% (95% CI 82.7-98), specificity was 62.39% (95% CI 52.6-71.5). CONCLUSION: Our study is the first to show the role of NBI in diagnosing H. pylori infection in children, as well as determining the sensitivity and specificity of the technique. The specificity is low; however, we suggest that the specific mucosal view of H. pylori gastritis provided by NBI is useful for identifying the areas from which the biopsies should be taken. Moreover, by using this technique, treatment of H. pylori infection may be initiated immediately without performing rapid urease test and without waiting for histopathology report and tissue culture.

Pediatric Gaucher experience in South Marmara region of Turkey.

BACKGROUND/AIMS: The aim was to represent the clinical characteristics of six children with Gaucher disease and to describe the results of three years' enzyme replacement therapy. MATERIAL AND METHODS: The data of six Gaucher patients treated with imiglucerase for more than three years were collected. Age, gender, anthropometric measurements, physical examination findings, ophthalmological evaluations, blood counts, liver function tests, liver and spleen sizes, and bone mineral density of the patients were recorded. Clinical presentations, progressions and therapeutic achievements were evaluated. RESULTS: At the time of diagnosis, all patients were clinically type 1 Gaucher disease. Bone lesions, thrombocytopenia and hepatosplenomegaly were found in all patients at diagnosis. After three years of therapy, normalization of blood cell counts, liver and spleen sizes, bone mineral density, and growth was achieved in all patients. Two patients developed neurological symptoms on enzyme replacement therapy, and the diagnosis in these patients was changed to Gaucher type 3. We observed progression of vertebral bone lesions in three patients despite treatment. CONCLUSIONS: The results of enzyme replacement therapy are satisfying, but the possibility of deterioration in clinical findings despite therapy should be kept in mind.

Do liver IL-12 levels predict sustained response to IFN-alpha therapy in children with chronic hepatitis B?

The aim of this study is to investigate the immunoregulatory role of interleukin-12 and interferon-gamma in children with chronic hepatitis B who are treated with interferon-alpha therapy. The patients were divided into 2 groups: Group I included 16 children with naive chronic replicative hepatitis B infection, and Group II included 6 children who are inactive hepatitis B virus (HBV) carriers. Group I received interferon-alpha subcutaneously (10 mU/m(2)/dose), 3 times a week during 4 months. Initial serum alanine aminotransferase (ALT) levels, hepatitis B serologic markers, serum interleukin-12 and interferon-gamma levels were measured. In Group I, laboratory tests were re-evaluated in the second and fourth months. Liver biopsy was performed in all patients and samples were used for tissue interleukin-12 level evaluation and histopathological examination. Hepatic activity index (HAI) and serum interferon-gamma were significantly higher in Group I (P < 0.05). Initial tissue interleukin-12 levels in Group I were low but a significant increase was observed at the fourth month (P < 0.05). While responder patients in Group I had marked elevation of tissue interleukin-12 levels, nonresponders did not reveal considerable changes at the fourth month evaluation. A negative correlation was found between serum HBV-DNA copies and interferon-gamma levels prior to therapy (P < 0.01, r: -0.66). The analysis of cytokine levels with serum transaminases demonstrated a positive correlation between the tissue interleukin-12 levels at the fourth month and serum ALT levels at the beginning and second month of the therapy (r: 0.77, P < 0.05 and r: 0.92, P < 0.05, respectively). This is the first study emphasizing the relationship between tissue cytokine levels and therapy success. Understanding the course of chronic hepatits B in the pediatric population will help us to clarify some debates on the treatment.

Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization.

Arthrogryposis, renal dysfunction and cholestasis syndrome (ARC) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells. Mutations in VPS33B account for most cases of ARC. We identified mutations in VIPAR (also called C14ORF133) in individuals with ARC without VPS33B defects. We show that VIPAR forms a functional complex with VPS33B that interacts with RAB11A. Knockdown of vipar in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC. Vipar- and Vps33b-deficient mouse inner medullary collecting duct (mIMDC-3) cells expressed membrane proteins abnormally and had structural and functional tight junction defects. Abnormal Ceacam5 expression was due to mis-sorting toward lysosomal degradation, but reduced E-cadherin levels were associated with transcriptional downregulation. The VPS33B-VIPAR complex thus has diverse functions in the pathways regulating apical-basolateral polarity in the liver and kidney.

Acquired generalized lipodystrophy associated with autoimmune hepatitis and low serum C4 level.

Lipodystrophies are a group of diseases characterized by loss of fat tissue and are associated with insulin resistance. A six-year-old girl followed with the diagnosis of autoimmune hepatitis showed a severe loss of fat tissue, hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and low serum complement 4 (C4) levels. She had coarse facial features with generalized loss of subcutaneous fat and prominent muscularity. Remarkable acanthosis nigricans was present over the neck, axilla, and umbilicus. Two hours after glucose loading, the glucose tolerance test revealed a glucose level of 258 mg/dL, a HbA1c value of 6.8%, and an insulin level of 642.9 mIU/mL, documenting a state of insulin resistance and type 2 diabetes mellitus. Acquired generalized lipodystrophy was diagnosed and metformin with dietary intervention was initiated. Low serum complement levels proved the autoimmune nature of the process. We conclude that the serum complement levels must be investigated in patients with acquired lipodystrophy, particularly when it is associated with autoimmune hepatitis.

Infantile hepatic hemangioendothelioma: clinical presentation and treatment.

BACKGROUND/AIMS: Hepatic hemangioendotheliomas are rare tumors in childhood. We report our 10-years' experience in a tertiary health center. METHODS: This retrospective analysis included eight patients with infantile hepatic hemangioendothelioma. RESULTS: The median age at diagnosis was 24 days (age range: 1 to 70 days) and the female/male ratio was 5/3. The main symptoms were abdominal distention and respiratory distress. Cutaneous hemangiomas were present in four cases. Three infants had Kasabach-Merritt syndrome. Four cases had single hepatic tumors while the others had multiple. The tumor size ranged from 2 cm to 10 cm in diameter. These lesions were located equally in the right and left hepatic lobes, and three babies had bilobar involvement. Most of the multifocal hepatic tumors were associated with skin hemangiomas. Treatment options were assessed individually. Systemic prednisolone therapy (2 mg/kg/d) was commenced in six patients. Five patients responded to corticosteroids. One boy with Kasabach-Merritt syndrome did not respond to this therapy. Interferon-alpha (1 million units (MU)/m2/day) was started, and the daily dose of the drug was increased up to 10 MU/m2, administered 3 times per week, until clinical improvement was achieved. The response was very good and we observed only constitutional adverse symptoms. Two cases were operated; one died from intraoperative bleeding. Other patients were alive and well for 11 to 66 months. Overall survival was 87% in our series. CONCLUSIONS: The treatment approaches depend on the center's experience. A multidisciplinary approach is required for the best treatment option.

Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis.

BACKGROUND: Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. METHODS: Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. RESULTS: Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 (p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change(p < 0.01). CONCLUSION: The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection.

Leptin concentration in breast milk and its relationship to duration of lactation and hormonal status.

BACKGROUND: Leptin, a hormone present in breast milk, is involved in energy regulation and metabolism. The objectives of this study were to assess leptin concentrations in breast milk during the first 180 days postpartum, and to determine the relationship between the concentrations of milk leptin and circulating hormone levels in lactating women. METHODS: Between April 2005 and January 2006, blood and breast milk samples were collected from 160 breastfeeding women enrolled either in the first three days (n = 37; colostrum), days 4-14 (n = 27; transitional milk), days 15-30 (n = 16; early mature milk), days 31-90 (n = 37; mature milk) or days 91-180 (n = 43; late mature milk) postpartum. Milk and serum leptin levels were measured by immunoradiometric assay. Cortisol was measured by radioimmunoassay method. Serum insulin, estradiol, prolactin and thyroxine were measured by chemiluminescent immunometric method. RESULTS: Leptin concentrations in breast milk were highest (3.28 +/- 0.41 ng/ml) in colostrum, decreased during the first 180 days of lactation, showing a significant inverse relation (r = -0.694, p < 0.001) with the days of lactation. Colostrum leptin concentrations correlated with maternal serum leptin (r = 0.425, p < 0.01), cortisol (r = 0.549, p < 0.01) and thyroxine (r = -0.530, p < 0.01). Mature milk leptin concentrations correlated with maternal serum leptin (r = 0.547, p < 0.001), insulin (r = 0.331, p < 0.05) and thyroxine (r = -0.329, p < 0.01). Serum leptin concentrations correlated with serum insulin (r = 0.648, p < 0.001), estradiol (r = 0.639, p < 0.001), prolactin (r = 0.530, p < 0.001) and thyroxine (r = -0.327, p < 0.05) concentrations during days 1-3 postpartum. During 15-180 postpartum days, serum leptin concentrations correlated with serum insulin (r = 0.271, p < 0.01), and thyroxine (r = -0.345, p < 0.001). CONCLUSION: Leptin concentrations in breast milk decrease with time during lactation and show significant relationships with other maternal hormones.

Comparison of two different regimens of combined interferon-alpha2a and lamivudine therapy in children with chronic hepatitis B infection.

AIM: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN-alpha2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. METHODS: A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6 months. In group I (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/- 3.8 years) 3TC was started 2 months prior to IFN-alpha2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months in nonresponders. RESULTS: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II, respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and II, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05). Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders. CONCLUSION: Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier antiHBe seroconversion and viral clearance than consecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can be administered for 24 months without any side effect and breakthrough rate is comparable with previous studies.

Current therapeutic approaches in childhood chronic hepatitis B infection: a multicenter study.

BACKGROUND AND AIM: The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection. METHODS: A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group. RESULTS: The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/- 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05). CONCLUSIONS: Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-alpha monotherapy group, no significant difference was found in the complete response ratios of all three groups.