Autoimmune liver diseases.

Autoimmune liver diseases are characterized histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by high levels of transaminases and immunoglobulin G (IgG) and positive autoantibodies, in the absence of a known etiology. In pediatrics, there are three liver disorders in which liver damage is likely to arise from an autoimmune attack: autoimmune hepatitis (AIH); autoimmune sclerosing cholangitis (ASC); and de novo autoimmune hepatitis after liver transplantation. The exact pathogenesis of AIH is still unknown, but it is known that unidentified environmental factors, and occasionally drugs, might trigger disease in genetically-susceptible individuals. The clinical spectrum of disease is very wide, ranging from asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical and histological parameters, and exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have intolerable side effects. The purpose of this review was to provide an overview of the current knowledge on pediatric autoimmune liver disease.

Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis.

OBJECTIVE: Waist circumference is widely accepted as a risk factor for cardiovascular disease and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome. A contribution of metabolic syndrome, and especially of waist circumference, to liver fibrosis in children with NAFLD is strongly suspected. DESIGN: Cross-sectional study. SETTING: Department of Hepatogastroenterology and Nutrition, Paediatric Hospital "Bambino Gesù", Rome, Italy. PATIENTS: 197 consecutive Caucasian children with NAFLD (136 males and 61 females) aged 3-19 years. MAIN OUTCOME MEASURES: Multivariable logistic regression models were used to examine the contribution of gender, age, body mass index (BMI) and metabolic syndrome components (waist circumference, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure and glucose) to the odds of liver fibrosis as detected by liver biopsy. RESULTS: 92% of the children had BMI > or = 85(th) percentile and 84% had a waist > or = 90(th) percentile for gender and age. Ten per cent of the children had metabolic syndrome and 67% had liver fibrosis, mostly of low degree. At multivariable analysis, waist was the only metabolic syndrome component to be associated with liver fibrosis. This was seen both when the components of the metabolic syndrome were coded as dichotomous (odds ratio (OR) = 2.40; 95% confidence interval (CI), 1.04 to 5.54) and continuous (OR = 2.07; 95% CI, 1.43 to 2.98 for a 5 cm increase). In the latter case, age was also associated with the outcome (OR = 0.70; 95% CI, 0.55 to 0.89 for a 1 year increase). CONCLUSIONS: Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy.

Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis.

OBJECTIVE: Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3-18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology. RESEARCH METHODS AND PROCEDURES: MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-beta cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity. RESULTS: MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (P< or =0.05). Prevalence of a grade of steatosis > or =2 (P=0.05) and fibrosis (P< or =0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis > or =2 with BMI z-score (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), beta-cell secretion (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P< or =0.0001), cholesterol (P< or =0.04) and white blood cells (P=0.025); fibrosis with body weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides (P=0.05), fasting insulin (P< or =0.0001) and mean values of the hormone at the OGTT (P=0.03), HOMA-IR (P< or =0.0001)). CONCLUSION: Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.

Mycophenolate mofetil in pediatric liver transplant patients with renal dysfunction: preliminary data.

The prolonged use of CNI has been associated with nephrotoxicity. MMF is a new immunosuppressive agent. In the present study, the consequences of introducing MMF and reduction of CNI in liver-transplant children were analysed. The present study included eight pediatric liver-transplant patients who had transplantation at least 5 yr previously, had stable graft function and had renal dysfunction as a probable side-effect of CNI therapy. CNI was replaced with MMF in all patients and serum creatinine, uric acid concentration, azotemia and creatinine clearance before and 6 months after study entry were measured. The patients were monitored closely for side-effects of MMF as well as graft function. Six months after study entry serum creatinine, uric acid concentration, azotemia and creatinine clearance improved in all the patients at the last follow-up. The aspartate aminotransferase and alanine aminotransferase concentrations were stable during the study period and did not observe any serum bilirubin increased as well. No side-effects were reported in patients on MMF. Only one patient reported temporary pruritus and nausea. The results indicate that renal dysfunction significantly improved when MMF therapy is started and CNI reduced. Furthermore present data suggest that the risk of acute allograft rejection is very low when the CNI desired reduction is achieved in not too short time and absolutely when the MPA levels are strictly monitored.

High dosage alpha-interferon for treatment of children and young adults with chronic hepatitis C disease.

BACKGROUND: There are limited data on the use of high interferon (IFN) dosage for treatment of children and young adults with hepatitis C virus infection and in those affected by thalassemia major (TM). OBJECTIVES: To assess the response of children and young adults with chronic hepatitis C disease, including those affected by TM, to high dose natural alpha-interferon (IFN-alpha). To evaluate the effect of iron overload in response to high dose IFN-alpha in young chronic hepatitis C virus thalassemia patients. METHODS: We conducted a therapeutic trial of natural IFN-alpha, using 10 million units/m2 three times a week for 6 months in 14 chronic hepatitis C patients ages 5 to 28 years; 7 also had TM. The follow-up period lasted 12 months. RESULTS: Ten patients (73%) showed normal or nearly normal alanine aminotransferase values at the end of follow-up (biochemical response), but only five (35%) were negative for serum hepatitis C virus-RNA (complete responders). Four of the patients (57%) with TM were sustained complete responders. No correlation was found between the initial serum concentration of ferritin and response to IFN therapy. Patients infected with genotype 1b showed a poor response although high dose of natural IFN was used. CONCLUSIONS: These results indicate that IFN-alpha can be used in children and young patients with chronic hepatitis C disease as well as in those affected by TM. Treatment with high dosage natural IFN-alpha in children and young adults with hepatitis C infection does not appear to be more effective than dosages previously used.

[Haemophilus influenzae type b in meningitis: antibiotic resistance in pediatric patients]. / Haemophilus influenzae tipo b: antibioticoresistenza in una casistica pediatrica di meningiti purulente (1985-1994).

A retrospective study on 357 children admitted to four Pediatric Infectious Disease Centers in Rome, affected by acute meningitis, during 10 years period, between January, 1, 1985 and December, 31, 1994 was carried out. Haemophilus influenzae type b was detected in 110 patients; all children aged between 1 month and 5 years; the maximum incidence (74.5%) was observed in patients under two years. The following diagnostic criteria were utilized: Gram stain of CSF; Latex test on CSF, blood, urine; CSF and blood cultures. The in vitro sensitivity of 65 isolates was tested by using the Kirby-Bauer method. We detected 15.3% of strains resistant to Ampicillin and 1.5% resistant to CAF. We also observed a high number of Hib strains resistant to Erythromycin and Cotrimoxazole. Only one strain Ceftriaxone resistant was isolated, confirming the high in vitro sensibility Hib to III generation cephalosporins that still remain the first choice drugs in Hib meningitis.

[Otomastoiditis caused by Mycobacterium avium: a case report]. / Otomastoidite da Mycobacterium avium: descrizione di un caso.

Non tuberculous Mycobacterial (NTM) Infections mainly affect immunocompromised patients, appearing as disseminated or pulmonary disease. In immunocompetent children the most common form of infection with NTM is cervical adenitis. Ear infection seems to be a rare disease. We present a case of otomastoiditis caused by Mycobacterium avium in a 15 months old child, immunologically normal. Patient was referred for persistent right otitis unresponsive to routine medical therapy. TC scan of the ear and temporal bones revealed: soft tissue in external auditory canal, Eustachian canal, and middle ear overlying ossicles with erosion of tegmen tympani. Tuberculin skin test was positive with 5 units PPD and culture yielded M. avium. The patient undergo timpanomastoidectomy and medical therapy with antituberculous drugs and Steroids, subsequently he was given Clarithromycin and Rifabutin. M. avium is an ubiquitous low grade pathogen found in soil, water, dust and food. There is no evidence of direct transmission. Only a few cases of otomastoiditis due to M. avium have previously been reported. The case presented underlines the importance of microbiological investigations. When a NTM infection is suspected surgeons and infectious diseases specialists should cooperate to find an optimal treatment regimen of this unusual disease.

[Bacterial meningitis and CSF cytokines]. / Meningiti batteriche e citochine liquorali.

Aim of study is the determination of concentrations of two important cytokines: TNF alfa and IL8 in children with bacterial meningitis to establish a correlation between infection, CSF concentration of cytokines and neurological sequelae. TNF alfa and IL8 concentrations in CSF have been measured by quantitative immunometric enzyme assay during the course of the disease. In the purulent meningitis we observed that CSF concentrations of these cytokines decreased to undectable values 24 to 48 hours after beginning of the antibiotic therapy. Conversely, in the 3 patients with mycobacterial meningitis (TBM) the concentrations of IL8 were higher for a longer period, being detectable in the CSF between 4 and 8 weeks after the beginning of the specific treatment. We found no significant differences of the values of IL8 in children with neurological sequelae compared with children without sequelae.

[Neurological complications of Mycoplasma pneumoniae infection. Description of a case of meningitis with clear cerebrospinal fluid]. / Complicanze neurologiche dell'infezione da mycoplasma pneumoniae. Descrizione di un caso di meningite a liquor limpido.

Mycoplasma pneumoniae (M.p.) is generally responsible of upper and lower respiratory tract infections in children in school age; in about 2% of cases can be also considered the cause of a NS infection: meningitis, encephalitis, cerebellitis, transverse myelitis and ascending polyradiculitis. The authors describe a case of meningitis following an acute otitis media in a 6 years old child. This patient presented also a fourfold or greater decrease in titer of complement fixing antibodies to M.p. The authors suggest a systematic research of M.p. in patients with clear CSF meningitis.