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P Vajro

Publications and source records attributed to P Vajro.

At least 55 records · Page 3Linked to original sources

Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection.

BACKGROUND: There is no generally accepted treatment for chronic hepatitis B (HB) infection in children. OBJECTIVES: To evaluate the efficacy of a prolonged course of high dose interferon alone or after prednisone priming in children with chronic HB infection. METHODS: The outcome of 31 children with HB e antigen (HBeAg)-positive chronic hepatitis who randomly received either no treatment (n = 9) or 10 million units of interferon alpha-2b/m2, alone (n = 13) or after prednisone priming (n = 9), three times weekly for 1 year was studied. RESULTS: One patient withdrew from treatment. By the end of the first year treatment induced a loss of HB virus DNA and HBeAg from serum in 10 of 21 patients (48%), and a loss of HB surface antigen (HBsAg) in 4 (19%). Alanine aminotransferase values became normal in one patient (4.8%). Response rates in the two groups of treated patients were similar. In controls only one patient lost HBeAg and HBV DNA (11%; P = 0.05), and none lost HBsAg or showed alanine aminotransferase normalization (P = 0.21 and 0.70, respectively). After a posttreatment 2-year follow-up there were still no differences in the response rates of the two treatments; of the 21 pooled treated patients, 61% lost HBeAg and DNA and 67% normalized alanine aminotransferase (vs. 33 and 44% of controls, respectively; P = 0.32 and 0.40). Reversion to HBeAg and HBV DNA negativity in treated patients occurred significantly earlier (P = 0.02 and 0.006, respectively) than in controls. No further patient lost HBsAg, but one reacquired HBsAg. Treated patients had posttreatment histologic scores better than controls (P = 0.03). CONCLUSIONS: Our medium term follow-up results indicate that a prolonged course of high dose interferon in children with chronic HB infection, regardless of prednisone priming, poorly affects response rates but significantly speeds termination of active viral replication.

Adolescent↗

Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.

Adolescent↗

Hepatitis C virus genotypes in chronic hepatitis C of children.

Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 33 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype 1b was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype 1a (16.6%), genotype 2 (11.1%), and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1 b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.

Adolescent↗

[Chronic idiopathic hypertransaminasemia].

The elevation of aminotransferase serum levels is frequently encountered in pediatric practice. We have retrospectively evaluated the clinical patterns of 108 patients with chronic, so called "idiopathic", alterations of aminotransferases, by sending a questionnaire to 11 Italian Pediatric Centers. The average period of follow-up was 22 months. Patients, whose ages ranged through all pediatric ages, were mostly asymptomatic and with a rather insignificant physical examination. The average rise of aminotransferases value was generally limited within 2 times the upper normal level and the highest value, during the period of follow-up, never exceeded 5 times the upper normal level. Other liver function tests did not result generally altered significant. Just 25,9% of the patients normalized aminotransferases serum level during the follow-up period. All maintained good physical status with no clinical signs of liver disease. A muscular cause of hyper-transaminasemia was excluded in all the cases. Possible infective causes (HBV and HCV) autoimmune hepatitis, Wilson disease, alfa1 antitripsine deficiency and hyperammoniemia were excluded. Ultrasound investigation did not seem to be a sensitive investigation, resulting negative in 54/82. Histologic liver examination was more informative. This evaluation, performed in 46/108 patients, showed infarct metabolic alterations (steatosis, nucleus glucogenic degeneration, cytoplasmatic clarification) in 65% of cases and inflammatory findings in only 13% of cases. In conclusion, our results suggest the opportunity to enclose liver histologic study in the diagnostic approach of children with hepatic idiopathic chronic hypertransaminasemia. This approach may address the clinician, in a more aimed way, towards further investigations.

Adolescent↗

Asymptomatic carriage of intestinal Cryptosporidium in immunocompetent and immunodeficient children: a prospective study.

Little information is available on asymptomatic carriage of Cryptosporidium in immunocompetent and immunodeficient children. We prospectively studied a group of asymptomatic children, 78 immunocompetent and 50 immunodeficient, to document the incidence of asymptomatic carriage of cryptosporidiosis in such a population. We also investigated whether the treatment of children who carried asymptomatic cryptosporidiosis could help in reducing their risk of gastrointestinal symptoms as well as the shedding of infectious oocysts. The occurrence of multiple infections with common intestinal pathogens including Giardia lamblia was also investigated. Asymptomatic cryptosporidiosis was documented in 6.4% of immunocompetent and 22% of immunodeficient children. In a control symptomatic population Cryptosporidium was found in 4.4% of immunocompetent and 4.8% of immunodeficient children. Asymptomatic carriage of Cryptosporidium was documented in 2 human immunodeficiency virus-infected children, one of whom also carried Giardia asymptomatically. Treatment with spiramycin (100 mg/kg daily for 14 days) reduced significantly the duration of the shedding of potentially infectious oocysts. Finally no gastrointestinal symptoms developed in children treated for asymptomatic infection with Cryptosporidium, whereas children who were not treated developed gastrointestinal symptoms.

Adolescent↗

Bile pigment composition and bilirubin esterification in the developing chick.

In vivo and in vitro bile pigment metabolism was studied in embryos, chicks, and mature White Leghorn hens. Biliverdin and bilirubin pigments were present in bile of embryos from the earliest stage examined (14 d). Bilirubin accounted for 2.5-11.5% of total bile pigments, with the higher percentages in the early embryo. Biliverdin was exclusively in unesterified form. In contrast, bilirubin was almost entirely (> 98%) in esterified form. Glucosides consistently predominated over glucuronides and xylosides (6:3:1). In serum, bilirubin and biliverdin were undetectable at all embryonic stages and after hatching. Bilirubin UDP-glycosyltransferase activities with UDP-glucuronic acid, UDP-glucose, and UDP-xylose were detectable in chick embryo liver and averaged 67, 72, and 102%, respectively, of the corresponding adult mean values, without significant change throughout development. We conclude that multiple bilirubin esterification systems mature early in the avian embryo. This is in marked contrast to the development of bilirubin metabolism in the mammalian fetus in which detoxication of this potentially toxic pigment is achieved by placental clearance, and bilirubin esterification matures only after delivery. These contrasting developmental patterns are consistent with an adaptive response to the different requirements in the avian embryo and mammalian fetus for self-protective detoxification of unconjugated bilirubin.

Animals↗

Recombinant interferon-alfa therapy in children with chronic hepatitis C.

The efficacy of recombinant interferon-alfa therapy in children with chronic hepatitis C has been evaluated in a randomized, controlled pilot study including 27 patients, aged 2 to 14 years, without underlying systemic diseases. On entry, all patients had abnormal alanine transaminase (ALT) levels, 22 were hepatitis C virus (HCV) RNA positive, 19 had mild chronic active hepatitis, and 8 had chronic persistent hepatitis on liver biopsy. Fourteen children received 5 MU/m2 of recombinant interferon-alfa2b thrice weekly for 4 months. If at this time ALT had been reduced to at least 50% the baseline level, treatment was continued up to 12 months. The other 13 children remained untreated. The whole follow-up period lasted 24 months. Interferon was stopped at 4 months in 4 children because of an ALT increase (2 cases), unchanged ALT and febrile convulsions (1 case), and slight ALT decrease (1 case). This latter patient, however, had normal ALT at 6 months and throughout further follow-up, and cleared HCV RNA, thus behaving as a sustained responder. All 10 children treated for 12 months had normal levels of ALT, and 9 were HCV RNA negative at the end of treatment. Of the 9 children who could be followed to 24 months, 4 relapsed soon after therapy withdrawal and 5 maintained a sustained biochemical and virologic response. Overall, 6 (43%) of 14 treated children had a sustained ALT normalization associated with HCV RNA clearance as compared with only 1 (7.5%) untreated child who had a sustained ALT normalization but did not clear HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Patterns of antibodies to hepatitis C virus and hepatitis C virus replication in children with chronic non-A, non-B hepatitis.

Antibodies to hepatitis C virus (HCV), investigated by second- and third-generation assays, were detected in 74% of 43 children with chronic non-A, non-B hepatitis. The polymerase chain reaction identified HCV ribonucleic acid in 26 (93%) of 28 seropositive and in 1 of 10 seronegative cases. Intermittent HCV ribonucleic acid positivity, suggesting low and fluctuating viremia, was frequent in younger patients.

Adolescent↗

Persistent hyperaminotransferasemia resolving after weight reduction in obese children.

Nine obese children were referred to our liver disease unit because of asymptomatic, long-standing (range, 4 to 49 months) hyperaminotransferasemia of unknown origin. Ultrasonography showed a "bright" liver in most patients. A hypocaloric diet was prescribed, and the hepatic abnormalities of the complaint patients showed a prompt and persistent improvement that paralleled the loss of excess weight.

Alanine Transaminase↗

Posttransfusion and community-acquired hepatitis C in childhood.

Following a longitudinal study of chronic non-A, non-B hepatitis in Italy and Spain, we evaluated the epidemiologic and clinical features of chronic hepatitis C in 77 consecutively observed children (35 male; mean age, 4 years) without underlying systemic diseases. All subjects were positive for antibody to hepatitis C virus in serum by second-generation tests. Forty-six patients had received blood transfusions in the perinatal period; 12 had a mother with antibodies to HCV in serum (five of these mothers were drug users or partners of a drug user); seven had a history of putative percutaneous exposure; and 12 had not been exposed to any risk factors for viral hepatitis. At presentation, only 22% were symptomatic, mean alanine-aminotransferase levels were three times the upper normal value, and liver histology showed active disease in only nine of 28 cases (32%). During a mean observation period of 6 years, only 11 of 57 patients (19%) complained of symptoms and 11 of 40 cases (27%) had histologic features of active hepatitis. Two patients had severe hepatitis with associated cirrhosis. However, only six of 57 cases (10%) achieved sustained biochemical remission. The clinical features and the outcome were similar in both the posttransfusion and the community-acquired cases. These results indicate that transfusions in the perinatal period are the single most important cause of hepatitis C in otherwise healthy children. Community-acquired cases represent an heterogeneous epidemiologic group in which maternal transmission, whether perinatal or postnatal, could be relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Elevated serum aminotransferase activity as an early manifestation of gluten-sensitive enteropathy.

Six children in whom long-standing hypertransaminasemia of unknown cause led to an initial diagnosis of chronic or protracted cryptogenic hepatitis were found to have asymptomatic celiac disease. Administration of a gluten-free diet caused a prompt improvement of both hepatic and intestinal biochemical/histologic abnormalities. Hepatic damage may be another "atypical" form of celiac disease in children.

Celiac Disease↗

Long-term evolution of chronic delta hepatitis in children.

Twenty-three children, aged 3 to 15 years, with chronic delta hepatitis have been followed for 5 to 12 years to evaluate long-term outcome. Although 83% of patients had chronic active hepatitis when first seen, with cirrhosis in 26%, the clinical and biochemical features of the disease remained reasonably stable during observation; liver histologic findings, obtained in 14 patients, worsened in only two.

Adolescent↗

Hepatitis C in childhood: epidemiological and clinical aspects.

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.

Acute Disease↗

Cryptogenic chronic liver disease and hepatitis C virus infection in children.

The clinical features of 'cryptogenic' chronic liver disease and the prevalence of antibody to hepatitis C virus (HCV) in serum have been investigated in 33 Italian children (mean age 5 years). The diagnosis was based on the persistence of increased alanineaminotransferase values for longer than 6 months after the exclusion of biliary diseases, of extra-hepatic causes of hypertransaminasemia, of infection with known hepatotropic viruses and of autoimmune or metabolic disorders. Five patients had been transfused early in life, three had undergone surgery and one girl's mother had had acute non-A, non-B hepatitis during pregnancy. The remaining patients had no history of overt parenteral exposure. At presentation only 11 patients were symptomatic, the others had been referred after a check-up for intercurrent diseases. Liver histology performed in 21 cases showed persistent or mild active hepatitis in 18 cases and severe hepatitis or cirrhosis in three cases. Anti-HCV antibodies were found in 48% of the cases, including 88% with obvious exposure and 33% of the remaining cases. During a mean follow-up period of 5 years (range 1-14 years) only 11% of the cases achieved sustained biochemical remission, although none developed signs of liver failure. There was no significant difference in the clinical features and outcome of the disease between anti-HCV-positive and -negative patients. The results of this study suggest that HCV is implicated in most cases of 'cryptogenic' chronic liver disease observed in Italian children with a history of parenteral exposure and in at least one-third of the cases without overt exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Vaccination against hepatitis B in preschool children with Down's syndrome.

Twenty-nine healthy HBsAg- and HBsAb-negative children with Down's syndrome who were living at home (mean age 42 months; 19 M, 10 F) were vaccinated against hepatitis B virus either with recombinant DNA or plasma-derived vaccine. Both groups of children responded well to the vaccination schedules, with HBsAb seroconversion rates close to 100%. Vaccination against hepatitis B in preschool children with Down's syndrome is effective in spite of the existing abnormalities of the immune function.

Child, Preschool↗