The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range 5 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) 5 83%-99.4%] and a specificity of 84.5% (95% CI 5 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 lg/24 hours (sensitivity 5 78.9%, 95% CI 5 62.7%-90.4%; specificity 5 87.9%, 95% CI 5 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively. Conclusion: Urinary copper excretion greater than 40 lg/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy. (HEPATOLOGY 2010;52:1948-1956 See Editorial on Page 1872 W ilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in a gene [ATPase, Cuþþ transporting, beta polypeptide (ATP7B)] encoding a copper-transporting, P-type ATPase.1 This disease leads to progressive copper accumulation in the liver and subsequent deposition in other organs, such as the nervous system, corneas, kidneys, bones, and joints. The distribution of the metal in diverse organs over time accounts for the wide range of clinical manifestations. 2 In the pediatric age bracket, most cases have a hepatic presentation. In the available series, the percentage of WD children presenting with isolated elevated serum aminotransferases ranges from 14% to 88%; this depends on the health policy and the type of health care provided.3-5 However, there is evidence that alterations in liver function tests may precede the onset of symptoms for a considerable time. Neurological symptoms are more frequent in adolescents and young adults [6][7][8] and are found in only 4% to 6% of pediatric cases with hepatic onset. 4,5,9 If WD is not recognized and adequately treated, the progression of hepatic and neurological damage can be very rapid, and fulminant liver failure can occur. Therefore, the prompt detection of this condition is vital. Unfortunately, the diagnosis of WD is an especi...

C hronic hepatitis B is a significant global health care problem that affects more than 350 million people worldwide, resulting in approximately 1 million deaths each year. 1 Despite the widespread availability of an effective vaccine, large numbers of children are infected. People infected early in life who have evidence of ongoing viral replication are at the highest risk for development of progressive liver disease and are a major source of infection in others. 2 Treatment options for children are limited. The goal of treatment is to prevent the progression of chronic hepatitis B to long-term complications, such as cirrhosis and hepatocellular carcinoma, that can result in premature death. 3 Interferon ␣ has demonstrated efficacy in achieving hepatitis B e antigen (HBeAg) loss and seroconversion with HBV DNA suppression in children over 1 year old with active hepatitis B. However, only one third of treated patients will respond, and there are significant side effects associated with interferon therapy, including influenzalike symptoms, gastrointestinal disorders, nausea and vomiting, neutropenia, thrombocytopenia, and transient impairment of growth. 4,5 Treatment with lamivudine, an oral nucleoside analog, has been shown to result in similar response rates as interferon in both adults and children. [6][7][8][9] The drug is well tolerated, but long-term efficacy can be compromised by the emergence of resistance. 10 Treatment with lamivu-

Background. Chronic hepatitis B seems to manifest as mild disease in children and young adults. However, data regarding the long-term course of hepatitis B in untreated and interferon-treated children are still scarce. This study investigates the long-term outcome of disease in a large series of untreated and treated children with hepatitis B virus (HBV) infection.Methods. Clinical, biochemical, virological, and histological features were evaluated in children (age range, 2-18 years) with chronic HBV infection who did not have concomitant chronic systemic diseases other than HBV infection and who were admitted to the liver unit in the Department of Pediatrics at University "Frederico II" (Naples, Italy) during the period 1981-2005.Results. One hundred eight consecutive patients observed for up to 24 years were studied. During the observation period, 67 children remained untreated, and 41 were treated with interferon-a. After a median period of observation of 12.1 years (range, 5-23 years), hepatitis B early antigen loss and serum HBV DNA clearance occurred in 43 untreated patients (69.3%) who were hepatitis B early antigen positive at study entry and in 33 treated children (80%; the P value is not statistically significant). In addition, 6 untreated patients (9.7%) and 4 treated patients (9.7%) became hepatitis B surface antigen positive at the end of the follow-up period. Histological assessment, evaluated for 57 children, showed mild-to-moderate disease in 91.2% of cases of HBV infection. No patient developed end-stage liver disease or hepatocellular carcinoma.Conclusions. Children with chronic HBV infection are symptom free, with morphologically mild liver disease. Considering that the overall long-term outcomes did not differ between treated and untreated patients, the real impact of therapy on the long-term course of HBV infection remains to be established. Additional studies are needed to confirm our conclusions.

Background/aims-The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha. Patients-A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months). Results-Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients. Conclusions-After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not diVer from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient. (Gut 2000;46:715-718)

No abstract