Budesonide versus prednisone with azathioprine for the treatment of autoimmune hepatitis in children and adolescents.

OBJECTIVE: To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH). STUDY DESIGN: Forty-six patients with AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects. RESULTS: We observed no statistically significant difference in the percentage of patients who met the primary endpoint between the budesonide (3 of 19; 16%) and prednisone groups (4 of 27; 15%) after 6 months, nor in the percentage of patients who experienced biochemical remission (budesonide, 6 of 19 [32%]; prednisone, 9 of 27 [33%]), lack of steroid-specific side effects (budesonide, 10 of 19 [53%]; prednisone, 10 of 27 [37%]). The mean weight gain was 1.2 ± 3.5 kg in the budesonide group and 5.1 ± 4.9 kg in the prednisone group (P = .006). A total of 42 patients received open-label budesonide treatment for another 6 months. After 12 months, 46% of these patients achieved complete remission. CONCLUSION: Oral budesonide with azathioprine can induce and maintain remission in pediatric patients with AIH and may be considered an alternative therapy to prednisone. The treatment causes fewer side effects and does not lead to weight gain; however, it may be less effective than prednisone in inducing remission.

Liver transplantation: A new risk factor for intestinal intussusceptions.

BACKGROUND: Intestinal intussusception in adults is associated with chronic inflammatory bowel disease, celiac disease, abdominal tumors or previous abdominal surgery but most often of unknown origin. AIM: The aim of our study was to evaluate circumstances and identify risk factors for intussusceptions. METHODS: All 65,928 abdominal ultrasound examinations performed at our tertiary medical center between January 2001 and June 2008 were analyzed retrospectively for the diagnosis "intussusception". After identifying individuals with sonographically proven intussusception we analyzed various patients' characteristics including age, gender and underlying disease as well as sonographic findings such as localization of the intussusception, absence or presence of ascites and lymph nodes. RESULTS: We identified 32 cases of intussusceptions [mean age 45 years (range 18 to 88); 18 patients were male]. Twelve patients (38%) had a history of abdominal surgery including 8 patients who had undergone liver transplantation (2 patients with primary sclerosing cholangitis, 1 patient with cystic fibrosis, 1 patient with sarcoidosis, 1 patient with hepatocellular carcinoma and HCV infection, 1 patient with autoimmune hepatitis, 1 patient with Crigler-Najar-syndrome and one patient with echinococcus). A hepaticojejunostomy had been performed in 4 of the patients after liver transplantation. Liver transplanted patients were significantly overrepresented in the intussusceptions group compared with the overall cohort of patients undergoing abdominal ultrasound examination (25% vs. 8%, Chi-Square-test, p = 0.0023). CONCLUSION: In our retrospective study liver transplantation, in particular with hepaticojejunostomy, was identified as a new major risk factor for intestinal intussusceptions

Anti-parietal cell autoantibodies (PCA) in primary biliary cirrhosis: a putative marker for recurrence after orthotopic liver transplantation?

INTRODUCTION: Liver transplantation (OLT) for primary biliary cirrhosis (PBC) is characterized by disease recurrence of up to one third of patients. The diagnosis of recurrence requires a cholestatic profile and a typical histology representing a challenge for transplant hepatologists. Antimitochondrial antibodies (AMA) establish the initial diagnosis, persist after OLT, and are thus of limited value for the diagnosis of recurrence. Aim of this analysis was to identify serological parameters associated with recurrent PBC. PATIENTS AND METHODS: OLT performed between 1992 and 2006 at Hannover Medical School were evaluated retrospectively including histology before and after OLT, autoimmune serological parameters and clinical characteristics. RESULTS: Between 1992 and 2006 72 patients underwent OLT with histologically confirmed PBC. Median follow up was 123 months. AMA persisted in 55 (76%) patients. Anti-parietal cell antibodies (PCA) were detectable in 41% of the patients before and 47% after OLT. Liver biopsies were obtained in 34 patients post OLT upon clinical suspicion, and recurrent PBC diagnosed in 28% after a mean of 71 months (range 13-161). Anti-PCA were detected in 100% of patients with recurrence before and following transplantation, 54% of patients with anti-PCA before OLT developed recurrence during follow-up. There were no differences in immunosuppressive regimen. DISCUSSION: Although unspecific for the diagnosis of PBC, anti-PCA prevalence increased after OLT, and was 100% in patients with recurrent PBC. Recurrent PBC developed in 54% of patients with anti-PCA before OLT suggesting a diagnostic role of anti-PCA as a simple and cost effective marker of recurrence.

Gilbert's syndrome and antiviral therapy of hepatitis C.

Treatment of chronic hepatitis C with type I interferons and ribavirin can be associated with exacerbation of hepatitis and sometimes liver decompensation. We report two patients with chronic hepatitis C virus infection who experienced a severe increase of bilirubin levels of up to 17 times upper the limit of normal value in the absence of deterioration of hepatic function during therapy with pegylated-interferon and ribavirin. A genetic disposition for Gilbert's syndrome explained the adverse events and permitted a continuation of therapy leading to a sustained clearance of chronic hepatitis C infection. Since one patient jaundiced already during a lead-in treatment period with ribavirin monotherapy we suggest that hyperbilirubinaemia during combination therapy is primarily caused by ribavirin rather than by effects of interferon alpha on UDP-glucuronosyltransferase activities. Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely.

New approaches and therapeutic modalities for the treatment of patients with chronic hepatitis C.

A major challenge in the field of hepatology is the fight against hepatitis C that affects more than 150 million people world-wide. Despite the enormous improvement that has been achieved in the therapy of chronic hepatitis C over the last decade, there is an urgent medical need for new therapeutic approaches. This review focuses on the optimization of the current standard therapy of hepatitis C and future treatment directions beyond pegylated interferon alpha and ribavirin.

Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases.

Autoimmune regulator gene mutations were identified in 3 children with type 2 autoimmune hepatitis and extrahepatic immune diseases, including 1 child with immune hepatitis recurrence after liver transplantation. These findings suggest that autoimmune regulator gene variants might predispose children to systemic autoimmune disease, a recurrence of immune disease, or both.