Current treatment options and response rates in children with chronic hepatitis C

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients.Stratified for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children

AIM： To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS： We investigated a large pediatric population of 155 European children （mean age 10.9 years） with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS： Seventy-four （48%） of the sequenced HBV strains were attributed to genotype D and 81 （52%） to genotype A. In the group of 90 HBeAg positive patients, 2 （2.2%） 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 （7.7%） were identified harbouring HBeAg-minus mutants. The difference was not statistically significant （P= 0.13）. CONCLUSIONS： HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.

Angiogenesis in gastrointestinal stromal tumors:From bench to bedside

Gastrointestinal stromal tumors(GISTs)are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000.They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach,but also the small intestine,the omentum,mesentery and rectosigmoid.The available treatments for GIST are associated with a significant rate of recurrent disease and adverse events.Thorough understanding of GIST’s pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this challenge.The present review summarizes the existing evidence about the role of angiogenesis in GIST’s development and progression and discusses its clinical underpinnings.

聚乙二醇干扰素α-2b联合利巴韦林治疗儿童及青少年慢性丙型肝炎

Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 μg/kg body weight once per week plus oral ribavirin (15 mg/kg x day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%)of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Overall, treatment was well tolerated. Nevertheless, some side effects were present in all treated patients. Eighty-three percent had leucopenia, but only 3 individuals required dose reduction and 10.3%developed thyroid autoantibodies and thyroid dysfunction. In conclusion, combination treatment of peginterferon alfa-2b with ribavirin showed encouraging results and was well tolerated in children and adolescents with chronic hepatitis C. Weekly dosing of peginterferon alfa-2b is a considerable advance for this age group. The treatment is not approved for children. Further controlled trials are needed.

Hepatomusculoskeletal disorders:Coining a new term might improve the management of the musculoskeletal manifestations of chronic liver disease

Chronic liver disease can affect many body systems including the musculoskeletal system.The pathogenetic crosstalk between the liver and organs such as the brain and the kidneys has already been described with compound terms merging the organs affected by the pathology,such as the hepatorenal syndrome.Nevertheless,the musculoskeletal manifestations of chronic liver disease have not been coined with such a term to date.Because of this shortage,documenting the musculoskeletal implications of chronic liver disease in both research and clinical practice is challenging.To fill this gap,the authors propose the term hepatomusculoskeletal disorders,a compound term of Greek origin that encompasses all the body structures involved in the aforementioned pathologic crosstalk.