RESUMO
Background: Egypt has the highest prevalence of hepatitis C virus [HCV] infection in the world [15%-25%] and the main [90%] genotype is type 4. Prevalence in Egyptian children was found to be 3% in Upper Egypt and 9% in Lower Egypt. Various human leucocytic antigen [HLA] alleles have been linked either persistence or clearance of the hepatitis C virus [HCV]. Several studies have aimed to identify the involvement of HLA with different outcomes of HCV infection, but the results have not been consistent
Aim of the work: To identify HLA association with different outcomes as regard treatment of chronic HCV [CHC] in Egyptian children with pegylated interferon-alpha2b [Peg-IFN-alpha-2b] and ribavirin [RBV]
Patients and methods: Forty clinically and laboratorial children diagnosed as CHC genotype 4 [ages 3-18 years, 14 females and 26 males]. Patients were treated using Peg-IFN-alpha 2b [Peg Intron] at a dosage of 60 ug/m[2] per week subsutaneously and RBV 15 mg/kg per day orally for 48 weeks. Serum HCV ribonucleic acid [RNA] was measured at the baseline, at the 12[th], 24[th] and 48[th] weeks during treatment, and after 24 weeks of post-treatment [study weeks 72]. Sustained virologic responders [SVR] were defined as patient with undetectable HCV-RNA in the serum at 24 weeks post-treatment, while non-responders defined as HCV-RNA remains detectable throughout the treatment phase. Genomic DNA was extracted from 1 ml peripheral blood in tubes containing EDTA. HLA typing was performed by polymerase chain reaction followed by detection using sequence-specific oligonucleotides probes
Results: Twenty-nine out of forty patients [72.5%] showed a sustained virological responders to Peg-IFN/RBV therapy, whereas eleven [27.5%] non-responders did not. The frequencies of DRB1[asterisk]11 was significantly higher in sustained virological responders than non-responders. On the other hand, DRB1[asterisk] 07 allele was significantly higher in non-responders than SVR. We also found that no statistically significant difference between SVR and non-responders as regards the demographic, laboratory and liver histopathology characteristics of patients
Conclusion: There is a trend of association between certain HLA alleles and the response to Peg-IFN/RBV in HCV infected children and a study on large number of patients to confirm this association is worthy
RESUMO
Fulminant hepatic failure [FHF] is one of the most dramatic and challenging syndromes in pediatric clinical medicine. In fact it is considered to be a true medical emergency that affect multiple organs and can lead to serious damage and multi-organ failure. Assessment of this challenging syndrome in children is still in need for highlights and we try to elucidate this issue and its interrelating factors. A retrospective review study of all patients younger than 17 years who presented to the National Liver Institute with FHF over a period of two years from 2003 - 2004 were investigated. Upon presentation and every 6 hours: blood glucose, arterial blood gases, electrolyte levels, prothrombin time and hematocrit were assessed. Upon presentation and daily: serum bilirubin, AST, ALT, serum albumin, creatinine and CBC, urine analysis total serum protein were assessed. All serum samples were tested for: HAV IgM antibodies, HBs Ag, IgM-anti HBc and IgM antibodies to HEV. All samples were screened for HCV RNA in nested PCR employing primers. Special investigations like alpha fetoprotein, copper studies, blood culture, drug levels, other metabolic studies were carried out whenever indicated. Detailed clinical evaluations including history, physical signs of liver cell failure and staging of encephalopathy were done. The mean age of patients presented with FHF was 55.667 +/- 66.12 months and, the age of the non survivals is younger than survivals though it was not significant. Males were affected more than females. The onset of coma was 14.791 +/- 12.43 days from the onset of the first symptom. Hepatomegaly was present in 66.7% of all the patients and ascites was present in 66.7 of them. Nearly 66.7% of the patients got bleeding tendency. 18/24 died while only six patients had survived with mortality rate of 75%. AST levels in these patients is higher on admission and on discharge than ALT, however, the rate of descent of ALT was higher than that of AST. Prothrombin time on admission was 39.6 sec +/- 18.36] and on discharge was 18.88. The mean level of total serum bilirubin on admission was 19.39 +/- 13.93 mg/dl, it reached a peak level of 38.5 +/- 15.592 mg/dl. On discharge it became 23.42 +/- 14.08 mg/dl. Regarding the etiologies in those patients, viral etiology was the main cause and hepatitis A virus was the commonest virus, among non survivals 44.4% of the patients got acute viral hepatitis. Others causes were discussed. None of the survivals had developed ascites. Encephalopathy was significantly present among non survivals, also, grades of coma tend to be significantly severer among them. Patients who did not survive tend to have leuckocytosis and anemia. They also had low pH and low serum sodium level. Mean total serum bilirubin, mean direct serum bilirubin [on admission and on discharge] and the peak level of both [total serum bilirubin and direct serum bilirubin] were significantly higher among nonsurvivals those patients who survived had got significantly lower level of prothrombin time on admission and on discharge. They also got significantly lower rate of descent of prothrombin time than the non-survivals. Regarding the etiologies in FHF hepatitis A virus was the commonest. The peak level of total serum bilirubin and the rate of change of the prothrombin time/day were found to be significant predictors of mortality in FHF