Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals.

OBJECTIVES: To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN: This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS: The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS: Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.

Urinary abnormalities in children and adolescents with Wilson disease before and during treatment with d-penicillamine.

BACKGROUND AND AIM: Renal abnormalities can occur at any time point during the course of Wilson disease (WD). We aimed to fill a literature gap in this respect by studying urinary abnormalities in children and adolescents with WD. METHODS: This study included 60 children with WD presenting to the Pediatric Hepatology Unit, Cairo University. The following data were retrieved from the patients' files including age, sex, liver function tests, serum ceruloplasmin, 24-h urinary copper, serum creatinine, blood urea nitrogen, urinalysis, urinary albumin/creatinine ratio, urinary calcium/creatinine ratio, urinary ß2-microglobulin, liver and renal biopsy results when available. RESULTS: All studied cases had no symptoms related to renal involvement. Microscopic hematuria was detected in 11% and 12% at baseline and within 5 years of therapy, respectively. Moderate microalbuminuria was detected in 34%, 50%, and 33% at baseline, within 5 years and > 5 years after therapy, respectively. Hypercalciuria was detected in 23% at baseline, 34% in those patients treated for up to 5 years and 37.5% > 5 years of therapy. Age and international normalized ratio were significantly higher in patients with high calcium/creatinine ratio compared with those with normal values at initial evaluation. Frequency of elevated urinary ß2-microglobulin was 36%, 36%, and 37% in patients at baseline, up to 5 years and > 5 years of therapy, respectively. CONCLUSION: Asymptomatic urinary abnormalities are present in patients with WD at any time point of the disease and during treatment with d-penicillamine. They have to be searched for, as early intervention may prevent progression to renal insufficiency.

Paediatric chronic hepatitis B virus infection: are children too tolerant to treat?

AIM: Guidelines for managing the hepatitis B (HB) virus infection in children are still evolving. We aimed to assess the eligibility of children with HB virus infections for treatment based on the current guidelines. METHODS: This observational study took place in 2016 and focused on children with isolated chronic HB infections, who attended the paediatric hepatology units at two centres in Egypt. We recruited all treatment-naïve children aged one year to 18 years who had completed at least 12 months of follow-up. RESULTS: The study comprised 103 children aged between 1.5-18 years. Of these, 51 (50%) had the HB e antigen-positive chronic infection, 28 (27%) had the HB-negative chronic infection, 11 (11%) had the HB e antigen-positive chronic hepatitis and none had the HB e antigen-negative chronic hepatitis. The remaining 13 (12%) children did not fulfil the criteria for chronic HB definitions. Only two of the children were candidates for treatment: both had HB e antigen-positive chronic hepatitis and had undergone liver biopsies. CONCLUSION: Only two of the 103 children with chronic HB were eligible for treatment according to the current guidelines and every measure should be taken to prevent the HB virus infection in children.

Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir.

OBJECTIVES: Recently, direct acting antivirals (DAAs), sofosbuvir (SOF) combined with ledipasvir (LED), were approved for treatment of hepatitis C virus (HCV)-infected children 12 years of age and older or weighting at least 35 kg for all HCV genotypes. The aim of this study was to assess the safety and efficacy of SOF/LED in genotype 4 HCV-infected Egyptian children and adolescents. METHODS: This observational study included 40 consecutive HCV-infected children of age 12 to <18 years old or weighing >35 kg, both treatment-naive and treatment-experienced. All of the children were hepatitis B virus-negative and had normal renal functions and heart rate. Patients received oral, fixed-dose combination tablet of SOF/LED (400 mg SOF, 90 mg LED [Harvoni]) once daily for 12 weeks. Potential side effects were recorded at weeks 4, 8, and 12 weeks of treatment. The study primary outcome was sustained virological response 12 weeks (SVR12) after end-of-treatment. RESULTS: The study included 40 children and adolescents, 24 were boys (60%); their age ranged between 11.5 and 17.5 years (mean 13.9 ±â€Š1.5). Baseline viral load ranged between 9630 and 24,600,000 IU/mL. HCV RNA became negative in 39 patients (97.5%) at 4 weeks and in all patients (100%) at weeks 8, 12, and SVR12. Asthenia was the commonest side effect, reported in 52.5% followed by headache in 47.5%. CONCLUSIONS: Treatment with all-oral DAAs (SOF/LED) for 12 weeks was well tolerated in Egyptian children and adolescents infected with genotype 4 HCV, with 100% SVR12 and negligible side effects.

Helicobacter pylori infection in children with portal hypertensive gastropathy.

BACKGROUND: Data about the association of Helicobacter pylori (H. pylori) and portal hypertensive gastropathy (PHG) are scarce in children. The present study aimed to fill the knowledge gap in this area. METHODS: The prevalence of H. pylori infection was studied in a group of infants and children with PHG using rapid urease test and histological demonstration of H. pylori in gastric mucosal biopsy obtained by upper gastrointestinal endoscopy. The results were compared to a control group who underwent endoscopy for other indications mainly hematemesis and/or dyspepsia. RESULTS: H. pylori was equally prevalent in both groups (~60%). Children with PHG were significantly stunted in height, had significantly lower hemoglobin, platelets and serum iron. Severe PHG was associated with higher grade of esophageal varices. Within the group with PHG, H. pylori infection was associated with lower hemoglobin, serum iron and serum ferritin. Moderate to severe PHG was more associated with H. pylori infection. CONCLUSIONS: H. pylori infection was not more commonly associated with PHG, however, it might contribute to the severity of PHG. The synergistic effect of PHG and H. pylori infection might contribute to the retarded growth and iron deficiency status noted in this group.

Focal hepatic lesions in Egyptian infants and children: the pediatric hepatologist perspective.

BACKGROUND: Hepatic focal lesions in the pediatric age group are diverse and can be broadly classified into congenital, neoplastic and infective. The aim of this paper was to describe the frequency, nature and clinical presentation of focal hepatic lesions from a pediatric hepatologist perspective. METHODS: Data were retrieved from files of all cases with focal hepatic lesions presenting to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, from January 2006 to December 2013, after the study protocol was approved by the department research committee and the institution ethical committee. RESULTS: Over an 8-year period, 38 cases had focal hepatic lesions. They constituted less than 1% of the 4475 new cases presenting to the unit over this period. The commonest lesion was hepatic hemangioma(s) (34%). Two-thirds were neoplastic lesions whether benign or malignant. Eighty percent were benign focal lesions. Infectious causes (fascioliasis and pyogenic liver abscess) accounted for 29% of cases. Hepatocellular carcinoma was the commonest malignant neoplasm; it occurred in 5 cases (13.2%) on top of a chronic liver disease. Hepatoblastoma was less common. CONCLUSIONS: From the hepatologist perspective, pediatric focal hepatic lesions are more likely to be benign. Hepatic hemangiomas are the commonest. Infectious causes are common in a developing country like Egypt. Hepatocellular carcinoma is the commoner malignant neoplasm and usually develops on a diseased liver. Screening infants and children with chronic liver disease for development of hepatocellular carcinoma is mandatory. Hepatoblastoma is less likely to present to the pediatric hepatologist as it is referred immediately to the oncologist or onco-surgeon.

Potential genetic markers for prediction of treatment response in Egyptian children infected with HCV genotype 4.

BACKGROUND: Egypt has a high prevalence of hepatitis C virus (HCV) infection. Limitations of the current HCV treatment in children are low rate of sustained virological response, significant side effects and high expenses, making prediction of treatment response crucial. AIM: This study aimed to investigate association of single nucleotide polymorphisms (SNPs) in interleukins (IL) 10, 28 and 29 genes in predicting the response to therapy in HCV infected children. METHODS: Sixty-six Egyptian children infected with HCV genotype 4, receiving pegylated interferon alpha 2b and ribavirin, were included. Genotyping of six SNPs in interleukin 10, 28B and 29 gene as well as HCV genotype were analyzed by real-time polymerase chain reaction. RESULTS: The CC genotype in IL28B; rs12979860 had 8.547 folds higher chance to develop sustained virological response than CT and TT genotypes (P=0.014). Genotype distribution of rs8099917 in IL28B gene (TG and GG genotypes) was found to be 3.348 more likely not to respond to treatment than the TT genotype (P=0.018). In multivariate analysis, interleukin 28 gene single nucleotide polymorphisms rs 12979860, interleukin 10 single nucleotide polymorphisms -592A > C and basal viral load were independent variables that significantly improved prediction of response to HCV therapy. CONCLUSION: This association can be translated into clinical decision making for HCV treatment.

Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis.

BACKGROUND: Occult hepatitis B virus infection (OBI) is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable HBsAg. Diagnosis of OBI requires a sensitive HBV DNA assay. AIM: We aimed at determining the frequency of OBI in infants, born to HBsAg-positive mothers, who received immunoprophylaxis at birth. METHODS: Sixty-four infants and children, born to HBsAg-positive mothers, who received hepatitis B immunoglobulin and HBV vaccine within 48 h after birth, were tested for HBV serological profile and HBV DNA by real-time PCR at least 1 month after last dose of HBV vaccine and not before 6 months of age. RESULTS: The median age of the studied infants and children was 8 months, ranging from 6 to 132 months; 54.7 % were females. HBV DNA was detected in 2 infants. One case had OBI; she was negative for HBsAg, anti-HBc total, HBeAg and was positive for anti-HBs (titer 267 mIU/mL) with low level of viremia (HBV DNA 1.13 x 10(3) IU/mL). Another infant showed immunoprophylaxis failure with positive HBsAg, anti-HBc total, HBeAg, negative anti-HBe and anti-HBs; HBV viral load was 1.7 × 10(8) IU/mL. Both mothers were HBsAg and HBeAg-positive. CONCLUSION: OBI may occur in infants born to HBsAg-positive mothers despite the receipt of immunoprophylaxis. OBI was detected in a low frequency in the present study. Anti-HBs positivity does not exclude OBI.

Extrahepatic portal vein obstruction in Egyptian children.

BACKGROUND AND AIM: Extrahepatic portal vein obstruction (EHPVO) is an important cause of portal hypertension in children. The aim of this study was to describe the clinical presentation, possible risk factors, upper gastrointestinal endoscopic findings, and treatment modalities of children with EHPVO. METHODS: After ethical approval of our study protocol by our institution review board, we analyzed available data from medical records of patients with EHPVO presenting to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for a period of 15 years from January 1996 to December 2010. RESULTS: The study included 169 patients. Their ages at presentation ranged from 1 month to 12 years (median 2.5 years, interquartile range 5); 101 were boys. Hematemesis was a presenting symptom in 58%, splenomegaly was present in 87%, esophageal varices were present in 94%, and fundal varices were present in 23%. Possible risk factors, in the form of umbilical catheterization, umbilical sepsis, and exchange transfusion, were elicited in 18%. Propranolol was associated with reduction in bleeding episodes (P < 0.001), but was associated with increased chest symptoms (P < 0.01). Both injection sclerotherapy and band ligation were effective in the management of bleeding varices and for primary and secondary prophylaxis; however, injection sclerotherapy was associated with the development of secondary gastric varices (P = 0.03). CONCLUSIONS: This large study of children with EHPVO demonstrates the efficacy of propranolol in the reduction of gastrointestinal bleeding in children with EHPVO. Both injection sclerotherapy and band ligation were effective in the management of esophageal varices, although the former was associated with the development of secondary gastric varices. Randomized clinical trials to choose the best modalities for the management of portal hypertension in children are still lacking.

Skeletal and cardiac muscle involvement in children with glycogen storage disease type III.

UNLABELLED: Glycogen storage disease type III (GSD III) may present with hepatic disease or may involve both skeletal and cardiac muscles as well. To assess the prevalence of neuromuscular and cardiac involvement in a group of children with GSD III, 28 children with GSD III, diagnosed by enzymatic assay, were enrolled in the study after an informed consent was obtained from their parents/guardians and after the study protocol was approved by our institutional ethical committee. Their mean age was 6.6 + 3.1 years. All cases were assessed neurologically by clinical examination, electromyography (EMG), and nerve conduction velocity. The heart was examined clinically by electrocardiogram and echocardiography. Seventeen patients (61 %) had myopathic changes by EMG, three of them had associated neuropathic changes. Creatine phosphokinase (CPK) was elevated in all myopathic cases except one. Children with myopathic changes were significantly older (p = 0.02), and CPK was significantly higher (p < 0.0001). Nine cases had left ventricular (LV) hypertrophy, seven of them had myopathic changes by EMG. CONCLUSION: Myopathic changes are not uncommon in children with GSD III. Myopathic changes tend to occur in older age and are associated with higher CPK level. Cardiac muscle involvement is less common in this age group and may, on occasion, occur alone without skeletal muscle involvement. Despite mild degrees of affection in this age group, it is recommended to perform prospective annual screening using EMG and echocardiography in order to augment dietary therapy regimen to prevent progression to life threatening complications.