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.

Secondary hepatic dysfunction in pediatric intensive care unit: Risk factors and outcome.

BACKGROUND: Hepatic dysfunction has a significant role in intensive care unit patients' morbidity and mortality. AIM: To study the frequency, risk factors and outcome of secondary hepatic dysfunction in children admitted to the pediatric intensive care unit. METHODS: Secondary hepatic dysfunction was defined as the development of abnormal liver functions in a patient without a previous liver disease during intensive care unit stay. The following data were collected: age, gender, indication of admission, type of organ dysfunction, presence of sepsis, shock, need for inotropic support or mechanical ventilation, administered medications and mortality scores. Liver function tests were done on admission and at 7-day intervals. RESULTS: One hundred and fifty-one patients were included. Forty-three (28.5%) acquired secondary hepatic dysfunction. Several risk factors were significantly associated with secondary hepatic dysfunction: sepsis (p<0.001), cardiovascular events (p<0.001), hypoxia (p<0.001), number of administered antibiotics (P = 0.001), use of inotropes (p<0.001) and mechanical ventilation (p = 0.001). Secondary hepatic dysfunction was significantly associated with mortality and prolonged length of stay (P=<0.001). CONCLUSION: Secondary hepatic dysfunction is a common finding in the pediatric intensive care unit. Sepsis, cardiovascular events and hypoxia, are the main risk factors for secondary hepatic dysfunction. Mortality and prolonged length of stay are strongly related to secondary hepatic dysfunction.

Causes of secondary non-alcoholic fatty liver disease in non-obese children below 10 years.

This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children < 10 years from hepatologist perspectives. Infants and children below 10 years of age with biopsy-proven fatty liver over a 6-year period were included. NAFLD activity score was used to detect the presence of non-alcoholic steatohepatitis (NASH). The study included 66 cases whose age ranged between 5 months and 10 years. Transaminases were elevated in 60% patients. Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). The cause of steatosis could not be identified in 28.8% of cases. There was a higher prevalence of secondary causes of NAFLD in patients < 10 years. Liver histopathological examination revealed preserved lobular architecture in 75.7% with minimal-to-mild fibrosis in 79%. Steatosis was macrovesicular in all specimens (severe steatosis in 39.4%). Four patients had NASH. Higher degree of steatosis was associated with more severe fibrosis (P = 0.01).Conclusion: GSD was the commonest cause of secondary NAFLD in Egyptian children < 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. The degree of fibrosis was significantly related to the degree of steatosis.What is Known:• Primary non-alcoholic fatty liver disease (NAFLD) is rare in children aged less than 10 years.• Secondary causes of NAFLD should be considered in patients who do not have traditional risk factors.What is New:• Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (< 10 years) with higher degrees of steatosis in younger patients.• The degree of liver fibrosis is significantly related to the degree of steatosis.

Drug-Drug Interactions in Children and Adolescents Receiving Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C Virus Infection.

BACKGROUND AND OBJECTIVE: Drug-drug interactions need to be considered to optimize the pharmacotherapeutic outcome of direct-acting antivirals. The aim of this study was to report on possible drug-drug interactions between ledipasvir/sofosbuvir and other medications received by children and adolescents with hepatitis C virus, in addition to suggested management for these drug-drug interactions. METHODS: Hepatitis C virus-infected children and adolescents, 12-17 years of age and/or weighing ≥ 35 kg, who presented to the Pediatric Hepatology Unit at Cairo University Pediatric Hospitals for ledipasvir/sofosbuvir treatment were included. Medication history was taken including long-term medications for chronic conditions and on-demand medications for inter-current illnesses. Medications were reviewed by the Kasr Alainy Drug Information Center to identify possible drug-drug interactions with prescribed ledipasvir/sofosbuvir and their management. HEP Drug Interactions provided by the University of Liverpool, Lexicomp®, and Medscape were the utilized references. Each drug-drug interaction was assigned a risk rating of A, B, C, D, or X. RESULTS: Sixty hepatitis C virus-infected children and adolescents assigned to receive ledipasvir/sofosbuvir were enrolled. Thirty percent of patients had associated chronic co-morbid conditions. The overall number of medications received was 48; 39 were prescribed as long-term medications with a median of 3 (interquartile range 4.24) medications per patient. Proton pump inhibitors, antacids, histamine H2 receptor antagonists, sodium bicarbonate, and colchicine were reported to be associated with a drug-drug interaction risk D necessitating therapy modification, which occurred prior to administration. CONCLUSIONS: Early identification and prompt response to drug-drug interactions with the aid of pharmacists optimize the pharmacotherapeutic outcome and eliminate possible morbidities when using direct-acting antivirals in children and adolescents with hepatitis C virus.

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.

Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis.

BACKGROUND: Hepatic osteodystrophy caused by vitamin D and calcium malabsorption is thought to develop in children with cholestatic liver disease leading to secondary hyperparathyroidism and rickets or osteomalacia. The aim of this study was to evaluate the dental and bone mineral densities and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical and laboratory parameters. METHODS: This is a cross-sectional study that include 50 patients presenting with cholestasis. Thirty age and sex matched controls recruited not complaining of liver disease. All cases were subjected to full history taking, clinical and dental examination, 25(OH)D level, ALT, AST, bilirubin, albumin, GGT, alkaline phosphatase, PT, INR, calcium, corrected calcium, phosphorus and DXA scan to those above 5 years old. Controls were subjected to measuring the serum levels of 25(OH)D, total bilirubin, direct bilirubin, ALT, GGT, AST, PT, INR, alkaline phosphatase, albumin, calcium and phosphorus. RESULTS: Out of the 50 cases; 23 were females (46%), with a mean age of 6.17±3.9 years ranging from 1.1 to 17 years. Twenty-eight of the cases had signs of rickets (56%), 6 of them had bone fracture (12%) and 42.8% had milky teeth caries. The level of 25(OH) vitamin D was below normal range in around half of the patients. There was significant difference between cases and controls in calcium and phosphorus levels, ALT and alkaline phosphatase. Low bone mineral density (BMD) was present in 50% and 5 cases (17.9%) were diagnosed as having osteoporosis. There was a negative correlation between the Z-score, BMD of total body, BMD and bone mineral content (BMC) of spine and total and direct bilirubin. There was a positive correlation between (BMD of total body, spine and BMC of spine) and serum phosphorus, alkaline phosphatase and albumin. There was a positive correlation between the Z-score of total body and serum calcium. CONCLUSION: Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was present in more than half of studied cholestatic patients correlated to the low serum calcium rather than the vitamin D level. The decreased BMD and the dental affection in cholestatic children is related to the level of hyperbilirubinemia.

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.

Blind percutaneous liver biopsy in infants and children: Comparison of safety and efficacy of percussion technique and ultrasound assisted technique.

BACKGROUND AND STUDY AIMS: Liver biopsy remains the most reliable method to diagnose various hepatic disorders in children. We aimed to assess the technical success and complication rate of ultrasound (US) assisted percutaneous liver biopsy versus transthoracic percussion guided technique in paediatrics. PATIENTS AND METHODS: This randomized controlled study included all cases performing liver biopsy at Paediatric Hepatology Unit, Cairo University Paediatric Hospital over 12months. RESULTS: Patients were 102 cases; 62 were males, with age range 18days to 12years. Fifty seven procedures were done using the percussion guided technique and 45 cases were US assisted. The total number of complicated biopsies was 14 (13.7%), with more serious complications occurring in the percussion group. Complications were more frequent with younger age, lower platelet count, number of passes and occurrence of hypotension. CONCLUSION: US assisted percutaneous liver biopsy, although more costly, but may be safer to perform particularly in younger age.

Safety and Efficacy of Combined Treatment with Pegylated Interferon Alpha-2b and Ribavirin for HCV Genotype 4 in Children.

Combined treatment with pegylated interferon (PEG-IFN)-α2b and ribavirin (RBV) is the only currently approved treatment for hepatitis C virus (HCV) infection in children. The aim of this study was to assess the safety and efficacy of combined treatment with PEG-IFN-α2b and RBV in Egyptian children and adolescents with genotype 4 (GT4) HCV infection. The study included 66 patients (3-17 years of age), of both sexes, infected with HCV GT4, treated with PEG-IFN-α2b (60 µg/m(2)), subcutaneously once weekly plus RBV (15 mg/kg/day) in 2 divided oral doses. Efficacy was assessed by achievement of sustained virological response (SVR). Safety was assessed by questionnaires directed to the patients at specific intervals, growth assessment and laboratory tests. SVR was achieved in 28 patients (42.4%). Nonresponders had significantly commoner history of treated malignancies (P = 0.03), baseline lower absolute neutrophil count (ANC; P = 0.009), higher gamma glutamyl transpeptidase (GGT; P = 0.003), and higher viral load (P = 0.03). Fever was the most frequently reported side effect occurring in 98.5% of the patients followed by musculoskeletal symptoms. Neutropenia was observed in 36 patients (54.6%) and necessitated treatment discontinuation in 1 patient. Decline in both weight and height percentiles was observed in 70% of children who received the combined therapy for a total of 48 weeks. In conclusion, the currently available treatment for HCV GT4 in pediatric patients has modest SVR with numerous adverse events necessitating meticulous monitoring to optimize care of the patients. Side effects could be managed with dose modifications and specific treatment when necessary.

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

OBJECTIVE: The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. PATIENTS AND METHODS: The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. RESULTS: IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. CONCLUSION: IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology.

Natural history and response to treatment of HCV infection among Egyptian survivors of childhood malignancy.

BACKGROUND: Children with cancer are at a high risk for hepatitis C virus infection due to immunosuppression secondry to chemotherapy and multiple transfusions of blood products. We aim to evaluate the presence of HCV infection in children with malignant diseases, risk factors, clinical course, laboratory, histopathological findings, and response to HCV treatment. METHOD: We described 31 patients referred to the pediatric hepatology clinic at Cairo University pediatric hospital and presenting with postmalignant virus C infection. Data collected included that of medical history, physical examination, and periodic evaluation clinically, laboratory, and histopathologically during their follow up. RESULTS: The mean age at diagnosis of HCV infection was 8 ± 3.3 years, the period of follow up of the patients in the hepatology clinic ranged from 0.3 to 15 years with a mean of 2.6 ± 2.3 years. Risk factors for HCV acquisition were chemotherapy in 93.5%, blood transfusions in 83.9%, and operations in 64.5%. Out of the 31 cases, 51.6% had leukemia. At first presentation, serum ALT level was elevated in 83.9% and AST level was elevated in 80.6%. Liver biopsy was performed in 26 cases; 96.1% had mild to moderate activity, 32% had no fibrosis, and 68% had mild to moderate fibrosis. Eighteen cases received HCV treatment. The response to HCV treatment was 27.7%. Although hepatitis C infection acquired by childhood cancer survivors was presented initially with high rate of elevated liver enzymes and PCR positivity, it seems to have a relatively benign clinical course with mild to moderate chronic hepatitis.

The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III.

AIM: To determine the individual fasting tolerance for patients with glycogen storage disease type III (GSD III) and to assess their linear growth velocity after tailoring of dose intervals of oral uncooked cornstarch. PATIENTS AND METHODS: A prospective cohort study included 32 patients with GSD III aged 6 months-11.5 years (median: 3.3 years). The fasting tolerance of each patient was determined as the time interval between starch administration until the drop in blood glucose level was below 60 mg/dL. RESULTS: Some 27 patients (84.4%) developed hypoglycemia. The intervals between oral cornstarch administration were tailored for each child according to his/her individual fasting tolerance. After a 6-month follow up there was a significant reduction in seizure attacks (p<0.01) and liver size (p<0.01), but there was no statistically significant difference in liver transaminase and serum lactate levels. There was a significant improvement in height (p<0.01) and linear growth velocity (p<0.05) of these patients after at least a 12-month follow up. CONCLUSION: Adjusting the intervals between the cornstarch doses for each patient with GSD III, according to individual fasting tolerance test was very beneficial and resulted in improvement of the linear growth velocity and reduction in the frequency of hypoglycemic seizures as well as the size of the liver. Individual scheduling of cornstarch doses prevents complications in those who develop hypoglycemia at short intervals; it also allows some relaxation in schedule for those who can tolerate longer fasting hours to improve their appetite and prolong their uninterrupted sleep hours.

Glycogen storage disease type III in Egyptian children: a single centre clinico-laboratory study.

BACKGROUND AND STUDY AIMS: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. PATIENTS AND METHODS: We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. RESULTS: Eighteen patients (58%) were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients (38.7%) had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Doll-like facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age (r=0.7 and P=<0.001), while serum triglycerides correlated negatively with age (r=-0.4 and P=0.05). CONCLUSION: Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level.

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children.

AIM: To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection. METHODS: Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493). RESULTS: Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well. CONCLUSION: Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Acute hemolytic anemia as an initial presentation of Wilson disease in children.

BACKGROUND: Wilson disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia in WD occurs in up to 17% of patients at some point during their illness. AIM: To screen for WD among children presenting with hemolytic anemia. METHODOLOGY: Twenty cases (mean age, 8.8 ± 3.9 y) with Coombs-negative hemolytic anemia, attending the hematology clinic of children hospital, Cairo University, were screened for WD by serum ceruloplasmin level, 24 hours urinary copper before and after D-penicillamine challenge test, and slit-lamp examination for detecting Kayser-Fleischer rings. RESULTS: No case had low ceruloplasmin, whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after D-penicillamine challenge test. According to the scoring system used, 1 case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a significantly higher urinary copper after penicillamine (P=0.000) when compared with group A (unlikely WD). CONCLUSION: WD is not uncommon in children with hemolytic anemia after exclusion of other common causes.

Limitations of Living Donor Liver Transplantation in Egyptian Children.

BACKGROUND/AIMS: In Egypt, the liver transplantation (LTx) program that became available since 2001 is a living donor program. We aimed to assess the obstacles to pediatric LTx. METHODS: Over a six-month-period, 41 pediatric patients were indicated for LTx; their ages ranged between 1.5 months to 17 years. Patients and potential donors were evaluated according to the program protocol. RESULTS: The obstacles for performing LTx were classified into recipient, donor and program obstacles or limitations. Each patient may have more than one limitation. Late presentation and co-morbid conditions were on the top of the recipient list of obstacles. Refusal of potential donors to donate was the commonest limitation on the donor side (33%). The commonest program limitations were young age and small size of the recipient. CONCLUSIONS: Limitations in recipient characteristics as well as donor shortage are still the main obstacles for living donor liver transplantation (LDLT) in our pediatric liver disease patients. Small weight and young age of potential LDLT candidates are the principle causes for delaying this life saving procedure. Increasing community awareness about living organ donation and nutritional support for end stage liver disease (ESLD) babies is pivotal, given our limitation to a living donor program.

Single-nucleotide polymorphisms of IL-10 and IL-28B as predictors of the response of IFN therapy in HCV genotype 4-infected children.

BACKGROUND AND AIMS: Single-nucleotide polymorphisms (SNPs) in the IL-10 gene (-1082 [rs1800896], -819 [rs3021097], and -592 [rs1800872]) and the IL-28B gene (rs12979860) in adults were shown to be associated with hepatitis C virus (HCV) clearance. The present study aimed to investigate the possible association of SNPs of IL-10 and IL-28B in predicting the treatment response of HCV genotype 4 in pediatric patients. PATIENTS AND METHODS: A restriction fragment length polymorphism-polymerase chain reaction and real-time polymerase chain reaction techniques were used to genotype 34 pediatric patients with HCV genotype 4 for IL-10 and IL-28B SNPs, respectively. Patients received pegylated interferon-α/ribavirin for 48 weeks subdivided according to their response to treatment into responders and nonresponders; also, 20 healthy individuals served as controls. RESULTS: A significant difference (P < 0.005) was observed in SNP of IL-28B rs12979860 frequencies between responders and nonresponders. In responders, CC genotype had greater frequency than CT and TT genotypes (60%, 30%, 10%), respectively, with C allele in its homozygous (CC) genotype more likely to respond to treatment than in its homozygous (TT) genotypes. SNPs of IL-10 at -819 (rs3021097) showed significant differences in their genotype frequencies between responders and nonresponders to therapy, and TT genotype had greater frequency in responders than CT and CC (55%, 20%, 25%), respectively. Genotypes with T allele (CT/TT) showed higher rates of response than those with no T allele (CC). CONCLUSIONS: SNPs of the IL-28B gene at (rs12979860) CC genotype as well as the IL-10 gene SNPs at -819 (rs3021097)TT genotype can be used for predicting response to treatment before patients are prescribed the expensive pegylated interferon-α/ribavirin therapy.

Intrafamilial transmission of hepatitis C infection in Egyptian multitransfused thalassemia patients.

OBJECTIVE: Detecting the current prevalence of hepatitis C virus (HCV) among Egyptian multitransfused thalassemic patients and evaluating the risk of its transmission within their family members. METHODS: Multitransfused Egyptian thalassemia patients (n = 137) were tested for HCV infection. Household contacts of positive members were compared with household contacts of HCV-negative patients. Antibodies to HCV were detected by enzyme immunoassay. Antibody-positive cases were retested for viral load using reverse transcriptase polymerase chain reaction. HCV genotyping was performed on positive samples of the patients and the positive household contacts. RESULTS: In all, 34.4% of patients (n = 47) were positive for HCV antibodies and RNA. The study of 24 families of HCV-positive patients showed 14 affected family members (19.2%). In 27 families of HCV-negative patients, four family members were affected (4.9%). HCV genotyping of seven families was similar in both patients and their family members. CONCLUSION: Our results support the role of intrafamilial transmission in the spread of HCV.

Assessment of coagulation and fibrinolysis in children with chronic liver disease.

We aimed at assessing the coagulation profile and detecting early evidence of fibrinolysis in pediatric patients with chronic liver disease. Seventy-six patients (40 boys) with a mean age of 9.8 ±â€Š3.4 years suffering from chronic liver disease were enrolled in this study. They were followed up in the Pediatric Hepatology Unit, Cairo University Children's Hospital. Thirty healthy children were included as controls. Patients were classified etiologically into four groups: chronic viral hepatitis, autoimmune hepatitis, miscellaneous and cryptogenic groups. Investigations to detect coagulopathy were done for all patients and controls: prothrombin time (PT), activated partial thromboplastin time, fibrinogen, fibrinogen degradation products, and D-dimer and complete blood count. Liver functions were done for all patient groups. A significantly lower platelet count, prolonged prothrombin time, with prolonged aPTT time was detected in all patients compared with controls (P < 0.001). The fibrinogen level showed no significant difference between patients and controls. D-dimer level was significantly higher in the miscellaneous and cryptogenic groups when compared to other patient groups and control group (P < 0.001). Significantly higher D-dimer levels were detected in patients with liver cirrhosis of child class A and B compared with noncirrhotic and control groups (P < 0.001). D-dimer correlated positively with PT (r = 0.290, P = 0.003), and negatively with platelet count (r = -0.324, P = 0.001) and prothrombin concentration (r = -0.270, P = 0.018). Fibrinolytic activity, as evidenced by high D-dimer, was detected in pediatric patients with chronic liver disease particularly if cirrhotic.