Enayet A, Afifi RA, Mogahed EA, El-Raziky MS, Abdellatif MA. Gallstones in Egyptian infants and children: risk factors, complications and outcome: a single center experience. Egyptian Liver Journal. 2020;10:30.
Mogahed EA, Ghita H, El-Raziky MS, El-Sherbini SA, Meshref D, El-Karaksy H. Secondary hepatic dysfunction in pediatric intensive care unit: Risk factors and outcome. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2020;52(8):889-94. Abstract

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.

Mogahed EA, El-Karaksy H, Abdullatif H, Yasin NA, Nagy A, Alem SA, et al. IMPROVEMENT IN LIVER STIFFNESS IN PEDIATRIC HCV PATIENTS AFTER TREATMENT WITH DIRECT ACTING ANTIVIRALS. The Journal of pediatrics. 2021. Abstract

OBJECTIVES: To assess the degree of liver stiffness using transient elastography (TE) in hepatitis C virus (HCV) infected Egyptian children at baseline and one-year after achievement of sustained virologic response (SVR) with direct acting antivirals (DAAs).

STUDY DESIGN: This prospective study included HCV infected children who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and one-year after achievement of SVR, the extent of hepatic fibrosis was assessed by TE using FibroScan to measure liver stiffness, in addition to non-invasive markers including aspartate aminotransferase (AST)/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 10-18 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, <0.001, 0.02 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. Co-morbid conditions and previous treatment with interferon were not associated with increased liver stiffness one-year after SVR.

CONCLUSIONS: Egyptian children infected with HCV GT4 achieved significant regression in liver stiffness after treatment with DAAs.

Mogahed EA, Sayed A-, Khalifa SE, El-Hennawy A, El-Raziky MS. Causes of secondary non-alcoholic fatty liver disease in non-obese children below 10 years. European journal of pediatrics. 2020. Abstract

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.

Abdullatif HM, Ramzi R, Mogahed EA, Ghobrial CM, El Rasheed Abd El Zaher BA, El Raziky MS, et al. Drug-Drug Interactions in Children and Adolescents Receiving Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C Virus Infection. Clinical drug investigation. 2019;39(9):857-64. Abstract

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 H 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.

El-Raziky ME, Fouad HM, Abd Elkhalak NS, Ghobrial CM, El-Karaksy HM. Paediatric chronic hepatitis B virus infection: are children too tolerant to treat? Acta paediatrica (Oslo, Norway : 1992). 2019;108(6):1144-50. Abstract

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.

Samra NM, Emad El Abrak S, El Dash HH, El Said El Raziky M, El Sheikh MA. Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis. Clin Res Hepatol Gastroenterol. 2018;42(4):368-77. Abstract

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.

El-Karaksy H, Mogahed EA, Abdullatif H, Ghobrial C, El-Raziky MS, El-Koofy N, et al. Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir. J Pediatr Gastroenterol Nutr. 2018;67(5):626-30. Abstract

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 ± 1.5). 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.

Mogahed EA, Mansy YA, Al Hawi Y, El-Sayed R, El-Raziky M, El-Karaksy H. Blind percutaneous liver biopsy in infants and children: Comparison of safety and efficacy of percussion technique and ultrasound assisted technique. Arab J Gastroenterol. 2016;17(4):168-75. Abstract

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.

El-karaksy HM, Mogahed EA, El-Raziky MS, Saleh D, Besheer M, Mubarak S. Safety and Efficacy of Combined Treatment with Pegylated Interferon Alpha-2b and Ribavirin for HCV Genotype 4 in Children. J Interferon Cytokine Res. 2016;36(1):1-8. Abstract

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.

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