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.

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.

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.

Covid-19 pandemic in Egyptian children with liver diseases: Incidence and impact on health care service delivery in a low/middle income country.

BACKGROUND AND STUDY AIMS: The coronavirus disease 2019 (COVID-19) pandemic has had considerable effects on health care services given the need for re-allocation of resources and interruption of medical care. COVID-19 poses a challenge to patients with liver disease who are at risk of infection and more severe disease course. The current study aimed to assess the incidence of COVID-19 in children with liver diseases and evaluate the extent to which health care delivery was affected during lockdown. PATIENTS AND METHODS: This cross-sectional analytical study conducted at the Pediatric Hepatology Unit, Cairo University Children's Hospital utilized a questionnaire to determine the incidence of COVID-19 in patients with liver diseases and the impact of COVID-19 on the patients' liver condition and health care service delivery. A presumed score was implemented to identify patients with probable COVID-19. RESULTS: Data from 349 children with liver diseases were analyzed. The overall incidence of COVID-19 was 8%. Patients with documented and probable COVID-19 were compared to improbable COVID-19 cases. Notably, COVID-19 cases were younger and had higher incidence rates of cholestatic liver diseases. COVID-19 patients experienced significantly higher rates of hepatic complications (43%) and had significantly greater need for medical services during the lockdown. All COVID-19 patients recovered after a median (IQR) duration of 3 (4) days, except for one patient who succumbed to COVID-19 and hepatic complications. CONCLUSIONS: COVID-19 affected the younger hepatic patients with cholestatic disorders of infancy. Hepatic complications were more common among COVID-19 infected children. Alternative ways of communication require development to prioritize patients who needs a hospital visit and monitoring. Clinical scores may help diagnosis of COVID-19 in low/middle income countries like Egypt to compensate for the deficient laboratory diagnostic facilities.

Resuming post living donor liver transplantation in the COVID-19 pandemic: real-life experience, single-center experience.

BACKGROUND: Solid organ transplantation (SOT) service has been disrupted during the current coronavirus disease 2019 (COVID-19) pandemic, which deferred the service in most centers worldwide. As the pandemic persists, there will be an urgency to identify the best and safest practices for resuming activities as areas re-open. Resuming activity is a difficult issue, in particular, the decision of reopening after a period of slowing down or complete cessation of activities. OBJECTIVES: To share our experience in resuming living donor liver transplantation (LDLT) in the context of the COVID-19 pandemic in the Liver Transplantation Unit of El-Manial Specialized Hospital, Cairo University, Egypt, and to review the obstacles that we have faced. MATERIAL AND METHODS: This study is a single-center study. We resumed LDLT by the 26th of August 2020 after a period of closure from the 1st of March 2020. We have taken a lot of steps in order to prevent COVID-19 transmission among transplant patients and healthcare workers (HCWs). RESULTS: In our study, we reported three LDLT recipients, once resuming the transplantation till now. All our recipients and donors tested negative for SARS-CoV-2 by nasopharyngeal RT-PCR a day before the transplantation. Unfortunately, one of them developed COVID-19 infection. We managed rapidly to isolate him in a single room, restricting one team of HCWs to deal with him with strict personal protective measures. Finally, the patient improved and was discharged in a good condition. The second patient ran a smooth course apart from FK neurotoxicity which improved with proper management. The third patient experienced a sharp rise in bilirubin and transaminases on day 14 that was attributed to drug toxicity vs. rejection and managed by discontinuing the offending drugs and pulse steroids. In addition, one of our head nurses tested positive for SARS-CoV-2 that was manageable with self-isolation. CONCLUSION: Careful patient, donor, personnel screening is mandatory. Adequate supply of personal protective equipments, effective infection control policies, and appropriate administrative modifications are needed for a safe return of LDLT practice.

Perinatal transmission of hepatitis C virus: an update.

Infection with hepatitis C virus (HCV) is a major health problem worldwide. A large proportion of perinatal HCV infections are silent and may present later in adulthood with long-term complications. HCV has no effective immune prophylaxis and hence appropriate follow-up of all infants born to HCV-infected mothers is necessary. Universal antenatal screening for HCV is largely debatable. Intrauterine and partum transmission of HCV are both possible and higher rates are associated with a high maternal serum viral load (> 106 copies per milliliter), concomitant HIV infection, prolonged or difficult delivery, and invasive fetal monitoring during delivery. Infection during pregnancy and infancy needs to be investigated more in order to design management strategies for perinatal transmission of HCV most effectively. The recently approved new-generation, oral, direct-acting antiviral drugs may open a new era in HCV therapy for pregnant women and infected infants if proved to be safe during conception and infancy.

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.

The prevalence of congenital heart defects in infants with cholestatic disorders of infancy: a single-centre study.

BACKGROUND: There is deficiency of data about congenital heart defects (CHDs) in cholestatic disorders of infancy other than Alagille syndrome (AGS). We aimed to define the prevalence and types of CHDs in infants with various causes of cholestatic disorders of infancy. METHODS: This cross-sectional study was conducted on 139 infants presenting with cholestasis whether surgical or non-surgical. The study was carried out at the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. Full examination and investigations were done in an attempt to reach an aetiologic diagnosis for cholestasis, in addition to a comprehensive echocardiographic study. RESULTS: The age at the onset of cholestasis ranged from 1 day to 7 months. Males constituted 61.2%. Biliary atresia (BA) was diagnosed in 39 patients (28%), AGS in 16 patients (11.5%), 27 patients had miscellaneous diagnoses and 57 cases had indeterminate aetiology. CHDs were detected in 55 patients (39.5%). Shunt lesions were detected in 24 patients (43.6%), pulmonary stenosis in 18 patients (32.7%) and combined lesions in 9 patients (16.4%). Three patients (5.5%) had abnormal cardiac situs. Only seven patients had clinical presentation suggestive of CHD. CHDs were detected in 14 patients with BA (35.9%), 15 patients with AGS (93.7%) and 26 patients in the remaining group (30.9%). CONCLUSION: CHDs are not uncommon among cholestatic infants and are mostly asymptomatic. Echocardiographic examination of cholestatic infants is recommended particularly for patients with BA before undergoing hepatic portoenterostomy as presence of CHD may impact the anaesthetic planning and affect the outcome of hepatobiliary surgery.

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.

Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis.

Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 µg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.

Effect of interleukin-10 gene promoter polymorphisms -1082 G/A and -592 C/A on response to therapy in children and adolescents with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Studying predictors of response to therapy for hepatitis C virus (HCV) infection in children may help avoid the inappropriate use of currently available costly therapy associated with numerous adverse effects. We tested the hypothesis that inheritance of single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) promoter gene might influence response to HCV treatment. PATIENTS AND METHODS: The impact of SNPs, -1082 G/A and -592 C/A, in the promoter region of IL-10 gene, on response to HCV therapy was assessed in a cohort of 40 children treated with a combination of pegylated interferon (Peg-IFN) α2b and ribavirin. RESULTS: Sustained virological response was achieved in 48.7%. High viral load was associated with non-response to therapy. There was no association between histopathological degree of inflammation or fibrosis and response to therapy. There was no direct statistically significant association between polymorphisms in the IL-10 gene (-1082G/A and -592 C/A) as regards inflammation or response to therapy in children. As for the SNP -592 C/A; there was a statistically significant association with the score of fibrosis (P<0.004), concluding that the A allele was protective from moderate and severe fibrosis. Meanwhile the SNP -1082G/A did not show any association with the fibrosis score. CONCLUSION: We could not associate response to therapy for HCV with IL-10 polymorphisms -1082 G/A and -592 C/A. For the SNP -592 C/A, the A allele protected from moderate and severe fibrosis.

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.

Chanarin-Dorfman syndrome: A case report and review of the literature.

UNLABELLED: Chanarin-Dorfman syndrome, a "neutral lipid storage disease with ichthyosis," is a multisystem inherited metabolic disorder associated with congenital ichthyosis and accumulation of lipid droplets in various types of cells. CASE REPORT: A 3-year-old male presented to the Pediatric Hepatology Unit, Cairo University Children's Hospital, Cairo, Egypt, with accidentally discovered hepatomegaly. He had generalised ichthyosis with dark skin pigmentation and bilateral ectropion. Abdominal examination revealed generalised abdominal distention with firm nontender hepatomegaly. His liver functions were deranged. Blood film showed many vacuolated neutrophils. Serum triglyceride and creatine kinase levels were elevated. Abdominal ultrasound showed a moderately enlarged liver with a bright echo pattern. Liver biopsy revealed marked diffuse macrovesicular fatty changes. The diagnosis of Chanarin-Dorfman Syndrome was made based on the dermatological, haematological, and liver biopsy findings.

Gene mutations in Wilson disease in Egyptian children: report on two novel mutations.

BACKGROUND AND STUDY AIMS: Wilson disease (WD) is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase (ATPase) encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation (p.H1069Q) in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. PATIENTS AND METHODS: Direct DNA sequencing was applied to exons (13, 14, 18, and 19) of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families (three families). RESULTS: We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution (p.A1074A) in 16% of patients and the other was predicted to be missense disease-causing mutations (p.T1076I) in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. CONCLUSION: Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations.