Health-related quality of life and cognitive function in children with Crigler-Najjar syndrome type 1.

BACKGROUND: The aim of the study was to assess the health-related quality of life (HRQOL) and cognitive function in patients with Crigler-Najjar syndrome (CNS) type I and its impact on their lives. METHODS: Twenty-one patients diagnosed with CNS type I aged 1 month to 18 years in the Paediatric Hepatology Unit of Cairo University Children's Hospital were enrolled in this cross-sectional observational study. The patients' health-related quality of life (HRQOL) was assessed using the World Health Organization Quality Of Life BREF questionnaire (WHOQOL-BREF) and the Short Form 36 Health Survey Questionnaire (SF-36). Cognitive function was assessed using the Stanford-Binet Intelligence Scale: Fifth Edition (SB5). RESULTS: All patients had a history of admission to a neonatal intensive care unit, 17 were managed by phototherapy only and 5 also underwent exchange transfusion. According to the WHOQOL questionnaire, 11 cases (52.4%) had a low QOL score, and 7 of 13 patients had an average score for their total IQ test. Cases with poor compliance to phototherapy had statistically significantly lower QOL scores (p=0.001), while, according to the SF36 survey, cases who received exchange transfusion had statistically significantly higher cognitive function (p=0.03). There was a positive correlation between the neurological effect as a complication of the disease and poor physical QOL. CONCLUSION: Paediatric patients with CNS have significantly lower HRQOL, especially physically, psychologically and environmentally. It is recommended that assessment of HRQOL should be a routine part of follow-up in CNS patients. Patients whose HRQOL is affected receive regular psychiatric counselling, social support and rehabilitation.Abbreviations: CNS: Crigler-Najjar syndrome; HRQOL: health-related quality of life; IQ: intelligence quotient; NICU: neonatal intensive care unit; QOL: quality of life; SB5: Stanford-Binet intelligence scale: 5th edition; SF-36: Short Form 36 Health Survey Questionnaire; UDGT: uridine diphosphate glucuronosyl transferase; UGT1A1: uridine 5'-diphosphate glucuronosyltransferase; WHOQOL-BREF: World Health Organization Quality of Life Brief Version.

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.

A study of exons 14, 15, and 24 of the ABCB11 gene in Egyptian children with normal GGT cholestasis.

BACKGROUND AND STUDY AIMS: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare inherited disorder caused by mutation in the ATP-binding cassette subfamily B member 11 gene (ABCB11) that encodes the bile salt export pump (BSEP), which is the main transporter of bile acids from hepatocytes to the canalicular lumen. Defects in BSEP synthesis and/or function lead to reduced bile salt secretion followed by accumulation of bile salts in hepatocytes and hepatocellular damage. This study aimed to detect variations in exons 14, 15, and 24 of the ABCB11 gene in patients with suspected PFIC2 among a group of Egyptian infants and children with normal gamma-glutamyl transpeptidase (GGT) cholestasis. PATIENTS AND METHODS: This observational case-control study was conducted on 13 children with suspected PFIC2 and 13 healthy subjects as controls. Genotyping of the ABCB11 gene was performed via DNA extraction followed by PCR amplification, purification, and then sequencing analysis of exons 14, 15, and 24 of the ABCB11 gene. RESULTS: The study detected two single nucleotide variations, c.1638+ 32T > C (rs2241340) in exon 14 and c.3084A > G (p.Ala1028 = ) (rs497692) in exon 24 of the ABCB11 gene. No variations were identified in exon 15. CONCLUSION: The study revealed two benign variants involving exons 14 and 24 of the ABCB11 gene. Exons 14, 15, and 24 are not hot spots for common mutations in Egyptian PFIC2 patients. Further study of other exons of the ABCB11 gene is necessary to confirm the diagnosis of PFIC2.

A pilot study of the value of a stool color card as a diagnostic tool for extrahepatic biliary atresia at a single tertiary referral center in a low/middle income country.

BACKGROUND AND STUDY AIMS: Biliary atresia (BA) is a major cause of hepatic failure and consequent liver transplantation in pediatrics. If BA is not diagnosed early and the proper surgical intervention is not performed before the age of 3 months, the survival of the affected infant is significantly reduced. In 1994, a stool color card (SCC) for early detection of BA was developed and used in Japan, a country where the parents' socioeconomic and education levels are high. We aimed to assess the value of using the SCC as a screening tool for early diagnosis of BA at a tertiary referral center in Egypt (a low/middle-income country). PATIENTS AND METHODS: This prospective study enrolled 108 infants (56 females) aged 1 day to 4 months who presented with cholestasis to the Hepatology Unit of Cairo University Children's Hospital from January 2018 to August 2019. In most of our patients, the mothers were the main caregivers and the parents' socioeconomic and education levels were generally modest or low. We utilized the SCC courtesy of the Perinatal Services BC (Vancouver, Canada) with an Arabic translation. This SCC contains nine colored stool photos: the first six are ranked as abnormal colors and the last three are ranked as normal. RESULTS: We found that almost all referring physicians were unfamiliar with or unaware of the SCC concept. Twenty-six of our babies' mothers were illiterate and 36 had not completed their primary school education. In spite of this low education level, 43 mothers of babies who were finally confirmed to have BA correctly matched a stool color of BA on the SCC with their babies' stools, and 56 mothers of babies who were finally confirmed not to have BA correctly matched a stool color not of BA with their babies' stools. Only nine mothers made a wrong match. Therefore, the overall "lay" mothers' sensitivity and specificity in diagnosis of BA using the SCC were 93.48% (95% confidence interval [CI] 82.1%-98.63%) and 90.32% (95% CI 80.12%-96.37%), respectively. CONCLUSION: To the best of our knowledge, this is the first study reporting the use of the SCC (with an Arabic translation) in a low/middle-income country. Despite the referring physicians' unfamiliarity with the SCC and the mothers' relatively low education level at our center; SCC proved to be a simple, efficient, highly sensitive, specific, and applicable method for early diagnosis of BA. Therefore, SCC screening might increase mothers (as well as physicians) awareness of BA, and we recommend that it be more publicized and used as a mass neonatal screening tool in low/middle-income countries such as Egypt.

Follow-up of chronic paediatric hepatitis C virus in a low-/middle-income country.

AIM: Follow-up of chronic hepatitis C virus (HCV) infection following Interferon (IFN) plus Ribavirin (RBV) or direct-acting antiviral (DAA) drug therapy in a cohort of paediatric outpatients as confirmed by a sustained virologic response (SVR). METHODS: This study included a cohort of 60 patients (6-18 years), divided into 2 groups: Group 1:21 patients who completed treatment with IFN/RBV. Group 2:39 treated with dual DAA therapy: 19 with Sofosbuvir/Ledipasvir (SOF/LED) and 20 with Sofosbuvir/Daclatasvir (SOF/DCV). RESULTS: Group 1:12 (57.1%) were cured, six were IFN/RBV treatment failure then subsequently treated with DAAs successfully, and three had liver transplants. IFN/RBV side effects were reported in all patients; however, fibrosis regressed in two cured patients. Group 2: all were cured. HCV RNA became negative in all DAAs-treated patients at weeks 2, 4 and 12 of treatment (100%) as well as SVR after 12 weeks (100%). Thirty patients reported no adverse side effects whereas only nine suffered minor side effects. CONCLUSIONS: In our cohort, SOF/LED therapy and SOF/DCV therapy were extremely safe and effective with 100% SVR and negligible short-term side effects. IFN/RBV therapy was much less effective (SVR 57.1%) and accompanied with short-term side effects. Fibrosis might stop and even regress with successful treatment.

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.