Prevalence of autoimmune thyroiditis among children with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is an organ specific autoimmune disease, which can manifest at any age of life. there is a high prevalence of extrahepatic autoimmune diseases in patients with AIH. Autoimmune thyroid diseases (ATDs) are the most frequent extrahepatic autoimmune disorders among patients with AIH. Aim of work is to detect the frequency of ATDs among Egyptian children with AIH. METHODS: This research is a cross-sectional study conducted on 58 children with AIH aged ≤ 18 years. All patients were tested for free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG). Thyroid ultrasound (US) and thyroid scan were performed for patients with abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG. RESULTS: The mean ± standard deviation (SD) for the age of the patients was 11.3 ± 4.5 years. Out of 58 patients of AIH, 28 patients (48.3%) had associated other autoimmune diseases. Autoimmune thyroiditis was the most common associated autoimmune disease being present in 10 patients (17.2%). The thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) was hyperthyroid. CONCLUSION: Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

Clinical experience with hepatorenal tyrosinemia from a single Egyptian center.

Although very recently, in Egypt, sick newborn screening has included screening for hepatorenal tyrosinemia, yet, it is not yet included in nationwide neonatal screening and hence diagnosis may be delayed. The aim of this study was to analyze data of all cases presenting with hepatorenal tyrosinemia to the Pediatric Hepatology Unit, Cairo University, Egypt from 2006 to 2019. Data were retrieved from patients' files including age of onset of symptoms, clinical signs, blood counts, liver functions, serum phosphorous, alpha-fetoprotein, succinylacetone and abdominal ultrasound. During this period, 76 patients were diagnosed with hepatorenal tyrosinemia if succinylacetone in dry blood spot was elevated above 1 µmol/L. These 76 cases came from 70 families; consanguinity was reported in 61 families. In our cohort we reported 30 affected siblings with a similar clinical presentation, who died undiagnosed. Presentation was acute in 26%, subacute in 30% and chronic in 43%. Abdominal distention was the commonest presenting symptom (52.6%). Coagulopathy was the commonest derangement in liver functions; hyperbilirubinemia and raised transaminases were less common. Ultrasound findings included hepatic focal lesions in 47% and enlarged echogenic kidneys in 39% and 45.3% respectively. Only 20 children were treated with Nitisinone because of unavailability and high costs; seven out of them underwent liver transplantation. In conclusion, although hepatorenal tyrosinemia is a rare inborn error of metabolism, in a large population country with high rate of consanguinity; this disease is not uncommonly diagnosed. The current treatment is not readily available because of the costs in a resource-limited country. Neonatal screening and subsidization of the costly medication need to be considered.

Autoimmune hepatitis in Egyptian children: A single center experience.

BACKGROUND AND AIM: Autoimmune hepatitis (AIH) has variable clinical manifestations and should be considered in the diagnostic work-up of any patient with cryptogenic liver disease. The aim of the study was to determine the clinical, biochemical, histopathological characteristics and treatment outcome of AIH in Egyptian children. PATIENTS AND METHODS: This observational study was conducted at the Pediatric Hepatology Unit at Cairo University Pediatric Hospital, Egypt. All children (<18 years of age) presenting from 2009 to 2016 with established diagnosis of AIH were included. Medical history, clinical examination, and results of investigations were retrieved from patients' files. The main outcome measures included the rate of remission, relapses, and mortality. RESULTS: The study included 34 children with AIH. Twenty patients (58%) presented with chronic liver disease. There was a history of concomitant autoimmune diseases in 5 patients. Transaminases were elevated in all patients. There was synthetic dysfunction in 58%. Twenty-four patients (70.5%) had AIH-1, while nine patients (26.4%) had AIH-2 and one patient (2.9%) had autoantibody negative AIH. Piecemeal necrosis was observed in the liver biopsy of 79% of our cohort. Approximately 80% achieved biochemical remission (88% received combined therapy of prednisolone and azathioprine). About half of the patients developed relapses. One patient died of liver cell failure. CONCLUSION: In children with liver disease, a diagnosis of AIH should be considered. In those patients, AIH-1 is more common than AIH-2. Prednisolone monotherapy or combined with azathioprine could achieve remission, but relapse is still common. Treatment non-adherence is the main risk factor for relapse.

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.

Hepatobiliary manifestations in children with inflammatory bowel disease: A single-center experience in a low/middle income country.

BACKGROUND: There has been a worldwide increase in the reported incidence of inflammatory bowel disease (IBD) in children over the past 2-3 decades. The hepatobiliary (HB) manifestations of IBD have been well-studied in children in industrialized and developed countries but are infrequently reported in low- and middle-income countries (LMIC) such as Egypt. AIM: To determine the prevalence of the HB manifestations in a cohort of Egyptian children with IBD. METHODS: This cross-sectional observational study was carried out over a period of 6 mo (between June 2013 to December 2013) at the Paediatric Hepatology and Gastroenterology Units of Cairo University Children's Hospital, which is the largest paediatric tertiary care centre in the country. RESULTS: The study included 48 patients with confirmed IBD based upon clinical, laboratory, endoscopic and histopathological features, 29 (60.4%) were male. Twenty-four patients (50%) had ulcerative colitis (UC), 11 (22.9%) had Crohn's disease (CD) and 13 (27.1%) had unclassified-IBD (IBD-U), which was formerly known as indeterminate colitis. The mean age of the patients at the time of presentation was 8.14 (± SD 4.02) years and the mean age at the time of study enrolment was 10.16 (± SD 4.19) years. All patients were screened for HB manifestations by physical examination, liver function tests, imaging and liver biopsy when indicated. HB disorders were confirmed in 13 patients (27.1%). Transaminases were elevated in 3 patients (6.3%). Two patients (4.2%) had elevated biliary enzymes (one was diagnosed as primary sclerosing cholangitis (PSC) and the other was diagnosed with PSC/autoimmune hepatitis overlap syndrome and the third patient had hepatitis C virus infection. Ten patients (20.8%) had bright echogenic liver on ultrasound suggesting fatty infiltration as a sequel of malnutrition or medication toxicity. CONCLUSION: The commonest HB disorders in Egyptian children with IBD were abnormal liver function tests, fatty infiltration and PSC. These HB manifestations in paediatric patients in LMIC may be relatively more common than in industrialized countries. Therefore, IBD patients in LMIC should be meticulously screened for liver disease to allow prompt diagnosis and management.

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.

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.

Ocular findings in patients with cholestatic disorders of infancy: A single-centre experience.

BACKGROUND AND STUDY AIMS: Neonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis. PATIENTS AND METHODS: This cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision. RESULTS: The study included 112 infants with various cholestasis; 73 (65.2%) were males. The median age was 2months. Diagnosis was reached in 39 cases: 14 had AGS, 14 had biliary atresia (BA), 4 had NPD, 4 had post-haemolytic cholestasis, 2 had cytomegalovirus neonatal hepatitis, and one case had hepatorenal tyrosinaemia. Thirteen cases were probably having progressive familiar intrahepatic cholestasis (PFIC) type 1 or 2 considering their persistent cholestasis in the presence of normal gamma-glutamyl transpeptidase; 28 were left with a diagnosis of "idiopathic neonatal hepatitis" (INH), and 32 (28.6%) had no definite diagnosis. Ophthalmologic abnormalities were found in 39 cases (34.8%). The commonest finding was unilateral/bilateral optic nerve drusen in 12 (10.7%), followed by posterior embryotoxon in 11 (9.8%). Ocular findings were observed in 64.3% patients with AGS, 50% patients with NPD, 30.8% cases with suspected PFIC type 1or 2, 28.6% infants with INH, and 14.3% patients with BA. CONCLUSION: Ophthalmologic findings are not uncommon among cholestatic infants. Ophthalmologic examination should be routinely performed, including assessment of anterior segment, fundus examination, and ocular ultrasound.

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.

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.

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.

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.