scholarly journals Clinical and Para Clinical Findings in Children with Progressive Familial Intrahepatic Cholestasis in Iran; A Referral Center Report

2020 ◽  
Author(s):  
Mohammad Zarenezhad ◽  
Seyed Mohsen Dehghani ◽  
Fardad Ejtehadi ◽  
Mohammad Reza Fattahi ◽  
Reza Kaboodkhani ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Clinical Manifestations ◽  
Clinical Findings ◽  
Nodule Formation ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Referral Center ◽  
Elevated Liver Enzymes ◽  
Clinicopathological Findings ◽  
Histopathologic Evaluation ◽  
End Stage

Abstract BackgroundProgressive Familial Intrahepatic Cholestasis (PFIC) is a heterogeneous group of disorders with various clinical and para-clinical manifestations. We report clinical and para-clinical findings in children with progressive familial intrahepatic cholestasis in Southern Iran.MethodsMedical records of 102 patients aged ≤18 years old diagnosed with PFIC who referred to our referral center were evaluated from 2008 to 2012. Baseline and clinical characteristics, outcomes and survival of these patients were recorded. ResultsThe study included 61 boys and 41 girls. Most common complaints were jaundice in 53 (51.96 %), pruritus and jaundice in 15 (14.70 %) and jaundice+elevated liver enzymes in 11 (10.78%) children. Main clinical findings in children were jaundice (51.96%), ascites (28.43%), pruritus (19.60%), fever (16.66%) and encephalopathy (14.70%). Inhomogeneous echogenicity (31.37%), splenomegaly (26.47%), hepatomegaly (17.64%), cirrhosis (9.80%) and ascites (6.86%) were the most common sonography findings among children with PFIC, respectively. Histopathologic evaluation showed cirrhosis (34.31%), followed by fibrosis (18.62%), cholestasis (10.78%), inflammation of liver tissue (4.90%), nodule formation (2.94%), and destruction of lobular and vascular architecture (1.96%). Liver transplantation, medical therapy and biliary diversion had been performed for 67%, 13% and 11% of the patients, respectively. Mean (SD) PELD and MELD scores among children with PFIC were 7.14±14.63 and 15.75±7.21, respectively. Three month mortality rate for PFIC patients with end stage liver disease was 13.1%.ConclusionInhere we reported invaluable clinicopathological findings among a large series of patients with PFIC.

scholarly journals Liver Transplantation in Progressive Familial Intrahepatic Cholestasis With Normal Gamma-Glutamyl Transferase: Evaluation of Post-Transplant Steatosis and Steatohepatitis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Hossein Anbardar ◽  
Seyed Mohsen Dehghani ◽  
Maryam Poostkar ◽  
Seyed Ali Malek-Hosseini
Keyword(s):  
Liver Transplantation ◽  
Growth Retardation ◽  
Intrahepatic Cholestasis ◽  
Clinical Manifestations ◽  
Gamma Glutamyl Transferase ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Post Transplant ◽  
End Stage Liver Disease ◽  
Glutamyl Transferase ◽  
End Stage

Background: Progressive familial intrahepatic cholestasis is a disease presenting with severe cholestasis and progressing to the end-stage liver disease later. Liver transplantation is a treatment modality available for progressive familial intrahepatic cholestasis, especially in patients with end-stage liver disease or those who are unsuitable for or have failed biliary diversion. Objectives: To evaluate clinical and pathological characteristics of progressive familial intrahepatic cholestasis patients who had undergone liver transplantation and to determine post-transplant steatosis and steatohepatitis. Methods: We evaluated 111 progressive familial intrahepatic cholestasis patients with normal gamma-glutamyl transferase that performed liver transplantation in Shiraz Transplant Center in Iran between March 2000 and March 2017. Results: The most common clinical manifestations were jaundice and pruritus. Growth retardation and diarrhea were detected in 76.6% and 42.5% of the patients. After transplantation, growth retardation was seen in 31.5% of the patients, and diarrhea in 36.9% of them. Besides, 29.1% of the patients died post-transplant. Post-transplant liver biopsies were taken from 50 patients, and 15 (30%) patients had steatosis or steatohepatitis, five of whom (10%) had macro-vesicular steatosis alone, and 10 (20%) had steatohepatitis. Only one patient showed moderate bridging fibrosis (stage III), and none of them showed severe fibrosis. Conclusions: Liver transplantation is the final treatment option for these patients, and it can relieve most clinical manifestations. However, post-transplant mortality rate was relatively high in our center. Diarrhea, growth retardation, and steatosis are unique post-transplant complications in these patients. The rate of post-transplant steatosis and steatohepatitis in patients with liver biopsy in our study was 30%, with a significant difference from previous studies.

scholarly journals Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mariam Goubran ◽  
Ayodeji Aderibigbe ◽  
Emmanuel Jacquemin ◽  
Catherine Guettier ◽  
Safwat Girgis ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Intrahepatic Cholestasis ◽  
Autoimmune Response ◽  
Compound Heterozygous ◽  
Biliary Cirrhosis ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Type 3

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. Case presentation We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient’s original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. Conclusions Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

Bronchiectasis and Bronchiolectasis With Severe Herniating Pattern Associated With STAT1 Gain-of-Function Mutation: Detailed Clinicopathological Findings

2021 ◽  
pp. 109352662098595
Author(s):  
Moe R Takeda ◽  
Manvi Bansal ◽  
Rory J Kamerman-Kretzmer ◽  
Joseph Church ◽  
Jianling Ji ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Cerebral Aneurysms ◽  
Clinical Findings ◽  
Chronic Mucocutaneous Candidiasis ◽  
Gain Of Function ◽  
First Case ◽  
Clinicopathological Findings ◽  
Main Driver ◽  
Autoimmune Conditions

STAT1 gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with STAT1 GOF mutation, they did not include histopathologic features. Herein, we describe the first case with detailed histologic findings in the lung of a 5-year-old patient with a de novo STAT1 GOF mutation, who presented with CMC and bronchiectasis. The biopsy showed severe bronchiolectasis with extensive airway dilatation and occasional disruptions. Peribronchiolar inflammation was not always present and evident mainly in areas of airway disruption; inflammation may have not been a main driver of the airway damage in this case. The airway dilatation often showed an interesting herniating pattern, possibly implying a connective tissue etiology. This case also demonstrates the diagnostic utility of whole exome sequencing as STAT1 GOF mutations are not detected by routine workup. The definitive diagnosis will lead to more specific treatments and increased surveillance for serious conditions, such as cerebral aneurysms and malignancies.

Progressive familial intrahepatic cholestasis type 4 in an Indian child: presentation, initial course and novel compound heterozygous mutation

2020 ◽  
Vol 13 (7) ◽  
pp. e234193
Author(s):  
Nida Mirza ◽  
Ravi Bharadwaj ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Smooth Muscle ◽  
Intrahepatic Cholestasis ◽  
Compound Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Cholestatic Liver Disease ◽  
Gamma Glutamyl Transferase ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Smooth Muscle Antibody ◽  
Elevated Liver Enzymes ◽  
Glutamyl Transferase

A 15-year-old boy who had a history of on and off pruritus and jaundice since many years found to have a novel mutation in TJP2 gene. On examination, he had clubbing, splenomegaly, grade 3 oesophageal varices and short stature. Investigation revealed direct hyperbirubinemia with elevated liver enzymes with normal gamma-glutamyl transferase (GGT). Antinuclear antibody (ANA), smooth muscle antibody (SMA) anti-liver kidney microsomal (anti-LKM) and viral markers for hepatitis were negative. However, IgG was elevated and anti-smooth muscle antibody (ASMA) was weekly positive (1:20). He was also given a trial of steroid and azathioprine for 1 year on the basis of liver biopsy findings, raised IgG and positive ASMA but finding no improvement stopped. Genetic testing by next-generation sequencing found a novel compound heterozygous missense variation in exon 17 of the TJP2 gene confirming progressive familial intrahepatic cholestasis type 4 as the aetiology of cholestatic liver disease.

scholarly journals A clinical and biochemical laboratory profile to measure the severity of dengue fever in paediatric population and their outcome

2021 ◽  
Vol 8 (3) ◽  
pp. 535
Author(s):  
Sandhya Rani Talari ◽  
Gangadhar Belavadi
Keyword(s):  
Dengue Fever ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Paediatric Population ◽  
Positive Outcome ◽  
Clinical Findings ◽  
Total Leukocyte Count ◽  
Presenting Symptoms ◽  
Elevated Liver Enzymes

Background: Aim of the study was to assess various clinical manifestations of dengue fever, and complications, to establish the diagnosis of dengue fever based on dengue antigen (NS 1) and antibody (IgM, IgG) and to find the association between the clinical findings with laboratory findings.Methods: 100 cases of suspected children below 18 years of age with clinical features suggestive of dengue infection and children presenting with fever of acute onset (<2 weeks), pain abdomen, vomiting, rash, flushed appearance and bleeding manifestation were studied. The cases were followed up for the clinical and laboratory parameters and were treated according to WHO guidelines.Results: Out of total 100 cases studied 36 were classified as classical dengue fever, 33 as DHF, 15 as DSS, 16 as DLI. It was observed that the disease was common in age group of 5-11 year (54%). Most of the patients were male (66%) with an M:F ratio of 1.94:1. The common presenting symptoms were fever (96%), vomiting (49%), abdominal pain (42%), headache (12%), myalgia (7%), arthralgia (4%), retro orbital pain (1%). General physical examination revealed presence of hypotension, tachycardia, rashes, facial puffiness (28%), pedal oedema (21%), and conjunctival congestion (18%). The skin bleeding was the most common manifestation noted in 12 cases (12%) followed by GIT bleeding like hematemesis 4 cases (4%) followed by epistaxis 4 cases (4%), haematuria 2 cases (2%) and gum bleeds 2 cases (2%). In systemic examination patients were found to have hepatomegaly (53%), ascites (13%), splenomegaly (8%), and pleural effusion (27%). 36 (36%) patients in the study had leucopoenia and mean total leukocyte count of 6014.5 cells/cu mm. The highest and lowest TLC was 22000 and 1400 cells/cumm respectively. 85% cases had thrombocytopenia in the present study. The mean platelet in the present study was 41870 cells/cu mm. Elevated liver enzymes and elevated serum creatinine count was found in complicated forms of disease.Conclusions: The treatment of dengue is mainly supportive, but early institution and meticulous monitoring are the corner stone for positive outcome. Much more awareness, vigilance and research in the diagnostic modalities is further needed to avoid unnecessary panic and platelet transfusions.

scholarly journals New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Eva Sticova ◽  
Milan Jirsa ◽  
Joanna Pawłowska
Keyword(s):  
Intrahepatic Cholestasis ◽  
Bile Salts ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Bile Secretion ◽  
Drug Induced ◽  
Benign Recurrent Intrahepatic Cholestasis ◽  
End Stage

Cholestasis is characterised by impaired bile secretion and accumulation of bile salts in the organism. Hereditary cholestasis is a heterogeneous group of rare autosomal recessive liver disorders, which are characterised by intrahepatic cholestasis, pruritus, and jaundice and caused by defects in genes related to the secretion and transport of bile salts and lipids. Phenotypic manifestation is highly variable, ranging from progressive familial intrahepatic cholestasis (PFIC)—with onset in early infancy and progression to end-stage liver disease—to a milder intermittent mostly nonprogressive form known as benign recurrent intrahepatic cholestasis (BRIC). Cases have been reported of initially benign episodic cholestasis that subsequently transitions to a persistent progressive form of the disease. Therefore, BRIC and PFIC seem to represent two extremes of a continuous spectrum of phenotypes that comprise one disease. Thus far, five representatives of PFIC (named PFIC1-5) caused by pathogenic mutations present in both alleles ofATP8B1,ABCB11,ABCB4,TJP2,andNR1H4have been described. In addition to familial intrahepatic cholestasis, partial defects inATP8B1,ABCB11,andABCB4predispose patients to drug-induced cholestasis and intrahepatic cholestasis in pregnancy. This review summarises the current knowledge of the clinical manifestations, genetics, and molecular mechanisms of these diseases and briefly outlines the therapeutic options, both conservative and invasive, with an outlook for future personalised therapeutic strategies.

Nutritional B12 Deficiency in Infants of Vitamin B12-Deficient Mothers

2011 ◽  
Vol 81 (5) ◽  
pp. 328-334 ◽  
Author(s):  
Oya Halicioglu ◽  
Sezin Asik Akman ◽  
Sumer Sutcuoglu ◽  
Berna Atabay ◽  
Meral Turker ◽  
...  
Keyword(s):  
Megaloblastic Anemia ◽  
Maternal Diet ◽  
Clinical Manifestations ◽  
Serum Vitamin ◽  
Failure To Thrive ◽  
Clinical Findings ◽  
Vitamin B ◽  
Animal Products ◽  
Hematological Evaluation ◽  
Nutritional Vitamin

Aim: Nutritional vitamin B12 deficiency in infants may occur because the maternal diet contains inadequate animal products. Clinical presentations of the infants who had nutritional vitamin B12 deficiency were analyzed in this study. Subjects and Methods: Patients with nutritional vitamin B12 deficiency were enrolled in the study between 2003 and 2010. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. Results: Thirty children aged 1 - 21 months constituted the study group. Poverty was the main cause of inadequate consumption of animal products of the mothers. All infants had predominantly breastfed. The most common symptoms were developmental delay, paleness, apathy, lethargy, anorexia, and failure to thrive. Hematological findings were megaloblastic anemia (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers had low serum B12 levels; eight of them had megaloblastic anemia. Conclusion: The unusual clinical manifestations of vitamin B12 deficiency may also be seen apart from neurological and hematological findings. Nutritional vitamin B12 deficiency due to maternal deficiency might be a serious health problem in infants. Therefore, screening and supplementation of pregnant and lactating women to prevent infantile vitamin B12 deficiency should be considered.

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