Prolonged Hyperbilirubinemia Research Articles

Full Robotic Whole Graft Liver Transplantation: A Step Into The Future.

To report the first European series of full robotic whole liver transplantation (RLT) with technical details and future perspectives. Few cases of liver transplantation with a minimally invasive approach using partial grafts have been reported so far, and no cases of robotic whole liver transplantation have been reported in the scientific literature. The adopted technique was full robotic liver hepatectomy, followed by robotic implantation after graft introduction through a small midline incision. Patients presenting with Hepatocellular Carcinoma (HCC) in liver cirrhosis with a small caudate lobe, low degree of portal hypertension, no porto-mesenteric thrombosis, as well as low MELD patients have been considered ideal candidates. Six patients underwent RLT between February and March 2024 at Lisbon and Modena University Liver Transplant Centers. Warm ischemia time during RLT ranged between 55 and 90 min, with a total surgery duration between 440 and 710 min. The median total operative time was 595 (±111,3) minutes. Only one recipient had prolonged hyperbilirubinemia, which was safely treated. The median in-hospital stay was 7.5 days, (±4.8 days). RLT is a promising technique to further reduce the impact of liver transplantation thanks to smaller incision, gentle tissue manipulation, high magnification and precision for vascular and biliary anastomosis, and reduced postoperative pain. This is the first step toward the demonstration of the feasibility of minimally invasive surgery in liver transplantation, although further selection and technical refinements are needed to improve reproducibility.

Clinico-Investigative Profile of Prolonged Hyperbilirubinemia in Newborns Presenting to Tertiary Health-Care Setup in Rural Maharashtra

Introduction Prolonged hyperbilirubinemia is defined as high bilirubin levels (>10 mg/dL) persisting beyond day 14 of life in term neonates and beyond day 21 in preterm neonates. Methods and Material A prospective cross-sectional study was conducted at a rural tertiary care hospital after obtaining an ethical approval and an informed consent. All infants under 6 months of age with hyperbilirubinemia after 21 days in preterm and 14 days in term were included. This study was designed to determine the proportion of prolonged hyperbilirubinemia and its causes and investigative profile in rural tertiary care. Results Out of total infants showing hyperbilirubinemia, 30.51% of patients had conjugated hyperbilirubinemia with female predominance, whereas 69.49% had unconjugated hyperbilirubinemia with male predominance. In our study, 38.14% were diagnosed with breast milk jaundice, followed by 33.90% caused by septicemia and 10.17% cases of cephalhematoma. In addition, hypothyroidism and TORCH infections were observed in 4.24% of cases, whereas a single case of cystic hygroma, subdural emphysema, pyloric stenosis, and G6PD deficiency was seen. In comparison, late-onset hemorrhagic disease of newborns was observed in 3.39% of cases. Conclusion Breast milk jaundice was the most frequently encountered etiologies of prolonged hyperbilirubinemia and hence, unnecessary investigation for unconjugated hyperbilirubinemia should be avoided.

Prevalence and Clinical Significance of Urinary Tract Infection among Neonates Presenting with Unexplained Hyperbilirubinemia in Lebanon: A Retrospective Study.

Neonatal jaundice is commonly seen in term and preterm newly born babies. It could be either physiologic or secondary to multiple underlying pathologies like urinary tract infection (UTI). Our main objective was to confirm the relationship between neonatal jaundice without apparent cause like hemolysis and the presence of UTI. We, retrospectively over a period extended from 2017 to 2020, included 496 babies admitted for elevated indirect hyperbilirubinemia for whom demographic, clinical, laboratory, and therapeutic data were collected through a detailed questionnaire. Our study included 496 neonates and showed a prevalence of UTI in 8.9% of neonates. The two most common microorganisms in urine culture were Escherichia coli (65.9%) and Klebsiella pneumoniae (25.0%). A multivariate logistic analysis showed that UTI was associated with male neonates (odds ratio [OR] = 2.366, 95% confidence interval [CI]: 1.173 - 4.774; P = 0.016), history of prenatal UTI (OR = 5.378, 95% CI: 2.369 - 12.209; P <0.001), poor feeding (OR = 3.687, 95% CI: 1.570 - 8.661; P = 0.003), and positive urine culture in catheter (OR = 2.704, 95% CI: 1.255 - 5.826; P = 0.011). The mean length of stay was higher in patients with positive UTI (Median = 216 hours) compared to patients with negative UTI (Median = 48 hours) (P <0.001). Neonatal sreening for UTI should be recommended whenever there is unexplaind early or prolonged hyperbilirubinemia with no evidence of alloimmune hemolysis or blood group incompatibility and to prevent the morbidity of urosepsis and congenital kidneys malformations.

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model

The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION". Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Gilbert or Crigler\u2013Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity

BackgroundSeveral mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c.1091C > T) in homozygous newborns. We describe the clinical, laboratory and therapeutic approach in two Chinese neonates with severe jaundice, homozygous for the P364L mutation.Case presentationTwo Chinese breastfed female infants presented prolonged unconjugated hyperbilirubinemia at the age of 1 month. Total bilirubin was higher than 15 mg/dl (D < 1). An exhaustive etiological work-up to detect possible causes of hyperbilirubinemia (notably hemolytic ones) was negative.The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. Both patients resulted homozygous for a variant site within the coding region of the gene in the 4 exon, c.1091C > T, p.Pro364Leu.In front of the persistently high level of unconjugated bilirubin, phototherapy was performed without persistent results. A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization. The therapy was stopped.ConclusionUGT1A1 enzyme activity associated with the P364L mutation has been described as 35.6% of the wild-type enzyme activity. Photo-therapy and phenobarbital can be useful in front of persistently high level of unconjugated bilirubin.Our cases presented high bilirubin values, overlapping between Gilbert syndrome (GS) and Crigler-Najjar syndrome type II (CNS), but the complete normalization of bilirubin makes GS more likely. Homozygous P364L variant can be associated with severe neonatal unconjugated hyperbilirubinemia in Chinese infants, but jaundice can completely resolve in a few months, contrary to what happens in Crigler-Najjar syndrome type II.

S1655 COVID-19-Induced Persistent Jaundice With Secondary Sclerosing Cholangitis

Introduction: The ongoing COVID-19 infection has demonstrated potential devastating organ damage including direct liver injury;however the long-term complications are limited. We demonstrate a case of post COVID-19 cholangiopathy with prolonged hyperbilirubinemia partially responsive to ursodiol. Case Description/Methods: Patient is a 59-year-old male presented with weakness and COVID-19 infection. His clinical course continued to deteriorate with multi-organ failure. After a prolonged ICU course, patient's respiratory failure improved, but had a persistent hyperbilirubinemia. Patient underwent ERCP showing a normal-appearing common bile duct with no evidence of any filling defects. He underwent autoimmune workup with positive ASMA with a titer 1:20, but negative ANA and AMA. HIDA scan showed poor clearance and no activity within the biliary tree, suggestive of underlying intrinsic hepatic abnormality. MRCP showed innumerable cystic dilation and areas of narrowing. Liver biopsy showed extensive cholestatic changes, perisinusoidal and bridging fibrosis, and iron deposition primarily within Kupffer cells. Repeat ERCP showed diffuse intrahepatic cholangiopathy in a pattern most consistent with PSC. Patient was started on ursodiol 250 mg three times a day with a mild improvement of bilirubin levels of about 25%. After a 6-month hospital course, patient was discharged to an acute care facility. Upon discharge, patient remained jaundice with persistent liver enzymes and a bilirubin of 21 mg/dL. Discussion: We described a case of an individual who recovered from severe sepsis secondary to COVID-19 developing significant post COVID-19 cholangiopathy. Despite recovery, patient continued to have chronic cholestasis and liver injury. Liver biopsy demonstrated predominant cholangiocyte injury with bridging fibrosis consistent with progression of secondary sclerosing cholangitis (SCC). Based on histopathological changes, it is postulated that damage occurs secondary to direct bile duct ischemia. While no standard therapies exist and only 1 case report showing post COVID-19 liver transplantion, many therapeutic options are limited. However, in our case, ursodiol demonstrated a significant improvement with a plateau of about 25% of the total bilirubin level. SCC carries a poor outcome in the general population without a liver transplantation. Early identification and treatment will be vital with the ongoing pandemic as SCC is associated with considerable morbidity and mortality left untreated.

Prolonged Hyperbilirubinemia after Contrast Use in a 16-Year-Old Boy with Gilbert's Syndrome: A Case Report and Literature Review

This paper reports a child with Gilbert's syndrome who underwent cholecystectomy and endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreaticography to removal of the gallstones, then experienced increase in bilirubin of unknown cause.

CLINICAL AND LABORATORY CHARACTERISTICS DEPENDING ON THE LEVEL OF BILIRUBIN IN THE OBSERVED NEWBORNS

Prolonged neonatal hyperbilirubinemia is commonin the neonatal period. Neonatal hyperbilirubinemia acquires its relevance because this condition, in parallel with its frequent manifestation, is of great interest in terms of the time of occurrence and its duration. According to numerous studies, the structure of prolonged neonatal hyperbilirubinemia is dominated by conjugational hyperbilirubinemia in newborns, where it is metabolically confirmed by metabolic changes such as hyperbilirubinemia in blood serum

The Thyroid Stimulating Hormone and Free Thyroxine Levels in Correlation with Serum Bilirubin in Neonatal Jaundice

Congenital hypothyroidism is known to cause prolonged hyperbilirubinemia in neonates. It also correlates with delayedmaturation of the activity of the uridine diphosphate glucoronosyltransferase (UDPG-T) enzyme. Thus, this study wasperformed to analyze the correlation of TSH and FT4 levels with serum bilirubin in neonatal jaundice. This observationalanalytical study with a cross-sectional approach was conducted on 64 neonatal patients with jaundice in Dr. MoewardiGeneral Hospital, Surakarta during September-November 2019. The data comparison and correlation were analyzed withMann-Whitney and the Spearman test. A p-value of &lt; 0.05 was considered significant with 95% Confidence Interval (CI). Thestudy variables comprised of total bilirubin of 12.7 (6.28-23.5) mg/dL, direct bilirubin of 0.8 (0.30-6.61) mg/dL, indirectbilirubin of 11.87 (3.16-22.94) mg/dL, TSH of 4.4 (0.40-23.06) uIU/L, and FT4 of 22.85±7.4 pmol/L. The TSH and FT4 weremoderately correlated with total bilirubin r=-0.444; p=0.001 and r= -0.467; p=0.001), with indirect bilirubin (r= -0.3362;p=0.03 and r=-0.411; p=0.001) and with direct bilirubin (r= -0.257; p=0.040 and r=0.232; p=0.065), respectively. A moderatecorrelation of TSH and FT4 with total and indirect bilirubin, as well as a weak correlation between TSH and direct bilirubinwere found, while no correlation was found between FT4 and with direct bilirubin. Thyroid function screening isrecommended in neonates with jaundice, due to the importance of thyroid hormones in the function and formation oforgans

Evaluating protocol of management of unconjugated hyperbilirubinemia in neonatal intensive care unit at Qena University Hospital

Background: Neonatal hyperbilirubinemia is a common problem in neonates with an incidence of about 60% in term babies and 80% in preterm babies. It is the commonest cause of admission to the hospitals in the newborn period. We should assess all babies for jaundice at every opportunity. Methods include visual assessment, transcutaneous bilirubinometer (TcB) or total serum bilirubin (TSB). Objective: This is a descriptive study aimed to evaluating the protocol of management of unconjugated hyperbilirubinemia in neonatal intensive care unit at Qena University Hospital. Patients and method(s): This descriptive study included neonates admitted to neonatology unit at Qena university hospital from (April to October 2019), Total number of admitted neonates in our NICU through this period were 1274, from which 517 neonates had jaundice as a primary cause of admission or developed during the course of NICU stay. Result(s): In this period the total number of NICU admission was 1274 cases, out of 517 jaundiced neonates, 100 (19.3%) were diagnosed to have unconjugated jaundice on admission without any associated other diseases and 417 (80.7%) of them were admitted due to other causes and developed jaundice during the course of the disease. The other 417 neonates were admitted to our NICU due to RD in 409 (79.1%) cases, 4 (0.8%) cases due to sepsis, two (0.4%) cases due to CHD and two (0.4%) cases due to surgical causes. The unconjugated neonatal jaundice represented (7.8%) (100 cases out of 1274 neonates admitted during the period of the study). Physiological jaundice represented 89.4% while pathological jaundice represented 10.6% of causes of neonatal jaundice. Regarding treatment of studied neonates 12% of cases need only follow up with no need for Phototherapy, 62.8% of cases needed single or double Phototherapy, 12.4% needed extensive Phototherapy (triple phototherapy), 12.8% of cases needed capsule Phototherapy and no cases needed neither exchange transfusion nor drug therapy. Only 0.4% of jaundiced neonates developed prolonged hyperbilirubinemia, while no complications were detected in 99.6% of cases. We started treatment based on measuring bilirubin by TSB in 62.3% of jaundiced neonates and 37.7% by TCB. The mean values of TSB in jaundiced neonates (11.46 ± 4.92) were significantly higher than the TCB (10.31 ± 4.61), P =0.0005. There was significant positive correlation between mean TSB and mean TCB (R= 0.946, P < 0.001). There was no significant difference regarding mean TSB between different gestational age groups p= 0.242). Conclusions: Hyperbilirubinemia is one of the most common causes of hospital admission in our nursery. Among the causes of hyperbilirubinemia, physiologic jaundice was the most common. Intensive phototherapy is effective in lowering TSB in unconjugated jaundice at / or near levels of exchange transfusion, and this may be helpful in decreasing needs for and risks of exchange transfusions. TcB measurements may underestimate the TSB values, so it should be considered only as a screen and samples should be sent to the laboratory for confirmation especially at high risk groups and high levels of TCB.

Planning principles for radical surgical intervention for liver alveococcosis based on computed and magnetic resonance imaging

Aim. To develop the planning principles for radical surgical intervention for liver alveococcosis based on the computed and magnetic resonance imaging data.Materials and methods. The data of computed tomography and magnetic resonance imaging, as well as the results of treatment of 189 patients with liver alveococcosis in 2011–2020 were analyzed.Results. A sequence of data analysis of CT-scan and magnetic resonance imaging, consisting of several stages, is proposed. CT-scan and magnetic resonance imaging data of all patients were analyzed according to the developed algorithm, which was adapted to the planning stages of surgical treatment. The accuracy of CT-scan and magnetic resonance imaging in determining the localization of the parasitic process by sections and predicting the need for a two-stage resection of the liver, the use of total vascular isolation technique was 100%. The accuracy of CT-scan in the defining of anatomical variants of extrahepatic arteries and the presence of a significant accessory right hepatic vein of the liver was 98.6%, type of division of the portal vein – 97.2%. Radiation semiotics of the relationship of parasitic masses with the main vessels of the liver and the inferior vena cava were determined. The accuracy of CT-scan in the diagnosis of involvement of the hepatic arteries, portal and hepatic veins was 96.9%, 91.2% and 91.4%, respectively. In predicting circular resection of the inferior vena cava we recommend to use the cut-off of contact of parasitic masses around it more than 180 ° (AUC = 0.950). With borderline volumes of liver remnant (30–35%), prolonged hyperbilirubinemia, suspected development of secondary biliary cirrhosis, magnetic resonance imaging with gadoxetic acid makes it possible to assess the functional state of the parenchyma. This may require additional preoperative therapy, planning a two-stage resection or the process may be considered unresectable in the diagnosis of severe fibrosis.Conclusion. The developed CT-scan/ magnetic resonance imaging data analysis algorithm allows to determine the clinical and surgical group of patients with liver alveococcosis and to plan the type of surgical intervention. Additional option of magnetic resonance imaging with gadoxetic acid in evaluating of functional state of liver remnant allows you to adjust surgical tactics in a number of clinical situations.

An insight into neonatal unconjugated hyperbilirubinaemia from the transfusion medicine perspective

Unconjugated hyperbilirubinaemia is a common cause of morbidity and mortality among neonates in Asian and African countries. The aetiology is multifactorial and has wide range of presentation ranging from simple physiological jaundice to severe HDN requiring prompt intervention to prevent long‐term neurological sequelae. Extensive detection of borderline raised bilirubin level in newborn is debatable as it may lead to inappropriately increased phototherapy and unnecessary increased hospital stay. However, those at risk like early presentation of hyperbilirubinaemia within 48 h, prolonged hyperbilirubinaemia, and family history in siblings or having history of HDN must be screened for immune as well as non‐immune causes to prevent the neonate from further severe form of complications. Along with direct antiglobulin test, elution, antibody screening/identification is performed to evaluate the immune causes. Improvement in the molecular technology leads to prompt diagnosis of non‐immune causes which were previously remained as idiopathic. This will aid in the early management like phototherapy or exchange transfusion as per the indication. This review will basically focus on the aetiopathogenesis of neonatal unconjugated hyperbilirubinaemia and approach to immune causes from transfusion medicine prospective.

Early hospital discharge and readmission jaundice in term babies

Background: Hyperbilirubinemia is a common and often benign disease in the neonatal period. It is the most common cause of readmission in early neonatal period. Prolonged hyperbilirubinemia can result in chronic bilirubin encephalopathy. Increasing the hospital stay of otherwise healthy neonates is not an acceptable solution for medical, social and economic constraints. So, identifying the risk factors for readmission assumes importance. Aim of our study is to identify the risk factors for readmission jaundice in our hospital.Methods: In this study, authors used a questionnaire to find out the risk factors for readmission in those babies who were readmitted with jaundice within 3 weeks of life to our hospital. During the study period, routine treatment practices were followed and there was no deviation from the standard of care for the purpose of research.Results: Of the 2297 deliveries during this study period, 93 babies (4%) were readmitted with jaundice.Among the 93 babies, prevalence of blood group incompatibility was one of the common causes of neonatal jaundice. 46.2% of the babies had an early discharge. Total Serum bilirubin levels were measured by a hospital-based bilirubin assay. Babies with serum bilirubin level above photozones as per American Academy of Pediatrics practice guidelines 2004 were identified and subjected to photo therapy. All the babies in this study responded to photo therapy. No other interventions were needed.Conclusions: Though an early discharge is the most cost-effective strategy in this era of high medical expenditure, we can identify certain high-risk babies, prone for readmission. Blood group incompatibility, infants of primiparous mothers and GDM mothers are more prone to readmission jaundice. Identifying these high-risk babies and educating the mothers is a more cost-effective strategy than prolonging the hospital stay for all babies.

Penggunaan Billy Blanket Pada Neonatus Dalam Menurunkan Kadar Bilirubin

Hiperbilirubinemia adalah peningkatan kadar bilirubin dalam darah, secara klinis di tandai dengan ikterus. Kondisi hiperbilirubinemia yang berkepanjangan dapat mengakibatkan kernikterus yaitu keadaan kerusakan pada otak akibat perlengketan kadar bilirubin pada otak. Penelitian ini bertujuan untuk mengetahui gambaran penurunan kadar bilirubin dengan penggunaan Billy Blanket pada neonates di RS X Jakarta. Metode penelitian ini adalah metode penelitian kuantitatif dengan desain deskriptif analitik. Populasi penelitian ini berjumlah 60 responden. Teknik pengambilan sampel yang digunakan adalah total sampling. Data yang dikumpulkan merupakan data sekunder yang berkaitan dengan karakteristik dan kadar bilirubin neonatus yang diperoleh melalui catatan rekam medik. Analisis data dengan menggunakan analisis univariat untuk mengetahui gambaran distribusi frekuensi dari karakteristik dan penurunan kadar bilirubin neonatus yang mengunakan Billy Blanket. Responden sebagian besar berjenis kelamin laki-laki (51,7%), responden dilahirkan pada usia kehamilan ≥ 37 minggu sebanyak 73,3%, responden berusia 2 hari sebanyak 40%, dan seluruh responden memiliki BBL≥2500 gram. Hasil penelitian menunjukkan bahwa kadar bilirubin setelah menggunakan Billy Blanket selama 24 jam dan 48 jam memiliki kadar bilirubin &gt; 10g/dl sedangkan penggunaan Billy Blanket selama 72 jam menunjukkan 51,7% memiliki kadar bilirubin 5-10 g/dl. Penggunaan Billy Blanket dapat dipertimbangkan menjadi salah satu intervensi keperawatan sehingga asuhan keperawatan lebih optimal.

Correlation between Prolonged Hyperbilirubinemia and Serum Zinc Level in Term Neonates

Background: Prolonged hyperbilirubinemia is defined as jaundice persisting more than two and three weeks of life in term and preterm neonates, respectively. In total, 15-40% of jaundiced neonates became prolonged. The most common causes of prolonged hyperbilirubinemia are breastfeeding, infection, hypothyroidism, and continued hemolysis. Given the fact that no study was conducted on the association between the serums zinc level and prolonged hyperbilirubinemia, this study aimed to compare the healthy neonates with newborns suffering from prolonged hyperbilirubinemia in terms of serum zinc level.Methods: This cross-sectional analytical descriptive study with a control group included all neonates who had a history of hospital admission and phototherapy due to hyperbilirubinemia at Amirkola Children’s Hospital, Babol, Iran. After discharge, on the 14th day of birth, all neonates followed up at the outpatient clinic. The serum bilirubin was checked and the neonates were assigned into the case (with prolonged hyperbilirubinemia) and control (without prolonged hyperbilirubinemia) groups. Both groups were matched regarding confounding factors. Serum zinc level was measured using the colorimetric method and the two groups were compared in this regard.Results: In total, 60 neonates in the case (n=30) and control (n=30) groups were investigated in this study. The serum zinc levels in the case and control groups were 83.7±35.35 and 92.73±38.13 μg/dl, respectively. There was no significant difference between the two groups in terms of the serum zinc level (P=0.34).Conclusion: There is no statistically significant correlation between the serum zinc level and prolonged hyperbilirubinemia in term neonates who had been treated with phototherapy.

TO STUDY THE INCIDENCE OF CONGENITAL HYPOTHYROIDISM IN BABIES WITH EXAGGERATED PHYSIOLOGICAL JAUNDICE

Background: Congenital hypothyroidism is well known cause of prolonged unconjugated hyperbilirubinemia and appears to be associated with the delayed maturation of hepatic uridine diphosphate glucoronyl transferase enzyme activity.&#x0D; Methods: This is a prospective, longitudinal and randomized study 100 babies are taken consisting of all newborn, age less than 28 days, admitted to hospital with exaggerated physiological jaundice.&#x0D; Results: One case of congenital hypothyroidism in exaggerated jaundice based on raised TSH levels. Rest of the cases (99%) having normal TSH levels. One case (1%) having TSH level of 48µu/ml on D7 of life indicating congenital hypothyroidism. TSB of this baby is 21.3 mg%. One baby is having TSH level of 30.4µu/ml on D3 of life which subsequently decreased to normal physiological limits on D7 of life.&#x0D; Conclusion: Though the present study is unable to make significant correlation between cause and effect relationship of neonatal exaggerated jaundice and congenital hypothyroidism, but as one case has diagnosed to be suffering from congenital hypothyroidism, TSH should be considered as a screening test for all babies suffering from exaggerated physiological jaundice besides the other predisposing factors responsible for causation of hypothyroidism.&#x0D; Keywords: Neonatal hyperbilirubinemia, Preterm, Congenital hypothyroidism

Selected Risk Factors of Developmental Delay in Polish Infants: A Case-Control Study

Despite a number of studies on the risk factors of developmental delay (DD) in children conducted in developed countries, Polish data are scarce, which hinder an early diagnosis and initiation of prevention/control measures. Objective: To assess selected risk factors of DD in infants. A case-control survey was conducted in 2017–2018 on 50 infants (≤1 year old) with DD and 104 healthy controls from three outpatient clinics in Szczecin, Poland. Data were collected using an anonymous questionnaire distributed among mothers. The most common risk factors in infants with DD were: Caesarian section (68%), infections (46%), and chronic diseases during pregnancy (48%). DD was significantly correlated with maternal infections and chronic diseases during pregnancy (both: p < 0.001), caesarian section (p < 0.001), preterm birth (p = 0.004), birth weight <2500 g (p = 0.03), Apgar score ≤7 (p < 0.01), prolonged hyperbilirubinemia (p < 0.001), and no breast-feeding (p = 0.04). This study reinforces multiple etiologies of DD. Preventive strategies regarding DD in Polish infants should focus on the pre/peri/postnatal risk factors identified in this study. Strategies that prevent and control such risk factors and those on early detection and intervention in high-risk infants are highly recommended.

Cholestasis as a Diagnostic Challenge

Cholestasis results from an impairment in the excretion of bile acids and is caused by numerous disorders. Most of the time, the etiology can be predicted with a good history, physical examination and rational diagnostic testing. The most common causes of cholestasis include biliary obstruction, acute hepatitis, advanced cirrhosis, drug-induced liver injury (DILI), sepsis and malignancy. Even when the cause of cholestasis is apparent, additional mechanisms can contribute to or aggravate underlying liver pathology that manifests with prolonged hyperbilirubinemia. Here we report a patient with severe cholestasis who underwent extensive evaluation for unresolved jaundice. A 75-year-old lady presented to the hospital with worsening jaundice, diffuse pruritus, dark urine, pale colored stools, weight loss, palpitations and thinning of hair. Ultrasound revealed common bile duct stones and an Endoscopic retrograde cholangiopancreatography (ERCP) was done to remove the stones. As her elevated bilirubin levels did not improve after ERCP, liver biopsy was performed which showed stage 3 fibrosis and marked cholestasis consistent with congestion and outflow obstruction leading to congestive hepatopathy.Thyroid function tests were done to evaluate as part of the evaluation for abnormal liver function tests and were consistent with hyperthyroidism. An ultrasound of the neck revealed two nodules without calcification and irregular margins. A thyroid uptake scan revealed a pattern of Graves' disease. Echocardiogram showed severe tricuspid regurgitation. Her bilirubin dropped to 24 mg/dl and she was discharged with metoprolol, methimazole and ursodiol. The patient returned to the hospital after 15 days with worsening jaundice and labs showed bilirubin of 26.7 mg/dl (table 1). Ultrasound imaging showed no evidence of biliary obstruction. During her second hospitalization, her bilirubin started trending down to 13 mg/dl with subsequent improvement of symptoms. In this case, we postulate that hyperthyroidism might have worsened her heart failure, which contributed to the severity of congestive hepatopathy. Patient's condition improved despite the use of methimazole, which rules out DILI. Hence, prolonged cholestasis after ERCP can be a diagnostic dilemma. One should consider other etiologies, especially intrahepatic causes of cholestasis such as congestive hepatopathy,hyperthyroidism,DILI and sepsis when cholestasis fails to improve after biliary decompression.2264 Figure 1. Laboratory trends in bilirubin during hospital course

Secondary Sclerosing Cholangitis in the Setting of Elective Bariatric Surgery

Secondary sclerosing cholangitis (SSC) is a rare, chronic, progressive condition of biliary tree fibrosis after an insult. It is a rare cause of preventable liver cirrhosis. Of 31 reported cases in the past decades most presented after surgical trauma, other causes include chronic cholestatis, cholangitis or ischemia.1 A 45-year-old female with a history of idiopathic pulmonary fibrosis presented with prolonged hyperbilirubinemia after gastric sleeve bypass, cholecystectomy, and hiatal hernia repair three months prior to admission. She presented with jaundice and elevated total bilirubin, direct bilirubin and alkaline phosphatase at 3.6 mg/dL, 3.0 mg/dL, and 217 U/L, respectively. MRCP revealed a stricture near the level of the cystic duct. ERCP showed a focal stricture at the distal common hepatic duct (CHD) requiring stent (Image 1). Due to worsened hyperbilirubinemia, a repeat ERCP was completed which revealed a highgrade stricture at the CHD that required dilation and another stent. Liver biopsy was also performed and showed canalicular cholestatis without intra-hepatic granulomas or ductal lesions, suggesting extrahepatic ductal obstruction (Image 2). She then underwent hepaticojejunostomy with surgical pathology of the common bile duct revealing a post-cholecystectomy traumatic neuroma. She was discharged after HIDA scan revealed no evidence of biliary leak, but returned to clinic 14 days later with progressive jaundice, new ascites, bilateral lower extremity edema, and acute kidney injury (AKI) with elevated creatinine of 1.76 mg/dL (baseline 0.4 mg/dL). A third liver biopsy was performed which showed findings consistent with portal edema, mixed inflammation, cholestasis and fibrosis (Image 3). Her bilirubin slowly improved without further intervention, but remained elevated at 14.2 mg/dL and she ultimately required dialysis. This patient was diagnosed with SSC in the setting of biliary tract fibrosis subsequent to traumatic injury of the biliary tract after cholecystectomy. Our presentation is unique as SSC was complicated by hemodialysis dependent renal dysfunction with microscopic evidence of acute tubular necrosis. This case is consistent with the common cause, histological characteristics and chronic nature of SSC. Future research is required to elucidate other organ complications that management of this disease may be optimized. 1- Ruemmele et. al. Secondary sclerosing cholangitis. Nat. Rev. Gastroenterol. Hepatol. 6, 287-295 (2009).Figure: ERCP showing common hepatic duct stricture.Figure: Cholestasis and edema.Figure: Portal tract with edema and fibrosis.

Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants

To determine whether a variant of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1*6) is a risk factor for prolonged hyperbilirubinemia in preterm infants. UGT1A1 genotypes in 46 Japanese preterm infants (<37 weeks of gestation) were compared with UGT1A1 genotypes in 38 control infants, using polymerase chain reaction-direct sequencing. Prolonged unconjugated hyperbilirubinemia was defined as serum total bilirubin concentration of >150 µmol/L (8.77 mg/dL) beyond 14 days of life. In the case group, 41 of 46 infants (89.1%) had a polymorphic variant, c.211G>A, p.G71R (UGT1A1*6). In the control group, 7 of 38 (18.4%) had UGT1A1*6. The allele frequency of UGT1A1*6 was 0.641 in the prolonged hyperbilirubinemia group, which was significantly higher than in the control group (0.092; P < .001). In total, 39 of 46 infants in the case group were breast fed, and only 10 infants in the control group were breast fed. These data suggest that UGT1A1*6 is a risk factor for prolonged unconjugated hyperbilirubinemia in preterm infants in Japan. Given the different rate of breast feeding in this study, additional data are necessary for drawing a definitive conclusion.