A New Hour-Specific Serum Bilirubin Nomogram for Neonates ≥35 Weeks of Gestation.

OBJECTIVE: To develop a statistically rigorous, hour-specific bilirubin nomogram for newborns based on a very large data set; and use it prospectively as a replacement for the 1999 Bhutani nomogram. STUDY DESIGN: This was a retrospective analysis of first total serum bilirubin (TSB) measurements from 15 years of universal bilirubin screening during birth hospitalizations at 20 Intermountain Healthcare hospitals. Hour-specific TSB values were assembled into a nomogram by percentile, and subgroups were compared. RESULTS: The information obtained included robust data in the first 12 hours after birth (which was not included in the 1999 nomogram), general agreement with the 1999 nomogram for values in the first 60 hours, but higher 75th and 95th percentile TSB values thereafter in the new version, no difference in TSB between male and female infants, higher TSB values among earlier gestation neonates (350/7-366/7 weeks vs ≥37 weeks, P < .0001), and lower TSB values in neonates of Black race (P < .0001) and higher values in neonates of Asian race (P < .001). CONCLUSIONS: An updated and more informative Bhutani neonatal bilirubin nomogram, based on 140 times the number of subjects included the 1999 version, is now in place in our health care system.

Association between Hyperbilirubinemia and Hearing Screen Failure in the Neonatal Intensive Care Unit in Infants Born Preterm.

OBJECTIVE: To characterize the association between hyperbilirubinemia and a failed newborn hearing screen in infants born at 22-32 weeks of gestation. STUDY DESIGN: We included infants with gestational ages of 22-32 weeks who were discharged from neonatal intensive care units in the US from 2002 to 2017 with available newborn hearing screen results obtained after 34 weeks postmenstrual age. We excluded infants with severe birth asphyxia or craniofacial abnormalities. We identified 95 672 infants from 313 neonatal intensive care units. We used multivariable logistic regression to examine the association between maximum total bilirubin at <21 days postnatal age with failed hearing screen, adjusting for important demographic and clinical risk factors. RESULTS: The median gestational age and birth weight were 30 weeks (IQR, 28-32 weeks) and 1330 g (IQR, 1010-1630 g), respectively. The median maximum total bilirubin was 8.3 mg/dL (IQR, 6.7-10.0 mg/dL), and 5275 infants (6%) failed their newborn hearing screen. On adjusted analysis, each 1 mg/dL increase in maximum total bilirubin was associated with a small, but significant, increase in odds of a failed hearing screen (OR, 1.03; 95% CI, 1.02-1.04). CONCLUSIONS: An increased maximum total bilirubin level was independently associated with hearing screen failure. Further prospective studies are needed to understand whether this increased risk of hearing screen failure translates to increased risk of hearing loss.

[Hyperbilirrubinemia as a predictive factor of perforated appendicitis]. / Hiperbilirrubinemia como factor predictivo de apendicitis perforada.

BACKGROUND: Recent studies considered hyperbilirubinemia as a marker to identify the presence of perforated appendix. The aim of the study is to verify that the presence of hyperbilirubinemia is a useful marker to identify the presence of perforated appendix before surgery, and thereby, provide early treatment to avoid progression of the disease and its complications. METHODS: This is a retrospective study, which identified 225 patients, who met the inclusion and exclusion criteria, from January 2012 to October 2014 at the IMSS General Hospital 29, taking into account laboratory results and postoperative, performing a univariate, bivariate and multivariate analysis. RESULTS: 56.9% showed bilirubin < 1, from which 16.4% presented perforation, while 43.1% showed bilirubin > 1, 62.88% presented perforated appendicitis. Hyperbilirubinemia increases 17 times the risk of perforated appendix (RMP: 17.63; IC 95%: 6.882-45.207; p < 0.001) which is statistically significant. CONCLUSIONS: Considering the limitations of this study, it can be inferred that hyperbilirubinemia is present in a great number of patients with perforated appendicitis, so it could be considered a relevant laboratory test to include within the protocol of appendicitis, which in turn, may determine a better planning for the surgical approach.

Introducción: en estudios recientes se considera la hiperbilirrubinemia como un marcador para identificar la presencia de apendicitis perforada. El objetivo del estudio es comprobar que la presencia de hiperbilirrubinemia es un marcador útil para identificar preoperatoriamente a los pacientes con presencia de perforación apendicular, y de esta manera proporcionar un tratamiento oportuno evitando la progresión de la patología y sus complicaciones. Métodos: estudio retrospectivo, con 225 pacientes, los cuales contaban con los criterios de inclusión y exclusión, del periodo de enero de 2012 a octubre del 2014 en el HGZ 29 del IMSS, tomando en cuenta resultados de laboratorio y posquirúrgico, realizando análisis univariado, bivariado y multivariado. Resultados: el 56.9% presentó bilirrubina < 1, de los cuales el 16.4% presentó perforación, mientras que el de 43.1% con bilirrubina > 1, el 62.88% presentó apendicitis perforada. La hiperbilirrubinemia incrementa 17 veces más el riesgo de presentar apendicitis perforada (RMP: 17.63; IC 95%: 6.882-45.207; p < 0.001), lo que resulta estadísticamente significativo. Conclusiones: considerando las limitaciones de este estudio, se puede inferir que la hiperbilirrubinemia está presente en un mayor número de pacientes con apendicitis perforada, por lo cual podría ser considerado como un estudio de laboratorio relevante para incluir dentro del protocolo de apendicitis, lo cual, a su vez, puede determinar una mejor planeación para el abordaje quirúrgico.

Hyperbilirubinaemia alone cannot distinguish a perforation in acute appendicitis.

BACKGROUND: The objective of the study was to verify the accuracy of hyperbilirubinaemia as a marker for acute perforated appendicitis. METHODS: A comprehensive search of the MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, Congress Abstracts and Grey literature from January 1969 to July 2014. We included cross-sectional and cohort studies, prospective and retrospective, which evaluated hyperbilirubinaemia level in perforated appendicitis and compared them with histological analysis of all appendectomy specimens. RESULTS: Eleven studies were analysed, which included 5395 patients. Pooled sensitivity was 54.6% (95% confidence interval (CI), 42.8-65.8) and specificity was 70.0% (95% CI, 54.7-81.9%) using STATA. The diagnostic odds ratio was 2.82 (95% CI, 1.38-5.72%). Summary receiver operating characteristic curves were constructed. The area under the curve was 0.65. CONCLUSION: This meta-analysis showed that the value of hyperbilirubinaemia alone cannot predict acute perforated appendicitis.

Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases.

Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.

Síndrome de Courvoisier - Terrier: presentación de un caso / Courvoisier terrier Syndrome: a case report

Se realiza un estudio sobre una paciente de sexo femenino del área Este del municipio de Guantánamo en el pasado año, 2013, con el objetivo de mostrar los hallazgos radiológicos que nos hacen pensar en una enfermedad poco conocida como esta. Esta afección es poco diagnosticada por no tenerse mucho conocimiento sobre la misma Se descubren signos radiológicos como estos en la Atención Primaria de Salud. Se recogieron datos generales de la historia clínica individual y familiar así como los resultados de exámenes realizados. Luego de culminado el estudio se llegó a la conclusión de que la paciente presentaba un Síndrome de Courvoisier–Terrier (AU)

A study of a female patient, East part of Guantánamo is done in the last year, 2013, with the aim of showing the radiological findings that make us think of a little known disease like this. This condition is under diagnosed due to the ignorance about this illness, on same radiological signs are discovered as these in Primary Health Care. General data were collected from individual and family medical records and the results of investigations. As a conclusion of the study, the patient had Courvoisiers-Terrier Syndrome

UGT1A1 genetic analysis as a diagnostic aid for individuals with unconjugated hyperbilirubinemia.

OBJECTIVE: To assess the clinical utility of UGT1A1 genetic testing and describe the spectrum and prevalence of UGT1A1 variations identified in pediatric unconjugated hyperbilirubinemia (UCH), and to characterize specific genotype-phenotype relationships in suspected Gilbert and Crigler-Najjar syndromes. STUDY DESIGN: A retrospective study was conducted to review clinical information and UGT1A1 genotyping data from 181 pediatric patients referred for UCH. In silico analyses were performed to aid in the assessment of novel UGT1A1 variants. RESULTS: Overall, 146/181 pediatric patients had at least one heterozygous UGT1A1 functional variant. Identified UGT1A1 variants included 17 novel variants, 7 rare star alleles, and 1 rare variant. There were 129 individuals who possessed the TA7 (*28) promoter repeat and 15 individuals who possessed the *6 (c.211G > A) variation. Out of the 104 individuals with accompanying bilirubin levels, 41 individuals did not have identifiable UGT1A1 variants that explained their UCH, although glucose-6-phosphate dehydrogenase deficiency and other causes of UCH could not be ruled out. CONCLUSION: Much of the observed UCH could be attributed to variation at the UGT1A1 locus, and UGT1A1 testing helped to substantiate a genetic diagnosis, thereby aiding in individual and family disease management. Although UGT1A1 variation plays a large role in UCH, genetic assessment of UGT1A1 alone may not be comprehensive. Assessment of additional genes may also be useful to evaluate genetic causes for UCH.

Short communication: fasting increases serum concentrations of bilirubin in patients receiving atazanavir: results from a pilot study.

Unconjugated hyperbilirubinemia resulting from therapy with atazanavir is physiologically related to hyperbilirubinemia in Gilbert's syndrome (GS). In patients with GS, changes in diet have a significant impact on bilirubinemia. Our aim was to investigate whether changes in diet affect the level of serum bilirubin in patients receiving atazanavir. Thirty patients on stable therapy with ritonavir-boosted atazanavir without evidence of GS were enrolled. Hemolysis and chronic hepatitis were excluded. After a baseline period of normal intake of calories, the patients were randomized to follow a 24-h 400-calorie diet (fasting), then a 48-h period of normal calorie intake and, afterward, a 24-h period of a high-calorie diet, or the same interventions in inverse order. Serum bilirubin concentrations were measured before and after each intervention. A high adherence to the recommended diet was observed. The mean unconjugated bilirubin concentration before the high-calorie diet was 2.79±1.53 mg/dl and after such intervention it was 2.70±1.40 mg/dl. The mean difference between preintervention and postintervention was -0.08±0.69 mg/dl (p=NS). The mean unconjugated bilirubin concentration before the fasting diet was 2.31±1.23 mg/dl and it was 3.84±1.90 mg/dl after. The mean difference between prefasting and postfasting was 1.53±1.17 mg/dl (p=0.001). According to these results, short periods of fasting seem to increase the unconjugated bilirubin concentration in patients on atazanavir. A high-calorie diet did not have any impact in bilirubin probably because most patients follow similar diets in their everyday life.

[Usefullness of the Kramer's index in the diagnosis of hyperbilirubinemia of the newborn]. / Utilidad diagnóstica del método de Kramer para la detección clínica de la hiperbilirrubinemia neonatal.

The objective of the present study was to correlate seric values of bilirubin with the Kramer's index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer's dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 +/- 3.41 mg/dL, and 62.8% of neonates were at Kramer's level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer's index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer's indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer's method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Utilidad diagnóstica del método de Kramer para la detección clínica de la hiperbilirrubinemia neonatal / Usefullness of the Kramer’s index in the diagnosis of hyperbilirubinemia of the newborn

El objetivo de la presente investigación fue correlacionar los valores séricos de bilirrubina con el índice de Kramer en un grupo de pacientes con ictericia neonatal de tres diferentes etnias. Representa un estudio prospectivo, aleatorio, observacional descriptivo-analìtico, longitudinal, comparativo y controlado en 50 recién nacidos con ictericia neonatal sin complicaciones. Se dividieron en 3 grupos: A (Control), n = 25 de origen caucásico; B, n = 15 de origen indígena local Wayúu y C, n = 10 de origen Afro americano. Al ingreso, a cada neonato se le determinaron las zonas dérmicas de Kramer y se le tomó una muestra de sangre venosa braquial para medir la bilirrubina de ingreso. Los valores al ingreso fueron: bilirrubina sérica 12,02 ± 3,41 mg/dL y el 62,8% estaban en nivel 3 de Kramer. No hubo diferencias entre los grupos étnicos estudiados y la correlación bilirrubina sérica-índice de Kramer fue de r= 0,93 (p < 0,005). Al 3er día se empezó a notar el descenso de la bilirrubina y de los índices de Kramer. El método de Kramer ofrece múltiples ventajas en la evolución del RN ictérico. No se encontraron diferencias raciales. Se recomienda implementar la aplicación de este método de Kramer en todas las unidades de neonatos en los hospitales, preferentemente en aquellas que carezcan de bilirrubinómetros transcutáneos.

The objective of the present study was to correlate seric values of bilirubin with the Kramer’s index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer’s dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 ± 3.41 mg/dL, and 62.8% of neonates were at Kramer’s level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer’s index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer’s indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer’s method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Gilbert's syndrome and antiviral therapy of hepatitis C.

Treatment of chronic hepatitis C with type I interferons and ribavirin can be associated with exacerbation of hepatitis and sometimes liver decompensation. We report two patients with chronic hepatitis C virus infection who experienced a severe increase of bilirubin levels of up to 17 times upper the limit of normal value in the absence of deterioration of hepatic function during therapy with pegylated-interferon and ribavirin. A genetic disposition for Gilbert's syndrome explained the adverse events and permitted a continuation of therapy leading to a sustained clearance of chronic hepatitis C infection. Since one patient jaundiced already during a lead-in treatment period with ribavirin monotherapy we suggest that hyperbilirubinaemia during combination therapy is primarily caused by ribavirin rather than by effects of interferon alpha on UDP-glucuronosyltransferase activities. Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely.

Gilbert's syndrome disclosed during the treatment of hematological malignancies.

Gilbert's syndrome (GS) is a benign, familial condition characterized by recurrent asymptomatic non-hemolytic low-grade indirect hyper-bilirubinemia. Conditions related to fasting, stress or co-morbidity might reveal the disease in asymptomatic individuals. Seven patients who were treated for a hematological malignancy were identified with reversible indirect hyper-bilirubinemia. Liver function tests in all of them, including bilirubin levels were normal before the therapeutic maneuver, which was the delivery of combined chemotherapy in three cases and a bone marrow transplantation in four (three allografts and one autograft). Bilirubin levels returned to normal in all five patients following treatment. GS should not be overlooked in individuals exposed to these treatments who develop hyperbilirubinemia and jaundice.

Síndrome de Dubin-Johnson y embarazo: primer caso clínico en Venezuela / Dubin-Johnson syndrome: first Venezuela case clinic

Se describe el primer caso nacional de una embarazada con síndrome de Dubin-Johnson. El síndrome se caracteriza por una hiperbilirrubinemia crónica a predominio de la directa de origen familiar, no hemolítica, debido a un trastorno del transporte de la bilirrubina del hepatocito hasta el canalículo biliar y depósito en el hepatocito de un pigmento oscuro, similar a la melamina. La ictericia, usualmente ausente en el primer trimestre, aumenta en el segundo y sobre todo en el tercer trimestre del embarazo. En nuestro caso, la paciente es II gesta, II para, en ambos embarazos se observó el patrón clínico y bioquímico, con exacerbación durante el tercer trimestre y valores más acentuados en el segundo embarazo. Las dos gestaciones cursaron normalmente y en ambos se obtuvieron recién nacidos normales sin posteriores complicaciones

Hepatitis crónica activa asociada con enfermedades reumáticas / Active chronic hepatitis associated with rheumatic diseases

Diversas alteraciones hepáticas se han encontrado en las enfermedades reumáticas. La hepatitis crónica activa (HCA) es una de ellas, aunque sus reportes según la revisión de la literatura que hemos efectuado, son escasos. El objetivo de este trabajo es presentar 7 casos de HCA asociados a enfermedades reumáticas autoinmunes, manejados en nuestro servicio. Todos los pacientes son del sexo femenino, con edad entre la cuarta y sexta décadas de la vida. Bioquímicamente muestran elevación de enzimas hepáticas, ligeramente de la bilirrubinas, y positividad para antígenos de VHC y VHB. No existe patrón obstructivo de conductos biliares por ultrasonido o gamagrafía. De las 7, tres cumplen criterios para AR y 4 para LEG. La supervivencia y clase funcional son satisfactorias. Consideramos que un fondo común de predisposición a la autoinmunidad puede intervenir en el desarrollo de ambas entidades