Expedited Laparoscopic Cholangiogram and Liver Biopsy in the Workup of Biliary Atresia.

PURPOSE: Recent studies demonstrate the success of Kasai portoenterostomy for biliary atresia (BA) is linearly related to infant age at time of Kasai. We sought to review the feasibility and safety of laparoscopic needle micropuncture cholangiogram with concurrent core liver biopsy (if needed) for expedited exclusion of BA in patients with direct conjugated hyperbilirubinemia. METHODS: Expedited laparoscopic cholangiogram and liver biopsy were instituted at our facility for infants with direct hyperbilirubinemia for whom clinical exam and laboratory workup failed to diagnose. A retrospective chart review was performed in infants <1 year with hyperbilirubinemia from 2016 to 2021. Demographics, preoperative evaluation, procedure details, and complications were reviewed. RESULTS: Two hundred ninety-seven infants with unspecified jaundice were identified, of which, 86 (29%) required liver biopsy. Forty-seven percutaneous liver biopsies were obtained including 8 (17%) in whom BA could not be excluded. Laparoscopic cholangiogram was attempted in 47 infants following basic workup; BA was diagnosed in 22 infants (47%) of which 3 were <18 days old. Biliary patency was demonstrated laparoscopically in 22 of 25 (88%); 3 (12%) required conversion to open cholangiogram. Infants with percutaneous liver biopsy had an average delay of 3 days (range: 2-36) to cholangiogram. Preoperative studies and liver biopsy alone did not reliably exclude the diagnosis of BA. CONCLUSION: Laparoscopic cholangiogram with liver biopsy is a safe procedure resulting in the confirmation or exclusion of BA in infants. Forty-seven percent of infants who underwent laparoscopic cholangiogram were found to have BA; those who were surgical candidates underwent Kasai during the same operation.

Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns.

BACKGROUND: Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels. OBJECTIVES: To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies. SELECTION CRITERIA: We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis. MAIN RESULTS: We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%. AUTHORS' CONCLUSIONS: The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.

Rolling stones: an instructive case of neonatal cholestasis.

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin. CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this is one of the more time-sensitive diagnoses that must be made in neonates with conjugated hyperbilirubinemia. He was ultimately found to have choledocholithiasis on magnetic resonance cholangiopancreatography. He was managed conservatively with optimizing nutrition and ursodeoxycholic acid therapy. CONCLUSIONS: We found that conservative management, specifically optimizing nutrition and treating with ursodeoxycholic acid, can be a sufficient approach to facilitating resolution of the choledocholithiasis and conjugated hyperbilirubinemia.

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.

Survey of newborn direct antiglobulin testing practice in United States and Canadian transfusion services.

BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.

Evaluation of role of hyperbilirubinemia as a new diagnostic marker of complicated appendicitis.

BACKGROUND: In appendicitis, elevated intra-luminal pressure and ischemic necrosis of mucosa causes tissue gangrene or perforation. This leads to cytotoxin facilitated progressive bacterial invasion or translocation into the hepatic parenchyma through portal system. This phenomenon interferes with the bilirubin excretion into the bile canaliculi. In the present study, establishment of a possible role of hyperbilirubinemia as a marker of gangrenous/perforated appendicitis has been studied. METHODS: After matching the inclusion and exclusion criteria, all cases of clinically diagnosed acute appendicitis were taken for this prospective, single center, observational study. Per-operative diagnosis was confirmed by histopathological examination. RESULTS: Out of 110 subjects of acute appendicitis 41 subjects (37.27%) had hyperbilirubinemia. Out of 35 subjects diagnosed as complicated appendicitis 32 subjects (91.42%) had raised total bilirubin levels, while the remaining 03 (8.58%) had normal levels. Among 75 subjects diagnosed as acute simple appendicitis 09 subjects (12%) had raised total bilirubin level, while the remaining 66 subjects (88%) had normal levels. It was Mixed Type of Hyperbilirubinemia in gangrenous/perforated appendicitis. The sensitivity of Total serum bilirubin in predicting complicated appendicitis was found 91.43% (76.942% to 98.196%), where as the specificity of this test was 88.00% (78.439% to 94.363%). positive predictive value and negative predictive value were 78.03% and 95.65% respectively. Positive likelihood ratio and negative likelihood ratio were found to be 7.619 and 0.097 respectively taking prevalence of complicated appendicitis be 31.80%. Receiver Operating Characteristic curve was obtained which shows optimal criterion at Total Bilirubin Level 1.06 mg/dl where sensitivity was 91.43% and specificity was 97.33% at 95% confidence interval with 31.8% disease prevalence. CONCLUSIONS: This is to conclude that Serum bilirubin level estimation, which is a simple, cheap and easily available laboratory test, can be added to the routine investigations in clinically suspected cases of acute appendicitis for early diagnosis of complications. Trial registration Registered with Clinical Trials Registry-India (ICMR-NIMS) with Registration number CTRI/2019/05/018879 Dated 01/05/2019. This was a prospective trial. Trial URL: http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=33113&EncHid=99780.32960&modid=1&compid=19%27,%2733113det%27 .

Time to peak bilirubin concentration and advanced AKI were associated with increased mortality in rheumatic heart valve replacement surgery patients with severe postoperative hyperbilirubinemia: a retrospective cohort study.

BACKGROUND: Hyperbilirubinemia after heart valve surgery (HVS) with cardiopulmonary bypass is frequently observed and associated with worse outcomes. We investigated the characteristics and prognosis of patients with severe hyperbilirubinemia after HVS for rheumatic heart disease (RHD) to identify the clinical outcomes and potential risk factors. METHODS: Between 2015 and 2018, patients who underwent HVS in the cardiac surgery intensive care unit of our hospital were retrospectively screened. Risk factors for acute kidney injury (AKI), the requirement for continuous renal replacement therapy (CRRT), and in-hospital and long-term mortality were identified by univariate and multivariate analyses. The patient survival proportion was graphically presented with the Kaplan-Meier method. RESULTS: A total of 149 patients who underwent HVS for RHD and had severe postoperative hyperbilirubinemia were included. Of the included patients, 80.5% developed postoperative AKI, and 18.1% required CRRT. The in-hospital mortality was 30.2%. Backward logistic regression analysis showed that the time to peak TB concentration (odds ratio [OR] 1.557, 95% confidence interval [CI] 1.259-1.926; P < 0.001) and advanced AKI (stage 2 and 3 AKI) (OR 19.408, 95% CI 6.553-57.482; P < 0.001) were independent predictors for in-hospital mortality. The cutoff value of the time to peak TB levels for predicting in-hospital mortality was 5 postoperative days. CONCLUSIONS: Severe postoperative hyperbilirubinemia is a life-threatening complication in patients who undergo HVS for RHD. Patients whose bilirubin levels continued to increase past the 5th postoperative day and who had advanced AKI (stages 2 and 3) were associated with a higher risk of mortality.

The prevalence and prognostic implications of pre-procedural hyperbilirubinemia in patients undergoing transcatheter aortic valve replacement.

Preoperative hyperbilirubinemia is associated with increased mortality and morbidity after cardiac surgery. However, this clinical significance is unclear with transcatheter aortic valve replacement (TAVR) procedures. The aims of this study were to determine the prevalence and prognostic implications of preoperative elevations of serum total bilirubin on TAVR outcomes. In 611 consecutive patients who underwent an elective TAVR procedure, 576 patients had recorded serum total bilirubin levels. Hyperbilirubinemia was defined as any value of serum total bilirubin ≥ 1.2 mg/dL obtained within 30-days prior to the TAVR procedure. The primary composite endpoint was post-TAVR all-cause in-hospital mortality or stroke. The overall prevalence of hyperbilirubinemia was 10% (n = 58). There were no patients with a prespecified diagnosis of liver cirrhosis. Pre-TAVR hyperbilirubinemia compared to normal bilirubin level was more common in younger (78 ± 10 vs. 82 ± 8 years old, p < 0.001) males (15 vs. 6%, p < 0.001), with history of pacemaker or ICD (33 vs. 18%, p = 0.005), congestive heart failure New York Heart Association class IV within 2 weeks from TAVR (35 vs. 14%, p < 0.001), severe tricuspid regurgitation (14 vs. 4%, p < 0.001), and atrial fibrillation or flutter (60 vs. 40%, p = 0.004, respectively). Pre-TAVR hyperbilirubinemia was independently associated with an increased post-TAVR in-hospital mortality (7 vs. 2% in normal bilirubin, p = 0.03), stroke (5 vs. 1%, p = 0.019, respectively), and a composite endpoint of death or stroke (12 vs. 3%, p < 0.001). Preoperative hyperbilirubinemia in patients undergoing TAVR is more prevalent than previously considered with multifactorial causes. Hyperbilirubinemia is independently associated with an increased post-TAVR in-hospital mortality and stroke.

A Neglected and Promising Predictor of Severe Hyperbilirubinemia Due to Hemolysis: Carboxyhemoglobin.

Aims: We investigated the relationship between total serum bilirubin (TSB) and carboxyhemoglobin (COHb) in term neonates with detected and treated hemolysis within a particular time frame with the aim of augmenting the case for early diagnosis and prevention of morbidity in hemolysis. Materials and Methods: The study group comprised term newborns who were above the 95th percentile for TSB, underwent intravenous immunoglobulin (IVIG) or applied total exchange transfusion due to hemolysis. Newborns without hemolysis who were above the 95th TSB percentile and required phototherapy comprised the control group. Results: At a cutoff COHb value of 2.2%, 80.8% sensitivity, 95.5% specificity, 18.1 likelihood ratio, positive predictive value of 94.7%, and negative predictive value of 83.2% were identified. Conclusion: We found that COHb is a sensitive and specific method for detecting hemolysis, and it can be used in the early diagnosis of hemolytic diseases causing early and severe hyperbilirubinemia.

Effect of Hyperbilirubinemia on Hepatic Hypertrophy after Portal Vein Embolization and Liver Failure after Hepatectomy in Primary Biliary Malignancy.

PURPOSE: To retrospectively investigate the impact of hyperbilirubinemia on future liver remnant (FLR) volume after percutaneous transhepatic portal vein embolization (PVE) and incidence of post-hepatectomy liver failure in primary biliary malignancy. MATERIALS AND METHODS: Eighty-seven patients (62 men, overall mean age 66.9 y) who underwent PVE, using Gelfoam and coils before major hepatectomy between January 2004 and June 2016, were included in this study and divided into a hyperbilirubinemia (serum total bilirubin level at PVE 5.80 ± 2.44 mg/dL; n = 41) group and a control group (1.09 ± 0.73 mg/dL; n = 46). Liver volume was measured from computerized tomographic data before and 18.5 days, on average, after PVE. Correlation between FLR hypertrophy (degree of hypertrophy and percentage increase in future liver remnant [%FLR]) and total bilirubin were analyzed. FLR hypertrophy and incidence of post-hepatectomy liver failure were compared. Simple and multiple regressions were used for univariable and multivariable analyses, respectively. RESULTS: Mean FLR volumes before and after PVE were 529.1 cm3 and 640.5 cm3, respectively. Degree of hypertrophy and %FLR were 7.64 ± 4.22 and 21.77 ± 13.34, respectively. There was no significant correlation between FLR hypertrophy and total bilirubin (P > .5). FLR hypertrophy was not significantly different between the 2 groups. Planned major hepatectomy was performed in 73 patients (83.9%). Grade 3 post-hepatectomy liver failure occurred in 6 patients (8.2%; 2 in the hyperbilirubinemia group and 4 in the control group), and its incidence was not significantly different between the groups (P = .354). CONCLUSIONS: Hyperbilirubinemia at the time of PVE seems to have no effect on FLR hypertrophy. The incidence of grade 3 post-hepatectomy liver failure is not likely to be influenced, either.

Non-urate transporter 1, non-glucose transporter member 9-related renal hypouricemia and acute renal failure accompanied by hyperbilirubinemia after anaerobic exercise: a case report.

BACKGROUND: Renal hypouricemia (RHUC) is an inherited heterogenous disorder caused by faulty urate reabsorption transporters in the renal proximal tubular cells. Anaerobic exercise may induce acute kidney injury in individuals with RHUC that is not caused by exertional rhabdomyolysis; it is called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). RHUC is the most important risk factor for ALPE. However, the mechanism of onset of ALPE in patients with RHUC has not been elucidated. The currently known genes responsible for RHUC are SLC22A12 and SLC2A9. CASE PRESENTATION: A 37-year-old man presented with loin pain after exercising. Despite having a healthy constitution from birth, biochemical examination revealed hypouricemia, with a uric acid (UA) level of < 1 mg/dL consistently at every health check. We detected acute kidney injury, with a creatinine (Cr) level of 4.1 mg/dL, and elevated bilirubin; hence, the patient was hospitalized. Computed tomography revealed no renal calculi, but bilateral renal swelling was noted. Magnetic resonance imaging detected cuneiform lesions, indicating bilateral renal ischemia. Fractional excretion values of sodium and UA were 0.61 and 50.5%, respectively. Urinary microscopy showed lack of tubular injury. The patient's older sister had hypouricemia. The patient was diagnosed with ALPE. Treatment with bed rest, fluid replacement, and nutrition therapy improved renal function and bilirubin levels, and the patient was discharged on day 5. Approximately 1 month after onset of ALPE, his Cr, UA, and TB levels were 0.98, 0.8, and 0.9 mg/dL, respectively. We suspected familial RHUC due to the hypouricemia and family history and performed genetic testing but did not find the typical genes responsible for RHUC. A full genetic analysis was opposed by the family. CONCLUSIONS: To the best of our knowledge, this is the first report of ALPE with hyperbilirubinemia. Bilirubin levels may become elevated as a result of heme oxygenase-1 activation, occurring in exercise-induced acute kidney injury in patients with RHUC; this phenomenon suggests renal ischemia-reperfusion injury. A new causative gene coding for a urate transporter may exist, and its identification would be useful to clarify the urate transport mechanism.

Direct hyperbilirubinemia in newborns with gastroschisis.

BACKGROUND: Patients with gastroschisis and prolonged total (or partial) parenteral nutrition (PN) commonly develop direct hyperbilirubinemia (DH). OBJECTIVE: To quantify the prevalence and severity of DH in newborns with gastroschisis and characterize the diagnostic work-up for DH in this patient population. DESIGN/METHODS: Retrospective chart review of patients born with gastroschisis between 2005 and 2015 for the first 6 months of life. RESULTS: 29 patients were identified with gastroschisis. Mean gestational age and birthweight were 36.4 (± 1.8) weeks and 2.5 (± 0.6) kg. 41% were treated with primary reduction versus staged closure. Peak total and direct bilirubin (DB) levels were 10.17 ± 6.21 mg/dL and 5.58 ± 3.94 mg/dL, respectively. 23 patients (79.3%) were diagnosed with DH and 78.2% underwent additional work-up for hyperbilirubinemia consisting of imaging and laboratory studies, none of which revealed a cause for DH other than the presumed PN-associated cholestasis. In all patients, DB began to decline within 1-10 days of initiation of enteral feeds. CONCLUSION(S): DH is common in patients with gastroschisis and is unlikely to be associated with pathology aside from PN. Additional work-up may lead to unnecessary resource utilization. LEVELS OF EVIDENCE: Case series with no comparison group, Level IV.

[Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia].

Objective: To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. Methods: A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ (2) test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test. Results: Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert's syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) µmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) µmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05). Conclusion: The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.

Diagnosis and evaluation of hyperbilirubinemia.

PURPOSE OF REVIEW: Jaundice, the physical finding associated with hyperbilirubinemia, results when the liver is unable to properly metabolize or excrete bilirubin. The purpose of this review is to examine some of the most common causes of jaundice in adults, provide insight into the diagnostic evaluation of jaundice, and review information on the outcomes of patients with jaundice. RECENT FINDINGS: An elevated level of bilirubin almost always indicates the presence of an underlying disease state. The best approach to evaluating a patient with jaundice is to start with a careful history and physical examination, followed by imaging assessment of the biliary tree and liver. There are algorithm models that incorporate bilirubin levels in their predictor models for outcomes in patients with chronic liver disease (i.e., the model for end-stage liver disease). However, there are few studies that have examined the outcomes of patients with jaundice. SUMMARY: Evaluation of patients with jaundice starts with a careful history and physical examination, followed by directed imaging of the biliary tree and liver. Although jaundice is generally believed to be a serious medical condition, there is little literature that addresses outcomes in patients with jaundice.

Persisting hyperbilirubinemia in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with eculizumab: The role of hepatocanalicular transporter variants.

BACKGROUND: Eculizumab-treated paroxysmal nocturnal hemoglobinuria (PNH) patients (pts) show a dramatic decrease in serum lactate dehydrogenase (LDH) activities and bilirubin concentrations. However, some pts remain hyperbilirubinemic, possibly indicating an inadequate response due to extravascular hemolysis. METHODS: Mutation analyses of hepatocanalicular transporter/nuclear receptor variants (ABCB4, ABCB11, ATP8B1, NR1H4) were performed in eight (five of eight males; mean age 38 years [range 26-68 years]) out of the 174 pts with PNH/-clone at our department due to a persistent increase in total bilirubin concentrations (median 3.4 mg/dL; range 2.1-8.1 mg/dL) during chronic eculizumab treatment and normal/or slightly increased serum aminotransferase activities. Median observation time was 70.1 months (range 10.6-135.2 months). All pts were treated according to German PNH guidelines. RESULTS: Homozygous and heterozygous procholestatic variants in the ABCB4, ABCB11, and ATP8B1 genes were identified in all eight pts. All carried the common ABCB4 c.787A>T polymorphism. The A(TA)7 TAA variant in the UGT1A1 promoter causing Gilbert syndrome was detected in three pts (5/8). CONCLUSIONS: Hyperbilirubinemia in PNH pts treated with eculizumab might not only be due to an insufficient response but rather a combination of mutations in hepatocanalicular transporter variants, Gilbert syndrome, and extravascular hemolysis. Our findings warrant further studies concerning transporter and enzyme variants in PNH to determine their clinical significance.

Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Cholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%-40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition-related) causes, each of which may have time-sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 µmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad-based next-generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.

Patients with Metastatic Colorectal Cancer and Hyperbilirubinemia Treated with FOLFIRI plus Bevacizumab as First-Line Treatment.

Metastatic colorectal cancer (mCRC) combined with hyperbilirubinemia is typically considered a contraindication to irinotecan-based therapy, a proven first-line treatment of mCRC. Herein, we present 6 consecutive patients with mCRC combined with hyperbilirubinemia who underwent UGT1A1 genotyping before receiving FOLFIRI plus bevacizumab. Dose escalation of irinotecan was performed according to the results of UGT1A1 genotyping in all patients. Improvement in the serum total bilirubin level to a normal range was noted in all 6 patients. Disease control was 100%. The median progression-free survival was 7.5 months and the median overall survival was 8.5 months. FOLFIRI plus bevacizumab as a first-line chemotherapy may achieve effective disease control and be safe in patients with mCRC and hyperbilirubinemia based on UGT1A1 genotyping. More prospective clinical studies are necessary to evaluate the clinical benefits and safety of this treatment approach.