Peak Bilirubin Research Articles

Use of prophylactic phototherapy for RhD neonatal disease in a referral service

ObjectiveThis study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. MethodA retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. ResultsThe incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). ConclusionThe low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study

Introduction: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. Methods: A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). Results: 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, p < 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, p < 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, p < 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, p < 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98–121, p < 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. Conclusion: G6PD-deficient infants with day four TSB levels of >180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.

Disparities in pegasparagase-induced toxicity in Hispanic patients with acute lymphoblastic leukemia.

e18590 Background: Hispanic individuals experience the highest incidence of acute lymphoblastic leukemia of any racial or ethnic group in the United States. While Hispanic individuals are known to have disproportionately increased mortality and higher therapy-related toxicity rates in ALL, there is a paucity of data regarding ethnic differences in rates of toxicity related to pegasparagase, a backbone of ALL treatment regimens. In our safety-net hospital system, we sought to evaluate disparities in rates of pegasparagase-induced hepatotoxicity between Hispanic and non-Hispanic patients. Methods: Pegasparagase infusions administered in adult ALL patients from 2011-2020 at Parkland Memorial Hospital in Dallas, Texas, were identified using the electronic medical record. Retrospective review of demographic, clinical, and socioeconomic data was conducted. For each infusion, dosing, timing, transaminase trends, and toxicity data were gathered. Statistical analysis was completed with Excel Analysis ToolPak and R Statistical Software. Accounting for baseline characteristics (age, BMI, sex, metabolic comorbidities, and baseline hepatic function), multiple linear regression models were constructed for peak transaminase and bilirubin levels. ANOVA testing, adjusted R2 values, and AIC were utilized to compare the contribution of race, ethnicity, and socioeconomic variables to modeling. Results: 47 individual patients received pegasparagase during the study period with 196 infusions evaluated. The mean age was 30 years, 29% were female and 73.4% white Hispanic. There were 64 grade 3-4 pegasparagase-related toxicities (54 hepatotoxicity, 4 pancreatitis, 6 thrombosis). 83.3% of grade 3-4 hepatotoxicity events were in Hispanic patients, and 16.7% in non-Hispanics. The median time from infusion to grade 3-4 toxicity was 18 days. Hispanic ethnicity was significantly associated with severe hepatoxicity (P = 0.0004). An interaction was identified with insurance status and primary language which significantly strengthened the impact of ethnicity and race on hepatotoxicity severity (P = 0.005, P = 0.02). Conclusions: In our safety-net population, Hispanic ethnicity was associated with significantly higher grades of hepatotoxicity when compared to non-Hispanic patients. Uninsured status and primary Spanish language use were not only independently associated with increased toxicity but also strengthened the effect of Hispanic ethnicity on the severity of liver dysfunction related to pegasparagase. These findings propose that Hispanic patients may benefit from closer monitoring during treatment with pegasparagase-containing regimens and highlight the need for further studies to improve risk-stratification of Hispanic patients when selecting ALL therapy.

Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of

To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Abnormal liver tests are not sufficient for diagnosis of hepatic graft-versus-host disease in critically ill patients.

Hepatic graft‐versus‐host disease (HGVHD) contributes significantly to morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Clinical findings and liver biomarkers are neither sensitive nor specific. The relationship between clinical and histologic diagnoses of HGVHD was assessed premortem and at autopsy. Medical records from patients who underwent HSCT at the National Institutes of Health (NIH) Clinical Center between 2000 and 2012 and expired with autopsy were reviewed, and laboratory tests within 45 days of death were divided into 15‐day periods. Clinical diagnosis of HGVHD was based on Keystone Criteria or NIH Consensus Criteria, histologic diagnosis based on bile duct injury without significant inflammation, and exclusion of other potential etiologies. We included 37 patients, 17 of whom had a cholestatic pattern of liver injury and two had a mixed pattern. Fifteen were clinically diagnosed with HGVHD, two showed HGVHD on autopsy, and 13 had histologic evidence of other processes but no HGVHD. Biopsy or clinical diagnosis of GVHD of other organs during life did not correlate with HGVHD on autopsy. The diagnostic accuracy of the current criteria was poor (κ = −0.20). A logistic regression model accounting for dynamic changes included peak bilirubin 15 days before death, and an increase from period −30 (days 30 to 16 before death) to period −15 (15 days before death) showed an area under the receiver operating characteristic curve of 0.77. Infection was the immediate cause of death in 68% of patients. In conclusion, liver biomarkers at baseline and GVHD elsewhere are poor predictors of HGVHD on autopsy, and current clinical diagnostic criteria have unsatisfactory performance. Peak bilirubin and cholestatic injury predicted HGVHD on autopsy. A predictive model was developed accounting for changes over time. Further validation is needed.

Immune-mediated liver injury following COVID-19 vaccination: A systematic review.

Immune‐mediated liver injury (ILI) following coronavirus disease 2019 (COVID‐19) vaccination is not well‐characterized. Therefore, we systematically reviewed the literature on ILI after COVID‐19 vaccination. We searched PubMed, Cochrane, Ovid, Embase, and gray literature to include articles describing ILI following COVID‐19 vaccination. Reports without confirmatory evidence from liver biopsy were excluded. Descriptive analysis, and study quality were reported as appropriate. Of the 1,048 articles found, 13 (good/fair quality; 23 patients) were included. Studies were primarily from Europe (n = 8), America (n = 2), Asia (n = 2), or Australia (n = 1). Patients were predominantly females (62.5%) of age 55.3 years (49.1–61.4), with an antecedent exposure to Moderna messenger RNA (mRNA)–1273 (47.8%), Pfizer‐BioNTech BNT162b2 mRNA (39.2%), or ChAdOx1 nCoV‐19 vaccine (13%). Pre‐existing comorbidities (69.6%) were common, including liver disease in 26.1% and thyroid disorders in 13% of patients. About two‐thirds of the patients were on concurrent medications (paracetamol, levothyroxine, statins, and non‐steroidal anti‐inflammatory drugs). Jaundice was the most common symptom (78.3%). Peak bilirubin, alanine aminotransferase, and alkaline phosphatase levels were 10.8 (6.8–14.8) mg/dl, 1,106.5 (757.0–1,702.5) U/L, and 229 (174.6–259.6) U/L, respectively. Histological findings were intense portal lymphoplasmacytic infiltrate with interface hepatitis. Steroids were used in 86.9% of patients, and complete response, recovering course, and death were reported in 56.5%, 39.1%, and 4.3% of patients, respectively. ILI following COVID‐19 vaccination is rare. The diagnosis is established on temporal correlation, biochemical findings, and histopathology. Prognosis is excellent with corticosteroids. Causality establishment remains a challenge.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.

Questioning Our Approach to Hyperbilirubinemia.

Questioning Our Approach to Hyperbilirubinemia.

Expanding donor pool for live donor liver transplantation: utilization of donors with non-alcoholic steatohepatitis after optimization.

Potential live liver donors with non-alcoholic steatohepatitis (NASH) are rejected upfront for donation in live donor liver transplantation (LDLT). Herein, we share our experience of the feasibility of live liver donation in donors with NASH after successful donor optimization. Prospectively collected data of 410 consecutive donor hepatectomies from June 2011 to January 2018 were analyzed. During the study period, NASH was diagnosed histopathologically in 17 donors. Four donors were rejected in view of grade 2 fibrosis on histology. Out of remaining 13 donors, six became eligible for donation following lifestyle changes, dietary modifications, and target weight reduction of ≥5%. Reversal of NASH was confirmed on repeat liver biopsy in all the 6 donors. Five out of 6 underwent right lobe (without MHV) donor hepatectomies, while one had left lobe donation. These donors had significantly higher peak bilirubin levels in the immediate post-operative period as compared to other non-NASH donors (4.00 ± 0.32 vs. 2.57 ± 1.77mg/dL, p = 0.043). In addition, post-hepatectomy normalization of hyperbilirubinemia, if any, was slower in donors with NASH (7 ± 1.3 vs. 5 ± 1.7days, p = 0.016). However, none of these donors had post-hepatectomy liver failure. All these donors were discharged after an average hospital stay of 8 ± 1.7days. Their respective recipients had uneventful post-operative courses without complications. Both the recipients and donors are having satisfactory liver functions after 46.7 ± 10.2months of follow-up. Scrupulous selection of live liver donors with NASH can open a door for expanding the organ pool in LDLT after a successful donor optimization program.

Epidemiological Characteristics and Clinical Manifestations of Hepatitis E in a Tertiary Hospital in China: A Retrospective Study.

BackgroundHepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide and one of the main causes of death in the last decade, causing chronic hepatitis and liver failure in some populations. The aging population and obesity are two major factors threatening human health. Therefore, we want to understand the relationship between these two groups and HEV infection.ObjectivesThe study aimed to analyze the epidemiological, clinical, and laboratory features of HEV infection and evaluate probable high-risk factors for disease progression and the current diagnostic strategies of hepatitis E infection.Study DesignPatients diagnosed with acute hepatitis E with symptoms and liver dysfunction were enrolled. For statistical analysis, clinical features and laboratory findings were collected between the elderly and non-elderly and HEV+ fatty liver disease (FLD) groups. Statistical analysis was performed using Excel and the platform VassarStats, and statistical significance was taken as P < 0.05.ResultsJaundice and the bilirubin peak were significantly deeper, the duration of hospitalization was significantly longer, and the proportion of ascites and liver failure was significantly higher in the elderly group. The aging population is one of the risk factors of severe hepatitis E. Hepatitis E becomes more serious in the HEV + FLD group, although the results did not reach statistical significance.ConclusionThe aging and FLD were suggested to aggravate HEV infection. However, the diagnosis of HEV infection remains a challenge. A prospective study with sufficient sample size is needed to confirm this conclusion.

Analysis of Prognostic Factors for Patients Undergoing Renal Replacement Therapy With Acute Kidney Injury Prior to Living Donor Liver Transplantation

Acute kidney injury (AKI) is a common complication in patients undergoing liver transplantation (LT) for end-stage liver disease (ESLD), and renal replacement therapy (RRT) is required in many cases. This study was performed to identify the prognostic factors for patients undergoing RRT owing to AKI before living donor liver transplantation (LDLT). From January 2010 to December 2018, LDLT was performed in 464 adult patients in our center. We reviewed 33 patients who underwent RRT before LDLT among 464 consecutive cases. Patients who continued to RRT after LDLT or who underwent subsequent kidney transplantation were considered to have not recovered from renal impairment. Among 33 patients, there were 23 patients in the recovery group and 10 patients in the nonrecovery group. The preoperative duration of RRT was shorter in the recovery group, but it was not statistically significant. In the nonrecovery group, diabetes mellitus was found to have a higher prevalence and ischemic time was longer. Other perioperative factors were not significantly different between the 2 groups. After LDLT, the peak total bilirubin level was higher, and the intensive care unit stay was longer in the nonrecovery group. The overall survival rate was higher in the recovery group. Liver transplant recipients who maintain RRT after LDLT have poor outcome. It is necessary to know the risk factors and manage them well, perioperatively.

Is perinatal asphyxia associated with an increase in serum bilirubin in neonates? A case-control study.

Perinatal asphyxia affects different organs of body depending upon the severity of hypoxemia and ischemia. This study was carried out to evaluate severity of hyperbilirubinemia in relation to severity of asphyxia. A case-control study. Asphyxiated newborns with Apgar score ≤7 at 1 min. and categorized as severe birth asphyxia according to the WHO classification of diseases (ICD10) were matched with controls without birth asphyxia. All babies were examined twice daily for dermal icterus until start of phototherapy. Babies with congenital heart disease, sepsis, cephalohematoma, blood group incompatibility were excluded. Arterial blood gas analysis was done along with serial TSB measurement as per standard guidelines. 50 cases and 50 matched controls were enrolled. The average birth weight and gestation in cases was 2427 ± 30.05 g and 35.9 ± 2.5 weeks and among control it was 2633 ± 378.62 g and 37.76 ± 0.116 weeks. Among cases, onset of jaundice was 56.64 ± 20.43 h compared to 63.36 ± 23 h in control group. In the cases, the average pH was 7.31 ± 0.06, CO2 was 41.52 ± 84, O2 was 94.98 ± 14.83, and HCO3 was 18.56 ± 2.04. The rise and peak of serum bilirubin differed between the case and control groups; in the cases, the peak occurred at the 22nd h of life, then plateaued from the 40th to the 78th hour of life, and ultimately fell at the 96th hour of life. In comparison, the rise and peak of serum bilirubin occurred comparatively late in the control group. The rise and peak in the control group occurred at the 80th and 96th h of life, respectively. The multiple linear regression analysis showed CRP, Apgar at 5 min. below 7 and male gender significantly affects the rise of serum bilirubin (P < 0.05). The peak serum bilirubin in asphyxiated newborns occurs earlier, and plateau for longer duration compared to normal newborns. Low Apgar at 5 min. has significant correlation to earlier rise of bilirubin.

Plasma Exchange Is an Effective Adjunct in the Management of Hyperbilirubinemia in Early Allograft Dysfunction and Small for Size Syndrome after Liver Transplant

Background: Management of early allograft dysfunction (EAD) and small for size syndrome (SFSS) after liver transplant remains challenging and care is largely based around supportive treatment. The role of plasmapheresis/plasma exchange in SFSS is not well established. However, it can potentially serve an important role as a salvage option by reducing the metabolic load of toxins including bilirubin and supplying important coagulation proteins to maintain coagulation homeostasis. Methods: We present three cases. A 19-year-old female underwent living-donor liver transplant (LDLT) and received a healthy right lobe graft. Graft-to-recipient weight ratio (GRWR) was 0.85. She developed SFSS and underwent one cycle of plasma exchange on post-operative day (POD) 8 (peak bilirubin 414umol/l) that was prematurely terminated as she developed an allergic response. A 58-year-old female underwent deceased-donor liver transplant and developed acute worsening hyperbilirubinemia on POD8-10 (from 116umol/l to 858 umol/l). She underwent one cycle of plasma exchange that was sufficient to serve as a bridge to treat the hyperbilirubinemia until liver biopsy diagnosis of acute cellular rejection was obtained and definitive steroid treatment was initiated. A 42-year-old female underwent LDLT and received a left lobe graft (GRWR 0.75). She developed SFSS despite portal inflow modulation performed during transplant. She underwent three sessions of plasma exchange (POD25,27,30). Results: In the three cases bilirubin levels improved significantly following plasma exchange, and graft recovery was evident. Conclusion: Our cases suggest the efficacy of plasma exchange as a potential adjunct for the supportive treatment of hyperbilirubinemia in EAD and SFSS to avoid re-transplantation.

Peg- Asparaginase induced hepatic injury-A concern for hepatologist

Background and Aim: Peg-L Asparaginase is an important chemotherapeutic agent prescribed in Acute Lymphoblastic Leukaemia (ALL). L Asparaginase is a recognised cause of liver toxicity and patient presenting with deranged liver function should be investigated for this cause apart from primary liver infiltration. Case summary: We report a case of 48-year-old male known case of DM, diagnosed with Early T Cell Precursor (ETP) ALL, treated with BFM 2002 protocol with Daunorubicin, Vincristine, L asparaginase and Methotrexate. He presented with right upper quaant pain with anorexia and jaundice in 4th week of induction. On investigation his peak bilirubin reached uptil 14 mg/dl of which 11 mg/dl was direct component. The peak INR reached till 1.45 and SGOT and SGPT reached upto 350 IU/L and 380 IU/L respectively. Imaging was done suggestive of hepatomegaly with fatty liver infiltration. Rest all other liver specific tests were negative. He was started on symptomatic treatment and with UDCA. The drug was stopped and he improved symptomatically. Conclusions: L asparaginase can cause liver toxicity which may be improved after drug stoppage.

Cord Bilirubin Value as a Predictor of Significant Hyperbilirubinemia in Abo Incompatiblity

Background: Hyperbilirubinemia is a condition in which the blood contains too much bilirubin and producing jaundice (yellow coloring of the eyes and skin). Low bilirubin levels in newborns are common and do not pose any problems; they will resolve on their own within the first week of life. Studying the cord bilirubin levels in new born babies is significant to predict the risk of abo incompatiblity.&#x0D; Methods: A total of 129 babies born to O blood group mother were included in the study. Out of which 111 babies were with risk of ABO incompatibility. Among them 17 babies developed pathological hyperbilirubinemia. None of the 0 positive babies developed pathological hyperbilirubinemia.&#x0D; Results: The peak bilirubin level was attained on 3rd and 4th day for all the babies and was taken as the outcome measure and cord serum bilirubin was taken as the predictive factor. The incidence of pathological hyperbilirubinemia is 13.2%. The mode of delivery had no positive association with the development of pathological hyperbilirubinemia. Male babies had positive ociation for pathological hyperbilirubinemia without any statistical significance. Incidence of pathological hyperbilirubinemia is higher in babies with a birth weight of &lt;3 kg.&#x0D; Conclusion: A cord bilirubin value of 2.65 mg/dL can be used as a cut off for predicting pathological hyperbilirubinemia. Infants with bilirubin level more than the cutoff values were subjected to early intervention with complete recovery. None of the babies had developed encephalopathy and its sequelae.

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Co-inheritance of G6PD deficiency and 211\u2009G to a variation of UGT1A1 in neonates with hyperbilirubinemia in eastern Guangdong

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world.ObjectiveTo investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia.MethodThe activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal bilirubin was collected and analyzed retrospectively.ResultsSeventy four cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubinin of the G6PD-deficient group of hyperbilirubinemia neonates was 334.43 ± 79.27 μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30 ± 68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G > T and c.1388G > A, and the peak bilirubin of neonates with these two variants were 312.60 ± 71.81 μmol/L and 367.88 ± 75.79 μmol/L, respectively. The bilirubin level of c.1388G > A was significantly higher than that of c.1376G > T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55 ± 84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50 ± 63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63 ± 57.52 μmol/L).ConclusionThe rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

S2674 A Subtle Case of Doxorubicin-induced Hepatotoxicity

Introduction: Doxorubicin is a common antineoplastic medication linked to hepatotoxicity and can be a major cause for Drug-Induced Liver Injury (DILI). This case illustrates a patient presenting with acute encephalopathy and Acute Liver Failure (ALF) found to have granulomatous hepatitis in the setting of recent Doxorubicin treatment. Case Description/Methods: A 49-year-old African-American female with a history of inflammatory breast cancer treated with radiation, chemotherapy, and bilateral mastectomy with breast expanders presented to the medical ICU with a one-week history of nausea, diarrhea, and altered mental status. She was previously treated with weekly Abraxane then switched to Doxorubicin for recurrent breast cancer and received one dose two weeks prior to presentation. Vitals were notable for tachycardia (HR 101) and exam notable for somnolence, lower abdominal pain, and left breast maceration. Labs significant for NH4 115, BUN 30, total bilirubin 7.2, alkaline phosphatase 161, ALT 27, AST 66, INR 1.88, and MELD-Na 21 with peak total bilirubin 13.8, alkaline phosphatase 663, ALT 74, and AST 230 two days following admission. Left breast wound culture showed growth of MSSA and E-faecalis. Further workup including hepatitis panel, CSF cultures, blood cultures, and CT head were negative. Abdominal US showed elevated hepatic vein velocities possibly representing Budd-Chiari Syndrome and CT Abdomen was without acute findings. Patient was started on broad spectrum antibiotics for breast cellulitis. Hepatology was consulted with recommendations for expectant management for DILI given recent Doxorubicin administration after ERCP showed no obstruction and liver biopsy was notable for multiple necrotizing granulomas and portal inflammation consistent with granulomatous hepatitis. During hospitalization, patient’s mentation returned to baseline and her two-month outpatient follow up showed improved liver enzymes and abdominal pain. Discussion: DILI is one of the most common causes of ALF. Doxorubicin’s mechanism of action in disrupting major enzymes in the antioxidant system causes oxidative stress and hepatic inflammation seen in this patient’s histological findings. While the hepatotoxic effects of Doxorubicin are dose-dependent, lower doses have been shown to cause hepatic necrosis and ALF. When a patient presents with acute encephalopathy in the setting of elevated liver enzymes, DILI and recent Doxorubicin treatment should be included in the differential diagnosis.

Immediate vs delayed cord clamping in preterm infants: A systematic review and meta-analysis.

To compare and evaluate the efficacy and safety of immediate cord clamping (ICC) and delayed cord clamping (DCC) in preterm infants. We performed a comprehensive and systematic meta-analysis of randomised controlled trials (RCTs) assessing ICC and DCC in preterm infants by searching PUBMED, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Database (from inception to 30 September 2020). Summary odds ratios or mean differences with 95% confidence intervals were calculated using a fixed- or random-effect model. A total of 20 RCTs with 1807 preterm infants were included in the study. DCC provided more benefits in increasing the haematocrit and haemoglobin levels at 24hours of life (%), thus reducing the incidence of anaemia, necrotising enterocolitis, length of hospital stay and mortality than when ICC was performed. No significant differences were found between ICC and DCC in terms of peak bilirubin level; need for blood transfusion, mechanical ventilation (MV) and phototherapy; duration of MV and phototherapy; and incidences of intraventricular haemorrhage, retinopathy of prematurity, patent ductus arteriosus, respiratory distress syndrome, sepsis, jaundice, polycythaemia, periventricular leukomalacia and bronchopulmonary dysplasia. DCC is a safe, beneficial and feasible intervention for preterm infants. However, rigorously designed and large-scale RCTs are necessary to identify the role and ideal timing of DCC.

Jaundice in patients with COVID-19.

Background and AimWhile many studies have reported on liver injury in patients with coronavirus disease 2019 (COVID‐19), none have specifically addressed the significance of hepatic jaundice. We aimed to determine the clinical consequences and etiologies of jaundice in patients with COVID‐19.MethodsWe retrospectively analyzed clinical features, laboratory abnormalities, and rates of survival and intensive care unit admission in 551 patients with COVID‐19, hospitalized between 1 March 2020, and 31 May 2020 at a tertiary care academic medical center. Hepatic jaundice was defined as a serum total bilirubin concentration >2.5 mg/dL and a direct bilirubin concentration >0.3 mg/dL that was >25% of the total. Liver injury was characterized as cholestatic, mixed, or hepatocellular at the time of peak serum total bilirubin concentration by calculating the R factor.ResultsHepatic jaundice was present in 49 (8.9%) patients and associated with a mortality rate of 40.8% and intensive care unit admission rate of 69.4%, both significantly higher than for patients without jaundice. Jaundiced patients had an increased frequency of fever, leukopenia, leukocytosis, thrombocytopenia, hypotension, hypoxemia, elevated serum creatinine concentration, elevated serum procalcitonin concentration, and sepsis. Nine jaundiced patients had isolated hyperbilirubinemia. Of the 40 patients with abnormally elevated serum alanine aminotransferase or alkaline phosphatase activities, 62.5% had a cholestatic, 20.0% mixed, and 17.5% hepatocellular pattern of liver injury.ConclusionHepatic jaundice in patients with COVID‐19 is associated with high mortality. The main etiologies of liver dysfunction leading to jaundice appear to be sepsis, severe systemic inflammation, and hypoxic/ischemic hepatitis.