Peak Bilirubin Levels Research Articles

Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202

Atazanavir-associated hyperbilirubinemia can cause premature discontinuation of atazanavir and avoidance of its initial prescription. We used genomewide genotyping and clinical data to characterize determinants of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202. Plasma atazanavir pharmacokinetics and indirect bilirubin concentrations were characterized in HIV-1-infected patients randomized to atazanavir/ritonavir-containing regimens. A subset had genomewide genotype data available. Genomewide assay data were available from 542 participants, of whom 475 also had data on estimated atazanavir clearance and relevant covariates available. Peak bilirubin concentration and relevant covariates were available for 443 participants. By multivariate analysis, higher peak on-treatment bilirubin levels were found to be associated with the UGT1A1 rs887829 T allele (P=6.4×10(-12)), higher baseline hemoglobin levels (P=4.9×10(-13)), higher baseline bilirubin levels (P=6.7×10(-12)), and slower plasma atazanavir clearance (P=8.6×10(-11)). For peak bilirubin levels greater than 3.0 mg/dl, the positive predictive value of a baseline bilirubin level of 0.5 mg/dl or higher with hemoglobin concentrations of 14 g/dl or higher was 0.51, which increased to 0.85 with rs887829 TT homozygosity. For peak bilirubin levels of 3.0 mg/dl or lower, the positive predictive value of a baseline bilirubin level less than 0.5 mg/dl with a hemoglobin concentration less than 14 g/dl was 0.91, which increased to 0.96 with rs887829 CC homozygosity. No polymorphism predicted atazanavir pharmacokinetics at genomewide significance. Atazanavir-associated hyperbilirubinemia is best predicted by considering UGT1A1 genotype, baseline bilirubin level, and baseline hemoglobin level in combination. Use of ritonavir as a pharmacokinetic enhancer may have abrogated genetic associations with atazanavir pharmacokinetics.

Correlation of antituberculosis drug-related liver injury and liver function monitoring: A 12-year experience of the Taiwan Drug Relief Foundation

Antituberculosis drug-related liver injury (ATLI) is the most prevalent hepatotoxicity in many countries. Whether monitoring liver tests is beneficial to prevent this potentially grave adverse drug reaction (ADR) is open to debate. The Taiwan Drug Relief Foundation (TDRF) was established by the Taiwan Food and Drug Administration to collect severe cases of ADR and carry out drug injury relief tasks. Our intention was to explore the role of monitoring liver tests in the susceptibility and severity of ATLI from the database of this foundation. All cases of suspected ATLI collected by the TDRF from 1999 to 2012 were reviewed. The basic demographic data, clinical course, and laboratory data of these patients were analyzed. A total of 57 cases with severe ATLI were verified and enrolled into this study. There was a high mortality (71.9%) in this cohort. Twenty-four cases (42.1%) were chronic viral hepatitis B carriers, who had higher baseline serum aminotransferase level than noncarriers. The patients without monitoring liver tests had higher peak serum alanine aminotransferase, bilirubin levels, and mortality (adjusted odds ratio, 8.87; 95% confidence interval = 1.32–59.41; p = 0.024) than those with monitoring liver tests. In conclusion, patients with severe ATLI whose records were collected by the TDRF have a high mortality. Patients without follow-up monitoring liver tests had more severe liver injuries and higher mortality than those with monitoring live tests. To alleviate this potentially grave ADR, checking of liver biochemical tests prior to antituberculosis treatment and periodic monitoring of these tests thereafter are highly suggested.

Measured versus Estimated Total Liver Volume to Preoperatively Assess the Adequacy of the Future Liver Remnant

To determine which method of liver volumetry is more accurate in predicting a safe resection. Before major or extended hepatectomy, assessment of the future liver remnant (FLR) is crucial to reduce the risk of postoperative hepatic insufficiency. The FLR volume is usually expressed as the ratio of FLR to nontumorous total liver volume (TLV), which can be measured directly by computed tomography (mTLV) or estimated (eTLV) on the basis of correlation existing with the body surface area. To date, these 2 methods have never been compared. All consecutive, noncirrhotic patients who underwent resection of 3 or more liver segments between April 2000 and April 2012 and for whom (i) preoperative computed tomographic scans and (ii) body surface area were available entered the study. The mTLV (calculated as TLV - tumor volume) was compared with the eTLV (calculated as -794.41 + 1267.28 × body surface area) using volumetric data (cm) and clinical outcome measures (specifically, hepatic insufficiency and 90-day mortality). Definition of hepatic insufficiency was peak postoperative serum total bilirubin level of more than 7 mg/dL or, in jaundiced patients, an increasing bilirubin level on day 5 or thereafter. Two-hundred forty-three patients who had undergone major (n = 135) or extended (n = 108) hepatectomies met the inclusion criteria. Twenty-eight patients (11.5%) developed hepatic insufficiency, whereas 7 patients (2.9%) died postoperatively. Compared with the eTLV, the mTLV underestimated the liver volume in 60.1% of the patients (P < 0.01). Forty-seven and 73 patients had an inadequate FLR based on mTLV and eTLV, respectively. Portal vein occlusion (PVO) was used in 44 patients. In patients (n = 162) in whom both methods did not evidence the need for PVO, postoperative hepatic insufficiency and mortality were 4.9% and 0.6%, respectively. Conversely, in patients (n = 27) in whom the eTLV but not the mTLV evidenced the need for PVO, and thus PVO was not performed, hepatic insufficiency (22.2%; P = 0.001) and mortality (3.7%; P = ns) were higher. The use of eTLV identifies a subset of patients (∼11%) in whom liver volumetry with the mTLV underestimates the risk of hepatic insufficiency.

Invited Commentary: Does Neonatal Hyperbilirubinemia Cause Asthma?

In an analysis of data from the US Collaborative Perinatal Project, Huang et al. (Am J Epidemiol. 2013;178(12):1691-1697) report an association between neonatal total serum bilirubin levels and childhood asthma. To consider the implications of this finding, we need to evaluate whether the association is causal. The results do not appear to be due to chance or any obvious biases. It is likely that the observed association is the result of a common cause of both hyperbilirubinemia and asthma (confounding). Polymorphisms in the glutathione S-transferase gene are a potential genetic confounder. The glutathione S-transferase M1-null phenotype has been linked to both neonatal hyperbilirubinemia and asthma in several studies. Before making any changes in practice aimed at lowering peak bilirubin levels to reduce asthma risk, it is vital to determine not only whether the association between higher bilirubin levels and asthma risk is causal, but also whether interventions to reduce peak bilirubin levels (or their duration) are associated with decreased risk of asthma (without evidence of other adverse effects). The study by Huang et al. should encourage further investigation of these questions.

Selection and outcomes of living donors with a remnant volume less than 30% after right hepatectomy

The evidence for defining a safe minimal remnant volume after living donor hepatectomy is insufficient. The aim of this study was to evaluate the outcomes of living donors with a remnant/total volume ratio (RTVR) < 30% after right hepatectomy according to the following selection criteria: the preservation of the middle hepatic vein (MHV), an age < 50 years, and no or mild fatty changes in healthy adults. All living donors who underwent right hepatectomy preserving the MHV at our institution between January 2005 and September 2011 were divided into 2 groups: group A with an RTVR < 30% and group B with an RTVR ≥ 30%. Perioperative data, complications by the Clavien classification, and outcomes with at least 15.1 months' follow-up were compared. Twenty-eight donors were enrolled in group A, and 260 were enrolled in group B. The estimated liver volume was strongly correlated with the actual graft weight (R(2) = 0.608, P < 0.001). The calculated donation liver volume and the RTVR were significantly different between the 2 groups (P = 0.03 and P < 0.001, respectively). The peak postoperative aspartate aminotransferase levels, alanine aminotransferase levels, and international normalized ratios did not differ between the 2 groups. The peak total bilirubin level was higher for group A versus group B (P = 0.04). The hospital stay was longer for group A versus group B (P < 0.001). All donors recovered completely, and there were no significant differences in overall complications between the 2 groups. In conclusion, right hepatectomy preserving the MHV with an RTVR < 30% can be safely indicated for carefully selected living donors less than 50 years old with no or mild fatty changes.

Autologous Intestinal Reconstructive Surgery to Reduce Bowel Dilatation Improves Intestinal Adaptation in Children With Short Bowel Syndrome

Intestinal failure (IF) is a common consequence of neonatal small bowel pathology. In our experience, bowel dilatation is often responsible for the IF state in patients who fail to adapt despite adequate residual bowel length. The aim of the present study was to investigate the role of surgery to reduce bowel dilatation, and thus favour PN independence, for these children. Data were collected prospectively for all of the patients referred to our unit for a 7-year period (2004-2011). Eight patients (2 congenital atresia, 2 gastroschisis with atresia, 1 simple gastroschisis, 3 necrotising enterocolitis) with gut dilatation who failed adaptation despite a bowel length >40 cm were identified. Preoperatively, all patients were totally dependent on parenteral nutrition (PN). Patients were managed by longitudinal intestinal lengthening and tailoring (n = 3), serial transverse enteroplasty (n = 2), or tapering enteroplasty (n = 3). Median age at time of surgery was 273 days (103-1059). Mean gut length increased from 51 (35-75) to 73 cm (45-120) following surgery (P = 0.02). Incidence of sepsis (P = 0.01) and peak serum bilirubin levels (P = 0.005) were reduced postoperatively. PN was discontinued after a median of 110 days (35-537) for 7 patients; 1 patient remains on PN 497 days after surgery. These data indicate that reconstructive surgery to reduce bowel diameter may be an effective technique for treating IF in patients with short bowel syndrome, without sacrificing intestinal length. We suggest that this technique may reduce the need for bowel transplantation in this group of patients.

Predicting early allograft failure and mortality after liver transplantation: The role of the postoperative model for end-stage liver disease score

Early allograft dysfunction (EAD) is a serious complication after liver transplantation (LT). There is no uniform definition of EAD, and most definitions are based on arbitrary laboratory values. The aim of this study was to devise a definition of EAD that maximizes the predictive power for early death and graft failure. In this single-center, retrospective study, the ability of the international normalized ratio (INR), total bilirubin, aspartate aminotransferase (AST), physiological Model for End-Stage Liver Disease (MELD) score, and serum albumin levels within 7 days after LT to predict 90-day mortality or graft loss was compared with 2 previously used definitions of EAD: (1) peak total bilirubin level >10 mg/dL on days 2 to 7 and (2) either a total bilirubin level >10 mg/dL or an INR >1.6 on day 7 or an AST or alanine aminotransferase level >2000 IU/L within the first 7 days. Of 572 enrolled LT patients 38 died or required retransplantation within 90 days. Peak INR, total bilirubin level, AST levels, and MELD scores were predictors of 90-day graft failure. MELD score on postoperative day 5 was the best predictor with an area under the curve of the receiver operating characteristic curve of 0.812 (95% CI: 0.739-0.886, P < 0.001). The best cutoff of MELD score on day 5 for predicting 90-day mortality or graft loss was 18.9. A MELD score >18.9 on postoperative day 5 was a better predictor than any other laboratory value or definition of EAD. This study has demonstrated that the MELD score can be a useful tool not only for pretransplant graft allocation but also for postoperative risk stratification.

Quantitative ADC in bilirubin encephalopathy

It was with great interest that we read the paper by Cece and colleagues [1] entitled ‘Diffusion-weighted imaging of patients with neonatal bilirubin encephalopathy.’ The authors conclude that quantitative apparent diffusion coefficient (ADC) measurement could be a promising marker of neonatal bilirubin encephalopathy. The article, however, raises several questions that merit clarification. First, there is little doubt that several in this cohort of infants with peak bilirubin levels in the range of 25–58 mg/dl developed permanent bilirubin-induced neuronal injury and adverse long-term neurodevelopmental sequelae of chronic bilirubin encephalopathy (CBE). Indeed, most demonstrated overt signs of intermediate to advanced stages of acute bilirubin encephalopathy (ABE) and/or peak TSB levels [35 mg/dl, a threshold in the US Pilot Kernicterus registry that was more often than not associated with moderate to severe chronic neurodevelopmental impairment [2, 3]. Some, however, may have had reversible ABE and escaped their hazardous bilirubin exposures unscathed given the timely use of exchange transfusion [4]. Neurological findings at the time of hospitalization discharge and long-term neurodevelopmental evaluations, however, are not reported. Similarly, auditory brainstem evoked responses are not detailed. It is important to distinguish infants who developed CBE from those who did not and compare ADC values between these two groups to ascertain whether ADC is a potential marker of CBE or a marker of ABE alone and not its progression to CBE. Follow-up MRI studies to confirm neuroradiographic evidence of CBE would be of interest in this regard but were not reported. Second, although quantitative ADC values were statistically increased relative to controls, the numeric difference was modest and its clinical relevance uncertain, particularly since ADC is sensitive to multiple technical and pathologic factors. In addition, the region of interest (ROI) depicted in Figure 1 does not selectively localize to the globus pallidus, but also includes a portion of the posterior limb of the internal capsule. There is no inter-rater/intra-rater reliability measurement given for the manual drawing of the ROI, which is prone to error. The subthalamic area is also known to be involved in kernicterus, and this region was not measured in the report. More details about the controls would be of interest as well, as there are very few neonatal cases that have a spinal disorder and a normal brain MRI. Third, Figure 3 demonstrates a statistically significant relationship between total bilirubin levels and ADC values. However, the reported r value of 0.41 indicates that only 16 % (r = 0.16) of the variability in ADC can be accounted for by total bilirubin, i.e., 86 % is accounted for by other factors. This comment refers to the article available at doi:10.1007/s11604-012-0166-4.

The Outcomes of Patients with Severe Hyperbilirubinemia Following Living Donor Liver Transplantation

Prolonged hyperbilirubinemia (HB) following living donor liver transplantation (LDLT) can be a risk factor for early graft loss and mortality. However, some recipients who present with postoperative hyperbilirubinemia do recover and maintain a good liver function. The purpose of this study was to investigate the risk factors for hyperbilirubinemia following LDLT and to identify predictors of the outcomes in patients with post-transplant hyperbilirubinemia. A total of 107 consecutive adults who underwent LDLT in Nagasaki University Hospital were investigated retrospectively. The patients were divided into two groups according to postoperative peak serum bilirubin level (HB group: ≥ 30 mg/dl; non-HB group: <30 mg/dl). These two groups of patients and the prognosis of patients in the HB group were analyzed using several parameters. Seventeen patients (15.9 %) presented with hyperbilirubinemia, and their overall survival was significantly worse than patients in the non-HB group (n = 90). Donor age was significantly higher in the HB group (P < 0.05). Of the 17 patients in the HB group, nine survived. The postoperative serum prothrombin level at the time when the serum bilirubin level was >30 mg/dl was significantly higher in surviving patients (P < 0.01). The use of a partial liver graft from an aged donor is a significant risk factor for severe hyperbilirubinemia and a poorer outcome. However, those patients who maintain their liver synthetic function while suffering from hyperbilirubinemia may recover from hyperbilirubinemia and eventually achieve good liver function, thus resulting in a favorable survival.

Cochrane Review: Prophylactic phototherapy for preventing jaundice in preterm or low birth weight infants

Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinaemia and jaundice that can lead to bilirubin encephalopathy. Phototherapy is the most common treatment for neonatal hyperbilirubinaemia and could be most effective in preventing the sequelae of hyperbilirubinaemia if initiated prophylactically. To evaluate the efficacy and safety of prophylactic phototherapy for preterm (< 37 weeks gestational age) or low birth weight infants (birth weight < 2500 g). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3) on 31 March 2011, MEDLINE (1950 to 31 March 2011), EMBASE (1980 to 31 March 2011) and CINAHL (1982 to 31 March 2011). Randomised controlled trials or quasi-randomised controlled studies evaluating the effects of prophylactic phototherapy for preterm or low birth weight infants. Two authors independently obtained data from published articles. We performed fixed-effect meta-analysis for the outcomes: rate of exchange transfusion, cerebral palsy or other neurodevelopmental impairment, peak serum bilirubin level and all-cause mortality. Nine studies of 3449 participants were included. The rate of exchange transfusion was reduced in one study with liberal transfusion criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but not in the other two more recent studies with stringent criteria (typical RR 0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies, 756 participants). However, one large study that reported on neurodevelopmental impairment (a composite outcome including cerebral palsy) found a slightly lower rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85; 95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57; six studies, 2319 participants) and had fewer neonates with peak unconjugated serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15 mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants). There was no statistically significant difference in the rate of all-cause mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four studies, 3044 participants). Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes.

Pattern of BAER abnormalities in neonatal hyperbilirubinemia

Article history: This study was done to determine the various abnormalities of Brain Auditory Evoked Response (BAER) in neonates with hyperbilirubinemia and to correlate the specific BAER abnormality with a particular range of bilirubin levels. Prospective study was done in 100 cases in a tertiary care hospital over a period from 2007-2008. All cases with hyperbilirubinemia were subjected to BAER test. Fifty five percent (n=44) out of 80 cases showed abnormal BAER test and 24 of them showed bilaterally in babies having peak serum bilirubin levels of more than 20mg/dL. Seventy five percent (n=33) showed prolong interpeak latency in wave III-V indicating that the conduction from superior olivary complex (wave III) to inferior collicullus (wave V) were more commonly affected with peak levels of bilirubin when compared to control which were found to be statistically significant (p<0.05). BAER is a simple and effective tool for determining the auditory functions in neonates with hyperbilirubinemia and could predict the impending encephalopathy or to identify subtle findings that could be reversed.

Model to Predict Hyperbilirubinemia in Healthy Term and Near-Term Newborns with Exclusive Breast Feeding

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia.

İndirekt Hiperbilirubinemili Hastalarda Kranial Manyetik Rezonans Görüntüleme Bulguları

Abstract Purpose: To describe the magnetic resonance imaging (MRI) changes in the patients with indirect hyperbilirubinemia. Methods: MRI findings of eighteen neonates with indirect hyperbilirubinemia were reported by us. The differences in imaging, clinical and biochemical data between three groups were evaluated statistically. Results: Peak bilirubin levels were between 20 and 24 mg per deciliter in 5 of the newborns (group 1), 25 and 29 mg per deciliter in 6 of the newborns (group 2) and 30 mg per deciliter or more in 7 newborns (group 3). There was statistically significant difference between the neurological findings and MRI findings of the patients between three groups. Conclusion: We always demonstrated MRI changes in the patients with kernicterus. Firstly, T1 weighted changes were described in patients with hyperbilirubinemia despite normal neurological examinations. Larger studies with clinical follow up are needed for further understanding of toxic effect of bilirubin in brain. Key words: Ozet

Neonatal Hyperbilirubinemia in infants with G6PD c.563C &gt; T Variant

BackgroundThere is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T.MethodsThis was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.ResultsG6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.ConclusionsWe concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.

Increased morbidity in acute viral hepatitis with glucose-6-phosphate dehydrogenase deficiency

Editor, Viral hepatitis usually manifests as a self-limiting illness. However, in the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, it may be complicated with renal failure, hemolysis, hepatic encephalopathy and even death. The incidence of G6PD deficiency in the general population in northern India ranges from 2.2 % to 14 % [1]. We retrospectively analyzed the clinical presentation and outcome of patients with G6PD deficiency and acute viral hepatitis. The case records of all patients admitted in our hospital with acute viral hepatitis between January 2007 and December 2010 and ten patients (mean age 16.1 years, M:F 4:1) with G6PD deficiency and acute viral hepatitis were identified. Fourteen patients (mean age 19.3 years, M:F 5:2) with acute viral hepatitis and without G6PD deficiency were randomly selected by draw of lots for comparison. Both the groups were analyzed on the basis of age, sex, etiology of hepatitis, peak bilirubin levels, peak creatinine levels, prothrombin time, requirement of hemodialysis, hospital stay and outcome. Seven patients in the study group had hepatitis A infection and three had hepatitis E infection. In the control group, eight patients had hepatitis A, five had hepatitis E and one had mixed hepatitis A and E infection. As noted from Table 1, the mean peak bilirubin was significantly higher in the study group (p<0.001). Peak creatinine value was not significantly increased when compared to the control group. The mean international normalized ratio and indirect bilirubin was significantly higher in the study group. The mean duration of stay was nearly two and a half times more in the study group than in the control group. Mild hemolysis is seen in acute viral hepatitis but is rarely of clinical significance [2]. When viral hepatitis occurs in G6PD deficient individuals, hemolysis may be severe [3]. Gotsman et al. reported a more severe initial presentation in patients with acute viral hepatitis A and G6PD deficiency though the clinical outcome was not affected [4]. Abid and Khan reported five patients with acute viral hepatitis E, severe intravascular hemolysis, hyperbilirubinemia and anemia. Two patients required hemodialysis and they advocated that measures to prevent renal failure should be taken in such patients [5]. Hemolysis may result from decreased levels of reduced glutathione in red blood cells [2], consequent to the accumulation of oxidants due to hepatic dysfunction. Renal tubular dysfunction occurs due to excess hematin and bilirubin which result in obstruction of renal tubules. Good hydration and avoiding nephrotoxic drugs helps in preventing renal failure. Tests for G6PD deficiency may be negative during the hemolytic phase and should be repeated after 8–10 weeks of recovery. Vitamin K should be avoided in these patients. Studies from various parts of India have recommended vaccination against hepatitis A and B in communities with high prevalence of G6PD deficiency [6, 7].

1105 BASELINE CHARACTERISTICS CAN HELP TO PREDICT HEPATIC DECOMPENSATION DURING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C AND ADVANCED LIVER CIRRHOSIS

loads (median delta of HCVRNA viral load 2.8 log10 IU/ml) versus CT/TT genotypes (1.4 log10 IU/ml) before initiation of therapy. The maximum viral load drop within 100 days after diagnosis was higher in patients with fluctuating viremia (FV) (median 2.9 log10 IU/ml) and in patients with SC (median 3.1 log10 IU/ml) in comparison to individuals with plateau viremia (median 0.5 log10 IU/ml). Patients with FV and SC together had higher median peak bilirubin (1.8 versus 0.8mg/dl) and ALT levels (1146 versus 265 U/l) in comparison to patients with plateau viremia. No mutational patterns within the NS3 protease were detected in correlation with the outcome of acute HCV infection. Conclusions: A maximal viral load drop ≥ 2.9 log10 IU/ml is associated with higher peak bilirubin and ALT levels and occurs in SC patients and in patients with FV and persistent outcome of acute HCV infection. Highly fluctuating HCVRNA concentrations were observed in patients with IL28B CC genotype in comparison to CT/TT genotypes.

Outcome and cost analysis of implementing selective Coombs testing in the newborn nursery

(1) To determine whether infants born to O+ mothers who had selective cord-blood testing would have higher rates of clinically significant hyperbilirubinemia compared with those newborns who had routine cord-blood testing. (2) To determine the amount of cost savings by implementing a policy of selective cord-blood testing in newborns born to O+ mothers. We conducted a retrospective pre/post intervention chart review on all infants in the normal newborn nursery at Loyola, born to blood type O+ women between 1 April 2008 and 1 April 2009. The pre-intervention group (routine testing) included infants born within 6 months before implementation of a new policy. The post-intervention group (selective testing) included infants born within 6 months following the implementation of a new policy. Data were collected for each of these groups regarding clinically significant hyperbilirubinemia. All 250 of the infants in the routine testing group had a cord-blood type and Coombs done, whereas 42 of 164 (25%) infants in the selective group had testing done. By the end of the 6 months following the policy change, only 8% of infants were undergoing cord testing. When comparing routine vs selective testing, there was no statistically significant difference in the 24-h serum bilirubin, rate of phototherapy during the birth hospitalization, rate of readmission for hyperbilirubinemia or peak serum bilirubin level at readmission. The 92% reduction of cord-blood typing and Coombs testing would lead to a cost saving of $4100 per year to our hospital and $18 900 per year to our patients, and 95 h per year of technician time to perform these tests. When extrapolated to Illinois births in 2008, this would lead to an annual cost saving of almost $800 000 to Illinois hospitals and about $3.6 million to patients. Selective newborn cord testing of infants born to O+ mothers can decrease the use of resources and costs without increasing the risk of clinically significant hyperbilirubinemia.

International Perspectives

After completing this article, readers should be able to: 1. Describe the unique characteristics of neonatal jaundice in Chinese infants. 2. Describe the major findings from a recent epidemiological survey of bilirubin encephalopathy or kernicterus in China. 3. Understand the primary causes and current problems for decreasing the incidence of bilirubin encephalopathy or kernicterus in China. 4. Outline future directions for obtaining population based data on bilirubin encephalopathy or kernicterus and formulating optimal management of neonatal jaundice. Hyperbilirubinemia is the number one reason for neonatal admission in most Chinese neonatal units. Early severe neonatal hyperbilirubinemia, resulting in bilirubin encephalopathy, may cause kernicterus, with residual hearing loss, cerebral palsy, neurodevelopmental disabilities, and other complications. It inflicts a heavy burden on both families and society. With the use of phototherapy, exchange transfusion, and other treatment technologies, kernicterus became less common, but an upward trend in incidence has been observed in recent years. China's large population, the very uneven distribution of medical resources between regions, and Asians being at high risk for hyperbilirubinemia suggest that the incidence of bilirubin encephalopathy and kernicterus should be higher than that in Western countries. Because of the lack of large-sample epidemiological surveys and population-based disease reporting systems, the specific incidence is not clear. In 1998, Yeung (1) summarized the characteristics of neonatal jaundice in China: 1) high unconjugated hyperbilirubinemia causing neonatal jaundice is particularly prevalent in South China; 2) he believes there is a “Chinese nonspecific neonatal jaundice” characterized by the clinical jaundice being more severe and longer lasting and having a delayed peak that occurs after the fourth day; 3) hemolytic disease of the newborn due to ABO incompatibility is the most common form of hemolytic jaundice; 4) in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an acute bilirubin encephalopathy can appear late in the neonatal period; and 5) resolution of …

Prophylactic phototherapy for preventing jaundice in preterm or low birth weight infants

Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinaemia and jaundice that can lead to bilirubin encephalopathy. Phototherapy is the most common treatment for neonatal hyperbilirubinaemia and could be most effective in preventing the sequelae of hyperbilirubinaemia if initiated prophylactically. To evaluate the efficacy and safety of prophylactic phototherapy for preterm (< 37 weeks gestational age) or low birth weight infants (birth weight < 2500 g). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3) on 31 March 2011,MEDLINE (1950 to 31 March 2011), EMBASE (1980 to 31 March 2011) and CINAHL (1982 to 31 March 2011). Randomised controlled trials or quasi-randomised controlled studiesevaluating the effects of prophylactic phototherapy for preterm or low birth weight infants. Two authors independently obtained data from published articles. We performed fixed-effect meta-analysis for the outcomes: rate of exchange transfusion, cerebral palsy or other neurodevelopmental impairment, peak serum bilirubin level and all-cause mortality. Nine studies of 3449 participants were included. The rate of exchange transfusion was reduced in one study with liberal transfusion criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but not in the other two more recent studies with stringent criteria (typical RR 0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies, 756 participants). However, one large study that reported on neurodevelopmental impairment (a composite outcome including cerebral palsy) found a slightly lower rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85; 95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57; six studies, 2319 participants) and had fewer neonates with peak unconjugated serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15 mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants). There was no statistically significant difference in the rate of all-cause mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four studies, 3044 participants). Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes.

Study of Glucose -6-Phosphate Dehydrogenase Deficiency In Neonatal Jaundice.

The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to damage by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. Screening for G6PD deficiency and recognition of prevalence of the enzyme deficiency in individual communities have got definite place in the investigation of cases with neonatal jaundice. To determine the frequency and effect of G6PD deficiency the study was conducted in the Special Care Neonatal Unit of Bankura Sammilani Medical College during the period from November 2010 to December 2011. All term and preterm babies up to seventh day of age admitted with clinically evident jaundice were taken for study. Of the total 176 neonates, 24 neonates( 13.63%) had G6PD deficiency, Most are males, Jaundice developed after 24 hrs of life,.The mean age of jaundice was 70.54 hrs. of age. Peak serum bilirubin was 30 mg/dl in 16.66% of cases. with All babies G6PD deficiency was administered phototherapy in the study to avoid high rise in the peak bilirubin level. Out of them13(54.17%n=24) responded to phototherapy alone & 11 (45.83%) neonates in this group required double volume exchange transfusion.