Increased Serum Bilirubin Research Articles

COVID-19 and liver

Abstract Background and aims The coronavirus disease 2019 (COVID-19) presents a significant health risk, affecting both healthy individuals and those with underlying health conditions, including liver diseases. This study aimed to evaluate the impact of COVID-19 on liver function in both hepatic and non-hepatic patients across varying degrees of disease severity, as confirmed by PCR testing. Methods In this prospective study, we included patients with confirmed COVID-19, both with and without liver conditions, who were admitted to the National Hepatology and Tropical Medicine Research Institute (NHTMRI) and Embaba Fever Hospital between November 2020 and July 2021. Results The study cohort consisted of 255 confirmed COVID-19 patients (mean age 52.16 years, 48.6% male, 24.3% with liver conditions). Among those with liver disease, 6.4% had mild symptoms, while 4.8%, 56.4%, and 33.8% experienced moderate, severe, and critical symptoms, respectively. Clinical characteristics were insignificantly different between hepatic and non-hepatic patients across the various COVID-19 severity grades, with the exception of the loss of taste and smell in severe cases and hepatic encephalopathy and oxygen saturation in critical cases. Laboratory findings similarly showed no significant differences, except that hepatic patients exhibited a notable decrease in platelet count and a significant increase in AST and bilirubin levels compared to non-hepatic patients. In critical COVID-19 cases, non-hepatic patients had significantly higher serum ferritin levels, while hepatic patients demonstrated increased serum bilirubin levels. Mortality was considerably higher in hepatic patients than in non-hepatic patients, particularly among those with severe and critical COVID-19. The study suggests that liver disease is associated with the progression to severe COVID-19, which includes a higher risk of mortality. Conclusion COVID-19 is linked to liver function impairment, with hepatic patients experiencing higher mortality rates compared to non-hepatic patients. Summary COVID-19, a novel coronavirus, presents a serious health threat to both healthy individuals and those with pre-existing health conditions. In this study, we evaluated its impact on individuals with liver disease compared to those without. The findings indicate that COVID-19 infection is associated with a decline in liver function and increased mortality rates in patients with liver disease.

New rabbit model for benign biliary stricture formation with repeatable administration

BACKGROUND The treatment of benign biliary strictures (BBS) is a challenging clinical problem. At present, there is a lack of ideal models for the study of BBS treatment. AIM To develop a novel animal model of BBS to simulate studies on the processes and mechanisms in the human condition. METHODS A rabbit model of benign bile duct stricture was established by surgical injury of the bile duct. After removal of the gallbladder, a drainage tube was placed through the cystic duct at the stump, and a BBS model was induced by surgical injury at the lower end of the common bile duct. RESULTS Compared with the control group, the model rabbits showed gross jaundice, increased serum bilirubin, and decreased liver function. Cholangiography showed segmental bile duct stenosis in the model rabbits. Pathological staining showed inflammatory cell infiltration and fibrosis in the biliary tract of rabbits in the model group. This was consistent with the clinical manifestations of BBS. This model provided serology, imaging, pathology, and other aspects of BBS. CONCLUSION We have successfully established an animal model of benign stricture of the lower bile duct with repeatable administration, which is consistent with the clinical manifestations of BBS.

Clinical Presentation And Etiology of Acute Hepatitis In Children: An Experience From A Tertiary Centre of Bangladesh

Background: The prevalence of Acute hepatitis is still high in developing countries even though the availability of vaccines, prophylactic measures and improved sanitation. Objective: To investigate clinical features, biochemical parameters and etiology of acute hepatitis among hospitalized children in a tertiary care center. Method: This cross sectional study was conducted in the Department of Pediatrics Dhaka Medical College Hospital between June 2021 to July 2022.A total of 120 children aged bellow 15 years who presented with acute hepatitis were included in the study. Results: Most of the studied children were in 5-10 years age group 73(61%).Most of the children presented with jaundice 112 (93.3%), nausea & vomiting 105(87.5%),low grade fever 73(61%),upper abdominal pain 79(65.8%), pruritus 15(12.5%), melena 12(10%), pale stool 10(8.3%), anicteric 8(6.6%). On physical examination tender hepatomegaly was found 110(91.6%) cases, just palpable spleen 8(6.6%), hepatic encephalopathy 6(5%), ascites 4(3.3%) cases. Among the studied patients 102 (85%) were having herbal or homeopathic medicines at the time of admission. All of patients had increase serum bilirubin and ALT and most of them 79(65.8%) had ALT between 500-1500 IU/L.AST was also raised. Increase prothrombin time/INR 17(14.1%) and low serum albumin was seen in7 (5.8%) cases. Majority cases were HAV 81 (67.5%), followed by HEV 10 (8.3%), non A and non B 9(7.5%), HBsAg & anti-HBcIgM were found with positive 4 (3.3%) cases, HAV with HEV co-infection 3 (2.5%). Other than viral hepatitis Salmonella positive 5(4.1%), drug induced hepatitis due to anti-TB and valproic acid 3(2.5%) cases,3(2.5%) cases Wilson’s disease and 2(1.7%) following Wasp bite. Conclusions: The study found the common presenting features of acute hepatitis were jaundice, anorexia, nausea, vomiting, fever, abdominal pain, tender hepatomegaly and ascites. Acute hepatitis due to HAV was the commonest followed by HEV. Vaccination programme should be taken by government to control hepatitis A in children. J Dhaka Med Coll. 2023; 32(1) : 32-37

Dietary garden cress (Lepidium sativum) seeds mitigate the effect of aflatoxin B1 contamination on growth, antioxidant status, AFB1 residues, immune response, and tissue architecture of Oreochromis niloticus

Dietary garden cress (Lepidium sativum) seeds mitigate the effect of aflatoxin B1 contamination on growth, antioxidant status, AFB1 residues, immune response, and tissue architecture of Oreochromis niloticus

Activity and safety of eltrombopag in combination with cyclosporin A as first‑line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study

Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200-400 μg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with ClinicalTrials.gov, NCT02998645, and has been completed. 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33-60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. Novartis Pharmaceuticals.

One year of treatment with elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis homozygous for the F508del mutation causes a significant increase in liver biochemical indexes.

Introduction: Modulators of cystic fibrosis transmembrane conductance regulator mutated protein significantly improved the outcome of patients with cystic fibrosis (CF). We describe 63 patients who were independently followed up in two CF regional centers (i.e., Campania and Tuscany regions). Methods: All patients were homozygous for the F508del mutation and were treated with lumacaftor/ivacaftor (LI) for 3years, followed by 1year of treatment with elexacaftor/tezacaftor/ivacaftor (ETI). We studied the biochemical parameters of liver damage and cholesterol metabolism. Results: Beyond the improvement of BMI and lung function with LI treatment and even more with ETI, we found that the 3years of LI treatment significantly improved liver function parameters (total and conjugated bilirubin, ALT, AP, and GGT), while the subsequent ETI treatment caused a significant increase of such parameters. Discussion: We confirm that treatment with LI does not correct hypocholesterolemia, whereas treatment with ETI significantly increases serum cholesterol. Such an increase is likely due to enhanced de novo biosynthesis, as indicated by the significant increase in serum lathosterol, and it is likely that the subsequent liver cholesterol accumulation may contribute to triggering inflammation and worsening liver biochemical indexes. The increase in serum bilirubin and ALT that we observed in approximately 94% and 84% of patients treated with ETI, respectively, suggests further investigation of the impact of ETI therapy on liver function indexes.

Association between serum bilirubin and estimated glomerular filtration rate in diabetic patients with chronic kidney disease

Background and objectives: Hyperglycemia induces oxidative stress in diabetic patients by increasing reactive oxygen species production, which ultimately damage the cells and cause micro and macrovascular complications including diabetic nephropathy. Increased serum bilirubin level, within physiological range, can inhibit oxidative stress; thereby, preventing development of diabetic nephropathy. The aim of this study was to find out association between serum bilirubin and estimated glomerular filtration rate (eGFR) in diabetic patients with or without chronic kidney disease (CKD). Materials and method: Both male and female participants aged 30 to 60 years were enrolled in the study. Enrolled participants included healthy individuals (Group-1), diabetic patients without CKD (Group-2) and diabetic patients with CKD (Group-3). Clinical and biochemical parameters namely blood pressure, body mass index (BMI), fasting blood glucose (FBG), HbA1c, eGFR, serum bilirubin and spot urine ACR were measured by appropriate methods. Pearson’s correlation coefficient, ANOVA and multiple linear regression models were used to analyze the data. Result: Total 189 respondents were enrolled in 3 study groups. Each group consisted of 63 cases. Of the 63 cases in Group-3, 49 and 14 belonged to CKD stage 3 and stage 4 respectively. The mean (± SD) serum bilirubin levels of healthy individuals, diabetic patients without CKD and diabetic patients with CKD were 0.66 ± 0.31, 0.64 ± 0.21, 0.46±0.18 mg/dL respectively. Mean serum bilirubin was significantly low (p<0.001) in diabetic patients with CKD compared to healthy and diabetics without CKD. A Stepwise multiple regression analysis using eGFR as an objective variable adjusted for risk factors as explanatory variables, showed that serum bilirubin (β=0.323, p<0.001) was significantly associated with eGFR, in addition to age, BMI, HbA1c and urinary ACR. Conclusion: The study has demonstrated that low serum bilirubin level is associated with CKD in diabetic patients and it could be used as a simple marker for CKD in diabetics. IMC J Med Sci. 2024; 18(1):006. DOI: https://doi.org/10.55010/imcjms.18.006 *Correspondence: Tanzia Tahfim, Department of Biochemistry, Shaheed Monsur Ali, Medical College, Uttara, Dhaka-1230, Bangladesh. Email: tanzia.uamc@gmail.com

The effectiveness of Lactobacillus reuteri on serum bilirubin levels in neonatal hyperbilirubinemia with phototherapy

Background Hyperbilirubinemia occurs in 60% of full term and 80% of premature infants. Phototherapy is the main treatment, but it has side effects, sometimes requires hospitalization, and causes the baby to be separated from the mother. Underdeveloped gut microflora and increased enterohepatic circulation in newborns contribute to increased serum bilirubin levels in early life.
 Objective To assess the efficacy of adding probiotic L. reuteri on phototherapy in full-term neonates with hyperbilirubinemia.
 Methods In this double-blind, randomized clinical trial, full term infants with hyperbilirubinemia at Dr. Zainoel Abidin Hospital, Banda Aceh, Aceh, Indonesia, were randomly assigned to either an intervention or control group. All subjects received phototherapy. The intervention group was also given five drops of L. reuteri once a day orally before phototherapy started, while the control group received a placebo. Bilirubin levels after 24-hour phototherapy were evaluated in both groups.
 Results A total of 42 term neonates met the inclusion criteria. The intervention group had a significantly greater decrease in total serum bilirubin (TSB) level (6,517 mg/dL) than did the control group (4,434 mg/dL) (P<0.001), as well in indirect bilirubin levels in the intervention group had decrease 6.40 mg/dL while in the control group 4.43 mg/dL after 24 hours of phototherapy (P<0.001).
 Conclusion In full-term neonates with hyperbilirubinemia who underwent 24-hour phototherapy, adding probiotic L. reuteri leads to a significantly greater reduction in total and indirect bilirubin levels compared to the control group.

Diagnosis and Management of Constipation and Obstipation in Canine: From Current Practices to Future

This study was conducted to understand the present diagnosis and management patterns of constipation and obstipation in dog and accessing about its future holds. A total of 68 dogs both healthy (n=34) and constipated (n=34) brought to a private pet hospital in Kathmandu were included in the study for two-months during Feb-April, 2019 were recorded. The protocol comprised history taking (age, sex, breed and chief complains), physical and clinical examination, hematology/Biochemistry followed by radiography in some cases. Statistical analysis was conducted using MS-Excel 2016 and SPSS v25. We found that starting from the dietary management, rehydration and medical management using laxatives, enemas, antibiotics and supporting liver medications were being followed to manage constipation and obstipation. Anorexia (82.4%) and dehydration were the most common clinical signs. Female dogs (52.9%) were found more affected than male dogs (47.1%). Large and small breed dogs (73.5%) were more prone to constipation than medium sized breeds (26.5%). Older Dogs (>60 months) (34%) were the most affected age groups. Haemato-biochemical blood findings showed significant increase in Total Leucocyte Count (Leukocytosis), Neutrophilia, ALP levels and Blood Urea Nitrogen (p ≤ 0.001) while there was also an increase in Serum bilirubin and Serum albumin levels (p ≤ 0.05) in constipated dog. This research showed increased risk of constipation in old and female dogs. Starting from high fiber diets, mild laxatives and enemas, the treatment can be proceeded to fluid therapy, antibiotic therapy and medications managing liver ailments after haemato-biochemical examination. Use of Novel prokinetic drugs practiced in humans like Cisapride and Pruracalopride, can be considered in veterinary practice. In situations of surgical management, most reliable would be the subtotal colectomy to manage idiopathic megacolon causing constipation and obstipation.

Clinical profile of term neonates requiring intervention for hyperbilirubinemia

ABSTRACT Introduction: Neonatal jaundice is the imbalance between bilirubin production and conjugation, resulting in increased serum bilirubin levels. It is visible in the skin and eyes, only when the total serum bilirubin level exceeds 5–7 mg/dl. Sixty percent of the term and almost 80% of the preterm babies develop neonatal jaundice. Objectives: To identify the etiology of neonatal hyperbilirubinemia in term neonates and to determine short-term outcomes in terms of rebound hyperbilirubinemia during hospital stay and other modalities of intervention in these babies. Methods: We did a cross-sectional, descriptive, and retrospective chart-based study. The clinical profile of term neonates treated for hyperbilirubinemia was procured from the inpatient medical records and neonatal intensive care unit (NICU) discharge summaries over 5 years from January 2017 to December 2021. Short-term outcomes, such as duration of hospital stay, rebound hyperbilirubinemia, and other modalities of treatment used, were noted. Results: A total of 252 term babies who fulfilled the inclusion criteria were included in the study. Two hundred and thirty-four babies were delivered vaginally, 10 by cesarean section, and 8 extracted by instrumental delivery. Ninety-eight babies had ABO incompatibility and 19 Rh incompatibility. Twelve babies had elevated cord thyroid-stimulating hormone levels. Seventy-one babies had signs of bilirubin encephalopathy. Thirty-nine babies had sepsis. Fifty-three of them had significant weight loss suggestive of improper feeding. Thirty-three babies had cephalhematoma. Nine babies were born to mothers with gestational diabetes mellitus. All 252 babies underwent phototherapy. Thirty-two babies required a prolonged hospital stay of more than 1 week and seven had rebound hyperbilirubinemia. Nine babies required exchange transfusion. Two received intravenous immunoglobulin. Conclusions: The most common risk factor associated was ABO incompatibility, followed by inadequate breastfeeding. As only nine neonates required exchange transfusion, early and prompt initiation of phototherapy remains the best modality of treatment. Emphasis on proper feeding technique can go a long way in preventing admission to NICU, as it is the second-most common preventable cause of hyperbilirubinemia.

Jaundice in relation to immune activation during Epstein-Barr virus-induced infectious mononucleosis

Liver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients with infectious mononucleosis and immune abnormalities associated with jaundice. We report on an adult patient with monoclonal B lymphocytosis and IgM-lambda gammopathy who developed a severe icteric hepatitis during infectious mononucleosis. We then reviewed the clinical records of 389 patients admitted to the hospital with infectious mononucleosis between 1995 and 2018 (51.7% male patients; median age, 19 years; range, 15-87 years) with focus on liver abnormalities and associated factors. Fifty-nine patients (15.1%) had serum bilirubin concentrations between 1.5 and 3mg/dL, and 47 patients (12.0%) had serum bilirubin >3mg/dL. Patients with increased bilirubin concentrations had a distinct clinical presentation, with more frequent abdominal pain, nausea and vomiting, and less frequent sore throat than patients with normal bilirubin. Age and sex were not significantly different for the patients with increased and normal serum bilirubin concentrations. The patients with increased serum bilirubin concentrations showed higher levels of immune activation markers than the patients with normal bilirubin, including blood lymphocyte counts, serum IgM, and β2-microglobulin concentrations. Heterophile antibody-positive patients (88.6%) showed similar bilirubin concentrations but higher aspartate aminotransferase and alkaline phosphatase levels than their heterophile-negative counterparts. Serum bilirubin elevations normalized quickly during follow-up. Transient hyperbilirubinemia is common during severe (in-hospital) infectious mononucleosis in adult patients. Patients with hyperbilirubinemia have less frequent pharyngitis symptoms and more frequent abdominal symptoms. Hyperbilirubinemia during infectious mononucleosis is associated with immune activation markers.

Dose- and Intensity-Response Associations Between Leisure-Time Physical Activity and Markers of Inflammation and Oxidative Stress in Older Adults.

This study aimed to investigate the dose- and intensity-response associations between leisure-time physical activity (LTPA) and markers of inflammation and oxidative stress in older adults. Multivariable linear regression was performed to evaluate the associations among 3,559 older adults in 2015-2018 National Health and Nutrition Examination Survey. LTPA was negatively associated with inflammatory markers including C-reactive protein, segmented neutrophil count and alkaline phosphatase, and positively associated with one marker of antioxidants albumin in older adults. Compared with vigorous LTPA, moderate LTPA could provide more benefits through further decreasing white blood cell count and alkaline phosphatase, and increasing serum bilirubin and albumin. The effects of LTPA on C-reactive protein and albumin were more significant in participants with chronic diseases including diabetes, hypertension, and cancer. In conclusion, this study demonstrates the dose- and intensity-response effects of LTPA on inflammation and oxidative stress and provides exercise prescription recommendations for older adults.

Association Between Serum Bilirubin, Lipid Levels, and Prevalence of Femoral and Carotid Atherosclerosis: A Population-Based Cross-Sectional Study.

Bilirubin may prevent lipid peroxidation and have important antiatherosclerotic effects. We determined associations of serum bilirubin and lipid with peripheral atherosclerosis. We included 4290 participants (35% men; median age, 60 years) from the southeast China who underwent B-mode ultrasound examination. Increased intima-media thickness or a focal structure encroaching into the arterial lumen by at least 0.5 mm or >50% of the surrounding intima-media thickness value was regarded as having atherosclerosis. Fasting serum bilirubin and lipid levels were measured. Cholesterol/(HDL [high-density lipoprotein] cholesterol+bilirubin), and LDL (low-density lipoprotein cholesterol)/(HDL+bilirubin) ratios were calculated. Unconditional and multinomial logistic regression models were used to examine associations of bilirubin or lipid with prevalence of peripheral atherosclerosis. Mediation analyses were performed to assess the effect of bilirubin on atherosclerosis risk mediated via lipid. Compared with participants with the lowest levels of bilirubin, those with the highest tertile were less likely to have carotid or femoral atherosclerosis (odds ratios were 0.55-0.74). The highest levels of bilirubin significantly reduced the odds of concurrent carotid and femoral atherosclerosis by 35% to 45%. Participants with the highest levels of cholesterol, LDL, cholesterol/(HDL+bilirubin), and LDL/(HDL+bilirubin) ratios had 2.8- to 3.7-fold increased odds of concurrent carotid and femoral atherosclerosis. LDL accounted for 25.65% of the total bilirubin-atherosclerosis association. LDL and cholesterol mediated the associations between direct bilirubin and atherosclerosis (proportion: 20.40%, 9.67%, respectively). Increased serum bilirubin levels are inversely associated with the prevalence of carotid or femoral atherosclerosis. LDL and cholesterol may mediate these associations.

S3177 The (Icteric) Eye of the Storm: A Case of Weil’s Syndrome

Introduction: Leptospirosis is one of the most prevalent zoonotic diseases affecting humans residing in tropical areas. We herein describe a case of a patient with leptospirosis acquired in the Bronx, NY. Case Description/Methods: A 63 year-old man with no significant medical history was evaluated for muscle pain, fatigue, and diarrhea of 3 days duration. He was feverish to 102 F and icteric. Laboratory evaluation revealed hemoglobin of 7.5 g/dL, total white count of 18 k/uL, platelet count of 40 k/uL, INR 1.5, creatinine of 5 mg/dL, urea nitrogen 85 mg/dL, creatine kinase 4000 U/L, alkaline phosphatase 192 U/L, total bilirubin 39 mg/dL, direct bilirubin > 23 mg/dL, AST 96 U/L, ALT 113 U/L and albumin 2.5 g/dL. Initial laboratory evaluation was negative for common and atypical infections. Radiologic evaluation revealed unremarkable non-contrast MRCP and US abdomen. Upon further detailed history, the patient reported that his basement was recently flooded by a devastating hurricane. Despite negative parasite blood smear and IgM antibodies for leptospira, empiric treatment for leptospirosis with Ceftriaxone resulted in resolution of all symptoms and lab abnormalities. Repeated blood work on follow-up visits at 4 weeks was noted with positive IgM antibodies for leptospira (Figure). Discussion: Leptospirosis is caused by a poorly staining gram-negative spirochetal bacteria. Transmission to humans occurs through mucous membranes, open skin wounds or after drinking, eating, swimming, or wading in water contaminated by stool or urine of infected rodents. Outbreaks have been documented in non tropical, urban areas affected by hurricanes, heavy rains or floods. In approximately 90% of cases, the disease is anicteric. Phase 1 includes viral-like illness, conjunctival suppuration followed by transient improvement. Phase 2 includes myalgia, nausea, vomiting, abdominal pain, hepatomegaly, increased serum bilirubin and serum aminotransferases. 10% of cases manifest as Weil’s syndrome, characterized by jaundice in the first phase, followed by second phase manifesting with high fever, profound jaundice with severely elevated serum bilirubin levels (up to 30mg/dL, mostly direct) and elevated serum transaminases. Renal and liver involvement are predominant and can lead to severe morbidity and death. Blood cultures, urine cultures and specific anti Leptospira IgM serology can assist with diagnosis. Antibiotic treatments, primarily Penicillin, 3rd generation Cephalosporins and Doxycycline, can benefit if administered at an early stage.Figure 1.: Laboratory evaluation during hospital stay and 4 weeks after discharge. Abbreviation: ALP, alkaline phosphatase; TB, total bilirubin; DB, direct bilirubin; AST, Aspartate transaminase; ALT, Alanine transaminase.

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.

Early Development of Ubiquitous Acanthocytosis and Extravascular Hemolysis in Lung Cancer Patients Receiving Alectinib.

Simple SummaryALK translocation is present in 4–5% of patients with non-small-cell lung cancer. Patients treated with alectinib invariably develop subclinical hemolysis, which is presumably caused by acanthocytic deformation and splenic trapping of blood erythrocytes. Morphologic red blood cell changes, decreased EMA testing, and reactive reticulocytosis develop in literally all patients early after the initiation of alectinib, but not other ALK inhibitors. These alterations are not associated with the efficacy of alectinib or the molecular features of ALK+ disease and resolve within a few months after a switch to other ALK–TKI but complicate any hematologic workup. Furthermore, the risk of long-term complications, such as cholelithiasis due to increased serum bilirubin in the majority of cases, remains unclear at present.Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study analyzed a prospective cohort of 24 consecutive alectinib-treated patients and controls in order to comprehensively characterize longitudinal erythrocyte changes under treatment with ALK inhibitors. Upon starting alectinib, all examined patients developed reticulocytosis and abnormal erythrocyte morphology with anisocytosis and a predominance of acanthocytes (64% of red blood cells on average, range 36–100%) in the peripheral blood smear within approximately 2 weeks. Changes were accompanied by a gradual reduction in Eosin-5-maleimide (EMA) binding, which became pathologic (<80% of cells) within 1–2 months in all cases, mimicking an abortive form of hereditary spherocytosis. The latter could be ruled out in 3/3 of analyzed cases by normal sequencing results for the ANK1, EPB42, SLC4A1, SPTA1, or SBTB genes. The direct Coombs test was also negative in 11/11 tested cases. Besides, anemia, increased LDH, and increased bilirubin were noted in a fraction of patients only, ranging between 42 and 68%. Furthermore, haptoglobin decreases were infrequent, occurring in approximately 1/3 of cases only, and mild, with an average value of 0.93 g/L within the normal range of 0.3–2 g/dL, suggesting that hemolysis occurred predominantly in the extravascular compartment, likely due to splenic trapping of the deformed erythrocytes. These changes showed no association with progression-free survival under alectinib or molecular features, i.e., ALK fusion variant or TP53 status of the disease, and resolved upon a switch to an alternative ALK inhibitor. Thus, alectinib induces mild, reversible erythrocyte changes in practically all treated patients, whose most sensitive signs are aberrant red cell morphology in the peripheral smear, a pathologic EMA test, and reactive reticulocytosis. Frank hemolytic anemia is rare, but mild subclinical hemolysis is very frequent and poses differential-diagnostic problems. Alectinib can be continued under the regular control of hemolysis parameters, but the risk of long-term complications, such as cholelithiasis due to increased serum bilirubin in most patients, remains unclear at present.

Prevalence of Hepatitis A and E Infection in a Suburban Tertiary Care Hospital

Background: Acute viral hepatitis causes high morbidity in children and young adults. Hepatitis A and E can lead to fulminant hepatitis in 0.1% -2%. Objective: To find prevalence of HAV and HEV among suspected cases of acute viral hepatitis and to co-relate the laboratory findings with clinical presentations, over a one year periodMaterial &amp; Methods:A retrospective analysis of 396 suspected acute viral hepatitis cases, whose samples were received in the laboratory during over a period of 1 year was performed. All sera samples were tested for IgM anti HAV &amp; IgM anti HEV using commercially available solid phase ELISA, in Microbiology laboratory, at our hospital.Results:Majority infected were male (69%) and young adults (98 %). Clinical presentations included fever (92%), jaundice/icterus (74%), nausea/vomiting (60%), hepatomegaly (45%), abdominal pain (40%), darkcoloredurine(15%), itching/rash (8.3%). ELISA revealed overall positivity :21.2% ; HAV: 38% ,HEV:62% and dual infection:5%. Increased serum bilirubin, AST and ALT occured in 68%.Conclusions:Awareness regarding sanitation and hygiene is imperative to curb the spread of acute viral hepatitis, especially in developing countries. Laboratory diagnosis is an essential supplementary tool in confirmation of suspected clinical cases and reduce transmission of this infection.

The relationship between serum bilirubin levels and early neurological improvement in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator

Background &amp; Objective: Acute ischemic stroke is defined as the development of sudden neurological deficits resulting from a focal injury due to vascular occlusion in the central nervous system. Intravenous tissue plasminogen activator (t-PA) therapy in these patients is an internationally accepted, evidence- based effective treatment. Previous data suggest that increased serum bilirubin may reflect the intensity of oxidative stress associated with stroke severity. This study aimed to investigate the effect of bilirubin levels on early neurological improvement after intravenous t-PA treatment and whether bilirubin is a determinant in in-hospital mortality. Methods: The determinant role of admission bilirubin levels in the severity of stroke, in-hospital mortality and early neurological improvement after intravenous t-PA was investigated. An independent association of bilirubin with mortality and neurological improvement were identified by multivariate logistic regression analysis. Results: A total of 184 ischemic stroke patients who received intravenous t-PA were included in the study. Serum direct bilirubin, indirect bilirubin, and total bilirubin of patients in the group without early improvement were significantly higher than the group with improvement (p= 0.041, p= 0.030, p= 0.026, respectively). Also, in binary logistic regression analysis, total bilirubin was found to be an independent predictor for early neurological improvement (OR 6.257, 95%CI 1.482-26.413, p=0.013). Conclusions: There was a significant relationship between the severity of the stroke and in-hospital mortality and increased serum bilirubin levels in our study. Again, there was a significant relationship between the lack of early neurological improvement after intravenous t-PA and increased serum bilirubin levels, and serum direct bilirubin levels were independent predictor of neurological improvement.

Carbamazepine mitigates parenteral nutrition-associated liver disease in a novel ambulatory piglet model.

Parenteral nutrition (PN) remains a critical therapeutic option in patients who cannot tolerate enteral feeding. However, although lifesaving, PN is associated with significant side effects, including liver injury, the etiology of which is multifactorial. Carbamazepine (CBZ), an antiepileptic medication, is known to modulate hepatic fibrosis and hepatocellular injury in a variety of liver diseases. We hypothesized that CBZ could prevent PN-associated liver disease (PNALD), which we tested by using our novel ambulatory PN piglet model. Piglets were fitted with jugular catheters and infusion pumps for PN and randomized to enteral nutrition (n = 7), PN (n = 6), or PN with parenteral CBZ (n = 6) for 2 weeks. Serum and liver tissue were analyzed via light microscopy, quantification of serum liver injury markers, Ki67 and cytokeratin-7 indexing, and real-time quantitative polymerase chain reaction. PN-fed piglets in our model developed manifestations of PNALD-particularly, increased serum bilirubin, gamma-glutamyltransferase, liver cholestasis, and Ki67 expression compared with that of EN-fed animals (P < 0.03). CBZ therapy in PN-fed animals led to a significant reduction in these markers of injury (P < 0.05). Investigation into the mechanism of these therapeutic effects revealed increased expression of sterol regulatory element-binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor alpha (PPAR-α), and fatty acid binding protein (FABP) in PN-fed animals receiving CBZ (P < 0.03). Further investigation revealed increased LC3 expression and decreased lysosomal-associated membrane protein (LAMP1) expression with CBZ (P < 0.03). CBZ administration mitigates PNALD severity, suggesting a novel therapeutic strategy targeting PN-associated side effects, and may present a paradigm change to current treatment options.

Machine learning approach identifies meconium metabolites as potential biomarkers of neonatal hyperbilirubinemia

The gut microbiota plays an important role in the early stages of human life. Our previous study showed that the abundance of intestinal flora involved in galactose metabolism was altered and correlated with increased serum bilirubin levels in children with jaundice. We conducted the present study to systematically evaluate alterations in the meconium metabolome of neonates with jaundice and search for metabolic markers associated with neonatal jaundice. We included 68 neonates with neonatal hyperbilirubinemia, also known as neonatal jaundice (NJ) and 68 matched healthy controls (HC), collected meconium samples from them at birth, and performed metabolomic analysis via liquid chromatography-mass spectrometry. Gut metabolites enabled clearly distinguishing the neonatal jaundice (NJ) and healthy control (HC) groups. We also identified the compositions of the gut metabolites that differed significantly between the NJ and HC groups; these differentially significant metabolites were enriched in aminyl tRNA biosynthesis; pantothenic acid and coenzyme biosynthesis; and the valine, leucine and isoleucine biosynthesis pathways. Gut branched-chain amino acid (BCAA) levels were positively correlated with serum bilirubin levels, and the area under the receiver operating characteristic curve of the random forest classifier model based on BCAAs, proline, methionine, phenylalanine and total bilirubin reached 96.9%, showing good potential for diagnostic applications. Machine learning-based causal inference analysis revealed the causal effect of BCAAs on serum total bilirubin and NJ. Altered gut metabolites in neonates with jaundice showed that increased BCAAs and total serum bilirubin were positively correlated. BCAAs proline, methionine, phenylalanine are potential biomarkers of NJ.