Elevated Serum Bilirubin Research Articles

The Extent of Intracellular Accumulation of Bilirubin Determines Its Anti- or Pro-Oxidant Effect.

Background: Severe hyperbilirubinemia can cause permanent neurological damage in particular in neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated bilirubin concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects. Methods: Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) and neuronal (SH-SY5Y) cell lines were exposed to increasing concentration of bilirubin. iUCB, cytotoxicity, intracellular reactive oxygen species (ROS) concentrations, and antioxidant capacity (50% efficacy concentration (EC50)) were determined. Results: Exposure of SH-SY5Y to UCB concentration > 3.6 µM (iUCB of 25 ng/mg) and >15 µM in H5V and HK2 cells (iUCB of 40 ng/mg) increased intracellular ROS production (p < 0.05). EC50 of the antioxidant activity was 21 µM (iUCB between 5.4 and 21 ng/mg) in HepG2 cells, 0.68 µM (iUCB between 3.3 and 7.5 ng/mg) in SH-SY5Y cells, 2.4 µM (iUCB between 3 and 6.7 ng/mg) in HK2 cells, and 4 µM (iUCB between 4.7 and 7.5 ng/mg) in H5V cells. Conclusions: In all the cell lines studied, iUCB of around 7 ng/mg protein had antioxidant activities, while iUCB > 25 ng/mg protein resulted in a prooxidant and cytotoxic effects. UCB metabolism was found to be cell-specific resulting in different iUCB.

Safety and Efficacy of Lenvatinib Treatment in Child-Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis.

PurposeTo assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).MethodsPatients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.ResultsBaseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5–7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.ConclusionLenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Fluted Pumpkin (Telfairia occidentalis) protects against phenyl hydrazine-induced anaemia and associated toxicities in rats

Xenobiotics have been documented to play crucial role in pathogenesis of human diseases. Phenyl hydrazine administration has been associated with hematotoxicity by altering iron metabolism and activating immune response. Telfaria occidentalis is a medicinal plant rich in phytochemicals and minerals that are immune boosters. This study investigated the effect of ethanol leaf extract of T. occidentalis against phenyl hydrazine induced anaemia and associated toxicities in rats. Phenyl hydrazine was exposed to rats through oral administration and ethanol leaf extract of T. occidentalis or vitamin E was administered to ameliorate the toxic effect of the toxicant. This was followed by evaluation of haematological parameters, body weight, and serum protein biomarkers like bilirubin, albumin, total bilirubin. Phenyl hydrazine induced anaemia with significant reduction of blood components like haemoglobin, erythrocytes, leukocytes with concomitant reduction in the body weight of the rat compared to the control. Phenyl hydrazine also compromised serum protein homeostasis as evidenced by elevated serum total protein, albumin, bilirubin and globulin levels. Nevertheless, treatment with ethanol leaf extract of T. occidentalis modulates all the anomalies suggesting its ameliorating effects against phenyl hydrazine-induced anaemia, and may be useful in the treatment/management of chemically induced anaemia or other related diseases.

Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats.

Liver fibrosis occurs in most types of chronic liver diseases and can develop into cirrhosis and liver failure. Bone marrow-derived mesenchymal stem cells (BMSCs) showed promising effects in the treatment of fibrosis. This study evaluated the possible role of Nrf2/HO-1 signaling in the ameliorative effect of BMSCs against carbon tetrachloride (CCl4)-induced liver fibrosis, oxidative stress, and inflammation in rats. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice per week for 6 consecutive weeks and rat BMSCs were administered intravenously. After 4 weeks, the rats were sacrificed, and samples were collected for analysis. CCl4-intoxicated rats showed elevated serum transaminases, ALP, γGT, bilirubin and pro-inflammatory cytokines, and decreased albumin. Hepatic NF-κB p65 and malondialdehyde (MDA) were significantly increased, and cellular antioxidants were decreased in CCl4-intoxicated rats. BMSCs ameliorated liver function markers, suppressed MDA, NF-κB p65, and inflammatory cytokines, and enhanced antioxidants in the liver of CCl4-intoxicated rats. BMSCs were engrafted within the liver tissue and prevented histological alterations and collagen accumulation induced by CCl4. In addition, BMSCs upregulated hepatic Nrf2 and HO-1 expression in CCl4-intoxicated rats. In conclusion, this study provides evidence that BMSCs suppress oxidative stress, inflammation, and liver fibrosis through a mechanism involving activation of the Nrf2/HO-1 signaling.

Elite Athletes Have Mildly Elevated Serum Bilirubin Concentrations

Bilirubin is a potent endogenous antioxidant and immune system-modulating substance, which is implicated also in the cell signalization and in various metabolic pathways. Mild elevation of its systemic concentrations seems to provide substantial protection against numerous pathological conditions such as atherosclerotic and inflammatory diseases. Scarce reports in the literature suggest that serum bilirubin might have relevance also to the physical performance. PURPOSE: The aim of the current study was to assess serum bilirubin concentrations in the Czech elite athletes and to compare them with the Czech general population. METHODS: The study was performed in 145 consecutive healthy Czech elite athletes (M:F ratio=1.78) and in 2597 individuals (M:F ratio=0.91) of the Czech post-MONICA study randomly selected from the Czech general population. Serum bilirubin concentrations as well as prevalence of benign hyperbilirubinemia >17 umol/L (1 mg/dL, a phenotypic sign of Gilbert´s syndrome) were evaluated. RESULTS: The medians of serum bilirubin concentrations in the elite athletes were substantially higher compared to the general population (11.75 vs. 9.6 umol/L, p<0.001), and this substantial difference was observed in both men (13.02 vs. 11.3 umol/L, p=0.006) and women (10.29 vs. 8.3 umol/L, p<0.001). Compared to the general population, the prevalence of a phenotypic Gilbert´s syndrome (known also as benign hyperbilirubinemia) was significantly higher in both male (18.4% vs. 31.1%, p=0.004) and female athletes (7.4% vs. 17.3%, p<0.001). CONCLUSIONS: Elite athletes have significantly higher serum concentrations of bilirubin, the most potent endogenous antioxidant substance. Simultaneously, also the prevalence of Gilbert´s syndrome is higher in elite athletes, suggesting that the presence of Gilbert´s syndrome may predispose to better physical performance. This study was supported by grant No. SVV 260156/2019 provided by Charles University.

Role of Hyperbilirubinemia as a Diagnostic Tool to Predict Gangrenous/Perforated Appendicitis: An Observational Study

Background: Elevation in serum bilirubin was reported recently, but the importance of the raised total bilirubin has not been stressed in acute appendicitis and appendicular perforation. The aim of the study was to establish the role of hyperbilirubinemia as a new diagnostic tool to predict gangrenous/perforated appendicitis. Subjects and Methods: This was a prospective observational study, which was conducted at the Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. A total of 100 patients clinically diagnosed as appendicitis from August 2018 to August 2019 at Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. Patients were clinically evaluated by detailed history, routine examination on initial contact with patients and the routine investigations as per surgery and anesthesia requirements with inclusion of serum total bilirubin. Based on histopathological examination patients will be categorized as positive (acute appendicitis with perforation and/or gangrene) and negative (acute appendicitis without perforation or gangrene). Results: Out of 100 patients, 20 were managed conservatively (mass formation) and was called for interval appendectomy after 6 weeks. In acute catarrhal appendicitis group 47 patients showed normal total bilirubin levels, whereas 8 patients showed increase in levels of total bilirubin. In gangrenous appendicitis group all 10 patients showed elevated serum total bilirubin levels In perforated appendicitis group consisted of 15, 11 patients showed elevated serum bilirubin levels and 4 patients showed normal total bilirubin levels. Conclusion: Serum bilirubin is easily available test and cheap and can be estimated from the sample of blood drawn for routine blood investigations.

Postsurgical Management of Dilated Biliary Tract in Children: Ultrasound-Guided Percutaneous Transhepatic Cholangial Drainage and Subsequent Percutaneous Ultrasound Cholangiography.

OBJECTIVE. The purpose of this study was to evaluate the feasibility of ultrasound (US)-guided percutaneous transhepatic cholangial drainage (PTCD) and consequent percutaneous US cholangiography in managing the dilated biliary tracts of children who have undergone hepatobiliary surgery. SUBJECTS AND METHODS. Sixteen children (11 boys, five girls; age range, 3-144 months) who underwent hepatobiliary surgery from December 2016 to October 2018 and had US evidence of biliary dilatation were included. All patients had undergone US-guided PTCD because of elevated postoperative serum bilirubin levels or bile duct infection. Immediately after the PTCD procedure, diluted sulphur hexafluoride microbubbles dispersion was injected through the PTCD tube to evaluate the anastomosis and the intrahepatic bile duct tree. Laboratory results, including those of serum bilirubin measurement, liver function tests, and routine blood tests, were evaluated before and after PTCD. Nine of 16 patients also underwent percutaneous transhepatic cholangiography (PTC). The percutaneous US cholangiography findings were evaluated and compared with the PTC findings. RESULTS. Liver enzyme levels decreased after PTCD with a statistically significant difference from the values before PTCD. Percutaneous US cholangiography showed that the anastomosis in 6 of the 16 patients (37.5%) was patent and depicted the morphologic featuresof intrahepatic bile duct tree in five of these patients. In the other 10 patients, the anastomosis was completely obstructed, and percutaneous US cholangiography depicted the morphologic features of intrahepatic bile duct tree in eight patients. In the nine patients who underwent PTC, the percutaneous US cholangiographic findings were the same as the PTC findings. CONCLUSION. US-guided PTCD is helpful in relieving jaundice and inflammation in children who have undergone hepatobiliary surgery and have biliary dilatation. Findings at consequent percutaneous US cholangiography are comparable to those of PTC in depicting the anastomosis in these patients.

Bilirubin as a signaling molecule.

For long time bilirubin was only considered as a potentially dangerous sign of liver diseases, but it now appears clear that it is also a powerful signaling molecule. Together with potent antioxidant activities that were only reported in the last few decades, many other biological effects have now been clearly described. These include especially profound inhibitory effects on almost all effectors of the immune system, with their clinical consequences in the bilirubin-mediated protection against autoimmune and inflammatory diseases. Separate from these, bilirubin activates various nuclear and cytoplasmic receptors, resembling the endocrine activities of actual hormonal substances. This is true for the "classical" hepatic nuclear receptors, including the aryl hydrocarbon receptor, or the constitutive androstane receptor; and also for some lesser-explored receptors such as peroxisome proliferator-activated receptors α and γ; Mas-related G protein-coupled receptor; or other signaling molecules including fatty acid binding protein 1, apolipoprotein D, or reactive oxygen species. All of these targets have broad metabolic effects, which in turn may offer protection against obesity, diabetes mellitus, and other metabolic diseases. The (mostly experimental) data are also supported by clinical evidence. In fact, data from the last three decades have convincingly demonstrated the protective effects of mildly elevated serum bilirubin concentrations against various "diseases of civilization." Additionally, even tiny, micromolar changes of serum bilirubin concentrations have been associated with substantial alteration in the risks of these diseases. It is highly likely that all of the biological activities of bilirubin have yet to be exhaustively explored, and thus we can expect further clinical discoveries about this evolutionarily old molecule into the future.

Elevated serum bilirubin in acute appendicular perforation as a newer serum marker: a diagnostic validation test

Background: Acute appendicitis is the commonest cause of acute surgical abdomen. Appendicectomy is the most frequently performed urgent abdominal operation and is often the first major procedure performed by a surgeon in training. Delay in diagnosis and treatment results in increased rate of perforation, morbidity, mortality and hospital stay.Methods: A prospective study where a total of 100 patients with clinical, radiological and histopathological diagnosis of acute appendicitis or appendicular perforation were studied. The liver function tests were carried out in all the patients.Results: In a study group of 100 patients (74 males and 26 females); 59 cases were acute appendicitis and 41 cases were appendiceal perforation proven histopathological. Out of which 48 cases had elevated serum bilirubin levels i.e., 17 in acute appendicitis group and 31 in appendicular perforation group. The mean serum total bilirubin is 1±0.4 in acute appendicitis cases and 1.9±1.13 in the appendicular perforation cases. Similarly, the sensitivity and specificity of elevated serum bilirubin as a diagnostic marker in appendicular perforation was found to be 75.6% and 71.2% respectively.Conclusions: Elevated serum bilirubin levels appears to be a promising new supplemental diagnostic serum marker in Appendicular Perforation and perhaps be a decision-making investigation.

Predictive Factors and Surgical Outcomes of Stent Dysfunction After Preoperative Endoscopic Biliary Stenting in Patients Who Underwent Pancreaticoduodenectomy.

Background: Endoscopic biliary stenting (EBS) using a plastic stent is currently widely performed for preoperative biliary drainage for periampullary cancer. The aim of this study was to investigate the risk factors and surgical outcomes of stent dysfunction after EBS in patients who underwent pancreaticoduodenectomy (PD). Patients and Methods: The subjects were 85 patients who underwent PD after EBS using a plastic stent for malignant biliary obstruction between November 2008 and January 2019. We retrospectively investigated the relationship between perioperative patient characteristics and the incidence of stent dysfunction. Stent dysfunction was defined as insufficient biliary drainage and the presence of various symptoms, including high fever and abdominal pain, with elevated serum hepatobiliary enzyme levels or bilirubin level. Results: Stent dysfunction occurred in 38% of patients. In univariate analysis, serum total bilirubin before the initial EBS ≥15 mg/dL (P = .0244) and a stent diameter of 7 Fr (P = .0044) were significant predictors of stent dysfunction. In multivariate analysis, the only significant independent predictor of stent dysfunction was a stent diameter of 7 Fr (P = .0227). In the patients without stent dysfunction, duration from the initial EBS to the operation was significantly shorter than that in the patients with stent dysfunction (P = .0055). Operation time, intraoperative blood loss, postoperative pancreatic fistula, and bile leakage were comparable between the two groups. Conclusion: Seven French stent was the significant independent predictor of stent dysfunction after EBS in patients who underwent PD.

Effect of laparoscopy on liver enzymes

Background: Laparoscopic procedures have gained popularity in recent days because of advantages like small incision, less postoperative pain and discomfort, short hospital stay, early ambulation and early discharge. Very few studies are available to correlate Laparoscopic Surgeries and liver enzyme elevation. This effect may be due to either CO2 pneumoperitoneum, diathermy extruding liver, injury to branch of the hepatic artery or general anesthesia. This study was done to evaluate the changes in liver enzymes pre-operatively and post-operatively following laparoscopy.Methods: This prospective study included 103 patients who underwent various laparoscopic surgeries over a period of 2 years in Bharati Hospital &amp; Research Centre, Pune, India. Serum AST, ALT and bilirubin levels were measured preoperatively and on post-operative day 1 and post-operative day 3. Patients with coexisting liver disease, Patients on long term use of hepatotoxic drugs, patients who developed complications such as CBD injury, obstruction, infection, leakage and high grade fever during surgery and in the post-operative period were excluded.Results: All laparoscopic procedures cause a transient elevation of serum bilirubin and liver enzymes. Elevation in the liver enzymes correlated directly with the duration of pneumoperitoneum. Elevation in the serum bilirubin but doesn’t correlates with the duration of pneumoperitoneum. These elevations do not have clinical significance in patients with normal hepatic function preoperatively.Conclusions: Duration of laparoscopic procedure should be kept to minimum and undue prolongation should be avoided. Decision to convert the operation to open surgery from a laparoscopic surgery should be prompt.

To study diagnostic efficacy of ultrasound and magnetic resonance cholangiopancreatography in obstructive jaundice

Background and Objective: Ultrasonography (??USG) and magnetic resonance cholangiopancreatography (??MRCP) are noninvasive modalities for evaluation of patients with obstructive jaundice. USG is widely available and less expensive compared to MRCP. But the value of USG is limited in obese patients and distal CBD evaluation due to poor window caused by bowel gas. With this knowledge, we planned to assess the diagnostic efficacy of USG and MRCP in detecting the level and cause of obstructive jaundice considering the gold standard being the final diagnosis made at surgery/Endoscopic retrograde cholangiopancreatography (ERCP). Settings and Design: Prospective observational study. Material and Methods: The study was conducted in the department of Radio Diagnosis, SVIMS, over a period of 18 ?months from March 2018–July 2019. This study includes thirty-seven consecutive patients who were referred to the department of Radiodiagnosis with the clinical suspicion of obstructive jaundice and elevated serum bilirubin levels. USG followed by MRCP were done in all the patients. Results: Of the thirty-seven patients with obstructive jaundice, twenty-nine patients had benign while eight patients had malignant etiology. For diagnosing the cause of obstructive jaundice, MRCP has a diagnostic accuracy of 97.2% and USG has a diagnostic accuracy of 86.4%. The sensitivity of MRCP is greater than USG in diagnosing the cause of obstructive jaundice. In diagnosing the level of obstruction, MRCP had an accuracy of 100%, while USG 81%. Conclusion: As MRCP has more diagnostic accuracy compared to ultrasound in detecting the level and cause of obstruction in cases of obstructive jaundice, USG may be considered as an initial screening test and MRCP for definitive treatment planning. The limitation of the study is the small sample size.

Eltrombopag for the treatment of primary immune thrombocytopenia in 23 pediatric patients

目的评估艾曲泊帕治疗儿童原发免疫性血小板减少症（ITP）的疗效和不良反应。方法回顾性分析2015年5月至2019年3月接受艾曲泊帕治疗的23例儿童ITP患者临床资料。结果23例患者中，男11例，女12例，中位年龄11（2~17）岁。新诊断ITP 4例（17.39%），持续性ITP 8例（34.78%），慢性ITP 11例（47.83%）。艾曲泊帕中位起始剂量为25.0（12.5~50.0）mg/d。基线中位血小板计数为14（2~82）×109/L，治疗后第2周（23例）、第4周（23例）、第3个月（16例）、第6个月（11例）的中位血小板计数分别为40（4~170）×109/L、20（4~130）×109/L、60（4~110）×109/L、70（18~160）×109/L，均高于基线水平（z=-3.440，P=0.001；z=-1.964，P=0.049；z=-4.339，P<0.001；z=-5.794，P<0.001）。7例（30.43%）患者的起效时间≤7 d，10例（43.48%）患者的起效时间≤2周，总有效率为60.87%（14/23）。<6岁（6例）、6~12岁（10例）、13~17岁（7例）组的总有效率分别为33.33%（2/6）、60.00%（6/10）、85.71%（6/7），组间比较差异均无统计学意义（P>0.05）。23例患者基线WHO出血评分0、1、2级分别有4、12、7例，治疗后分别为13、7、3例，出血症状得到明显改善（χ2=7.558，P=0.006）。治疗过程中发生转氨酶、胆红素增高各4例，轻度恶心、呕吐及头晕各1例，对治疗均未造成影响。结论艾曲泊帕作为二线用药治疗儿童ITP疗效及耐受性均较好。

Follow-Up of Neuropsychological Development During the First Postnatal Year in Infants with Neonatal Jaundice

Summary It is believed that 98% of newborns have elevated serum bilirubin levels, but only about 60% have clinic of jaundice. Severe late neurological effects should not be observed if the serum bilirubin levels are well controlled. To follow-up the motor and mental development during the first year of life in infants suffered from neonatal jaundice. The study includes 92 term babies, divided in four groups: A – without jaundice, B – with jaundice treated by phototherapy in the 1st week , C - intensive jaundice during the first 14 postnatal days , D – intensive prolonged jaundice . Studied indicators: birth weight , gestational age, sex, delivery mode, Apgar score, maternal age and education, domicile, bilirubin serum levels during hospital stay, transcutaneous bilirubin levels ambulatory. Neuro-psychological development was assessed monthly until the 1-year-age.We found that groups were comparable across the all indicators except for residence, with significant difference for groups B and D. There was a statistically significant development delay in the Group D compared to the other three groups in the all studied age periods. All the cases of prolonged jaundice were resolved until the age of 3rd month. According to our data, prolonged jaundice compromises the first-year-psychomotor- development of the infants.

Yellow Means Caution: Correlations Between Liver Injury and Mortality with the Use of VA-ECMO

Abnormalities in markers of liver injury after venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiation are of unclear distribution and clinical significance. This study included all consecutive adult patients from a single institution who underwent VA-ECMO cannulation between May 2012 and September 2016 and had liver function panels drawn during their admission (n = 223). Data points include: age, sex, body mass index, diagnosis, duration of ECMO cannulation, duration of hospitalization, pre-ECMO cardiac arrest, central nervous system (CNS) injury, the presence of chronic kidney disease or acute renal failure, renal replacement therapy utilization, lactate levels, duration of pre-ECMO intubation, admission and peak bilirubin/aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) levels, and time to peak bilirubin/AST/ALT/ALP in relation to cannulation. Multivariate Poisson regression analyses were performed to determine associations with mortality. In-hospital mortality was 66%. Serum bilirubin elevation appeared to significantly correlate continuously with mortality. Other markers of liver injury were not significant in final multivariate models. As a univariate factor, no patient survived with a total serum bilirubin greater than 30 mg/dl, and specificity for 90% mortality was crossed at 11 mg/dl. Mortality was also significantly associated with the presence of CNS injury and elevation of lactic acid levels. Postcannulation liver injury is significantly associated with increased mortality and total serum bilirubin appears to be a biomarker of considerable clinical significance.

2415 Seeing Is Believing: Conjunctival Suffusion in a Jaundiced Patient Diagnosed With Leptospirosis

INTRODUCTION: The broad differential in the workup of infectious causes of abnormal liver enzymes can be narrowed by a good history and physical. Bilateral Conjunctival suffusion, characterized by non-purulent conjunctivitis, is present in 55% of patients with leptospirosis and is uncommon in other infectious diseases. We report a case of leptospirosis in a patient with conjunctival suffusion, abnormal liver enzymes, jaundice, and recurrent fevers. CASE DESCRIPTION/METHODS: A 44-year-old previously healthy Hispanic male presented with painless jaundice, subjective fevers, nonproductive cough, and a morbilliform rash for 14 days. He reported no recent travel, sick contacts, bad habits, or hepatotoxic herbal medications, and he worked in a slaughterhouse. He denied joint pain, abdominal pain, and pruritus. On exam, he had a temperature of 38.2°C and was tachycardic to 117 with normal blood pressure. He had bilateral non-purulent conjunctivitis with mild scleral icterus and a faint morbilliform rash over both his thighs. Laboratory data was remarkable for leukocytosis (14.9 WBC/mm3), elevated bilirubin (4 mg/dL total, 2.3 mg/dL direct), Alkaline phosphatase (517 U/L), AST (84 U/L) and ALT (162 U/L). Imaging studies revealed hepatic steatosis with no other findings. Infectious workup indicated that leptospira antibody to IgM were likely present based on DOT BLOT testing (ARUP labs). Serologic testing for other infectious causes were unremarkable. The patient was started on doxycycline 100 mg twice a day for one week for mild leptospirosis with improvement in his symptoms, labs, and clinical exam. DISCUSSION: Leptospirosis, although endemic in the tropics, is a rare cause of jaundice and abnormal liver enzymes in the United States. It is associated with environmental exposure such as animal urine, contaminated water or soil, or infected animal tissue. Gastrointestinal clinical features include abdominal pain, jaundice, elevated hepatic transaminases and serum bilirubin. An important but frequently overlooked clinical finding is bilateral conjunctival suffusion, which is rare in other infectious diseases. Diagnosis is made by serologic testing for IgM antibodies. Treatment involves supportive care with oral doxycycline in mild cases and IV antibiotics for hospitalized patients. An astute physician should have a high index of suspicion for leptospirosis if non-purulent conjunctivitis is found in the infectious workup of fever and abnormal liver enzymes as it may save time and prevent excessive testing.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B.

Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.

Predictors of Major Bleeding and Mortality in Dengue Infection: A Retrospective Observational Study in a Tertiary Care Centre in South India.

We conducted a retrospective observational study to describe the clinical profile and outcomes of patients admitted with a diagnosis of dengue fever in a tertiary hospital in South India. A total of 159 patients admitted from April 2014 to October 2018 were included in the study. Vomiting (70.4%), myalgia (60.4%), headache (42.1%), abdominal pain (38.4%), bleeding (38%), and rash (37.1%) were the most common symptoms at presentation. The mean duration of hospital stay was 4.9 days (SD ± 2.4), and the median cost was INR 19,708 ($285) (IQR INR 12,968–32,056 ($188–$305)). Major bleeding was associated with elevated SGOT and SGPT, severe dengue, and secondary dengue. Mortality was associated with elderly age; elevated total leukocyte count, serum bilirubin, serum creatinine, SGOT, and SGPT; and high SOFA score. In view of these observations, we recommend stratifying patients according to the WHO classification of dengue and avoiding the use of thrombocytopenia as a single marker of the severity of the illness.

Antituberculosis Drug-induced Hepatotoxicity in Pediatric Tuberculosis

Background : Hepatotoxicity is the most serious side effect caused by using oral antituberculosis (OAT) drugs. This study was performed to determine the characteristics of patients who had antituberculosis drug-induced hepatotoxicity (ADIH) among pediatric inpatient with pulmonary tuberculosis. Methods : This was a cross-sectional study with a total sampling of medical records taken from January–December 2012, including pediatric pulmonary tuberculosis inpatients aged &lt;14 years old at the Department of Child Health of Dr. Hasan Sadikin General Hospital Bandung. The inclusion criteria were children with pulmonary tuberculosis who received OAT drugs. Patients with liver disease were excluded. Data on alanine and aspartate aminotransferase were collected and an increased level of serum aminotransferase was designated as hepatotoxicity. Results : In total, 86 medical records were obtained of whom 24 had ADIH, predominantly occurred in girls (71%), aged 5–9 years old (42%) and in the intensive phase of therapy (58%). Elevated serum alanine aminotransferase (58%), aspartate aminotransferasen (92%), and bilirubin (0.8%) were found. Malnutrition (46%) was common. The difference indeviation of liver function was statistically significant (p&lt;000) between subjects with and without ADIH. Conclusions : Hepatotoxicity is most prominent in patients with malnutrition, girls aged 5–9 years old and in the intensive phase of therapy. Children with malnutrition during antituberculosis therapy are suggested to have a periodic liver function test monitoring to prevent the development of ADIH.

Liver function assessment using indocyanine green plasma disappearance rate in a young male with icteric leptospirosis: a case report

BackgroundLeptospirosis is one of the leading global zoonotic causes of morbidity and mortality. It is induced by a pathogenic spirochete of the genus Leptospira. The icteric form of leptospirosis is characterized by pronounced hyperbilirubinemia and associated with significantly increased mortality. Conventional static liver function tests insufficiently assess hepatic damage and have limited prognostic value. Dynamic tests, such as indocyanine green plasma (ICG) clearance, more adequately reflect hepatic functional status. In this case report we describe the ICG plasma disappearance rates (ICG-PDR) in a patient with leptospirosis and massive hyperbilirubinemia, expanding our knowledge of liver dysfunction in icteric leptospirosis.Case presentationA 21-year-old Caucasian man presented with acute-onset jaundice, myalgia, fever and headaches. Laboratory tests upon admission revealed, most notably, acute kidney failure and hyperbilirubinemia of 17 mg/dl with mild elevation of aminotransferases. In the course of the following 4 days, total serum bilirubin increased to 54 mg/dl. The clinical outcome was favorable with intravenous ceftriaxone and doxycycline. Presumptive diagnosis of leptospirosis was later confirmed by PCR-based amplification of leptospiral DNA in the blood. ICG-PDR values, bilirubin as well as aminotransferases were recorded throughout hospitalization and a 3-month follow-up period. Initially dramatically reduced ICG-PDR (2.0%/min, normal range: 18–25%/min) rapidly normalized within 10 days, while bilirubin remained elevated up to week 7. Mild elevation of serum alanine aminotransferase was at its peak of 124 U/l by day 12 and reached close to normal levels by week 7 upon admission.ConclusionsMarkedly diminished ICG-PDR values presented in this case report suggest severe liver function impairment in the acute phase of icteric leptospirosis. Prolonged elevation of serum bilirubin may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis in addition to the static tests.