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Background & Aims: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients., Methods: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN., Results: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge., Conclusion: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis., Lay Summary: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC., Methods: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS)., Results: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006)., Conclusion: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC., Lay Summary: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: It is controversial to test for urinary tract infection (UTI) in patients with unexplained indirect hyperbilirubinemia in the first 2 weeks of life. We aimed to study the prevalence and significance of UTIs in such neonates who were requiring phototherapy., Methods: Subjects were 2- to 14-day-old neonates with indirect bilirubin levels above phototherapy limit with no other abnormality in their bilirubinaemia-related etiologic workup. UTI was diagnosed by 2 consecutive positive cultures obtained by catheterisation, documenting growth of >10,000 colonies of the same microorganism with consistent antibiograms. The UTI (+) patients were evaluated by renal ultrasonography (US), and some were followed up for possible recurrent UTI., Results: 262 neonates were included in the study. UTI prevalence was 12.2%, and bacteraemia was 6.2% among UTI (+) patients. The two most common pathogens (81.2%) were Escherichiacoli and Klebsiella. pneumonia. All UTI (+) patients had undergone US, revealing 12.5% pelvicaliectasis, other 12.5% increased renal parenchymal echogenicity, 3.1% concurrent pelvicaliectasis and increased renal parenchymal echogenicity. 53.1% of UTI (+) patients had undergone follow-up, after which 23.5% recurrent UTI were found at the end of a mean of 52 months., Conclusion: We suggest that the neonates with unexplained pathological jaundice should be tested for possible UTI. Consequently, all newborns with UTI shall be evaluated by the urinary US and followed up for recurrent UTI., (Copyright © 2017. Published by Elsevier B.V.)

Background: Liver dysfunction in left ventricular assist device (LVAD) recipients is common both before and after implantation. Postoperative liver dysfunction (PLD) develops in some LVAD recipients without preoperative liver dysfunction. The aim of this study was to assess clinical outcomes in such patients., Methods: Records of all patients undergoing implantation of a HeartMate II (HM II, St. Jude Medical, Inc, Minneapolis, MN) LVAD at a single center at the University of Minnesota from January 2005 through June 2014 were analyzed. PLD was defined by hypertransaminasemia or hyperbilirubinemia, or both, during the hospitalization for LVAD implantation., Results: During the study period, 284 patients underwent HM II implantation. Excluded from analysis were 14 recipients with preoperative liver dysfunction. In the final cohort (n = 270), there were no major difference in preoperative characteristics among those patients with versus without PLD. PLD developed in 129 (47.8%) recipients: 16 (12.4%) had isolated hypertransaminasemia (group I), 76 (58.9%) had isolated hyperbilirubinemia (group II), and 37 (28.7%) had combined hypertransaminasemia and hyperbilirubinemia (group III). Group III LVAD recipients had significantly greater rates of 30-day, 90-day, and 1-year mortality, along with significantly higher transfusion requirements and higher rates of renal replacement therapy, prolonged ventilation, and vasopressor use. Moreover, their mortality risk was significantly higher than that of PLD-free LVAD recipients (hazard ratio, 4.6; 95% confidence interval, 2.1 to 10.1; p < 0.001)., Conclusions: Isolated hyperbilirubinemia is common after LVAD implantation. In this study, it was not associated with an increase in early or midterm postoperative mortality. However, postoperative combined transaminasemia and hyperbilirubinemia was associated with a significant increase in early and midterm morbidity and mortality. Further research into the pathogenesis of post-LVAD PLD is necessary., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis., Methods: Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed., Results: PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN., Conclusions: This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This animal model serves as an experimental model to further investigate the pathogenesis of PNALD inflicted by steatosis and cholestasis., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Parenteral fish-oil (FO) therapy is a safe and effective treatment for intestinal failure-associated liver disease (IFALD). Patients whose cholestasis does not resolve with FO may progress to end-stage liver disease., Objective: We sought to identify factors associated with the failure of FO therapy in treating IFALD to guide prognostication and referral guidelines., Design: Prospectively collected data for patients treated with FO at Boston Children's Hospital from 2004 to 2014 were retrospectively reviewed. Resolution of cholestasis was defined as sustained direct bilirubin (DB) <2 mg/dL, and treatment failure as liver transplantation or death while DB was >2 mg/dL as of July 2015. Demographics, laboratory values, and medical history at FO therapy initiation were compared between patients who achieved resolution of cholestasis and those who failed therapy., Results: Among 182 patients treated with FO, 86% achieved resolution of cholestasis and 14% failed therapy. Patients who failed therapy had median (IQR) lower birth weight [1020 g (737, 1776 g) compared with 1608 g (815, 2438 g); P = 0.03] and were older at FO initiation [20.4 wk (9.9, 38.6 wk) compared with 11.7 wk (7.3, 21.4 wk); P = 0.02] than patients whose cholestasis resolved. Patients who failed therapy had more advanced liver disease at therapy initiation than patients whose cholestasis resolved, as evidenced by lower median (IQR) γ-glutamyltransferase [54 U/L (41, 103 U/L) compared with 112 U/L (76, 168 U/L); P < 0.001], higher DB [10.4 mg/dL (7.5, 14.1 mg/dL) compared with 4.4 mg/dL (3.1, 6.6 mg/dL); P < 0.001], and a higher pediatric end-stage liver disease (PELD) score [22 (14, 25) compared with 12 (7, 15); P < 0.001]. A PELD score of ≥15, history of gastrointestinal bleeding, age at FO initiation ≥16 wk, presence of nongastrointestinal comorbidities, and mechanical ventilation at FO initiation were independent predictors of treatment failure., Conclusions: Most infants with IFALD responded to FO therapy with resolution of cholestasis, and liver transplantation was rarely required. Early FO initiation once biochemical cholestasis is detected in parenteral nutrition-dependent patients is recommended. This trial was registered at clinicaltrials.gov as NCT00910104., (© 2016 American Society for Nutrition.)

This prospective study assessed the incidence, clinical profile and outcome of malarial hepatopathy and its association with other complications in patients with malaria, proved by peripheral blood smear examination and rapid malaria test. Hyperbilirubinemia (Serum bilirubin >3mg/dL) with >3-fold rise in serum aminotransferases in absence of a different explanation for such derangement was considered as malarial hepatopathy. Of 134 (falciparum-81, vivax-48 and mixed falciparum and vivax-5) malaria cases, hyperbilirubinemia occurred in 41.04%. Serum aspartate aminotransferase (AST) was raised >3-fold in 17.16% and serum alanine aminotransferase (ALT) in 4.47% cases. Malarial hepatopathy was observed in 4.47% (falciparum-5 and vivax malaria-1) cases, but had insignificant association with the type of malaria (p=0.532). Serum bilirubin, AST and ALT levels were higher while age was lower in both overall (p<0.05 each) and falciparum malaria cases with hepatopathy than without hepatopathy (p<0.05 each). Malarial hepatopathy was associated with a higher incidence of cerebral malaria, shock, acute respiratory distress syndrome (ARDS) and acute kidney injury in both overall (p<0.05 each) and falciparum malaria (p<0.05 each) and hyponatremia and disseminated intravascular coagulation only in overall malaria (p<0.05). Malarial hepatopathy had significant association with duration of hospitalization, parasite clearance time, fever clearance time and jaundice clearance time in overall (p<0.05 each) and falciparum (p<0.05 each) but not vivax malaria cases (p>0.05 each). Mortality occurred in 1 (20%) case of falciparum-induced hepatopathy with an overall mortality of 16.66%. ARDS (p=0.003) and shock (p=0.026) were independently associated with malarial hepatopathy overall while only ARDS with falciparum-induced hepatopathy (p=0.006). Thus, hepatocellular dysfunction is common in malaria but that qualifying as malarial hepatopathy is not common. Malarial hepatopathy is likely to occur in presence of other malarial complications. It is an epiphenomenon in severe malaria and indicative of severe disease. Establishing a particular association with malaria or mortality would require a larger case-control study of severe malaria., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We report the case of a newborn presenting with hemolytic anemia, thrombocytopenia, hyperbilirubinemia, and renal failure in the first hours of life. An early plasmatherapy was undertaken, with good outcome. The specific von Willebrand factor-cleaving protease activity (ADAMTS 13 for a disintegrin and metalloprotease with thrombospondin type 1 repeats) was found to be low. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura (TTP). This disease of constitutional thrombotic microangiopathy is rare. The prognosis, usually life-threatening, was completely transformed given the better understanding of the pathogenesis of the disease and therapeutic progress., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Patients with liver disease have multisystem organ dysfunction that leads to physiological perturbations ranging from hyperbilirubinaemia of no clinical consequence to severe coagulopathy and metabolic disarray. Patient-specific risk factors, clinical scoring systems, and surgical procedures stratify perioperative risk for these patients. The anaesthetic management of patients with hepatic dysfunction involves consideration of impaired drug metabolism, hyperdynamic circulation, perioperative hypoxaemia, bleeding, thrombosis, and hepatic encephalopathy.

Context: Non-falciparum malaria is less studied than Plasmodium falciparum malaria, both in endemic and non-endemic zones., Patients and Method: A retrospective study was made of the medical files of patients managed for attacks of malaria due to Plasmodium vivax or Plasmodium ovale, between 2000 and 2009, in two French military teaching hospitals., Results: Seventy-five percent of attacks occurred after a stay in French Guiana, in the Comoros Archipelago, or in the Ivory Coast Republic. The most frequent symptoms two months after coming back were a flu-like syndrome with headaches, and occasional digestive symptoms, without any difference between the first attack and recurrence. One third of patients presented with anemia, 78% with thrombocytopenia, and 12% with liver dysfunction., Discussion: This study was the most important made in France on imported non-falciparum malaria. Military patients and immigrants accounted for a majority of patients due to the specificity of military hospitals and local recruitment. Clinical and biological features were not specific and did not allow guiding the diagnosis. Diagnostic tools were less sensitive for P. ovale., Conclusion: Patient management could be optimized by more efficient diagnostic tools, specific guidelines for the diagnostic and therapeutic management, and a dedicated medical training for family practitioners as well as hospitals practice., (Copyright © 2013. Published by Elsevier SAS.)

Surgical repair of a left ventricular pseudoaneurysm is challenging. Percutaneous closure with an AMPLATZER Septal Occluder (AGA Medical Corporation, Golden Valley, MN) has evolved to be an effective alternative to conventional surgery with less complication. We report a case of severe hemolytic hyperbilirubinemia and acute renal failure after percutaneous left ventricular pseudoaneurysm endoprothesis repair, which required conventional surgical repair through a left thoracotomy to treat this complication. The rationale and results of such an off-the-label usage of AMPLATZER Septal Occluder were reexamined. Residual leakages were not rare findings in the reviewed literature. The indications for this approach should be individualized., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old., Methods: We prospectively evaluated 120 asymptomatic jaundiced and 122 healthy neonates without jaundice younger than 4 weeks old for UTI. Patients with UTI, defined as >10,000 colony-forming units of a single pathogen per milliliter urine obtained by bladder catheterization, were evaluated for sepsis., Results: Of 120 asymptomatic jaundiced neonates with a mean age of 7 ± 4 days, 15 (12.5%) had a UTI. Of 122 healthy neonates, positive urine cultures from a urine bag were found in eight cases; however on reevaluation, urine cultures from bladder catheterization were negative. The most common pathogen isolated from the UTI cases was Klebsiella pneumoniae. Also, unconjugated hyperbilirubinemia was detected in all jaundiced patients with UTI., Conclusion: UTI was found in 12.5% of the asymptomatic jaundiced neonates with the onset of unconjugated hyperbilirubinemia in the first week of life. Therefore, we suggest that urine culture should be considered as a part of the diagnostic evaluation of jaundiced neonates older than 3 days with an unexplained etiology., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Parenteral nutrition-associated conjugated hyperbilirubinemia (PNAC), commonly defined as direct bilirubin ≥2 mg/dL (34.2 μmol/L), is primarily a pediatric disease with premature infants being the most susceptible. Severe morbidity and increased mortality are associated with bilirubin >10 mg/dL (171.0 μmol/L). The lack of knowledge regarding the cause of PNAC has stymied development of prevention and treatment strategies. A systematic search of published reports was conducted to provide data on histopathology of PNAC and to review prospective, randomized, controlled trials in hospitalized infants. In experiments of young animals, parenteral nutrition (PN) with and without soy oil emulsion is directly linked to hyperbilirubinemia, and the effects are exaggerated by overfeeding. In infants, the most consistently reported risk factor for PNAC is the duration of PN. The only known effective modality is the transition to full enteral feeding and discontinuation of PN. Emerging clinical research is evaluating the role of lipid source (soy vs fish) and motility agents, such as erythromycin. Different trace element preparations are associated with varying severity of cholestasis, a finding that also deserves more study. This article reviews the prevalence, risk factors, clinical presentation, and treatment options for PNAC in neonatal intensive care units., (Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the efficiency of blood tests (blood group, direct antiglobulin test) to assess severe hyperbilirubinemia in full-term newborns, delivered from mothers with rhesus negative or O group and to determine clinical and biological factors that may improve the prediction characteristics of this blood test., Patients and Methods: We included all the full-term newborns, delivered from mothers with rhesus negative or O group, in a tertiary maternity ward, in 2005, from January6th to December31st., Results: One thousand and ninety-two children were included. Newborns of A, B or AB group delivered from a mother 0 were at increased risk of presenting severe hyperbilirubinemia (OR=2.35 [1.22-4.52]). The negative predictive value was 96%. Yet, the determination of the Coombs test does not increase NPV., Conclusion: Systematic performance of blood test for newborns delivered from mother with O group does increase the ability to predict severe hyperbilirubinemia in a newborn infant. Direct antiglobulin test systematic performance remains questionable., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Objectives: To describe clinical, biological characteristics and virological aspects of patients with hepatocellular carcinoma (HCC)., Patients and Methods: Sera obtained from consent patients with clinical suspicion of HCC. Routine biochemical tests and serological markers of hepatitis B virus (HBV), hepatitis D virus (HDV) and hepatitis C virus (HCV) were searched. A hepatic ultrasound scan was realized and, when a suspected mass lesion was observed, ultrasonographic-guided fine needle aspiration of the hepatic mass lesion was made to ascertain the diagnosis of HCC., Results: One hundred and seventy-five sera were collected from 99 men and 76 women. Approximately 96.6% (169/175) of them had previous contact with HBV. HBs surface antigen was positive in 41% (69/169) of whom 53.6% (37/69) were co-infected by the HDV. Three patients (1.71%=3/175) were positive for anti-HCV antibodies. The other three patients (1.71%=3/175) did not present any markers for HBV or HCV. At the time of diagnosis, right upper quadrant pain, hepatomegaly, cachexia, were present in all patients. An increase in serum transaminases (70%), high bilirubin concentrations (40%), high AFP levels (40%) and low prothrombin levels (52%) were the most frequent biological abnormalities. Only 17 guided fine needle aspirations of mass lesions were realized. The diagnosis of HCC was confirmed by cytopathological examination for 14 of them., Conclusions: HCC is a frequent pathology in the Central African Republic (CAR). According to the ultrasound imaging data, patients consult at terminal stage of the disease. This study confirms also the association between HBV and HCC in CAR. Moreover, in 26.5% of patients HDV is associated with severe forms of the disease., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Liver injury is a frequent, serious complication of allogeneic hematopoietic cell transplantation (HCT) following myeloablative preparative regimens. We sought to determine the frequency and severity of hepatic injury after nonmyeloablative conditioning and its relationship to outcomes. One hundred ninety-three consecutive patients who received 2 Gy total body irradiation with or without fludarabine were evaluated for end points related to liver injury. Patients with diseases treatable by HCT who were ineligible for conventional myeloablative allogeneic HCT because of advanced age and/or comorbid conditions were included. Fifty-one patients (26%) developed hyperbilirubinemia of 68.4 microM (4 mg/dL) or greater, most commonly resulting from cholestasis due to graft-versus-host disease (GVHD) or sepsis. Pretransplantation factors associated with liver dysfunction were a diagnosis of aggressive malignancy (hazard ratio [HR] 1.9; P =.04) and the inclusion of fludarabine in the conditioning regimen (HR 1.8; P =.07). Overall survival at 1 year was superior for patients who had maximal serum bilirubin levels in the normal (78%) or minimally elevated (22.23-66.69 microM [1.3-3.9 mg/dL]) ranges (69%) compared with those in the 68.4 to 117.99 microM (4-6.9 mg/dL; 20%), 119.7 to 169.29 microM (7.0-9.9 mg/dL; 17%), and 171.0 microM (10 mg/dL; 19%) or greater groups. In summary, significant jaundice occurred in 26% of patients and was predominantly due to cholestasis resulting from GVHD and/or sepsis. Aggressive malignancies (mainly advanced disease) and later development of jaundice after transplantation predicted inferior survival.

During liver failure there is an accumulation of toxic substances secondary to the loss of liver function. In order to eliminate these substances various extracorporeal depuration therapies have been employed. Recently, we have used a new treatment, MARS (Molecular Adsorbent Recirculating System), in 3 patients diagnosed with severe liver failure. This system consists of an albumin rich (20%) dialysate circuit, with two areas of depuration. In one area, the albumin dialysate is in contact with blood through a high-flux albumin coated membrane, where albumin bound substances are eliminated. In the other area, the albumin dialysate is in contact with a standard bicarbonate dialysate through a low-flux membrane, which permits the elimination of water soluble substances. The albumin of the circuit is continuously regenerated through charcoal and ion exchanger filters. In order to determine those liver failure patients suitable to receive MARS therapy we established several inclusion criteria. All patients underwent a complete clinical and biochemical evaluation before and after each treatment. All of them showed an improvement of their clinical (attenuation of pruritus and encephalopathy) and biochemical (decrease of bilirubin levels) parameters. During the period of treatment 2 patients developed an increase in plasma creatinine levels together with a decrease of urinary volume. There were no hemodynamic or technical complications during the treatment. These promising results deserve further controlled studies large enough to permit confirmation.

Background/aims: Mdr2 P-glycoprotein deficiency in mice (Mdr2(-/-) leads to formation of cholesterol/cholesterol-depleted bile and reduced plasma HDL cholesterol. We addressed the questions: (1) does HDL in Mdr2(-/-) mice normalize upon phospholipid and/or cholesterol feeding, and (2): is the Mdr2(-/-) liver capable of handling excess dietary cholesterol., Methods: Male and female Mdr2(-/-) and Mdr2(+/+) mice were fed diets with or without additional phosphatidylcholine and/or cholesterol. Plasma, hepatic and biliary lipids as well as liver function parameters and expression of transport proteins involved in bile formation were analyzed., Results: Feeding excess phospholipids and/or cholesterol did not affect lipoprotein levels in Mdr2(+/+) or Mdr2(-/+) mice. Dietary cholesterol caused hyperbilirubinemia (male +100%; female +500%) and elevated plasma bile salts (male +200%; female +1250%) in Mdr2(-/-) mice only, independent of phospholipids. Bile flow nor biliary bile salt and bilirubin secretion were affected in cholesterol-fed Mdr2(-/-) mice. Elevated plasma bile salts may be related to cholesterol-induced reduction of hepatic Na+-taurocholate cotransporting protein expression in Mdr2(-/-) mice., Conclusion: Excess dietary phospholipids and cholesterol do not normalize low HDL associated with Mdr2 P-glycoprotein-deficiency. Induction of hyperbilirubinemia and hypercholanemia by dietary cholesterol in Mdr2(-/-) mice delineates the important role of biliary lipid secretion in normal hepatic functioning.

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean +/- SD) was significantly (P < .001) elevated in patients with VOD (321.6 +/- 161.2 ng/mL) as compared with patients with GVHD (22.8 +/- 8.4 ng/mL) or other hepatic damage (32.8 +/- 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 +/- 230.0 ng/mL in patients with VOD, 41.0 +/- 20.6 ng/ mL in patients with GVHD, and 44.6 +/- 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.

Patients with Gilbert's syndrome were placed on low calorie diets and isocaloric diets sequentially severely reduced in carbohydrate, protein, or fat content. Significant increases in the serum bilirubin concentration occurred after the low calorie diet, but not after the isocaloric nutrient-depleted diets. Thus caloric deprivation per se and not changes in dietary components is responsible for diet-induced hyperbilirubinemia.

Hyperbilirubinemia may be of several etiologies in the individual patient. An 18-year-old man presented with extreme hyperbilirubinemia (direct bilirubin 23.0 mg/dl, total bilirubin 60.0 mg/dl), hepatosplenomegaly, and anemia. Hematologic studies prelaparotomy documented the presence of hereditary spherocytosis. Intraoperative liver biopsy revealed moderately reduced levels of glucuronyl transferase activity (Gilbert's syndrome). Common bile duct obstruction secondary to choledocholithiasis was found, and a cholecystectomy and splenectomy were performed. This case stresses the potential confusion among several diseases which may present with hyperbilirubinemia.

A case is reported of an elevation in values in the measurement of delta optical density at 450 nm in a patient with SS disease, mild hyperbilirubinemia, and anti-E antibody, with the birth of a nonsensitized infant. The role of maternal bilirubin in causing this spurious elevation is discussed.

Erythroblastosis fetalis, hemolytic disease of the newborn, occurs when an isoimmunized mother produces antibodies that cross the placenta and cause hemolysis of fetal red blood cells. This hemolysis can be accompanied by severe anemia, ascites, pleural and pericardial effusions, congestive heart failure, and neurological damage with resultant perinatal mortality. Rh isoimmunization in pregnancy still occurs in spite of the advent of Rh immune globulin. This article describes the complex management and nursing implications associated with caring for the neonate with erythroblastosis fetalis.

Patients with documented serious infection and total bilirubin values of greater than 2 mg/dl were surveyed for serial changes in bilirubin and other laboratory and clinical features. Of 19 patients studied, 12 (Group A) had persisting or increasing hyperbilirubinemia, and 7 (Group B) had decline in bilirubin after infection onset. None demonstrated marked changes in other liver tests. Only one patient had infection directly involving the hepatobiliary system. There were no significant differences between the two groups with respect to underlying illnesses, active hepatobiliary diseases, pathogens, bacteremia, or administration of cholestatic drugs. All Group A patients died because of uncontrolled infections, whereas all Group B patients survived with resolution of infection (p less than .001). Ten of 15 patients with available preinfection liver tests demonstrated serial bilirubin increases without marked changes in other liver tests prior to clinical recognition of infection. These findings demonstrate that hyperbilirubinemia disproportionate to increases in other tests may manifest before recognition of infection and that persistent or progressive hyperbilirubinemia is indicative of ongoing active infection.

Patients on long-term home parenteral nutrition (HPN) are known to frequently develop hepatic steatosis or steatohepatitis. The etiology of this steatosis or steatohepatitis is unknown, but carnitine deficiency has been one of the postulated mechanisms. The importance of L-carnitine in hepatic fatty acid oxidation and the steatosis observed in primary and acquired carnitine deficiencies prompted us to determine plasma carnitine levels in 37 patients receiving long-term HPN. Thirteen patients (35%) had low total and free plasma carnitine levels. Fifteen of the 37 HPN patients were matched for age and sex with 15 patients with Crohn's disease who did not require HPN. Mean total and free plasma carnitine values were significantly lower (p less than 0.001) in these 15 HPN patients (32.2 +/- 11.9 and 28.4 +/- 10.8) when compared to Crohn's patients not requiring HPN (49.1 +/- 10.9 and 46.4 +/- 11.5). Associations were not detected between plasma carnitine and clinical or biochemical parameters that might have explained the low values.

In 80 newborn infants ABO-incompatible with their mothers, the lysis-inducing effect of the maternal IgG anti-A or anti-B antibodies in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay and the antigen density of A or B antigens on the red cells of the children were measured. On the basis of the results, the children were divided into two groups--24 children in whom increased haemolysis was to be expected, and 56 children in whom it was not. Signs of haemolysis and serological features of ABO haemolytic disease of the newborn (ABO-HDN) were compared in these two groups and a control group of 120 ABO-compatible infants. The effect of the maternal antibodies in the ADCC assay, the titres of maternal IgG anti-A or anti-B antibodies, the results of the direct antiglobulin test on the red cells in the cord blood, and the titre of IgG anti-A or anti-B antibodies in the serum of the infants were compared for their ability to predict the severity of ABO-HDN. This was also done for the combination of the ADCC assay results plus the A or B antigen density and the direct antiglobulin test plus the titre of maternal IgG anti-A or anti-B antibodies. The ADCC assay with maternal serum was the most sensitive assay to predict ABO-HDN, and the combination of the ADCC assay with A or B antigen density determination the most specific test.