Mean Total Bilirubin Level Research Articles

Donor Risk in Adult-to-Adult Living Donor Liver Transplantation: Impact of Left Lobe Graft

To ensure donor safety in adult-to-adult living donor liver transplantation, we established a selection criterion for donors in which left lobe (LL) was the first choice of graft. Two hundred six consecutive donors were retrospectively studied. Donors were divided into two groups according to graft type: LL graft (n=137) and right lobe (RL) graft (n=69). Although mean intraoperative blood loss of LL was significantly increased compared with RL, mean peak postoperative total bilirubin levels and duration of hospital stay after surgery were significantly less for LL than RL (P<0.05). No donor died or suffered a life-threatening complication during the study period. The overall complication rate was 34.0%, including biliary complications in 5.3%. The number of biliary complications was four (2.9%) in LL and seven (10.1%) in RL (P<0.05). Logistic regression analysis revealed that only graft type (LL vs. RL) is significantly related to the occurrence of biliary complications (odds ratio 0.11; P=0.0012). The cumulative overall graft survival rates in the recipients with LL were not significantly different from that in the recipients with RL. LL grafting should be considered favorably when selecting donors for adult-to-adult living donor liver transplantation.

Changes in Liver Stiffness after Acute or Chronic Liver Injury due to Viral Hepatitis - Does Fibrosis Exist after Recovery from Acute Viral Hepatitis?

Liver stiffness (LS) measurement by transient elastography can estimate the degrees of liver fibrosis in patients with chronic liver disease. However, longitudinal data of LS after recovery of acute viral hepatitis are still lacking. In the present study, we aimed to evaluate among LS of patients at various stages of viral hepatitis and normal control. Patients who had admitted at Korea University Ansan Hospital between January 2006 and January 2007 due to acute viral hepatitis and recovered were recruited (group A, n=22). We compared the liver biochemistry and LS of group A with those of healthy control group (group B, n=23), current acute viral hepatitis group (group C, n=49), and chronic viral hepatitis group (group D, n=66). Mean ALT, total bilirubin, and LS level of group A were not different from group B (p=0.318, p=0.116, p=0.125, respectively). However, group A had lower ALT, total bilirubin, and LS values compared to group C (all p<0.001), and lower ALT and LS values compared to group D (p=0.007, p<0.001). The mean total bilirubin was not significantly different from group D (p=0.117). Our data suggest that liver fibrosis is a long-term sequela of chronic hepatitis, and not developed in patients who recovered from acute viral hepatitis.

Impact of preoperative hemodynamic support on early outcome in patients assisted with paracorporeal Thoratec® ventricular assist device

Mechanical circulatory support has become a well-established procedure for some patients with cardiogenic shock. However, patient selection and timing of implantation remains critical. This retrospective study was undertaken to identify preoperative predictors of survival in ICU of patients requiring mechanical circulatory support. Between 1996 and 2006, 71 patients (61 men, 10 women, aged 41.6+/-12.2 years) with primary cardiogenic shock were assisted using the paracorporeal Thoratec VAD. Twenty-seven (38%) patients needed preoperative mechanical ventilation. Preoperative IV hemodynamic drug support included dobutamine in 63 (89%), vasopressors (adrenaline, noradrenaline or dopamine > or =5 microg/kg min) in 47 (66%), and intraaortic balloon counter-pulsation in 22 (31%) patients. Mean preoperative blood creatinine and total bilirubin levels were 162.2+/-72.4 micromol/l and 36.4+/-53.9 micromol/l, respectively. Fifty-six (79%) patients required biventricular and 15 (21%) left ventricular support. Patients were assisted for a mean duration of 73.1+/-93.6 days (extremes, 1-480 days). Twenty-five patients (35%) died while on support. Among these, 18 patients (25%) never recovered sufficiently to allow dismissal from ICU, and died after a mean of 15.4+/-14.3 days. Logistic regression identified preoperative IV adrenaline as sole predictor for ICU death (OR, 5.48; 95% CI, 1.45-20.7, p=0.012). The need for preoperative IV adrenaline therapy appeared to be the sole independent risk factor for death in ICU in patients assisted with the Thoratec paracorporeal VAD. This suggests that, besides hemodynamic and metabolic consequences of cardiogenic shock, preoperative activation of the inflammatory cascade could influence the prognosis of patients undergoing mechanical circulatory support.

Correlation Between the Serum Bilirubin Level and the Coronary Microvascular Integrity in Diabetic Patients

Background and Objectives: Bilirubin has a protective role in suppressing atherosclerosis and coronary artery disease by its potent physiological antioxidant properties. There has been no comparative study on the relation between the bilirubin level and the coronary microvascular function in diabetic patients. This study investigated whether the bilirubin level correlates with the coronary microvascular integrity in diabetes by assessing the coronary flow velocities after successful percutaneous coronary intervention (PCI). Subjects and Methods: Fifty patients (31 males and 19 females, mean age 60±11) with angina and who received elective PCI were studied. Using an intracoronary Doppler wire, the coronary flow velocity reserve (CFR), the hyperemic microvascular resistance index and the phasic coronary flow velocity patterns were measured after PCI. Results: The mean value of the fasting blood glucose was 211±88 mg/dL, the man value of glycated hemoglobin A1c (HbA1c) was 8.1±1.6% and the mean serum total bilirubin level was 0.59±0.21 mg/dL. CFR was significantly correlated with the serum bilirubin level (r=0.485, p<0.001), HbA1c (r=-0.432, p=0.003) and the fasting blood glucose (r=-0.361, p=0.011). On multivariate analysis, HbA1c, bilirubin and left ventricular hypertrophy showed independent relationships with coronary microvascular dysfunction (p=0.003, p=0.004, p=0.033, respectively). Conclusion: These results suggest that glycemic control and elevated serum bilirubin may protect diabetic patients from coronary microvascular dysfunction. (Korean Circ J 2008;38:425-431)

Liver Transplantation for Biliary Atresia

Biliary atresia is the most common indication for liver transplantation (OLT) in children. We present our experience with OLT as a treatment for end-stage liver disease in children with biliary atresia. We performed a retrospective review of 20 biliary atresia patients (11 male, 9 female patients; mean age, 21.4 months; range, 6 to 84 months) who had undergone OLT. Mean preoperative weight and height were 10.1 ± 5.8 kg and 72.5 cm, respectively. Thirteen recipients were younger than 1 year of age, and 15 weighed less than 10 kg at the time of OLT. Fourteen recipients had undergone a Kasai operation prior to the OLT. The mean serum total bilirubin level was 22.56 mg/dL before OLT. Eighteen left lateral segment grafts and two whole grafts were transplanted. The mean recipient operative time was 9.25 hours. The mean recipient intraoperative blood loss was 1.81 U. Two hepatic arterial thromboses and one biliary leak occurred soon after surgery. Portal vein stenoses developed in two recipients at 10 and 12 months after OLT; both were treated with balloon dilatation. Two biliary stenoses, which occurred at 10 months and 3.5 years after surgery, were treated with balloon dilatation. Two recipients died at 2 and 12 days after OLT because of respiratory distress syndrome and sepsis, respectively. The remaining 18 (90%) recipients are alive with good graft function. The overall rejection rate was 31.25%. OLT is an effective treatment for children with biliary atresia and a failed Kasai procedure. Living related liver grafts represented an excellent organ supply for these patients.

Effect of clofibrate in non-hemolytic indirect hyperbilirubinemia in full term neonates

Jaundice is a common clinical problem in neonatal period which may result in brain damage even in healthy full term newborns, when it is severe. The aim of this study was to characterize the therapeutic effect of clofibrate in full term neonates who present with nonhemolytic jaundice. A clinical controlled study was performed on 60 full term neonates who presented with non- hemolytic jaundice. 30 neonates were treated with a single oral dose of clofibrate (100 mg/Kg) plus phototherapy (case group), while 30 neonates received only phototherapy (control group). Both groups were compared in regard to post therapeutic mean total and indirect plasma bilirubin levels, admission duration and the rate of exchange transfusion. The reduction rate of total and indirect plasma bilirubin levels were significantly higher in the clofibrate- treated group as compared with the control group (P< 0.05). The mean duration of admission was found to be reduced from 2.9 +/- 0.9 days in the control groupl to 2.2 +/- 0.6 days in clofibrate- treated group (P=0.002). The mean plasma total bilirubin level was lower in the clofibrate- treated group. No cases required phototherapy after 48 hour in clofibrate- treated group, while 9 neonates (30%) and 2 neonates (6.7%) required phototherapy after 72 hour and 96 hour respectively in the control group. There was no difference between both the groups for sex, the time of developing jaundice and the rate of exchange transfusion. A single dose of clofibrate (100 mg/Kg) along with phototherapy is more effective than phototherapy alone in treating non-hemolytic hyperbilirubinemia in term healthy newborn infants.

The role of interferon in the treatment of acute hepatitis C

Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. Even the latest approach--combination therapy with pegilated interferon alfa 2-a or 2b and ribavirin--eliminates the virus in only 54% to 56% of cases with chronic infection. The aim of this study is to determine whether treatment during the acute phase prevents the development of chronic infection. Between 2001 and 2004, 27 patients with the diagnosis of acute hepatitis C were treated at the hepatology Department of Institute of Infectious and Tropical Diseases. Among them, 19 were treated with recombinant interferon alfa 2-a. Acute hepatitis C was defined by clinical and laboratory test results and by exclusion of other causes of acute liver disease. The mean age of our patients was 32.7 years, whereas the mean incubation time was 61.7 days. The mean serum aminotransferase levels were 1119 U/l and the mean total bilirubin levels were 106 mmol/l. At the end of therapy, 81.8% of patients had undetectable levels of HCV RNA, but 94.7% of patients had normal serum alanine aminotransferase levels. At the end of folow up, 84.6% of patients had normal alanine antimiransferase levels and 83.3% of patients had undetectable levels of HCV RNA. One patient had undetectable antibody to HCV the end of follow-up. The results reported here demonstrate that in the acute phase of HCV infection, interferon treatment is associated with a high rate of virological and biochemical response. We concluded that early treatment of acute heptitis C may prevent chronic hepatitis C.

Phenotype/genotype relationships in sickle cell disease: a pilot twin study

The roles of genetic and non-genetic factors in the haematology, growth and clinical features of sickle cell disease have been studied in nine identical twin pairs (six homozygous sickle cell disease, three sickle cell-haemoglobin C disease). A comparison group of 350 age-gender matched sibling pairs, selected to have an age difference of <5 years, was used for assessing the concordance of numerical data. Attained height, weight at attained height, fetal haemoglobin, total haemoglobin, mean cell volume, mean cell haemoglobin and total bilirubin levels showed significantly greater correlation in identical twins than in siblings. Twins showed similarities in the prevalence and degree of splenomegaly, susceptibility to priapism, and in onset of menarche, but other clinical complications were discordant in prevalence and severity. These findings suggest that physical growth and many haematological characteristics are subject to genetic influences, but that non-genetic factors contribute to the variance in disease manifestations.

Efficacy of repeated high‐dose hepatitis B vaccine (80 μg) in patients with chronic liver disease

Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.

Impact of Graft Hepatic Vein Inferior Vena Cava Reconstruction with Graft Venoplasty and Inferior Vena Cava Cavoplasty in Living Donor Adult Liver Transplantation Using a Left Lobe Graft

Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft. Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out. The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9+/-5.5, 28.2+/-2.9, and 34.1+/-3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8+/-9.3 mg/dl in control group and 7.0+/-3.3 mg/dl in venoplasty group (P<0.05). Mean amount of ascites on POD 7 and 14 are 1576+/-1113 and 1397+/-1661 cc in control group, and 736+/-416 and 550+/-385 cc in venoplasty group, respectively (P<0.05). Two-year survival rate is 75.2 % in control group and 86.6 % in venoplasty group (P<0.05). We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function.

Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi2 and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone.

O0061 MEASUREMENT OF APAP-CYS ADDUCTS IN CHILDREN WITH ALF OF INDETERMINATE ETIOLOGY

Introduction: Acetaminophen (APAP) overdose causes liver injury through generation of a reactive metabolite that covalently binds to cellular proteins as 3-(cysteine-S-yl)-acetaminophen (APAP-CYS) adducts. Following overdose, these adducts are released into serum and can be detected by HPLC-EC assay. This pilot study examined serum samples from children with acute liver failure (ALF) of indeterminate cause to identify patients with APAP associated liver toxicity, despite a negative clinical history. Methods: Patients enrolled had no prior evidence of chronic liver disease, biochemical evidence of liver injury, and uncorrectable coagulopathy (INR > 1.5 with encephalopathy (EN) or INR > 2.0 without EN). Data were collected at 17 participating sites. Serum samples were analyzed for APAP-CYS adducts in patients with indeterminate hepatitis (n=19), known APAP overdose (n=5), and various other diagnoses (n=10) Results: The assay identified all 5 presumptive APAP toxicity cases, mean 3.87 (range, 0.10–9.41) nmol APAP-CYS/mg protein. Six patients with presumed metabolic disease, 2 with autoimmune hepatitis and 1 with Wilson’s tested negative. Of the 19 indeterminate cases, four (21%) tested positive for APAP-CYS adducts (Table). All four patients survived without transplant. The mean serum ALT and Total bilirubin (T Bili) levels of the 9 that tested positive for APAP-CYS adducts were compared to the remaining 25 patients. The patients with detectable adducts had higher median ALT values 7,771 (range 976–18,524) vs. 942 (range 25–5,760) IU/L, p=0.002 and lower T Bili levels 3.5 (range 0.6–4.5) vs. 15.1 (range 0.8–23.7) mg/dl, p=0.0007.Table 1Conclusion: Surreptitious APAP toxicity may contribute to the development of ALF in children with ALF of indeterminate cause. Low serum bilirubin associated with high ALT may help identify this group and the HPLC-EC assay for APAP-CYS may serve a diagnostic role in these patients. This study was supported by NIH grant RO1-DK58369–01

Donor liver uridine diphosphate (UDP)-glucuronosyltransferase-1A1 deficiency causing Gilbert's syndrome in liver transplant recipients.

Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, has been attributed to two extra (TA) bases in the TATAA-box of the promoter region of its gene, where the A(TA)6TAA allele corresponds to the normal gene and A(TA)7TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirubinemia in liver transplant recipients was due to Gilbert's syndrome acquired through the liver allograft. From 305 patients followed in our Liver Transplant Clinic, five patients with isolated unconjugated hyperbilirubinemia in the absence of hemolysis, recurrent viral hepatitis, and biliary tract pathology were identified; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extracted from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosyltransferase-lA1 promoter region by polymerase chain reaction and acrylamide gel electrophoresis. Homozygosity for the (TA)7 allele was considered diagnostic of Gilbert's syndrome. The mean serum total bilirubin level of the study patients was 2.28 mg/dl (range 1.8-3.0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0.4-1.1). The liver tissue from all five patients in the study group possessed the homozygous A(TA)7TAA genotype that was not observed in their lymphocytes. None of the liver tissue from the control patients demonstrated homozygosity for the A(TA)7TAA allele. Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients.

Biliary indocyanine green excretion as a predictor of hepatic adenosine triphosphate levels in patients with obstructive jaundice

Background: Correlation of the hepatic adenosine triphosphate (ATP) level with indocyanine green (ICG) excretion into bile was examined in patients with obstructive jaundice after the relief of hyperbilirubinemia by preoperative percutaneous transhepatic biliary drainage (PTBD). Methods: Patients with complete bile duct obstruction, the mean serum total bilirubin concentration being 13.6 ± 8.5 (SD) mg/dL, underwent PTBD prior to surgery. Within a few days before surgery when the mean serum total bilirubin level decreased to 1.2 mg/dL, ICG (0.5 mg/kg) was intravenously injected, and the whole bile was collected at 1-hour intervals for 5 hours. The ICG concentration in bile, bile flow rate, amount of ICG excreted in bile, and biliary ICG excretion rate as percentage of the injected dose were determined. At the time of surgery, a small liver tissue sample was obtained immediately after laparotomy without any ischemic procedures, and ATP concentrations were determined. Results of hepatic ATP levels were correlated with laboratory and clinical determinations. Results: The bile flow rate was essentially constant during the 5-hour period, the mean value being 21 mL/hour. The ICG concentrations in bile gradually increased, reached the maximal level in 3 hour, and declined thereafter. The biliary ICG excretion rate for 5 hours was 40% ± 18% of its injected dose. The biliary ICG excretion rate and amount of ICG excreted in bile for 5 hours significantly ( P <0.05) correlated with the hepatic ATP level. The decline index of serum bilirubin during PTBD was also correlated with the hepatic ATP level. The serum ICG retention rate, bile flow rate, maximal ICG concentration in bile, and other liver function tests including serum albumin and cholinesterase levels did not correlate with the hepatic ATP level. Conclusions: Both the amount of and excretion rate of ICG in bile reflect the hepatic ATP level. Determination of biliary ICG excretion contributes to precise evaluation of hepatic energy status before surgery in patients with obstructive jaundice.

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity. Methods: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation. Results: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p = 0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9 ± 8.9 months for resectable and 6.7 ± 3.6 months for unresectable patients (p = 0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered. Conclusions: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

An Analysis of Infectious Failures in Acute Cholangitis

To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninetyfour (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin ≥ 2.2 mg/dl, ≥ 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level ≥ 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest. In conclusion, patients with acute cholangitis who have an increased chance to fail initial therapy can be identified, and treatment altered accordingly.

Total parenteral nutrition-associated cholestasis: Clinical and histopathologic correlation

Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infants and children. The pathogenesis of this syndrome is poorly understood. The aims of this study were: (1) to define the histologic liver injury in relation to the clinical course of infants on TPN and (2) to determine whether enteral feeding will reverse or halt these changes. We identified 31 infants treated for severe gastrointestinal disease for whom liver histology was available from 1987 to 1991. Clinical records and liver biopsy (23) or autopsy specimens (13) were reviewed. Five patients had biopsies at two subsequent operations. The clinical diagnosis was necrotizing enterocolitis (24), atresia or stenosis (3), midgut volvulus (2), Hirschsprung's disease (1), and sepsis (1). Twenty-one of 31 infants were premature and had a mean birth weight of 1,868 g. Twenty-five of 31 were on TPN and 28 of 31 had received some enteral feeding by the time of the biopsy. Enteral feeding was begun as early as possible in all infants even if continued TPN was necessary for full support. Cholestasis occurred in 71% of premature infants versus 22% of full-term babies. Infants with cholestasis had been on TPN for a longer time (37 days v 18) with a correspondingly shorter period of enteral feeding (17 days v 27). Mean total bilirubin level was 14 in patients with cholestasis and 5 in those without, but the bilirubin level did not correlate with the extent of histological injury and was frequently normal despite marked histological damage.(ABSTRACT TRUNCATED AT 250 WORDS)

NEONATAL JAUNDICE AND MATERNAL OXYTOCIN INFUSION

A prospective study of 78 neonates provides evidence for an association between maternal oxytocin infusion and neonatal jaundice. On the second and fifth days infants of mothers whose labour had been induced by amniotomy followed immediately by intravenous oxytocin (group C) had mean total bilirubin levels significantly higher (P Though these findings suggest a dose dependent effect of oxytocin, other possible explanations are suggested which take into account other drugs administered to the mother and also differences in the corticosteroid status of the groups of infants.

The constitutional hyperbilirubinemia in Japan studies on the 139 cases reported during the period from 1963 to 1969

Statistical observations were performed in 139 cases of constitutional hyperbilirubinemia which were reported during 7 years from 1963 to 1969 in Japan. Male was predominant in Dubin Johnson syndrome (Dubin-Johnson), but there was no difference with sex in Rotor’s type of hyperbilirubinemia (Rotor) and Gilbert’s disease (Gilbert). The age, at which jaundice first noticed, was distributed in the youngest among patient with Rotor, and age was young in Rotor, Gilbert and Dubin-Johnson as in order. The mean total bilirubin level in serum showed the highest value in Rotor and it showed higher in Dubin-Johnson than in Gilbert. Abnormal retention of BSP a 45 minutes wsa observed in 80% of Dubin-Johnson and in all cases of Rotor. The secondary rise of BSP in serum was observed in almost all cases of Dubin-Johnson during from 120 minutes to 180 minutes after an injection. Of other liver function tests there were no common changes. Of cholecystography one third of the cases in Dubin-Johnson demonstrated a visualized gallbladder both on oral and intravenous method, while in Rotor the positive rate increased on oral method more than on intravenous method. The black colored liver and the lipofuscin-like pigments in liver cells were observed in all patients of Dubin-Johnson, except patients with hepatic inflammatory changes. In Rotor and in Gilbert the pigments were observed in several patients.