Hyperbilirubinemia In Patients Research Articles

Carboxyhemoglobin and postsurgical hyperbilirubinemia in patients undergoing esophagectomy.

Carboxyhemoglobin and postsurgical hyperbilirubinemia in patients undergoing esophagectomy.

Postoperative hyperbilirubinemia after surgery for gastrointestinal perforation.

The aim of this study was to evaluate the risk factors and outcome of patients with hyperbilirubinemia after surgery for generalized peritonitis. We retrospectively analyzed data from 229 patients with generalized peritonitis caused by gastrointestinal (GI) perforations. Postoperative hyperbilirubinemia defined as a value of > or =5 mg/dl, within 1 month, developed in 39 patients. Postoperative hyperbilirubinemia was related to age ( P = 0.0102), poor nutritional status ( P = 0.0388), decreased base excess ( P = 0.0037), delay until surgery ( P = 0.0276), preoperative serum bilirubin ( P = 0.0321) and postoperative persistent infection ( P < 0.0001). Higher mortality was seen in patients with hyperbilirubinemia (59%) than in those without hyperbilirubinemia (4%). The patients with hyperbilirubinemia who survived had decreased serum bilirubin levels after 3-5 postoperative days whereas a continuous increase was seen in the patients who ultimately died. Preoperative shock ( P = 0.0003), a decreased preoperative platelet count ( P = 0.0152), postoperative infection ( P = 0.0050), and postoperative hyperbilirubinemia ( P < 0.0001) were risk factors for overall mortality. These results indicate that postoperative hyperbilirubinemia in patients with GI perforation is related to persistent postoperative infection and associated with poor prognosis.

The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function

OBJECTIVES: Percutaneous transhepatic biliary drainage (PTBD) has been believed to reduce hyperbilirubinemia in patients with obstructive cholestasis and to lessen liver injury through bile acid retention. The efficacy may be closely related to the capability of cholestatic liver to produce and secrete bile, which in turn depends on the expressions and functional activities of plasma membrane transporters in the liver. The aim of the present study was to determine the expression levels of these transporters in the cholestatic liver of patients undergoing PTBD. METHODS: A total of 24 patients who had experienced obstructive cholestasis and had undergone preoperative PTBD were included in the study. Liver biopsy specimens were analyzed to determine the expression levels of the multidrug resistance-associated proteins (MRP) MRP2 and MRP3 and the canalicular bile salt export pump BSEP in the liver. RESULTS: The messenger RNA (mRNA) levels of MRP2, the canalicular bilirubin conjugate export pump, and bile salt export pump (BSEP) were unchanged in liver specimens from the 14 patients well drained by PTBD but were reduced in specimens from the 10 patients poorly drained, compared to the levels of control subjects. Immunostainings of MRP2 and BSEP outlined the canalicular membrane domain but seemed fuzzy to varying degrees in specimens obtained from cholestatic liver, especially in specimens from liver that had been poorly drained, in contrast to the linear and intense localization in the liver of control subjects, correlating with the impaired bilirubin conjugate and bile acid secretion. The mRNA of MRP3, functioning as an inducible export pump for bilirubin conjugate and bile acid, was expressed not only in the cholestatic liver but also in the liver of control subjects, and the mRNA level was increased in specimens from both the cholestatic liver that had been well drained and from the liver that had been poorly drained. Immunostaining of MRP3 was observed in the epithelia of intrahepatic bile ducts in the liver of both control subjects and cholestatic patients, and in the epithelia of proliferated bile ductules and the hepatocytes surrounding the portal tracts in the cholestatic liver. CONCLUSIONS: From the results of the present study, it is concluded that 1) the mRNA and immunohistochemical expression levels of MRP2 and BSEP may be altered in the cholestatic liver of patients undergoing PTBD; 2) both the decreased mRNA levels and the diminished canalicular membrane localization may be associated with the impairment of bile formation and secretion, i.e., the efficacy of PTBD; and 3) upregulated MRP3 in the cholangiocytes and hepatocytes may play a significant role in bile acid transport in the cholestatic hepatobiliary system.

The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function

Percutaneous transhepatic biliary drainage (PTBD) has been believed to reduce hyperbilirubinemia in patients with obstructive cholestasis and to lessen liver injury through bile acid retention. The efficacy may be closely related to the capability of cholestatic liver to produce and secrete bile, which in turn depends on the expressions and functional activities of plasma membrane transporters in the liver. The aim of the present study was to determine the expression levels of these transporters in the cholestatic liver of patients undergoing PTBD. A total of 24 patients who had experienced obstructive cholestasis and had undergone preoperative PTBD were included in the study. Liver biopsy specimens were analyzed to determine the expression levels of the multidrug resistance-associated proteins (MRP) MRP2 and MRP3 and the canalicular bile salt export pump BSEP in the liver. The messenger RNA (mRNA) levels of MRP2, the canalicular bilirubin conjugate export pump, and bile salt export pump (BSEP) were unchanged in liver specimens from the 14 patients well drained by PTBD but were reduced in specimens from the 10 patients poorly drained, compared to the levels of control subjects. Immunostainings of MRP2 and BSEP outlined the canalicular membrane domain but seemed fuzzy to varying degrees in specimens obtained from cholestatic liver, especially in specimens from liver that had been poorly drained, in contrast to the linear and intense localization in the liver of control subjects, correlating with the impaired bilirubin conjugate and bile acid secretion. The mRNA of MRP3, functioning as an inducible export pump for bilirubin conjugate and bile acid, was expressed not only in the cholestatic liver but also in the liver of control subjects, and the mRNA level was increased in specimens from both the cholestatic liver that had been well drained and from the liver that had been poorly drained. Immunostaining of MRP3 was observed in the epithelia of intrahepatic bile ducts in the liver of both control subjects and cholestatic patients, and in the epithelia of proliferated bile ductules and the hepatocytes surrounding the portal tracts in the cholestatic liver. From the results of the present study, it is concluded that 1) the mRNA and immunohistochemical expression levels of MRP2 and BSEP may be altered in the cholestatic liver of patients undergoing PTBD; 2) both the decreased mRNA levels and the diminished canalicular membrane localization may be associated with the impairment of bile formation and secretion, i.e., the efficacy of PTBD; and 3) upregulated MRP3 in the cholangiocytes and hepatocytes may play a significant role in bile acid transport in the cholestatic hepatobiliary system.

Phase I trial of simultaneously administered GM-CSF and IL-6 in patients with renal-cell carcinoma: Clinical and laboratory effects

Metastatic renal-cell carcinoma is a neoplasm that is minimally responsive to cytotoxic chemotherapy. Tumor regression following therapy with cytokines such as interferon alpha and or interleukin-2 is seen in selected subsets of patients. Investigations with other immunomodulatory cytokines, such as GM-CSF and IL-6 are therefore of interest. A phase I trial of concomitantly administered granulocyte macrophage-colony stimulating factor (3.0 mcg/kg/day s.c. d1-14) and escalating doses of interleukin-6 (1.0, 5.0 or 10.0 microg/kg/day d1-14) was conducted in patients with metastatic renal-cell carcinoma to explore the toxicity of the combination and its hematologic effects. The most common side effects seen were fever, fatigue and arthralgias. Dose limiting toxicity included thrombocytosis and hyperbilirubinemia in patients receiving 10 microg/kg/day of IL-6. The hematologic effects of IL-6 and GM-CSF included leukocytoses and thrombocytosis, with increases in peripheral blood progenitors (BFU-E, CFU-GM, and CFU-GEMM). Evidence of platelet activation demonstrated by increased platelet expression of CD62 was found. No clinical responses were observed. The combination of IL-6 and GM-CSF has pleotropic hematologic effects. Further studies with this combination for the treatment of renal-cell carcinoma are not recommended.

Inflammatory cytokines and hepatic sinusoid endothelial dysfunction play a role in hyperbilirubinemia in patients following implantation of an LVAS: M. Nishimura, S. Ohtake, Y. Sawa, N. Fukushima, T. Yamaguchi, H. Matsuda, Osaka University, Suita, Osaka, Japan

Inflammatory cytokines and hepatic sinusoid endothelial dysfunction play a role in hyperbilirubinemia in patients following implantation of an LVAS: M. Nishimura, S. Ohtake, Y. Sawa, N. Fukushima, T. Yamaguchi, H. Matsuda, Osaka University, Suita, Osaka, Japan

Hepatic Sinusoid Endothelial Dysfunction Plays a Role in Hyperbilirubinemia in Patients Following Implantation of an LVAD

Hepatic Sinusoid Endothelial Dysfunction Plays a Role in Hyperbilirubinemia in Patients Following Implantation of an LVAD

Isotretinoin-associated normalization of hyperbilirubinemia in patients with Gilbert's syndrome

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Hyperbilirubinaemia in patients treated with recombinant human interleukin-2 (rIL-2)

Hyperbilirubinaemia in patients treated with recombinant human interleukin-2 (rIL-2)

Clinical Significance and Pathogenesis of Hyperbilirubinemia Associated with Staphylococcus aureus Septicemia

Our goal was to examine the clinical significance of hyperbilirubinemia in patients with Staphylococcus aureus endocarditis. In addition, preliminary data concerning the possible mechanism of cholestasis observed during S. aureus septicemia are presented. This study had two parts: a clinical investigation and a laboratory investigation. In the former, patients with endocarditis were identified through chart review. Those with admission total serum bilirubin levels of 2.0 mg/dl or greater were considered to have hyperbilirubinemia. In the latter investigation, the hepatic storage capacity and transport maximum for sulfobromophthalein (BSP), an organic dye that is rapidly taken up and excreted by the liver, were determined by measuring the change in serum concentration and the corresponding hepatic removal rate at various BSP infusion rates. Measurements were conducted before and after the infusion of Escherichia coli-derived lipopolysaccharide in some rabbits, after the infusion of resuspended S. aureus in others, and after the infusion of lipoteichoic acid in the remainder. Eleven of 47 consecutive patients with S. aureus endocarditis were noted to have hyperbilirubinemia without clinical or laboratory evidence of hepatic bacterial infection. Compared with the remaining 36 patients, these 11 patients had a significantly lower mean platelet count and a higher serum creatinine level and white blood cell count. Although none of the 47 patients were hypotensive on admission, four of the 11 hyperbilirubinemic patients died of overwhelming sepsis, compared with two of the 36 remaining patients (p less than 0.05). When one of the clinical isolates of S. aureus or lipoteichoic acid was infused into conscious rabbits, there was a marked decrease in the hepatic transport maximum and an increase in the relative hepatic storage capacity of sulfobromophthalein. Similar changes were noted following the administration of lipopolysaccharide. Our data suggest that the presence of hyperbilirubinemia in patients with S. aureus sepsis may identify persons at high risk of dying from overwhelming sepsis. It further suggests that lipoteichoic acid may play an important role in causing defective hepatic excretory function that is responsible for hyperbilirubinemia.

Benign course of extreme hyperbilirubinemia in sickle cell anemia: Analysis of six cases

Since the approach to the management and outcome of extreme hyperbilirubinemia in patients with sickle cell anemia is not clearly defined, we reviewed our experience with marked hyperbilirubinemia in six children with sickle cell disease. Intrahepatic sickling (sickle hepatopathy) rather than hepatitis or biliary stones appeared primarily responsible for the extreme jaundice in at least four children and possibly in all six. Signs and symptoms were few, and laboratory abnormalities were not striking other than marked hyperbilirubinemia (total serum bilirubin concentrations ranging from 20.4 to 57.6 mg/dl with approximately one half conjugated). All of the children improved within days to weeks and currently are well, without recurrence of hyperbilirubinemia or evidence of chronic liver disease. The patients described here suggest that sickling within the liver, previously reported to be a serious and even fatal syndrome, usually is a benign and self-limited process.

Sickle cell disease and viral hepatitis.

A review of patients with hepatitis who were hospitalized over a 7-year period revealed 6 cases with predominantly S hemoglobin and 10 with sickle cell trait. The clinical, laboratory, and liver biopsy pictures in these patients were comparable with findings in patients without sickle cell hemoglobinopathy, whether or not anemia was present. The only significant difference was severe hyperbilirubinemia in patients with sickle cell anemia. The bilirubinemia appears to represent the increased load of red cell breakdown products on an acutely damaged liver and is not an effect of anemia per se or a reflection of underlying liver disease. Biopsy specimens failed to demonstrate intrahepatic sickling as the cause of the acute illness or as a complicating factor. The liver disease of sickle cell anemia, frequently attributed to intrahepatic sickling, may also reflect unrecognized viral hepatitis or its sequels.