Elevated Total Bilirubin Levels Research Articles

Hepatoprotective and Antioxidant Effects of Stereospermum suaveolens on Carbon Tetrachloride-Induced Hepatic Damage in Rats

The ethanol extract of Stereospermum suaveolens (EESS) bark was evaluated for its hepatoprotective and antioxidant activities against carbon tetrachloride (CCl4)-induced liver damage, in wistar albino rats. The ethanol extract of Sterespermum suaveolens (EESS) bark (200 and 400 mg/kg body weight, p.o.) was administered to the experimental rats for 14 days. Silymarin (50 mg/kg body weight (b.w.) was given as the standard drug. The hepatoprotective activity was assessed using various serum biochemical parameters as glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, and total proteins. Malondialdehyde (MDA) level as well as the activities of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were determined to explain the possible mechanism of activity. The hepatoprotective activity was also supported by histopathological studies of liver tissue. The substantially elevated levels of serum GOT, GPT, ALP and total bilirubin, due to CCl4 treatment, were restored towards near normal by EESS, in a dose dependent manner. EESS also increased the serum total proteins of CCl4-intoxicated rats. Reduced enzymatic and non-enzymatic antioxidant levels and elevated lipid peroxide levels were restored towards near normal, by administration of EESS. A histological study showed a reduction of fatty degeneration and liver necrosis in EESS-treated rats. The results revealed that, the ethanol extract of Sterespermum suaveolens afforded significant dose dependent hepatoprotective and antioxidant effects in CCl4-induced hepatic damage.

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass.

To study the diagnosis of hepatocellular carcinoma (HCC) presenting as bile duct tumor thrombus with no detectable intrahepatic mass. Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration, were collected. Their clinical and imaging data were retrospectively analyzed. The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings. Jaundice was the major clinical symptom of the patients. The elevated serum total bilirubin, direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease. Of the 6 patients showing evidence of viral hepatitis, 5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9, and 1 was positive for serum carcinoembryonic antigen. No patient was correctly diagnosed by ultrasound. The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct, with large filling defects presenting as casting moulds in the expanded bile duct, hypervascular intraluminal nodules, debris or blood clots in the bile duct. No obvious circular thickening of the bile duct walls was observed. Even with no detectable intrahepatic tumor, bile duct HCC thrombus should be considered in patients predisposed to HCC, and some imaging signs are indicative of its diagnosis.

Hepatoprotective activity of ethanolic extracts of bark of Zanthoxylum armatum DC in CCl 4 induced hepatic damage in rats

Aim of the study Zanthoxylum armatum DC is described as a hepatoprotective in Ayurveda, the Indian system of medicine. However, there is no scientific basis or reports in the modern literature regarding its usefulness as a hepatoprotective agent. The present study was carried out to evaluate the hepatoprotective activity of ethanolic extract of bark of Zanthoxylum armatum DC in CCl 4 induced hepatotoxicity in male Wistar rats. Materials and methods Ethanolic extracts at doses of 100, 200, and 400 mg/kg were administered orally once daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum bilirubin, total protein and serum antioxidant enzymes along with histopathological studies of liver tissue. Results The substantially elevated serum enzymatic levels of serum transaminases, alkaline phosphatase and total bilirubin were significantly restored towards normalization by the extracts. Bark extracts significantly increased the levels of antioxidant enzymes: superoxide dismutase, catalase and glutathione. Phytochemical analysis revealed presence of isoquinoline alkaloid, berberine, as well as flavonoids and phenolic compounds, which have been known for their hepatoprotective activities. Conclusions Zanthoxylum armatum DC possesses significant protective effect against hepatotoxicity induced by CCl 4 which may be attributed to the individual or combined action of phytoconstituents present in it.

Hiperbilirrubinemia en apendicitis: ¿Es un factor predictivo de perforación?

Hyperbilirubinemia in appendicitis - is a predictive factor of perforation? Background: An elevated total bilirubin level can be a marker for perforated appendicitis. Aim: To assess and compare the predictive value of total bilirubin, C-reactive protein (CRP), white-blood cell count, the lapse of symptoms evolution, and systemic inflammatory response syndrome (SIRS) for the diagnosis of perforated appendicitis. Material and Methods: Prospective study of 134 consecutive patients aged 33 ± 16 years (63 males) operated for acute appendicitis of whom 49 had a perforated appendix. A preoperative blood sample was obtained to measure total bilirubin, C reactive protein and complete blood count. A systemic inflammatory response score was calculated. Results: The lapse of symptoms before operation was higher in patients with perforated appendicitis compared with their counterparts without perforation (105.2 ± 79.3 and 38.6 ± 17.5 hours respectively). C reactive protein values were 176 ± 82.6 and 80 ± 76 mg/l respectively, (p = 0.01). Serum bilirubin values were 0.7 ± 0.3 and 1.0 ± 0.5 mg/dl, respectively (p = 0.05). Sixty five percent of patients with perforated appendicitis had a SIRS score between 3 and 4 points. A C reactive protein over 76.7 mg/l, a lapse of symptoms over 34.5 hours and a SIRS score of three or more had the best performance for the prediction of perforated appendicitis. Conclusions: The diagnosis of perforated appendicitis may be suspected based on CRP, SIRS, and the lapse of symptoms before operation. We do not recommend the use of total bilirubin to predict perforation in appendicitis.

Pharmacokinetic, tolerability, and bioequivalence comparison of three different intravenous formulations of recombinant human erythropoietin in healthy Korean adult male volunteers: An open-label, randomized-sequence, three-treatment, three-way crossover study

Background: Existing formulations of recombinant human erythropoietin (rhEPO) in Korea contain human serum albumin. To avoid the potential risk of infection by human serum albumin, a new albumin-free rhEPO has been developed. Objective: This study was conducted to characterize and compare the pharmacokinetic and safety profiles and the bioequivalence of a newly developed albumin-free rhEPO (Aropotin® [TS Corporation, Seoul, South Korea]) with 2 existing rhEPO formulations (Espogen® [LG Life Sciences, Seoul, South Korea]; Recormon® [Roche, Basel, Switzerland]) with albumin in healthy Korean subjects. Methods: This was an open-label, randomized-sequence, 3-treatment, 3-way crossover study in which healthy, nonobese (±20% of ideal weight), male volunteers between the ages of 19 and 50 years were assigned to 1 of 2 dose levels (50 IU/kg or 100 IU/kg) of 3 formulations. Blood was collected over 32 hours and plasma rhEPO concentrations were determined using a validated enzyme immunoassay. There was a 14-day washout between periods. The pharmacoki-netic parameters of the 3 formulations were compared using the bioequivalence criteria of the US Food and Drug Administration, which requires that the 90% CIs of the geometric mean ratios for AUC 0−t, AUC 0−∞, and C max fall within 0.80 to 1.25. Tolerability was evaluated by physical examination with measurements of vital signs, clinical laboratory tests, and electrocardiogram. Subjects were followed up for 2 weeks after the last administration of study drug. Results: Twelve Korean male volunteers were enrolled and completed the study. Six subjects (mean [SD] age, 22.0 [1.7] years; weight, 63.3 [6.2] kg; height, 172.3 [3.5] cm) received a single 50 IU/kg IV bolus dose of study drug and the remaining 6 subjects (mean [SD] age, 23.7 [1.5] years; weight, 66.3 [4.8] kg; height, 174 [4.7] cm) received 100 IU/kg. After a single 50 IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/Espogen was 1.04 (0.91–1.19) IU/L/h for AUC 0−t and 1.02 (0.89–1.17) IU/L for C max. The geometric mean ratio (90% CI) for Aropotin/Recormon was 1.01 (0.88−1.15) IU/L/h for AUC 0−t and 1.01 (0.89–1.16) IU/L for C max. After a single 100-IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/ Espogen was 0.98 (0.86–1.13) IU/L/h for AUC 0−t and 0.99 (0.87–1.13) IU/L for C max. The geometric mean ratio (90% CI) for Aropotin/Recormon was 0.99 (0.861.14) IU/L/h for AUC 0−t and 0.96 (0.84–1.10) IU/L for C max. The most frequent adverse events (AEs) were 3 occurrences of elevated serum creatine phosphokinase and serum lactate dehydrogenase levels in the Recormon 100-IU/kg group (n = 3), 3 events of elevated serum lactate dehydrogenase levels in the Espogen 100-IU/kg group (n = 3), and 4 events of elevated serum total bilirubin levels in the Aropotin 100-IU/kg group (n = 3). All formulations were well tolerated with no serious AEs. Conclusion: The new formulation of rhEPO met the regulatory criteria for bioequivalence in these healthy Korean adult male volunteers. All formulations were generally well tolerated.

Laparoscopic cholecystectomy and common bile duct exploration for cholecystocholedocholithiasis with a left-sided gallbladder: Report of a case

A 75-year old woman was admitted to our hospital with right upper quadrant pain, vomiting, and jaundice. Laboratory findings showed elevated total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, and C-reactive protein levels. Abdominal ultrasonography (US) and drip infusion cholangiographic computed tomography (DIC-CT) showed not only cholecystocholedocholithiasis, but a gallbladder located left of the round ligament and close to the lateral segments of the liver. We performed laparoscopic cholecystectomy (LC) with choledocholithotomy for suspected cholecystocholedocholithiasis with a left-sided gallbladder. Routine ports were inserted in the American configuration for LC. The gallbladder was normogradely separated from the gallbladder fossa, and the fundus of the gallbladder was lifted ventrally and toward to the patient's right shoulder. These procedures provided the usual view for laparoscopic choledochotomy. The patient recovered uneventfully and was discharged on postoperative day 10. To our knowledge, this is the first report of laparoscopic common bile exploration in a patient with a left-sided gallbladder.

Gallbladder wall thickening in patients with acute hepatitis

Gallbladder wall thickening (GWT) is often observed in patients with acute hepatitis (AH). However, little is known regarding the relationship between AH and GWT. We analyzed the characteristics of GWT in patients with AH. Between April 2002 and April 2007, 232 patients with AH underwent a sonographic examination. The clinical and laboratory findings of patients with GWT were evaluated and compared with patients without GWT. Data were recorded for the following variables: gender, age, laboratory findings, duration of symptom, presence of gallstone, and etiology of GWT. A total of 147 (63%) patients with AH had GWT. GWT in patients with an alanine aminotransferase level more than 500 IU/l (5.2 +/- 3.4 mm) was greater than that in other patients (3.9 +/- 2.3 mm; p < 0.05). Hepatitis A virus infection (odds ratio = 3.17 [1.42-7.09]), female gender (odds ratio = 2.47 [1.34-4.56]), and an elevated total bilirubin level (odds ratio = 1.09 [1.03-1.15]) were positively associated with GWT. The incidence of GWT in patients with AH was 63%, and there was an association with hepatitis A virus infection, female gender, and an elevated total bilirubin level.

Thrombotic thrombocytopenic purpura associated with myelodysplastic syndrome

Thrombotic thrombocytopenic purpura (TTP), a lifethreatening disseminated thrombotic microangiopathy (TMA) syndrome, is characterized by bicytopenias with thrombocytopenia and hemolytic anemia (HA) with schistocytes, neurological disturbances, acute renal failure, and pyrexia. It has an incidence of 2–7 per million person per year with a peak incidence between the ages of 30 and 40 [1, 2]. Myelodysplastic syndrome (MDS) is also characterized by multilineage cytopenias due to ineffective hematopoiesis, and predominantly affects the elderly with a peak incidence between the ages of 60 and 75. Compared with other disorders, such as aplastic anemia, phenomena secondary to leukemias, autoimmune disorders, such as systemic lupus erythematosus or Evans syndrome, viral infection, or adverse drug effects, both MDS and TTP are less common as causatives for multilineage cytopenias in young patients. This report describes a rare case of MDS associated with TTP in a young female presented with multilineage cytopenias. A 21-year-old female was referred to our hospital with complaints of purpura, petechiae, headache, numbness and pancytopenia. She was not pregnant, showed no sign of recent infection and had no recent history of drug exposure. Peripheral blood count findings were pancytopenia with white blood cells at 2.4 9 10/L (3.4–7.3 9 10) (neutrophils 47%, lymphocytes 44%, abnormal cells 0%), red blood cells at 2.21 9 10/L (3.62–4.99 9 10), hemoglobin at 7.3 g/dL (11.7–15.1) and platelet count of 20.0 9 10/L (160–327 9 10). Blood examination also demonstrated the presence of HA, shown by elevated serum levels of total bilirubin 2.2 mg/dL (0.2–1.0), and lactate dehydrogenase 453 IU/L (114–243), serum haptoglobin reduced to below detectable levels and the presence of schistocytes. Serum vitamin B12 and folic acid were normal, 384 ng/L (180–914) and 3.9 lg/L ([3.1), respectively. Coombs test, Ham test, and the cell surface expression of glycosyl phosphatidilinositol-anchored proteins were all negative. Other examinations showed no evidence of autoimmune disorders. Bone marrow (BM) examination revealed hypercellular marrow with 300 9 10/L BM nucleated cell counts, and multilineage dysplasia, such as pseudo-Pelger neutrophils or micromegakaryocytes, but with no abnormal increase of myeloblasts at 1.6% of all BM nucleated cells (Fig. 1). Chromosome aberration was not identified by either Gbanding or spectral karyotyping analysis. According to the WHO classification criteria, the patient was diagnosed as MDS, comprising refractory cytopenia with multilineage dysplasia (RCMD) [3]. One month later, she suddenly showed various neuropsychological symptoms, such as disorientation, aphypnia, and anxiety neurosis. Serum urea nitrogen and creatinine levels were normal, 21.1 mg/dL (8.0–23.0) and 0.7 mg/dL (0.4–1.2), respectively. Coagulation tests, such as prothrombin time, activated partial thromboplastin time, or plasma levels of fibrinogen or fibrin degradation product, were normal (data not shown), while a decrease in ADAMTS13 activity (\0.5%) and an increase in the autoantibody for ADAMTS13 (14 Bethesda unit/ml), which functions as an inhibitor of ADAMTS13, were detected in her serum. We diagnosed her as having N. Sasaki J. Kuroda (&) M. Taniwaki Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: junkuro@koto.kpu-m.ac.jp

Evaluation of the antioxidant effects of Ziziphus mauritiana Lam. Leaf extracts against chronic ethanol-induced hepatotoxicity in rat liver.

Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1 ml/100 g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.

Mirizzi syndrome presenting as painless jaundice: a rare entity diagnosed by EUS

A 55-year-old woman presented with a 3-week history of flu-like symptoms, 15-pound weight loss, steatorrhea, and painless jaundice. Laboratory investigations showed elevated total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels.

Coinfection with Leptospirosis and Scrub Typhus in Taiwanese Patients

We retrospectively analyzed patients with leptospirosis (n = 35), scrub typhus (n = 45), and coinfection (leptospirosis and scrub typhus [n = 7]) to facilitate the detection of coinfection. Our data showed that factors favoring these disease entities included animal contact, an aspartate aminotransferase/alanine aminotransferase ratio > 2 (for leptospirosis); outdoor exposure, lymphadenopathy, splenomegaly, eschar, and elevated alkaline phosphatase levels (for scrub typhus and coinfection); calf tenderness, conjunctival suffusion, jaundice, oliguria, elevated total bilirubin levels and serum creatinine levels (for leptospirosis and coinfection); and maculopapular rash (for scrub typhus). Patients at risk for leptospirosis are often at increased risk for scrub typhus and vice versa. Lack of knowledge of coinfection may jeopardize the health of affected patients. Our study serves as a reminder of potential coinfection and provides clues for its detection.

Usefulness of Bile Cultures and Predictive Factors for Bacteriobilia in Percutaneous Cholecystostomy in Patients with Acute Cholecystitis

Bile cultures have been used to diagnose and predict the prognosis of acute cholecystitis (AC). As the standard treatment for AC has changed, the appropriate timing and clinical usefulness of bile cultures should be reevaluated. We analyzed the incidence of positive bile cultures in cholecystostomy and cholecystectomy, and attempted to see if a positive bile culture is related to the laboratory and imaging parameters and postoperative infections. Included in the study were 86 patients with AC who underwent percutaneous cholecystostomy (PC) and then laparoscopic cholecystectomy (LC). We performed hematologic, biochemical, and radiological analyses at admission and bile cultures with each surgical procedure. The patients were followed for two months for postoperative infections. Bile cultures were positive in 40.7% of the patients at PC, significantly higher than at LC (12.8%). The group with positive cultures showed a higher median age and elevated levels of alkaline phosphatase (ALP) and total bilirubin (TB) than the group with negative cultures. Univariate analysis identified three preoperative factors as predictors of positive bile cultures: age (>55 yr), ALP (>100 IU/L) and TB (>1.2 mg/dL). Infectious complications after LC were mild and the incidence of postoperative infections was not different between the groups. The sensitivity of bile cultures is low for diagnosing AC, and the adequate timing of bile cultures is at PC, rather than LC. An old age and factors (ALP & TB) manifesting an advanced stage of bile stasis are associated with positive bile cultures. No correlation was found between positive bile cultures and postoperative infections.

Survey of anti-tuberculosis drug-induced severe liver injury in Japan

To clarify the incidence and clinical significance of anti-tuberculosis drug-induced liver injury. Questionnaire was sent out by mail to 114 hospitals, to ask whether there were patient(s) from 1994 to 2003 with liver injury induced by anti-tuberculosis drugs with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of more than 1000 IU/l and/or total bilirubin level of more than 2 mg/dl. As for the cases of severe hepatic injury, their backgrounds and clinical courses were investigated. Seventy cases were reported from 24 out of 68 hospitals which treated at least 8095 tuberculosis patients in 2003. Incidence rate of severe liver injury by anti-tuberculosis drugs was 0.50 to 0.59 percent in three hospitals with good surveillance system, and overall incidence was estimated to be between 0.1 to 0.5 percent. We could analyze 33 cases; one was HB antigen positive, one had HCV positive liver cirrhosis, 2 had other hepatic disease, and 17 had other underlying disease including diabetes mellitus. Twenty-three were treated by regimens with isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA), and 8 by regimens without PZA but with INH and RFP and one was a multidrug-resistant case and was treated by regimen with ethionamide and PZA. The onset of liver injury was within 2 months after starting anti-tuberculosis chemotherapy in 28 (85%) cases. In twenty-eight cases which both ALT and total bilirubin level are known, total bilirubin level at the onset of liver injury was more than 2 mg/dl in 14 cases and most of the cases were hepatocellular type of liver injury. Six out of 10 cases with total bilirubin level more than 5 mg/dl died by liver failure. Total birilubin was less than 2 mg/gl in two of the dead cases; in one case antituberculosis drug were continued despite elevated level of ALT and another case complicated with gastric bleeding. Treatment for liver injury was conservative in most cases, 6 were treated by plasmapheresis and no liver transplantation was carried out. Eight cases died of liver failure, one died of tuberculosis and only 15 were treated successfully for tuberculosis. Incidence rate was high comparared with that by other drugs reported previously. The risk factor of liver injury by antituberculosis drugs was not detected, but elevated total bilirubin level more than 5 mg/dl was an alarming sign for poor prognosis.

Hyperbilirubinemia in Appendicitis: A New Predictor of Perforation

This study examines the relationship between hyperbilirubinemia and appendicitis. It was hypothesized that an association exists between the presence of appendiceal perforation and hyperbilirubinemia. Patients with liver function tests on admission and pathologically confirmed appendicitis were included in the study. Age, duration of symptoms, temperature, white blood cell counts, systemic inflammatory response score, and bilirubin levels were independent variables in a logistic regression analysis assessing factors predicting the presence or absence of appendiceal gangrene/perforation. Elevated total bilirubin levels (>1 mg/dl) were found in 59 (38%) of 157 patients. Patients with gangrene/perforation were significantly (p = 0.004) more likely to have hyperbilirubinemia than those with acute suppurative appendicitis. No statistical differences were observed for any of the other variables. On logistic regression the only significant relationship between the presence or absence of appendiceal gangrene and perforation was the presence of hyperbilirubinemia (p = 0.031, 95% confidence interval 1.11–7.6). The odds of appendiceal perforation are three times higher (odds ratio 2.96) for patients with hyperbilirubinemia compared to those with normal bilirubin levels. Hyperbilirubinemia is frequently associated with appendicitis. Elevated bilirubin levels have a predictive potential for the diagnosis of appendiceal perforation.

A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan

Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 x 10(9) copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted.

Steroid-Resistant Late Acute Rejection after a Living Donor Liver Transplantation: Case Report and Review of the Literature

The majority of acute cellular rejection occurs in the first few months after liver transplantation. It has been, however, reported that some recipients experience late acute rejection, which occurs more than 3 months after transplantation. We herein report a case of late acute rejection that occurred nearly 10 years after liver transplantation. The patient is a 27-year-old male who underwent a living donor liver transplantation when he was 17 years old. At 9 years 6 months after transplantation, the patient presented with the elevated serum levels of liver enzymes and total bilirubin. A liver biopsy showed acute cellular rejection. Steroid bolus therapy was not effective, but we successfully used deoxyspergualin as a rescue therapy. Late acute cellular rejection that occurs nearly 10 years after transplantation has so far been rarely reported. It is generally believed that late acute rejection may be more resistant to treatment and be associated with a higher rate of graft loss, as well being associated with the development of chronic ductopenic rejection. In this report, we have shown that deoxyspergualin is safe and effective for treatment of steroid-resistant late acute rejection, preventing from graft loss of chronic rejection.

Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function

Previous studies have shown that donor hypernatremia and possibly recipient hyponatremia negatively impact graft function after orthotopic liver transplant (OLT). The purpose of this retrospective investigation was to determine whether measured differences in serum sodium values between cadaveric donors and OLT recipients (DeltaNa(+)) influence immediate postoperative allograft function and short-term patient outcomes. Two hundred and fifty patients that underwent OLT from January 2001 to December 2005 were included in this study. The DeltaNa(+) for each donor recipient pair was correlated with standard postoperative liver function tests as well as recipient length of intensive care unit stay (LOICUS), length of hospital stay (LOHS) and recipient survival. The relationship between donor hypernatremia (serum sodium >or= 155 mEq/mL), recipient hyponatremia (serum sodium level <or= 130 mEq/mL), and postoperative outcomes were analyzed as well. Adjustments were made for baseline potential confounders, including model for end-stage liver disease (MELD) score, preservation solution used (HTK vs. UW), recipient and donor demographics and cold ischemia time (CIT). DeltaNa(+) as well as donor hypernatremia and recipient hyponatremia were not found to be associated with immediate postoperative allograft function, intraoperative blood product usage, LOICUS, LOHS or short-term patient survival. However, both the preoperative MELD score and HTK preservation solution used were significantly associated with several patient outcomes. A higher MELD score was associated with both increased red blood cell (RBC) (P < 0.001) and fresh frozen plasma (FFP) usage (P = 0.002), elevated postoperative total bilirubin levels (P < 0.001), increased LOHS (P = 0.04), and a higher 30-day post transplant mortality (P = 0.02). The use of HTK preservation solution was associated with higher mean postoperative aspartate aminotransferase levels (P = 0.02) and decreased mean RBC (P < 0.001) and FFP usage (P = 0.009) compared to UW preservation solution use.

Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction

We evaluated the dosing requirements in argatroban-treated patients with heparin-induced thrombocytopenia (HIT) and hepatic dysfunction, and compared efficacy and safety outcomes with historical control patients. Retrospective analysis. Inpatient setting. Patients with hepatic dysfunction, defined as total bilirubin > 25.5 micromol/L (1.5 mg/dL), aspartate aminotransferase >100 IU/L, and/or alanine aminotransferase >100 IU/L, were identified from previous multicenter, historical-controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times (aPTTs) 1.5 to 3 times baseline in the experimental group, vs no direct thrombin inhibition in the historical control patients. The analysis population included 82 argatroban patients and 34 historical control patients with hepatic impairment, of whom approximately 50% in each group had renal dysfunction (defined as a serum creatinine level > 1.3 mg/dL). The argatroban dosage was 1.6 +/- 1.1 microg/kg/min (mean +/- SD) over a mean 5-day course of therapy. Significantly lower doses were used in patients with elevated vs normal total bilirubin levels (0.8 +/- 0.6 microg/kg/min vs 1.7 +/- 0.8 microg/kg/min, p = 0.0063) and in patients with hepatic/renal dysfunction vs hepatic dysfunction alone (1.2 +/- 1.1 microg/kg/min vs 2.0 +/- 1.1 microg/kg/min, p < 0.001). The aPTT 24 h after argatroban initiation was 69 +/- 22 s, with 80% of patients having a therapeutic level of anticoagulation. Thirty-four argatroban-treated patients (41.5%) and 17 control patients (50.0%) experienced the 37-day composite end point of death, amputation, or new thrombosis (p = 0.32). Argatroban significantly reduced new thrombosis (8.5% vs 26.5%, p = 0.012). Major bleeding was similar between treatment groups (4.9% vs 2.9%, p = 0.684). Hepatic dysfunction affects argatroban dosing, with reduced doses required particularly in patients with serum total bilirubin levels > 25.5 micromol/L (1.5 mg/dL) or combined hepatic/renal dysfunction. Individual mean aPTT-adjusted doses typically remain > or = 0.5 microg/kg/min, supporting the recommendation of 0.5 microg/kg/min as a conservative initial dose for most patients with hepatic impairment. Argatroban, with proper initial dosing and monitoring, can provide safe and effective antithrombotic therapy in patients with HIT and hepatic impairment.

Spontaneous Hepatic Decompensation in Patients Coinfected with HIV and Hepatitis C Virus during Interferon-Ribavirin Combination Treatment

Spontaneous hepatic decompensation was observed in 7 of 383 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving treatment with interferon and ribavirin. Multivariate analysis identified the following risk factors: didanosine use (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.2-102.3; P < .02), cirrhosis, (OR, 8.8; 95% CI, 1.2-104.2; P<.02), and elevated total bilirubin level (OR, 7.9; 95% CI, 1.08-93.3; P<.03). Didanosine should thus not be given to patients with cirrhosis, particularly when treatments for HCV and HIV infections have to be administered concomitantly.

ABNORMAL LIVER FUNCTION IN SCRUB TYPHUS

Scrub typhus is one kind of rickettsial disease and may cause fever, cough, and skin rashes in infected humans. Regarding liver involvement, it was uncommon to be reported in previous medical literature from Western countries. This study observes the relationship between scrub typhus and liver function. From January 1998 to August 2003 in Kaohsiung Chang Gung Memorial Hospital in Taiwan, we observed 30 patients with scrub typhus, and 29 of them had liver function abnormality. In these patients, we found 89.3% with elevated aspartate aminotransferase (AST) levels, 91.7% with elevated alanine aminotransferase (ALT) levels, 84.2% with elevated alkaline phosphatase (ALP) levels, and 38.5% with elevated total bilirubin levels. In our study, there is a close relationship between scrub typhus and impaired liver function tests. Therefore, if patients are found with fever of unknown origin and abnormal liver function, we should take scrub typhus into consideration.