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PubMed1992

[Clinical characteristics and liver dysfunction in lymphocyte stimulation test-positive elderly].

In order to clarify the characteristics of the side effects of drugs in the elderly, we evaluated clinical features and liver function in 40 lymphocyte stimulation test (LST)-positive elderly. Their ages ranged from 64 to 90 years, with a mean age of 75 years. The major causative agents were antituberculosis agents, antibiotics and antiinflammatory agents, comprising 28%, 22% and 12% of whole drugs, respectively. Liver dysfunction, skin eruptions and fever were the major causes for carrying out LST. The mean latent period was 15 days, and in 80% of the cases, the side effect developed within four weeks after administration of the causative agent. Major clinical symptoms noted during the course were detected in more than the half of the cases. As for liver dysfunction, elevation of GOT, ALP and total bilirubin levels were noted in 76, 63 and 34% of the cases, respectively. These results showed that the hypersensitive side effects of the drugs could appear at any age even in the elderly, and clinical symptoms were often nonspecific and obscure. It was suggested that the presence of mild liver dysfunction and eosinophilia could be helpful markers for the early detection of drug-induced organ dysfunctions as well as careful observation. The possibility of the occurrence of the side effects must be considered on every drug administration. Presence of mild liver dysfunction and eosinophilia may be helpful markers for the early detection of drug-induced organ dysfunction.

Aged↗
PubMed1996

Disorganization of microtubular network in postischemic liver dysfunction: its functional and morphological changes.

Microtubules in the hepatocytes have been implicated to serve as lines of cytoplasmic transport of secretory materials, but are highly labile structures sensitive to pathological conditions in the cytosol. We examined the role of ischemia/reperfusion-induced cytoskeletal alterations in postischemic liver dysfunction. Rabbit livers were subjected to 60-min warm ischemia followed by 1 h or 24 h of reperfusion. Liver function was assessed by directly measuring hepatic clearance of indocyanine green (ICG), an organic anion whose cytoplasmic transport is assumed to depend on intact microtubules, using near-infrared spectroscopy. Structural alterations of microtubules were observed immunohistochemically using tissue sections stained with monoclonal anti-beta-tubulin antibody. ICG removal from hepatocytes into bile canaliculi deteriorated 1 h but reversed 24 h after reperfusion. Immunohistochemistry showed fragmentation of microtubules at the end of liver ischemia. This cytoskeletal alteration was evident 1 h but was not observed 24 h after reperfusion. Treatment with prostaglandin E1 exerted its beneficial effect by preserving ICG clearance and microtubular network. These results demonstrate that liver ischemia and subsequent reperfusion both affect the organization of microtubular network and suggest that structural disruption of microtubules may be a cause of postischemic liver dysfunction.

Actin Cytoskeleton↗
PubMed1996

Uncoupling of rat and human mitochondria: a possible explanation for tacrine-induced liver dysfunction.

BACKGROUND & AIMS: Tacrine administration (1-3 mg/kg) may lead to sinusoidal concentrations in the micromolar range and produce liver dysfunction in 50% of recipients. The aim of this study was to determine the cellular effects of tacrine that account for liver dysfunction. METHODS: The effects of tacrine on mitochondrial function were determined in isolated rat liver mitochondria, cultured rat hepatocytes, and isolated human lymphocytes. RESULTS: In vitro, tacrine was taken up by rat liver mitochondria, decreased their membrane potential, and stimulated their respiration. Ex vivo, respiration was increased in rat mitochondria isolated 30 minutes after the administration of 2 mg of tacrine per kilogram. After 7 days of culture, tacrine (2.5 mumol/L) decreased rat hepatocyte adenosine triphosphate levels. Ten micromolar decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium reduction and neutral red uptake without modifying cell glutathione, the morphology of the endoplasmic reticulum, or protein synthesis. Tacrine (1.25 mumol/L) decreased levels of adenosine triphosphate in human lymphocytes. CONCLUSIONS: The weak base tacrine exerts a protonophoric effect in mitochondria that wastes energy and decreases levels of adenosine triphosphate in rat and human cells. These effects are visible after clinically relevant doses of tacrine and might be involved in tacrine-induced liver dysfunction.

Animals↗
PubMed2004

Therapeutic options in patients with lymphoma and severe liver dysfunction.

OBJECTIVES: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of 37 had an intermediate-high International Prognostic Index. The median total bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and 12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient improvement in liver function to receive subsequent standard chemotherapy. Nine patients (22%) are alive and disease-free at a median of 31 months (range, 4 to > or = 87 months) after mechlorethamine treatment. Factors associated with improved overall survival included improvement in bilirubin levels (P < .001) and receiving subsequent standard chemotherapy (P = .001). CONCLUSION: Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic interventions for this unique group of patients with lymphoma and severe liver dysfunction. Substantial clinical improvement and long-term survival are possible.

Adrenal Cortex Hormones↗
PubMed2002

Prolonged liver dysfunction caused by hemosiderosis in a renal transplant recipient.

BACKGROUND: Liver dysfunction is a frequent complication that arises in the period following kidney transplantations, often resulting in death. We reported a case proving hemosiderosis as a cause of prolonged liver dysfunction after cadaveric kidney transplantation. METHODS: A 47-year-old man, who had been undergoing hemodialysis, was referred to our hospital on 2 November 1999. On the same day, cadaveric kidney transplantation was performed, and serum creatinine level reached a normal level within 2 weeks after surgery. However, serum transaminase gradually increased in the postoperative period. Serum ALT rose up to 116 IU/L on day 20 after the operation and 215 IU/L on day 30. Microscopic examination by needle biopsy revealed hemosiderosis of the liver. Recombinant human erythropoietin was administered and phlebotomy was performed. Liver function improved as a result. CONCLUSION: Early histological diagnosis can be a useful marker in predicting the course of chronic liver disease.

Cadaver↗
PubMed2003

Relation between post-partum liver dysfunction and anti-cytochrome 2D6 antibodies.

PROBLEM: Autoimmune thyroid disease frequently aggravates or develops after delivery through the immune rebound mechanism. However, little is known about the post-partum development of autoimmune hepatitis (AIH). METHOD OF STUDY: We examined 18 patients who developed liver dysfunction after delivery or abortion. Serial examinations were performed in 10 of these cases. Anti-cytochrome 2D6(CYP2D6) antibodies, which are liver-specific autoantibodies, were measured using a sensitive radioligand assay. RESULTS: Liver dysfunction developed between 1 and 5 months after delivery and was mild and transient except in one case. One patient developed liver dysfunction after abortion. Eight of 10 patients who underwent serial serologic examinations were positive for anti-nuclear antibodies, but anti-smooth muscle antibodies were positive in only three patients, and were present only at low titer. None of the patients had anti-mitochondrial antibodies. Nine of these 10 cases were diagnosed as definite or probable AIH according to the international scoring system of AIH. Nine of these 10 patients were positive for anti-CYP2D6 antibodies. The increase of anti-CYP2D6 antibodies was slightly delayed compared to increase of aminotransferase. Of the 18 patients who developed liver dysfunction, 15 cases (83.3%) were positive for anti-CYP2D6 antibodies. Of the 77 post-partum control subjects only three (3.9%) had positive antibodies. CONCLUSIONS: Autoimmune hepatitis developed after delivery, similarly to the development of post-partum autoimmune thyroid disease. Measurement of anti-CYP2D6 antibodies by a sensitive radioligand assay could provide information important for the detection of post-partum AIH.

Adult↗
PubMedDate not supplied

Influence of transcatheter arterial chemoembolization on the prognosis after hepatectomy for hepatocellular carcinoma in patients with severe liver dysfunction.

BACKGROUND: The influence of preoperative transcatheter arterial chemoembolization (TACE) on postoperative survival and recurrence of hepatocellular carcinoma (HCC) after resection is still controversial. The effect of preoperative TACE on the prognosis of HCC after hepatectomy in 243 patients with liver dysfunction was evaluated. MATERIALS AND METHODS: Among 243 patients who underwent curative resection of HCC between 1992 and 2005, 124 patients had an indocyanine-green retention rate at 15 min (ICGR15) of <17% (49 underwent TACE), while 119 patients had an ICGR15 of > or =17% (66 underwent TACE). The clinical characteristics, operative results and long-term survival were compared between patients with and without preoperative TACE who had mild or severe liver dysfunction. RESULTS: There was no significant difference in the recurrence-free and overall survival rates between the TACE and no TACE groups with an ICGR15 <17%. Among the 119 patients with an ICGR15 > or =17%, there were no significant differences of preoperative characteristics, operative findings, or histology between the two groups. However, the post-resection disease-free and overall survival rates of 66 patients who underwent TACE were significantly better than those of 53 patients who did not have TACE (p = 0.009 and p = 0.0099, respectively). Using multivariate analysis, preoperative TACE was independently associated with better disease-free and overall survival after resection in patients with an ICGR15 > or =17% (p = 0.0309 and p = 0.0162, respectively). CONCLUSION: Preoperative TACE did not alter the prognosis after resection of HCC in patients with mild liver dysfunction, but it did improve the prognosis of patients with severe liver dysfunction.

Aged↗
PubMed1995

[The usefulness of monitoring hepatic venous saturation during open heart surgery for a patient with severe liver dysfunction].

We report the usefulness of monitoring hepatic venous saturation (ShVO2) during open heart surgery for a patient with severe liver dysfunction. The patient was a 55-year-old man who had been suffering from acute aortic regurgitation due to bacterial endocarditis. Indocyanine green retention test at 15 min was 55%. Serum GOT, GPT and T bilirubin were 56 U.l-1, 35 U.l-1 and 1.5 mg.dl-1 respectively. Aortic valve replacement was scheduled in spite of severe liver dysfunction because amelioration of congestive heart failure after the operation was expected to improve liver dysfunction to the previous chronic state. Anesthesia was induced and maintained by intermittent administration of diazepam and low dose of fentanyl with 100% oxygen. After induction, we inserted a balloon tipped pulmonary catheter with ultra-red beam into hepatic vein by fluoroscopy guidance and monitored ShVO2 as an index of hepatic oxygen supply/demand balance. During re-insertion of a thoracic catheter, we could detect the continued decrease in hepatic vein saturation even after the improvement of systemic circulatory state. Postoperatively, liver function became slightly worse for a short period and improved thereafter. These results suggest that ShVO2 monitoring is clinically useful in detecting hepatic oxygen supply/demand imbalance which circulatory monitoring could not uncover during open heart surgery.

Aortic Valve↗
PubMed1993

[Hyperlipidemia, hypoalphalipoproteinemia and liver dysfunction in Japanese school-age children with obesity].

Three hundred and twenty nine obese children (206 boys, 123 girls) whose obesity index were above 40% were screened among 6,278 school-age children living in Ibaraki Prefecture. Six hundred and fifty-eight school-age children without obesity were used as controls. The mean levels of total cholesterol and triglyceride of obese boys were significantly higher than those of control boys. The mean levels of HDL-cholesterol of both boys and girls with obesity were significantly lower than those of controls. Hypercholesterolemia, hypertriglyceridemia and hypoalphalipoproteinemia in the boys with obesity were significantly more frequent than those in control boys. In the girls with obesity, hypoalphalipoproteinemia was significantly more frequent than that in control girls. Liver dysfunction (GPT > or = 40 IU/l) in obese children was significantly more frequent than in controls: Although none of controls had liver dysfunction, 24.8% of obese boys and 11.4% of obese girls had liver dysfunction. These findings indicated that atherogenic dyslipidemias and liver dysfunction were common in Japanese school-age children with obesity, especially in boys.

Adolescent↗
PubMed1999

Anorexia nervosa with severe liver dysfunction and subsequent critical complications.

A twenty-year-old woman with anorexia nervosa (body mass index=11) suffered from severe liver dysfunction (aspartate aminotransferase 5,000 IU/l, alanine aminotransferase 3,980 IU/l, prothrombin time 32%), hypoglycemia (serum glucose 27 mg/dl), and pancreatic dysfunction (amylase 820 IU/l, lipase 558 IU/l). She fell into a depressive state with irritability, which was not improved by intravenous glucose. Despite treatment with plasmapheresis for the liver dysfunction, she subsequently developed pulmonary edema, acute renal failure, gastrointestinal bleeding, and disseminated intravascular coagulation. Hemodialysis, mechanical ventilation and drug therapy including prednisolone, prostaglandin E1, and branched-chain amino acid, improved her critical condition. In this case, malnutrition may have been the cause for the liver dysfunction and subsequent complications.

Acute Kidney Injury↗
PubMed1998

Nitric oxide synthase activity is increased in relation to the severity of liver dysfunction.

1. Nitric oxide is a potent vasodilator which plays a major role in the control of blood pressure. The hyperdynamic circulation of cirrhosis has been linked to nitric oxide.2. We measured neutrophil nitric oxide synthase activity in relation to the level of hepatic dysfunction in patients with liver disease of varying aetiology and severity.3. Neutrophils were isolated from 21 patients (7 Child-Pugh score A, 6 grade B and 8 grade C) aged 28-76 (median 49) years. Nitric oxide synthase activity was measured using the conversion of oxyhaemoglobin to methaemoglobin by nitric oxide and expressed in terms of cell protein. Blood pressure and biochemical indices were recorded. Data were assessed using Kruskal-Wallis one-way analysis of variance, Mann-Whitney U-test or Pearson correlation as appropriate.4.Systolic, mean arterial and diastolic blood pressures decreased with increasing hepatic damage (P=0.031, P=0.01 and P=0. 038 respectively). Nitric oxide synthase activity increased with the degree of liver dysfunction (P=0.033) and was highest in patients with Child-Pugh score C. Systolic blood pressure correlated with nitric oxide synthase activity in patients with Child-Pugh score C (P=0.029).5. Our results show that nitric oxide synthase activity increases with increasing Child-Pugh score and is associated with the development of systemic hypotension. These data may support the involvement of nitric oxide in the haemodynamic disturbances seen in liver disease.

Adult↗
PubMed1981

Liver dysfunction in children and adolescents during hemodialysis and after renal transplantation.

Liver dysfunction is common in patients on hemodialysis or during the posttransplant period. Twelve children in the End-Stage Renal Disease Program at the University of Florida ranging in age from 4 to 18 years, developed persistent, elevated liver enzymes (SGOT or SGPT greater than 100 IU/liter) during hemodialysis in preparation for renal transplantation. Eleven of 12 developed enzyme elevations within six weeks of the initiation of hemodialysis. The other child exhibited enzyme elevations after one year on dialysis while awaiting a second transplant. Most of the children were anicteric and asymptomatic. Potential hepatotoxic drugs were discontinued when serum transaminase elevations were noted. Hepatitis B surface antigenemia was associated with enzyme elevations in one patient; cytomegalovirus seroconversion had occurred in eight patients, but only three had associated enzyme elevations. Liver biopsies were performed in all the patients before or at the time of renal transplantation. The histology was variable and ranged from normal in six patients, mildly abnormal with changes compatible with acute hepatitis in four patients, and granulomatous hepatitis in one patient, to severely abnormal with chronic hepatitis inthe remaining patient. Seven of the 12 children underwent successful transplantation with return of enzyme levels to normal in five and persistent elevations in the others. These findings suggest that evaluation of liver histology provides the only accurate means of assessment of persistent liver dysfunction in children and adolescents on hemodialysis and after renal transplantation.

Adolescent↗
PubMed1994

Hepatitis C virus infection detected by antibody tests and the polymerase chain reaction as a cause of liver dysfunction in renal transplant recipients.

Hepatitis C infection (HCV) is more prevalent in patients who have received kidney transplants than in the general population but the morbidity and mortality associated with infection in this group is unclear. Sera taken from 36 renal transplant recipients with chronic liver dysfunction and from 42 with normal liver function were tested for HCV infection by second generation ELISA (Abbott Laboratories) and second generation recombinant immunoblot assay (Chiron Corporation) (RIBA-2). Evidence of HCV replication was sought by reverse transcription polymerase chain reaction (RT PCR) using primers from the 5' nontranslated region (5'NTR). Infection was detected in 20/36 (54%) and in 2/42 (4.8%) controls (P < 0.01). Twelve liver dysfunction patients were positive by all three tests, six were positive by ELISA and RT PCR but had indeterminate RIBA-2, one was positive by ELISA and RIBA but negative by RT PCR, and one was positive only by RT PCR. Of two infected control patients, one was positive by all three tests and one who was later found to have been in the early stage of infection was positive only by RT PCR. Follow-up of infected patients showed persistence of viraemia in 14/15 (93%). Evidence of infection with different types of HCV was shown by the lack of amplification by RT PCR by primers with mismatching bases with HCV types 2 and 3. It is concluded that in our renal transplant patients, chronic HCV infection is usually associated with liver dysfunction and persistent infection is common.

Adult↗
PubMed1990

[Chemotherapy with fluoropyrimidines for MOPC-104E plasmacytoma transplanted in mice with CCl4 induced chronic liver dysfunction].

The masked compounds of 5-fluorouracil (5-FU) have been widely used for chemotherapy in digestive organ cancer. Among them it has been considered that FT (Tegafur) is metabolized into the active form by the drug-metabolizing enzyme P-450 in the microsomes of hepatocytes, and that their activation and anti-tumor activity may decrease under the condition of chronic liver dysfunction. However, this hypothesis has never been experimentally proved. In the present study the therapeutic effect and metabolism of 5-FU and its masked compounds: FT, UFT (uracil + FT), HCFU (Carmofur), 5'-DFUR (Doxifluridine) were assessed by using MOPC-104E plasmacytoma transplanted subcutaneously in BALB/c mice with CCl4-induced chronic liver dysfunction. Agents were administered daily directly into the stomach with stainless steel canule over days 7 to 13 after tumor transplantation, and the tumor weights, drug concentrations in the liver or the tumor, and serum levels of GOT, GPT and LDH were measured on day 14. In mice with chronic liver dysfunction the tumor-inhibitory effect of 5-FU, FT, UFT and HCFU did not necessarily decrease and serum levels of GOT, GPT and LDH of mice administered with 5-FU, FT, HCFU and 5'-DFUR were higher than in normal animals treated with them. By contrast UFT had no influence on them. The most remarkable difference was observed in uracil concentrations, which were significantly lower in the tumor and the liver of mice with chronic liver dysfunction than in those of normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[A case of suspected liver dysfunction induced by sevoflurane anesthesia].

We report a case of suspected liver dysfunction after general anesthesia with sevoflurane. A 30 day old male infant underwent inguinal herniorrhaphy under sevoflurane anesthesia (sevoflurane concentration: 1.3-1.5% with 50% oxygen and nitrous oxide). Two days after the operation, he developed frequent vomiting, anorexia and fever. GOT, GPT and LDH values were 242 Ku, 326 Ku and 901 Wu, respectively and peaked at 520 Ku, 709 Ku and 1000 Wu 12-16 days after the operation. Clinical symptoms and the laboratory data became normal within 2 months. The antibody titers of EB-virus, cytomegalo-virus and HA-virus were all within normal ranges and HBs antigen was negative. There were no blood transfusion or antibiotics administration before the onset, and no epidemic of hepatitis around him. His mother had no history of hepatitis during her pregnancy. Lymphocyte stimulation test for indication of sevoflurane allergy was also negative. From these evidences, toxic (not allergic) liver dysfunction due to exposure to sevoflurane was considered to be the most probable diagnosis.

Anesthesia, Inhalation↗
PubMedDate not supplied

Does a long pre-operative hospital stay before hepatectomy improve liver dysfunction in HCC patients with chronic liver disease?

BACKGROUND/AIMS: We retrospectively evaluated whether or not hepatic dysfunction improved in patients with chronic liver disease who had been waiting to undergo a hepatectomy after admission. MATERIALS AND METHODS: Fifty-two hepatocellular carcinoma patients had been admitted for more than 2 weeks prior to undergoing a hepatectomy. They had a liver function test twice, at admission and just before surgery, during the hospitalization period. Twenty-six of them were histologically diagnosed as having chronic hepatitis while the remainder had liver cirrhosis. In the liver function test, the serum levels of albumin, total bilirubin, glutamic pyrubic transaminase (alanine transaminase), total cholesterol and the Child grade were examined. RESULTS: First, including the pre-operative treatment cases for small tumors under angiography, the total bilirubin and transaminase levels improved in the chronic hepatitis patients with a statistically significant difference, but no difference was observed in the Child grade. In the examined cirrhotic patients, no significant difference was shown in the tests. Second, after excluding the pre-operative treatment cases, we performed the same investigation as that for chronic liver disease cases and only the transaminase level significantly improved. CONCLUSIONS: A long pre-operative hospital stay might only by justified in patients with a high level of transaminase corresponding to chronic active hepatitis.

Adult↗