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PubMed1989

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.

Aged↗
PubMed2004

Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients.

BACKGROUND: Cirrhotic patients who present for elective and emergent surgery pose a formidable challenge for the surgeon because of the high reported morbidity and mortality. The Child-Turcotte-Pugh (CTP) score previously has been used to evaluate preoperative severity of liver dysfunction and to predict postoperative outcome. Recently, a more objective scoring classification, the model for end-stage liver disease (MELD), has been shown to predict accurately the 3-month mortality for cirrhotic patients awaiting transplantation. We sought to compare the CTP and MELD scores in predicting outcomes in cirrhotic patients undergoing surgical procedures requiring general anesthesia. METHODS: During the study period, 40 patients with a history of cirrhosis who required elective (E) or emergent (EM) surgical procedures under general anesthesia were reviewed (E = 24, EM = 16). The preoperative CTP and MELD scores were calculated and patient short- (30-day) and long-term (3-month) outcomes were recorded. RESULTS: There was a significant difference in the 1-month and 3-month mortality rates between the emergent and elective groups (EM group: 1 mo = 19%, 3 mo = 44%; E group: 1 mo = 17%, 3 mo = 21%, P <0.05). There was good correlation between the CP and MELD scores, which was greater in the emergent groups as compared with the elective group (EM: r = 0.81; E: r = 0.65). CONCLUSIONS: Our study shows that cirrhotic patients who undergo surgery under general anesthesia have an extremely high 1- and 3-month mortality rate that progressively increases with severity of preoperative liver dysfunction. Additionally, the MELD score correlates well with the CTP score, providing a more objective predictor of postoperative mortality in cirrhotic patients undergoing surgery.

Adult↗
PubMed1992

Metabolic clearance rate of arginine vasopressin in patients with cirrhosis.

Metabolic clearance rate and half-time of arginine vasopressin were measured in 43 cirrhotic patients and 10 control subjects. Synthetic arginine vasopressin was infused intravenously at a rate of 500 pg/min/kg of body weight for 75 min. The metabolic clearance rate was significantly reduced, and the half-time of arginine vasopressin after stopping the infusion was significantly increased in patients with cirrhosis, particularly in those with ascites and in those with moderate or severe liver dysfunction. Changes in metabolic clearance rate and half-time of arginine vasopressin correlated with the score of the liver dysfunction, prothrombin activity and levels of serum albumin and bilirubin but not with parameters of kidney function (serum creatinine levels and clearance of creatinine). We conclude that reduced metabolic clearance rate and prolonged half-time of vasopressin in plasma are frequent findings in cirrhotic patients with poor liver function. This impaired catabolism of antidiuretic hormone may contribute to maintaining elevated plasma levels of this hormone in these patients and may be an additional factor leading to fluid retention and to dilutional hyponatremia.

Adult↗
PubMed1994

Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage.

To examine the hypothesis that serum levels of 7 alpha-hydroxycholesterol reflect bile acid synthesis in the liver, we analyzed serum 7 alpha-hydroxycholesterol and bile acid output in 13 patients with obstructive jaundice after relief of biliary obstruction. Before biliary drainage, the serum level of 7 alpha-hydroxycholesterol was 92 +/- 12 pmol/ml (mean +/- S.E.M.) and was significantly lower than the control value (226 +/- 26 pmol/ml, p < 0.01). After biliary drainage, serum 7 alpha-hydroxycholesterol level and biliary bile acid outputs began to rise in some patients, indicating reversible liver dysfunction. In other patients, serum 7 alpha-hydroxycholesterol levels and bile acid outputs did not increase, suggesting severe or irreversible liver dysfunction. On and after the third day of biliary decompression, serum 7 alpha-hydroxycholesterol levels correlated well with bile acid excretion (p < 0.01, r = 0.93). Other liver function parameters, such as serum bilirubin, serum bile acids, albumin, and bile flow, also revealed significant correlation with serum 7 alpha-hydroxycholesterol levels. We conclude that the serum 7 alpha-hydroxycholesterol level clearly reflects bile acid synthesis in the liver and that it may serve as a useful parameter for the assessment of hepatic functional recovery in patients with obstructive jaundice after biliary drainage.

Aged↗
PubMed1999

Troglitazone. Is it all over?

In January 1997 a drug from a new pharmacological class, the thiazolidinediones, became available: troglitazone. Troglitazone indirectly enhances peripheral insulin sensitivity. In this way it lowers the levels of both glucose and insulin. Troglitazone also has a lowering effect on the levels of triglycerides. In clinical trials only mild side effects had been observed. Therefore, troglitazone seemed a promising drug. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. Although this side effect is reversible in most cases, six deaths have been described due to liver damage. Troglitazone was to be introduced in Europe in 1998 but registration procedures and clinical trials have been stopped because of its side effects on the liver. In the United States and Japan troglitazone is still being used, albeit with extra precautions. Troglitazone is a valuable addition to the arsenal of antidiabetic drugs for type 2 diabetes. It can be particularly useful, both as an additive and as a replacement, in patients for whom metformin is not suitable because of contraindications or side effects. The risk of severe liver dysfunction is a reason to reserve troglitazone as a second-line drug.

Animals↗
PubMed2001

Development of fulminant hepatitis B (precore variant mutant type) after the discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis patient.

A 75-year-old female rheumatoid arthritis patient who was positive for hepatitis B surface antigen and for antibodies to hepatitis Be antigen showed liver dysfunction, and therefore methotrexate (MTX) therapy was discontinued. Her drug lymphocyte stimulation test indicated positivity for MTX. Her liver dysfunction improved briefly, but she developed fulminant hepatitis with elevated levels of hepatitis B virus (HBV)/DNA polymerase and subsequently died. HBV/DNA analysis performed with polymerase chain reaction-mutation site-specific assay revealed that the fulminant hepatitis was caused by a precore mutant virus. Sudden reactivation of the immune system by discontinuation of MTX may have led to the attack on infected cells. Even when hepatitis Be antibodies are present, MTX should not be used in patients who have chronic infection with HBV.

Arthritis, Rheumatoid↗
PubMed1992

Chronic ethanol abuse and membrane fluidity changes in liver disease.

The long-term effect of ethanol on human red cell membrane fluidity was studied, by fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene as a probe, in 11 healthy subjects, 9 chronic alcoholics without evidence of liver disease, 12 chronic alcoholics with biopsy-proven alcoholic liver disease and 9 abstemious patients with chronic active liver disease, most of them cirrhosis of the liver. Fluorescence polarization values were not significantly different in the two groups without liver disease. Patients with alcoholic and non-alcoholic liver disease showed higher fluorescence polarization values than patients without liver disease. These changes correlated with the severity of liver dysfunction and were not related to alcohol consumption. In conclusion, the decrease in fluidity of the erythrocyte membrane in alcoholic patients with chronic liver disease, is related to liver dysfunction but not to chronic ethanol ingestion. Changes in membrane fluidity in chronic alcoholics are found only in the presence of liver disease.

Adult↗
PubMed1985

[Preliminary report of adjuvant chemo-endocrine therapy for breast cancer].

Preliminary analysis of adjuvant chemo-endocrine therapy for 193 breast cancer patients was performed. The patients consisted of 38 cases of Stage I, 124 cases of Stage II and 31 cases of Stage III. Therapeutic regimen was randomly divided into three groups; (1) Tamoxifen (TAM), (2) TAM + ftorafur (FT-E) and (3) TAM + FT-E + Adriamycin. Side effects among the three therapeutic groups were comparatively studied. Anorexia and nausea were observed in 1.4%, 17.1% and 60% of the patients, respectively. Leucopenia of less than 3,000 and alopecia were remarkably seen in the patients treated with regimen 3. Liver dysfunction was observed in 10.9% of group 1, 29.5% of group 2 and 13.3% of group 3, respectively. Gastrointestinal symptoms and liver dysfunction were important side effects.

Adult↗
PubMed2007

Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease.

Niemann-Pick type C (NPC) disease is a multisystem disorder resulting from mutations in the NPC1 gene that encodes a protein involved in intracellular cholesterol trafficking. Significant liver dysfunction is frequently seen in patients with this disease. The current studies used npc1 mutant mice to investigate the association between liver dysfunction and unesterified cholesterol accumulation, a hallmark of NPC disease. Data from 92 npc1(-/-) mice (age range, 9-56 days) revealed a significant positive correlation between the plasma activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and whole liver cholesterol content. In 56 day old npc1(-/-) mice that had been fed from 35 days of age a rodent diet or the same diet containing either cholesterol (1.0%, w/w) or ezetimibe (a sterol absorption inhibitor; 0.0125%, w/w), whole liver cholesterol content averaged 33.5 +/- 1.1, 87.9 +/- 1.7, and 20.8 +/- 0.9 mg, respectively. Again, plasma ALT and AST activities were positively correlated with hepatic cholesterol content. In contrast, plasma transaminase levels remained in the normal range in npc1(+/+) mice, in which hepatic esterified cholesterol content had been increased by 72-fold by feeding a high-cholesterol, high-fat diet. These studies suggest that the late endosomal/lysosomal content of unesterified cholesterol correlates with cell damage in NPC disease.

Animals↗
PubMed1999

Pharmacokinetics and pharmacodynamics of vecuronium in rats with systemic inflammatory response syndrome: treatment with NG-monomethyl-L-arginine.

BACKGROUND: Insufficient detoxification caused by nitric oxide-related inhibition of cytochrome P450 may be important for metabolism of numerous drugs, including vecuronium. The present study investigated the pharmacodynamics and pharmacokinetics of vecuronium in rats with inflammatory liver dysfunction. METHODS: Male Sprague-Dawley rats (n = 56) were randomly allocated into two groups: In the sepsis group, liver inflammation was established by injection of 56 mg/kg heat-killed Corynebacterium parvum; control rats received the solvent. At day 4, groups were subdivided according to treatment with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (250 mg/kg) or placebo. The aminopyrine breath test was performed to assess cytochrome P450 activity. Rats were anesthetized with propofol and mechanically ventilated. Duration of action of vecuronium (1.2 mg/kg) was measured by evoked mechanomyography (stimulation of the sciatic nerve, contraction of the gastrocnemius muscle). In seven rats of each subgroup a 50% neuromuscular blockade was established by a continuous vecuronium infusion. Vecuronium plasma levels were measured and plasma clearance of vecuronium was calculated. Nitric oxide synthesis was assessed by measuring nitrite/nitrate serum levels. RESULTS: In sepsis/placebo rats, vecuronium-induced neuromuscular blockade was prolonged (144% of contro/placebo), vecuronium plasma levels at 50% neuromuscular blockade were increased (122% of control/placebo), and plasma clearance was decreased (68% of control/placebo). N(G)-monomethyl-L-arginine therapy in rats with sepsis improved cytochrome P450 activity and plasma clearance of vecuronium, shortened duration of action of vecuronium, but did not alter the elevated vecuronium plasma levels. CONCLUSIONS: A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to and a decreased elimination of vecuronium. Modulation of nitric oxide synthesis may be a strategy that can be used in the future to improve xenobiotic metabolism in sepsis.

Alanine Transaminase↗
PubMed2005

The liver in pregnancy: disease vs benign changes.

Liver dysfunction in a pregnant woman may be caused by the pregnancy, it may be unrelated to the pregnancy, or it may be a chronic condition that existed before the pregnancy. In any case, the clinical clues of liver dysfunction in pregnancy are not specific, and certain "abnormalities" in liver function tests may represent benign changes of pregnancy. On the other hand, prompt recognition of the signs of liver disease in pregnant patients leads to timely management and may save the life of both mother and baby.

Diagnosis, Differential↗
PubMed1993

Cyclophosphamide as an alternative to azathioprine in cardiac transplant recipients with suspected azathioprine-induced hepatotoxicity.

AZA has been reported to cause liver dysfunction in some recipients of solid organ transplants. To assess the safety and efficacy of cyclophosphamide in maintenance immunosuppression in the setting of AZA-induced liver dysfunction, we retrospectively reviewed the records of 320 surviving cardiac transplant recipients in Utah. Cyclophosphamide was substituted for AZA in 29 patients due to elevated liver enzymes. Patients were switched to cyclophosphamide 689 +/- 104 days after transplantation; total follow-up after initiation of cyclophosphamide was 540 +/- 56 days. The dose of cyclophosphamide after 2 and 6 months of cyclophosphamide therapy was 62 +/- 6 mg/day (0.8 +/- 0.1 mg/kg/day) and 48 +/- 5 mg/day (0.6 +/- 0.1 mg/kg/day), respectively, compared with 233 +/- 20 mg/day (2.9 +/- 0.2 mg/kg/day) of AZA. The substitution of cyclophosphamide for AZA was associated with a significant improvement in liver function tests. Liver enzymes decreased by up to 49% (P = 0.027), while serum bilirubin decreased by 58% (P < 0.001). Rejection frequency did not increase; neither corticosteroid nor CsA dosage was altered significantly after the substitution of cyclophosphamide. Significant bone marrow suppression was not observed; specifically, no significant change in white blood cell count or hematocrit occurred. Complications of treatment with cyclophosphamide were few; only 1 patient discontinued cyclophosphamide because of alopecia. We conclude that cyclophosphamide appears to be safe in maintenance immunosuppression, permitting the discontinuation of AZA in patients with AZA-induced hepatic dysfunction without necessitating the augmentation of either corticosteroids or CsA.

Alanine Transaminase↗
PubMed2002

Delayed neuropsychologic dysfunction after liver transplantation for acute liver failure: a matched, case-controlled study.

Although several studies have identified posttransplant neurologic sequelae in patients with acute liver failure (ALF), the effects of these sequelae on neuropsychologic functioning after transplant is unknown. This study compared neuropsychologic functioning of ALF patients with chronic liver disease patients after liver transplantation. After liver transplantation, seven ALF patients were compared with a matched control group of patients who had been transplanted for chronic liver disease. The patients were matched by gender, age (within 5 years), and time since transplantation (within 2 years). Patients completed a 2-hour battery of tests, which included measures of attention, memory, motor performance, abstract conceptualization, and visuospatial perception. There were no significant differences between the groups on measures of socioeconomic status or education. Significant differences were found on three separate tests: WAIS-III Vocabulary, WAIS-III Similarities, and WMS-III Paired Associate Learning II. Although these tests measure distinct functions (vocabulary knowledge, abstract conceptualization, and delayed verbal recall), they may be influenced by broader verbal functions, such as verbal fluency, conceptualization, and the ability to articulate ideas. When patients were asked what functions had noticeably deteriorated since transplantation, nearly all complained of memory difficulties, and there was no difference between groups. However, more ALF than chronic liver disease (CLD) patients complained of concentration difficulties. The results of this study suggest that ALF patients may experience more neuropsychologic dysfunction after transplant. Further studies are required to expand on these initial observations with the potential to improve patient care and referral to appropriate rehabilitative services.

Acute Disease↗
PubMed2003

Preoperative portal vein embolization for extended hepatectomy.

OBJECTIVE: To examine the authors' experience with preoperative ipsilateral portal vein embolization (PVE) and assess its role in extended hepatectomy. SUMMARY BACKGROUND DATA: Extended hepatectomy (five or more liver segments) has been associated with higher complication rates and increased postoperative liver dysfunction than have standard hepatic resections involving lesser volumes. Recently, PVE has been used in patients who have a predicted (postresection) future liver remnant (FLR) volume less than 25% of total liver volume in an attempt to increase the FLR and reduce complications. METHODS: Sixty patients from 1996 to 2002 were reviewed. Thirty-nine patients had PVE preoperatively. Eight patients who had PVE were not resected either due to the discovery of additional unresectable disease after embolization but before surgery (n = 5) or due to unresectable disease at surgery (n = 3). Therefore, 31 patients who had PVE subsequently underwent extended hepatic lobectomy. A comparable cohort of 21 patients who had an extended hepatectomy without PVE were selected on the basis of demographic, tumor, and liver volume characteristics. Patients had colorectal liver metastases (n = 30), hepatocellular carcinoma (n = 15), Klatskin tumors (n = 9), peripheral cholangiocarcinoma (n = 3), and other tumors (n = 3). The 52 resections performed included 42 extended right hepatectomies, 6 extended left hepatectomies, and 4 right hepatectomies extended to include the middle hepatic vein and the caudate lobe but preserving the majority of segment 4. Concomitant vascular reconstruction of either the inferior vena cava or hepatic veins was performed in five patients. RESULTS: There were no differences between PVE and non-PVE groups in terms of tumor number, tumor size, tumor type, surgical margin status, complexity of operation, or perioperative red cell transfusion requirements. The predicted FLR was similar between PVE and non-PVE groups at presentation. After PVE the FLR was higher than in the non-PVE group. No complications were observed after PVE before resection. There was no difference in postoperative mortality, with one death from liver failure in the non-PVE group and no operative mortality in the PVE group. Postoperative peak bilirubin was higher in the non-PVE than the PVE group, as were postoperative fresh-frozen plasma requirements. Liver failure (defined as the development of encephalopathy, ascites requiring sustained diuretics or paracentesis, or coagulopathy unresponsive to vitamin K requiring fresh-frozen plasma after the first 24 hours postresection) was higher in the non-PVE patients than the PVE patients. The hospital stay was longer in the non-PVE than the PVE group. CONCLUSIONS: Preoperative PVE is a safe and effective method of increasing the remnant liver volume before extended hepatectomy. Increasing the remnant liver volume in patients with estimated postresection volumes of less than 25% appears to reduce postoperative liver dysfunction.

Adult↗
PubMed2000

Tolcapone and hepatotoxic effects. Tasmar Advisory Panel.

Four patients with Parkinson disease have recently been described in whom severe hepatic dysfunction developed in association with tolcapone therapy. These reports led to the introduction of a "black box" warning and more intensive monitoring requirements in the United States. A review of these cases and all clinical trials indicates that liver dysfunction did not develop in any patient who had received monitoring of liver function according to the original prescribing information. Virtually all instances of liver enzyme abnormality and clinical liver dysfunction occurred within 6 months of initiating treatment. To assess the current role of tolcapone therapy in Parkinson disease, a panel of neurologists and hepatologists was convened. Consensus was reached with respect to the following: (1) Tolcapone is an effective agent in the treatment of patients with fluctuating Parkinson disease. (2) The risk of developing irreversible liver injury is negligible with appropriate monitoring. (3) It may be possible to reduce the frequency of monitoring after 6 months of treatment. (4) The requirement that tolcapone be withdrawn if liver enzymes are elevated above the upper limit of normal on a single occasion is unnecessarily restrictive. It was concluded that tolcapone, when used as an adjunct to levodopa, is an effective anti-parkinsonian agent and that less frequent monitoring after 6 months, with an action limit of 2 to 3 times the upper limit of normal, is sufficient to ensure safety in patients who are deriving benefit from the drug.

Aged↗
PubMed1999

Acute pseudohepatitis in a chronic substance abuser secondary to occult seat belt injury.

Causes of a massive elevation in serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in the substance-abusing patient include viral hepatitis and drug hepatotoxicity. A patient chronically addicted to injection heroin and cocaine presented to the emergency room in a confused state and was admitted to a medical ward with an AST of 4120 U/L, ALT 3820 U/L and right upper quadrant discomfort. Investigations for viral and hepatotoxic causes for the liver dysfunction revealed only hepatitis C seropositivity. A computed tomogram of the abdomen, however, revealed a significant contusion to the right lobe of the liver consistent with traumatic injury. A motor vehicle accident, in which the patient was wearing a seat belt, and which had occurred a few days before admission and had been thought to be minor, was the cause of the liver dysfunction. Significant blunt abdominal traumatic injuries are usually managed exclusively by surgical trauma units. This case underlines the need for medical specialists to be aware of hepatic contusion injuries and to have a high index of suspicion when investigating unexplained hepatocellular dysfunction in chronic substance abusers who have been in motor vehicle accidents.

Accidents, Traffic↗
PubMedDate not supplied

Extended surgery--left upper abdominal exenteration plus Appleby's method--for type 4 gastric carcinoma.

BACKGROUND: The prognosis after surgical treatment for type 4 gastric cancer, including linitis plastica, remains poor. The most frequent recurrence mode is retroperitoneal involvement. To remove the tumor and microinvasion surrounding the stomach, extended surgery, left upper abdominal exenteration plus the Appleby's method (LUAE + Apl), has been performed for type 4 cancers since 1983. PATIENTS AND METHODS: A total of 54 patients with type 4 cancer underwent extended surgery (LUAE + Apl) over the past 11 years. In the LUAE + Apl surgical procedure, the whole stomach, pancreas body and tail, spleen, gallbladder, transverse colon, and left adrenal were removed en bloc. The results of this treatment are reported and the most beneficial application of this procedure (group A) is evaluated and compared with findings in similar patients who underwent common surgery between 1973 and 1983 (group B). RESULTS: As postoperative complications, pancreatic fistula (30%; control 19%), liver dysfunction (15%; 14%), anastomosis failure (6%; 9%), and infection (4%; 1%) were observed (NS). In group A, one patient died of liver dysfunction and another of multiple organ failure due to major pancreatic fistula. In stage III, the 5-year survival rate of group A (40%) was better than that of group B (20%; p < 0.05). In stage IV, the 5-year survival rate of group A (5%; 3% in group B) was not improved. CONCLUSION: LUAE + Apl improved the survival of patients with scirrhous cancer in stage III, but it was not effective for those in stage IV. To improve the survival of patients in stage IV, a new concept of treatment and supportive therapy needs to be used.

Adenocarcinoma, Scirrhous↗
PubMed2004

[Beneficial effect of glucocorticosteroids for esophageal varices due to idiopathic portal hypertension following systemic lupus erythematosus].

A 54-year-old female experienced morning stiffness and arthralgia of the hands from November 2001 and consulted her local doctor in January 2002. Hematological data showed liver dysfunction and antinuclear antibody was positive. In February 2002, the patient was admitted to our hospital to investigate these abnormalities of liver function further. The features of arthritis, thrombocytopenia with elevated platelet-associated IgG, positive antinuclear antibody, and anti-DNA antibody lead to a diagnosis of systemic lupus erythematosus. Liver biopsy revealed infiltration of Glisson's capsule by plasma cells, compatible with autoimmune hepatitis. We performed hepatic venography to investigate severe pancytopenia, remarkable splenomegaly and esophageal varices. Wedged hepatic venous pressure was mildly elevated, and hepatic veins displayed sharp angles, smooth walls and development of anastomosis with each other. These findings suggested idiopathic portal hypertension. Cytopenia and liver dysfunction gradually improved on treatment with 40 mg/day prednisolone. Esophageal varices were disappeared, and splenomegaly had improved after 6 months. As autoimmune factors are considered to underlie the development of idiopathic portal hypertension with systemic lupus erythematosus, steroid administration represents a therapeutic option in this condition.

Esophageal and Gastric Varices↗