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Malignant histiocytosis with marked cellular atypia--an autopsy case with an immunohistochemical study on neoplastic histiocytes.

A 71-year-old male presenting high fever, pancytopenia, liver dysfunction and jaundice died without a confirmed diagnosis. Microscopically, histiocytes with marked atypia and erythrophagocytosis had infiltrated the spleen, enlarged lymph nodes, liver, and bone marrow. From the above features this case was diagnosed as malignant histiocytosis. The infiltrating histiocytes were classified into three categories: 1) phagocytic cells, 2) atypical, mostly non-phagocytic cells, and 3) bizarre cells including multinucleated giant cells. An immunohistochemical study of histiocyte markers demonstrated that lysozyme was positive in the atypical cells and some phagocytic cells, whereas alpha-l-antitrypsin tended to be localized in the phagocytic cells. Bizarre cells were negative for both markers. No S-100 protein was demonstrated in the neoplastic cells. These immunohistochemical features suggested monocyte-phagocytic origin of the tumor in this case.

Aged↗

[Alcoholic liver injury accompanied with various metabolic and endocrinological disorders--a case report].

We report a young female case of alcoholic liver injury accompanied with various metabolic and endocrinological disorders. A 29 year-old woman was admitted because of general fatigue and hyperlipidemia. She was a heavy drinker. Laboratory data on admission revealed liver dysfunction and hyperlipidemia (type II b) with a quite high serum gamma-glutamyltranspeptidase (gamma GTP) level. The microscopic finding of the liver biopsy specimen showed fatty metamorphosis and ballooning of hepatocytes, and she was diagnosed as heavy alcoholic liver injury. The endocrinological examination revealed the elevated plasma cortisol level, though the urinary 17-hydroxycorticoids (17-OHCS) and 17-ketosteroids (17-KS) excretion and the plasma adrenocorticotropic hormone (ACTH) level were reduced. Cortisol secretion showed the normal circadian rhythm and the normal response to ACTH provocation. The levels of plasma triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also reduced. These endocrinological and metabolic disorders were normalized in company with recovery of the liver function by temperance, diet therapy and nutritional education. Thus, these abnormalities were considered to be resulted from the alcoholic liver injury and the effect of the ethanol to the hypothalamic-pituitary system.

Adult↗

Chronic liver failure induced by long-term administration of tegafur: a case report.

A 55 year-old man was admitted with massive ascites. Although the laboratory data on admission were compatible with hepatic cirrhosis and remarkable esophageal varices were observed during endoscopy, the imaging findings such as computed tomography and ultrasonographic examination did not confirm hepatic cirrhosis. The patient had no history of alcohol abuse, blood transfusions or acute hepatitis. Serological markers related to viral and autoimmune hepatitis were all negative. Seven years ago, the patient had undergone an operation for colon cancer and has been taking tegafur since then for a total of 55 months. Tegafur was suspected as the causative agent for the liver dysfunction of this patient and the administration of tegafur was stopped. His laboratory data improved gradually and the ascites vanished. The first liver biopsy performed 6 months after discontinuation of tegafur still revealed chronic active hepatitis. However, at the liver biopsy performed 18 months after withdrawal of tegafur, inflammatory activity had subsided and the third liver biopsy, performed 34 months thereafter, revealed further improvement of the pathological changes that had occurred in the liver. We therefore conclude that the administration of tegafur may have caused chronic active liver injury with portal hypertension manifested as ascites and esophageal varices.

Antimetabolites, Antineoplastic↗

Acute portal hypertension reflecting shear stress as a trigger of liver regeneration following partial hepatectomy.

The concept of injury in liver regeneration after partial hepatectomy (PHx), and the reason hepatocytes that have not been directly injured regenerate, remain unclear. It is known that shear stress resulting from blood flow plays an important role in the mechanism of remodeling blood vessels, and portal pressure reflects shear stress. This study was conducted to determine whether acute portal hypertension (APH) can become a trigger of liver regeneration as shear stress following PHx in a rat model. Portal pressures became elevated immediately after 70% and 90% PHx, peaking on postoperative day (POD) 3, and thereafter decreasing in proportion to the diminution of liver regeneration. The portal pressures after 90% PHx were significantly higher than those after 70% PHx even on POD 7, while those of the portocaval (PC) shunt groups decreased following PC shunting both with and without 70% PHx. The liver/body weight (LW/BW) ratio also decreased in the PC shunt both with and even without 70% PHx. The gradient expressions of class I antigen on sinusoidal endothelial cells (SEC) were found only in the periportal area, which has the highest portal pressure in the healthy rat liver. However, after hepatectomy these expressions were detected from the periportal area to the central venous area. These results suggest that APH as shear stress following PHx may not only become a trigger of hepatocyte regeneration, but also of SEC regeneration, and that surplus APH induces liver dysfunction.

Animals↗

Vitamin A hepatotoxicity: a cautionary note regarding 25,000 IU supplements.

Vitamin A hepatotoxicity has been reported at doses exceeding 50,000 IU/day. At 25,000 IU vitamin A per day, although elevated liver enzymes may be seen, hepatotoxicity is rare. We report a case of severe hepatotoxicity associated with the habitual daily ingestion of 25,000 IU of vitamin A bought as an over-the-counter dietary supplement. With the general availability of high-dose supplements and recent literature emphasizing the importance of vitamin A adequacy, the potential for vitamin A hepatotoxicity may increase. Health professionals should remain aware of the potential for vitamin A hepatotoxicity and elicit a vitamin A history in all patients being evaluated for liver dysfunction.

Fatal Outcome↗

Electrophoretic identification of an isoenzyme of amylase which increases in serum in liver diseases.

Isoenzymes of amylase were studied in serum from 72 persons by means of polyacrylamide gel electrophoresis and a direct saccharogenic assay for amylase activity. In 37 normal individuals, there were two major peaks of amylase actvity with mobilities similar to pancreatic and salivary amylases. In 11 patiets with acute pancreatitis, the area of activity corresponding with pancreatic amylases increased disproportionately. Electrophoretic patterns of amylase activity in normal and pancreatitis urine were almost identical to the respective serum patterns from the same persons. In contrast, a prominent slower-moving peak of amylase activity occurred in the serum of 8 of 12 patients who had hyperamylasemia associated with various liver diseases. Traces of this third peak were identifiable in one-third of normal serum specimens, but no increases in its activity were observed in any specimen from 11 patients with pancreatitis or from 12 other patients with hyperamylasemia unassociated with liver disease. The slower-moving peak was absent from the urine of patients whose serum contained it. The origin of the slower-moving serum amylase appearing in patients with liver disease is not established by these studies. It is possible either that a hepatic amylase is liberated from damaged liver cells or that the metabolism of an amylase not originating in the liver is altered as a result of liver dysfunction.

Amylases↗

Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

Adult↗

Alcohol use after liver transplantation in alcoholics: a clinical cohort follow-up study.

The purposes of this study were to determine among a cohort of long-term alcoholic survivors after liver transplantation (1) the incidence of alcohol use, (2) its effect on allograft integrity and extrahepatic health, and (3) the validity of the pretransplant alcohol prognosis screening process. Retrospective clinical cohort study of all alcoholic patients undergoing orthotopic liver transplantation at a single center from February 1987 until January 1991 with follow-up through December 1994, giving a median duration of follow-up of 63 months (range, 6-89 months). Multidisciplinary liver transplantation program at a tertiary-care academic medical center. Fifty alcoholic, long-term liver transplant recipients. The frequency of alcohol relapse, defined as any alcohol use in the period after transplantation, was determined by two questionnaire studies and by clinical follow-up. Allograft integrity was assessed by coded review of serial percutaneous allograft biopsies. Potential systemic effects of alcohol relapse were assessed by chart review. The alcohol prognosis screening process was evaluated by retrospectively comparing pretransplant estimates of putative indicators of alcoholism prognosis in posttransplant alcohol users and abstainers. Thirty-three recipients (66%) consistently denied any alcohol use throughout the duration of posttransplant follow-up, whereas 17 (34%) were identified as having consumed alcohol at least once since the transplant. There were no significant differences at the time of evaluation between abstainers and alcohol users in age, sex distribution, severity of liver dysfunction, median duration of abstinence, or University of Michigan alcoholism prognosis score. The median interval from transplantation to alcohol relapse was 17 months, with a range of 3 to 45 months. Recurrent alcohol use was associated with significant medical complications sufficient to require admission to the hospital in 6 patients. One patient died of graft dysfunction, noncompliance with immunosuppressant medications, and presumed graft rejection while drinking. Mild or progressive hepatitis, which was the most common abnormality in posttransplant liver biopsy findings, was equally distributed between both alcohol users and abstainers and sometimes occurred in the absence of antibody to hepatitis C virus antibodies. There was a similar frequency of biopsy-proven acute cellular rejection in alcohol users and abstainers. Typical histological features of alcoholic liver injury were present in posttransplant biopsies from 1 alcohol user only. Alcohol use by alcoholics is uncommon in the first 5 years after liver transplantation, and alcohol-associated liver injury is unusual. Mild nonspecific hepatitis is common in both alcohol users and nonusers alike. Among a small subset of alcoholic transplant recipients, drinking behavior after liver transplantation is associated with considerable morbidity, requiring hospital admissions and occasionally leading to graft loss and death.

Alcohol Drinking↗

[Acute ventricular septal perforation in a patient with autoimmune hemolytic anemia].

A 71-year-old woman with autoimmune hemolytic anemia underwent an emergency endocardial patch repair for ventricular septal perforation after acute myocardial infarction. Use of washed red blood cells was effective in averting hemolytic crisis throughout perioperative period. In spite of improvement of her hemodynamics, liver dysfunction which had been present preoperatively deteriorated after the operation. Finally she died of hepatic failure on the 21st postoperative day. Deterioration of liver function could not be associated with autoimmune hemolytic anemia. To date, little information is available concerning the influence of cardiopulmonary bypass on hemolysis in patients with autoimmune hemolytic anemia. Therefore, prudent management and use of washed red blood cells transfusion would prevent hemolytic aggravation even in open heart surgery.

Acute Disease↗

Survival of patient with late onset hepatic failure by living-related liver transplantation from maternal donor with incompatible blood type.

A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years.

ABO Blood-Group System↗

Taurine protects against ischemia-reperfusion injury in rabbit livers.

Ischemia-reperfusion injury is of major clinical relevance during liver transplantation. In the present study, the therapeutic efficacy of taurine to protect against ischemia-reperfusion injury was investigated in rabbit livers. We demonstrated that intravenous injection of taurine attenuated liver dysfunction as evidenced by reductions in serum alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The recovery of morphological and ultrastructural changes in the liver was also promoted by taurine. The mechanism of the protective effect of taurine seems at least to rely on antioxidation, since the lipoperoxides contents in liver tissues were significantly reduced among taurine-treated rabbits. These results suggest that taurine is a potent useful reagent to protect the rabbit liver from ischemia-reperfusion injury.

Animals↗

Potential interaction between ritonavir and carbamazepine.

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.

Adult↗

Efficacy of steroid therapy on liver metastasis of thymic carcinoid.

We present a 61-year-old man who was hospitalized because of dyspnea, abdominal pain and liver dysfunction accompanied by ascites due to hepatic metastasis of a thymic carcinoid 20 years after the primary tumor was excised. His symptoms and liver function were well controlled by prednisolone, 30 to 60 mg daily, for the next 2 years, with a reduction in the size of the hepatic tumors and in the accumulation of ascites. He subsequently contracted pneumonia due to methicillin-resistant staphylococci, developed disseminated intravascular coagulation (DIC) and died. Thus, prednisolone should be considered for treating patients with metastasis of a thymic carcinoid.

Carcinoid Tumor↗

[A case of Sjögren's syndrome associated with inflammatory pseudotumor of the liver].

A 71-year-old man had noticed a dry sensation in the mouth with swelling of bilateral parotid glands in 1988. He was given a diagnosis of Sjögren's syndrome (SS) on the basis of characteristic findings of sialography and a minor salivary gland biopsy. He was admitted to our department in Febuary 1995 because of general fatigue of 2 month's duration. Laboratory data showed both positive anti-SSA and anti-SSB antibodies, liver dysfunction, hypoalbuminemia, and thrombocytopenia. Abdominal CT and MRI demonstrated a 2-cm intrahepatic mass (S 6) with enhanced areas at the periphery. The liver biopsy yielded fragments from the intrahepatic mass and hepatic parenchyma. The former was composed of plasma cells, lymphocytes, and histiocytes, compatible with the diagnosis of inflammatory pseudotumor of the liver. The pathological diagnosis of the latter specimen was primary biliary cirrhosis, although antimitochondrial antibody was negative. The intrahepatic mass gradually decreased in size without treatment. Inflammatory pseudotumor is considered to be a benign inflammatory condition simulating a neoplasma and the possibility of an autoimmune reaction is suggested on the basis of etiology. This is the first report of an inflammatory pseudotumor associated with Sjögren's syndrome developing in the liver. The inflammatory pseudotumor should be considered as a possible diagnosis in cases where the tumor is embedded in the liver.

Aged↗

[Study of the liver changes by B-ultrasound and histopathology in severe pregnancy induced hypertension].

OBJECTIVE: To investigate the liver changes in severe pregnancy induced hypertension (PIH) on B-ultrasound and pathological examination and to detect a possible connection with fatty liver of pregnancy. METHODS: From Jan 1992 to Nov 1997, 90 pregnant women in the third trimester were enrolled for study. They were divided into 3 groups: the pregnant women with liver diseases; mild and moderate PIH; and severe PIH (30 cases each). Ultrasonography of the liver was performed on each patient after admission. 15 percutaneous liver biopsies were performed under the guidance of real-time ultrasound scans on 15 severe PIH patients with or without liver dysfunction. Tissues were stained with specific lipid staining (Sudan) and with hematoxylin-eosin. All specimens were analyzed by light microscopy. RESULTS: Fatty liver was observed by B-ultrasound in 2 and 12 cases of the pregnancy with liver diseases group and the severe PIH group, respectively. 14 of the 15 liver biopsy specimens showed fatty infiltration of varying degrees. however, only 8 of the 14 cases were detected fatty liver by B-ultrasound. CONCLUSIONS: These findings suggest that liver involvement in severe PIH is a pathological change. Severe PIH and acute fatty liver in pregnancy could have related pathogenesis components of the same.

Adult↗

Pulmonary, gastrointestinal and liver vascular malformations in Rendu-Osler disease.

Hereditary hemorrhagic telangiectasia (HHT) is an angiodysplastic disorder transmitted in autosomal dominant fashion. This case report describes a 46-year-old woman with multiple arteriovenous malformations that eventually caused multiorgan failure. The diagnosis was made in the early childhood based on frequently recurring episodes of severe epistaxis. Telangiectases were found in the skin, the visible mucosal linings, gastrointestinal and bronchial mucosa and liver. Episodes of severe hemoptysis necessitated partial resection of the right lung middle lobe at the age of 22. Liver dysfunction associated with the primary disease was diagnosed by the characteristic clinical picture, laboratory findings and instrumental examinations including abdominal ultrasonography, upper endoscopy, liver CT venography.

Blood Vessels↗

Acne, hypervitaminosis A and hypercalcaemia. A case report.

The ingestion of vitamin A, which is often prescribed for the treatment of acne, may lead to hypervitaminosis A. This syndrome has a wide spectrum of clinical features, hypercalcaemia being of special note since it has been reported in 4 previous cases only. Hypervitaminosis A has been described as resulting from excess ingestion of vitamin A for prevention of sunburn and treatment of minimal brain dysfunction. With the present glut of health foods, this condition should be borne in mind when patients present with symptoms of hypercalcaemia and liver dysfunction.

Acne Vulgaris↗