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PubMed1990

[Clinical significance of thrombin-antithrombin III complex and plasmin-alpha 2 plasmin inhibitor complex in chronic liver diseases].

Thrombin-antithrombin III complex (TAT) and Plasmin-alpha 2 plasmin inhibitor complex (PIC) were examined in fifty two cases of various chronic liver diseases. TAT was significantly elevated in cases of hepatocellular carcinoma (HCC), but PIC did not show significant changes in any chronic liver diseases. Elevations of TAT and PIC were seen in cases of HCC accompanied by tumor enlargement and extensive tumor thrombosis. In cases of HCC undergoing transcatheter arterial embolization (TAE), TAT and PIC increased on the next day after TAE, and tended to recover with time, returning to almost normal at fourth week. Prolongation of prothrombin time, elevation of FDP and positive FM test were noted more often in liver cirrhosis with disseminated intravascular coagulation (DIC) than in severe liver dysfunction without DIC. Of five cases confirmed as DIC, only three cases were diagnosed as DIC by DIC score. On the other hand, TAT and PIC were significantly elevated in DIC cases. Especially, TAT exceeded 30 ng/ml in all DIC cases. TAT was regarded to be useful for the diagnosis of DIC in severe liver dysfunction.

Antifibrinolytic Agents↗
PubMed1995

[Chronic inflammatory demyelinating polyneuropathy associated with chronic liver disease due to type B and type C hepatitis virus].

A patient with chronic inflammatory demyelinating polyneuropathy (CIDP) associated with type B and type C hepatitis virus infection is reported. A 54-year-old female who had a blood transfusion at the age of 31 years was diagnosed as a carrier of hepatitis B virus at the age of 43. Liver dysfunction was first noted in 1987 and gradually grew worse year by year. Beginning in early June 1992, the patients general fatigue became worse, her serum GOT and GPT levels became elevated, and she complained of a tingling sensation in her arms and legs. Neurological examination revealed moderate sensory disturbance of the glove-and-stocking type in all of her extremities. Deep tendon reflexes were all diminished. Hepatitis C antibody was detected in the serum at this time. On June 12, 1993, progression of her sensory disturbance was found to be associated with generalized muscle weakness. Cerebrospinal fluid studies showed increased protein without pleocytosis. Motor nerve conduction studies revealed marked prolongation of terminal latencies, reduction of conduction velocities, and abnormal temporal dispersion of the motor potentials. No sensory potentials could be evoked at any of the sites stimulated. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation. A diagnosis of CIDP was made. Treatment with corticosteroids was started, but there was little improvement in neurological function. The liver dysfunction progressed further and ultimately the patient died of hepatic failure. An autopsy demonstrated liver cirrhosis, but no malignant tumors were evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1990

[A case of polymyositis associated with chronic active hepatitis].

A case of polymyositis associated with chronic active hepatitis was reported. A 53-year-old man, who had no previous history of blood transfusion nor hepatitis, noticed proximal dominant muscle weakness on January 29, 1985. He was admitted to Kyoto National Hospital on February 7, and laboratory studies disclosed the elevation of serum enzyme levels; creatine kinase (CK) 9845 IU/L (normal 54-263), glutamate oxaloacetate transaminase (GOT) 834 IU/L (9-31), glutamate pyruvate transaminase (GPT) 491 IU/L (4-34), lactate dehydrogenase (LDH) 2135 IU/L (248-464). Also serum gamma globulin was high (1.8 g/dl) and LE-like cell was found. The diagnosis of polymyositis was made and prednisolone therapy (60 mg/day) was started on February 23. The elevated serum enzymes decreased gradually, but severe muscle weakness persisted for about one month. On April 3, he was admitted to our hospital. Physical examination revealed moderate proximal dominant muscle weakness without skin eruption, jaundice or hepatosplenomegaly. The serum enzymes were still high; CK 1826, GOT 173, GPT 232 (GOT less than GPT), LDH 1548. However, alkaline phosphatase (ALP) and bilirubin were normal. Hepatitis B surface antigen (HBsAg) was not detected. Antinuclear antibody was positive. The electromyogram study showed myopathic change, and the muscle biopsy demonstrated myopathic change and cell infiltration, compatible with polymyositis. These results suggested liver dysfunction associated with polymyositis. Prednisolone therapy was continued and muscle weakness decreased. From December, 1985, serum enzymes (CK, GOT, GPT, LDH) elevated again and muscle weakness also slightly increased. Anti-smooth muscle antibody was positive. It was suggested that both polymyositis and liver dysfunction deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1999

Efficacy and safety of docetaxel (Taxotere) in heavily pretreated advanced breast cancer patients: the French compassionate use programme experience.

The aim of this investigation was to assess retrospectively docetaxel safety and efficacy in advanced breast cancer patients in a French compassionate use programme. Patients had received > 1 prior chemotherapy regimen for advanced disease, were either anthracycline-resistant (that is progressed within 6 months after anthracycline-based chemotherapy) or had received the maximum cumulative dose. The recommended docetaxel dose was 100 mg/m2/cycle (75 mg/m2 in case of liver function impairment: transaminases > 1.5 x upper limit of normal (ULN), alkaline phosphatases > 3 x ULN). Between August 1993 and December 1995, 889 patients were treated in 67 French centres, of whom 870 were evaluable for safety and 825 were evaluable for patient and treatment characteristics and efficacy. 20.5% (of the 825 patients evaluable for baseline characteristics) had poor performance status (PS > or = 2), 49.3% liver metastasis and 9.6% biological liver dysfunction. 98.4% had been previously treated by anthracyclines, 50.8% had resistant disease and 37.1% had received > 2 prior palliative chemotherapy lines. The most frequent severe toxicity, febrile neutropenia (reported in 223/870 (25.6%) patients evaluable for safety), caused 10 deaths, 6 of these being patients with severe liver impairment before inclusion. Fluid retention syndrome and other common non-haematological toxicities were well tolerated. 3.1% (28/889) of all patients and 11.4% of those with liver dysfunction, died from treatment-related causes. The overall response rate in 825 assessable patients was 22.9% (95% confidence interval (CI): 20.2-26.2%). Median time to treatment failure was 4 months (95% CI: 3.6-4.3) and median survival was 9.8 months (95% CI: 8.8-10.7). This report on the largest series of unselected advanced breast cancer patients treated with docetaxel, supports previous phase II studies, confirming docetaxel's utility in patients relapsing after failing anthracycline-containing palliative chemotherapy.

Adult↗
PubMed1995

Relationship between free iron level and rat liver mitochondrial dysfunction in experimental dietary iron overload.

The concentration of total iron in the hepatic tissue and mitochondria from rats fed a 2.5% carbonyl iron supplemented diet progressively increased up to 40 days, then reached nearly a steady-state. By contrast the level of free iron (desferrioxamine-chelatable) exhibited a transient but significant increase at 40 days of treatment, only in this period of treatment the induction of lipid peroxidation and the resulting mitochondrial abnormalities in calcium transport was observed too. The enhancement of the energy dissipating mitochondrial calcium cycling was found to be associated with a significant decrease of endogenous mitochondrial ATP content. As to the pathophysiological mechanism for hepatocellular injury in iron overload, these results indicated that the transit pool of free iron may play a critical role in initiating organelle dysfunctions, at least in this experimental model of iron overload.

Animals↗
PubMed2006

[A collective review of Vibrio vulnificus infection in Japan].

Vibrio vulnificus is found globally in marine coastal waters. Infection with this organism, via ingestion of raw shellfish or exposure to marine water, can cause necrotizing fasciitis and sepsis, which have high mortality and short latency. In Japan, many cases have been reported since 1980, mainly from hospitals in western prefectures. However, because of the sporadic nature of infection outbreaks, a thorough epidemiologic survey has not been done. We studied the epidemiological and clinical characteristics of Vibrio vulnificus infections reported in Japan from 1975 to 2005. We identified 185 cases using the medical article search engines Ichushi (Japan Medical Abstracts Society), CiNii (Citation Information by National Institute of Informatics), and PubMed over 30 years. The median age of patients was 59. The number of male patients was eight times the number of female patients; however, no significant difference in mortality was found between genders. In yearly distributions of patients, 20 cases were reported in 2001, a year in which we experienced more rainfall and a longer rainy season in Northern Kyushu. In monthly distribution, about 80% of cases were reported from July to September when sea water temperatures rise. About 40% of cases were reported in four prefectures around the Ariake Sea. The underlying disease indicated liver dysfunction in 90% of patients, but mortality was the same regardless of the infection pathway (oral ingestion or wound). Because of its rapid aggravation and high mortality rate, public education is important to prevent new cases. It is also highly recommended that patients with preexisting liver dysfunction avoid raw fish and limit exposure to marine water during the summer.

Adult↗
PubMed1998

Donor hepatitis C virus status does not adversely affect short-term outcomes in HCV+ recipients in renal transplantation.

BACKGROUND: Recipient hepatitis C virus (HCV) seropositivity has been associated with inferior outcomes in renal transplantation (RTx). We sought to determine whether donor HCV+ status influenced the incidence of rejection, liver dysfunction, and graft survival in HCV+ recipients. METHODS: We reviewed 44 HCV+ recipients (R+) receiving RTx from HCV+ (D+) and HCV- (D-) donors between February 1991 and September 1996. All patients were followed to the end of the study period (mean=36 months, range=12-60 months). We compared the R+ group with a demographically matched cohort of 44 HCV- recipients (R-). RESULTS: Of the 44 R+, 25 (57%) had a total of 48 rejection episodes. Among the 44 R-, 32 (73%) had 58 rejection episodes (P>0.1). Within the R+ group, 28 were D+/R+; of these 14 (50%) had 27 rejection episodes, whereas among the 16 D-/R+, 11 (68%) had 21 rejection episodes (P>0.3). Graft and patient survival was similar in both the groups (86.4% and 91%, respectively). Liver dysfunction was slightly increased in the R+ group (4/44 vs. 0/44, P>0.1), with one death due to liver failure in this group. CONCLUSION: Donor HCV+ status had no influence on outcomes in HCV+ recipients after kidney transplantation in the short term. The incidence of rejection, graft loss, and mortality was comparable between the D+/R+ and D-/R+ groups. Furthermore, rejection, graft loss, and death were identical in R+ and R-groups throughout the 5-year study period. We therefore conclude that HCV+ recipients can safely receive kidney transplants without concern about donor HCV status or fear of adverse events from their own HCV+ status.

Adult↗
PubMed1986

[Treatment of hepatocellular carcinoma by alcohol injection into the tumor and irradiation of the tumor].

Small hepatocellular carcinoma has come to be diagnosed by imaging modalities recently progressed. However, in patients with the carcinoma surgery is often contraindicated due to liver dysfunction. From such reason intratumor alcohol injection therapy has been developed and the efficacy has been clearly demonstrated in hepato cellular carcinoma with tumor under 3 cm is diameter. While in radiation therapy has been effective in that with tumor up to 10 cm in diameter. In treatment of hepatocellular carcinoma, it is important to choose a therapeutic method by considering the degrees of cancer progress and liver dysfunction.

Administration, Topical↗
PubMed1992

A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion.

A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion.

Acute Kidney Injury↗
PubMedDate not supplied

Parenteral feeding in a patient with hypertriglyceridemia and increased liver enzyme levels.

OBJECTIVE: To discuss nutritional support in a patient with hypertriglyceridemia and liver dysfunction. METHODS: We describe the hospital course of a critically ill patient with hepatic dysfunction and hypertriglyceridemia who required nutritional support, and we provide an overview of lipid metabolism. RESULTS: A 27-year-old man with hepatic dysfunction and hypertriglyceridemia, who had undergone kidney transplantation 4 months previously, was admitted to the intensive-care unit with upper gastrointestinal bleeding. He was unable to tolerate enteral feeding, and central parenteral nutrition was initiated. Calories from dextrose and fat were limited because of the presence of increased liver enzyme levels and hypertriglyceridemia. A modified regimen of parenteral nutrition was developed for the patient. The short-term reduction of total calories to 75% of the predicted need is safe. CONCLUSION: Nutritional support in patients with liver dysfunction and hypertriglyceridemia is complicated and may require temporary underfeeding because of the need to limit fat and dextrose intake.

Journal Article↗
PubMed1998

The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA.

The serum concentrations of CA19-9 and carcinoembryonic antigen (CEA) were measured in 150 consecutive patients with histologically proven liver disease admitted to a liver unit for transplant assessment. A significant proportion of the cases studied had a CA19-9 above the upper limit of the reference range (35 kU/L): alcoholic liver disease (73%), primary sclerosing cholangitis (61%), primary biliary cirrhosis (60%), chronic hepatitis B (71%), chronic hepatitis C (84%), autoimmune hepatitis (36%) and hepatocellular carcinoma (54%). CEA was only elevated in a small proportion of the patients with benign liver disease and the degree of elevation was small (15-37 micrograms/L). Significantly raised CEA was observed in two patients (15%) with hepatocellular carcinoma. Statistically significant correlations were observed between the serum CA19-9 concentration and standard parameters of liver dysfunction: positive correlations with aspartate aminotransferase, alkaline phosphatase and bilirubin and negative correlations with albumin and gamma-glutamyltransferase. Positive relationships were also observed between CA19-9 and both CEA and creatinine. Both increased production of CA19-9 from biliary epithelial cells and decreased clearance due to cholestasis may be contributing to the elevation of CA19-9 in the bloodstream. Our data indicate that caution is needed in the interpretation of CA19-9 results in the presence of liver dysfunction.

Biomarkers, Tumor↗
PubMed2002

Regenerative activity and liver function following partial hepatectomy in the rat using (31)P-MR spectroscopy.

The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic (31)P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [(3)H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios (P <.05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham- and nonoperated controls (P <.05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [(3)H]thymidine incorporation (r = -0.61, P <.005), PCNA protein expression (r = -0.62, P <.005), and serum bilirubin (r = -0.49, P <.05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, (31)P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function.

Adenosine Triphosphate↗
PubMed1996

Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity.

To evaluate liver dysfunction in patients with obstructive jaundice (OJ), morphological and functional hepatic mass was analyzed in comparison with cirrhosis (LC). Total hepatic parenchymal ratio (THPR) was estimated by morphometric analysis and hepatic functional mass by galactose tolerance test (GaTT) in 30 patients who underwent hepatectomy. The value of GaTT in patients with LC was remarkably depressed compared to those with normal liver function (p < 0.001). It was also depressed in OJ (p < 0.05 vs. normal liver), but less than in LC (p < 0.05). However, THPR decreased only in LC (p < 0.05 vs. either normal liver or OJ). A significant correlation between the value of GaTT and THPR was revealed in patients with LC, but not in OJ. These results suggested that liver dysfunction in OJ was independent of the decreased number of hepatocytes, differing from LC.

Adult↗
PubMed2000

Reactive hemophagocytic syndrome presenting as a component of multiple organ dysfunction syndrome.

OBJECTIVE: To report two cases of severe reactive hemophagocytic syndrome (RHS), to discuss their impact, and to present evidence that RHS may be a constitutive part of multiple organ dysfunction syndrome (MODS). DESIGN: Case-report. SETTING: Pediatric intensive care unit (PICU). PATIENTS: Two patients with RHS and MODS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Case #1: A 3 yr-old boy with Mucha-Haberman syndrome (pityriasis lichenoides) was admitted to the PICU for septic shock, acute respiratory distress syndrome, capillary leak, acute renal failure, liver dysfunction, and RHS (pancytopenia and hemophagocytosis on bone marrow aspirate). The pancytopenia was severe (white blood cell count, 0.9 x 10(9)/L; hemoglobin, 59 g/L; platelets, 36 x 10(9)/L), required many transfusions, and resolved 2 months later. The patient needed mechanical ventilation for 6 wks. Length of stay in PICU was 2 months. Case #2: A previously healthy 4 yr-old girl was admitted to the PICU for respiratory failure. She developed acute respiratory distress syndrome, cardiomyopathy with complete atrioventricular block, shock, capillary leak, liver dysfunction, and RHS (pancytopenia and hemophagocytosis on bone marrow aspirate). The pancytopenia was severe (white blood cell count, 1.92 x 10(9)/L; hemoglobin, 65 g/L; platelets, 58 x 10(9)/L) and necessitated transfusional support. Serology for respiratory syncytial virus was positive. RHS duration was 20 days; the patient recovered completely. Length of mechanical ventilation was 16 days and length of stay in PICU was 3 wks. CONCLUSIONS: These cases show that RHS may be a significant cause of pancytopenia in the PICU. It needs to be recognized as a clinical entity because it can be reversible and nonneoplastic. RHS and MODS share some pathophysiologic elements and could be related to each other.

Biopsy↗
PubMed1996

Molecular diagnosis of hepatitis C viral infection.

With the evolution of confirmatory assays for hepatitis C viral infections, bulk populations of unknown hepatitis were diagnosed as hepatitis C virus (HCV)-mediated chronic liver dysfunction throughout the world. More recently, several systems for molecular diagnosis of hepatitis C viral infections were developed. These are commonly performed for efficient antiviral therapy using interferon. Now we are at the crossroads studying hepatitis virology for the development of sensitive and powerful treatment against HCV-mediated chronic liver dysfunction. Here we introduce the current strategy for the advanced diagnosis of hepatitis C viral infection and discuss the exploration of novel hepatitis viruses.

Flaviviridae↗
PubMedDate not supplied

Clinical utility of TPS, TPA and CA 19-9 measurement in pancreatic cancer.

UNLABELLED: The aims of this study were to (1) evaluate the diagnostic utility of a new tumor marker, TPS, with respect to TPA and CA 19-9 in patients with pancreatic cancer; (2) ascertain the reliability of the markers in predicting survival, and (3) evaluate the effect of liver dysfunction on the results. CA 19-9, TPA and TPS were measured in the serum of 19 control subjects, 42 patients with pancreatic cancer, 29 with chronic pancreatitis, and 52 with extrapancreatic diseases. CA 19-9 was confirmed to be the best serological indicator of pancreatic cancer, while TPA and TPS lacked both sensitivity and specificity. Pancreatic cancer patients with liver metastases had higher mean CA 19-9 and TPA, but not TPS, values than pancreatic cancer patients without metastases. A shorter survival time was associated with the presence of liver metastases and with higher serum tumor marker levels. CA 19-9, TPA and TPS were found to be correlated with liver function test results (ALT, ALP and bilirubin). IN CONCLUSION: (1) TPS adds no significant information to that obtained using CA 19-9 in the diagnosis of pancreatic cancer; (2) CA 19-9 and TPA, but not TPS, are influenced by the presence of liver metastases; (3) the main factor to influence survival is advanced disease, which is in turn associated with higher tumor marker levels, and (4) liver dysfunction can influence not only CA 19-9 and TPA, as already described, but also TPS.

Adult↗
PubMed2006

Predicting the toxicity of weekly docetaxel in advanced cancer.

OBJECTIVES: To determine the safety profile of 40 mg/m(2) docetaxel administered weekly to a mixed population of advanced cancer patients and identify predictors of toxicity and survival following treatment with weekly docetaxel in this population. PATIENTS AND METHODS: 68 patients with advanced cancer were enrolled into the study. Various patient characteristics, including inflammatory and nutritional status, docetaxel pharmacokinetics and liver function were investigated. Predictors of treatment-related toxicity and survival were analysed using multivariate logistic regression and Cox proportional hazards analysis, respectively. RESULTS: 27 patients (40%) experienced grade 3 or 4 toxicity, mainly gastrointestinal toxicities (20%), leukopenia (16%) and neutropenia (12%), during the first 8 weeks of docetaxel treatment. Docetaxel pharmacokinetics were the only predictive factor for haematological toxicity. The odds of severe haematological toxicity were approximately 9-fold higher for patients with reduced docetaxel clearance (e.g. <30 L/h). The odds of non-haematological toxicity were about 3-fold higher for patients with elevated levels of inflammatory markers: alpha(1)-acid glycoprotein (AAGP) >1.5 g/L or C-reactive protein >10 mg/L). Multivariate analysis indicated that weight loss, liver dysfunction and elevated levels of AAGP were independently significant predictors of survival. CONCLUSION: This is the first description of factors predictive of the toxicity and survival following weekly administration of docetaxel. Patients with reduced clearance of docetaxel and elevated markers of inflammation experienced worse adverse effects, while patients with weight loss, liver dysfunction and elevated markers of inflammation had worse survival.

Adult↗
PubMed2001

[Case report of systemic lupus erythematosus patient with hemophagocytic syndrome, treated with plasma exchange, with specific reference to clinical profile and serum cytokine levels].

A 42-year-old woman was diagnosed as systemic lupus erythematosus (SLE), because of the findings of polyarthritis, leukopenia, positive antinuclear antibody, and positive anti DNA antibody. She was treated with predonisolone (PSL) at 10 mg per day. She was admitted to our hospital on October 2000 because of spiking high fever, skin eruption, and lymph node swelling. Since her illness of SLE was considered to be worsening, high dose of corticosteroids were given. However, high fever persisted and liver dysfunction was developed with increased serum ferritin. Her bone marrow smear showed hemophagocytosis. We made a diagnosis of hemophagocytic syndrome (HPS) complicated by disseminated intravascular coagulation (DIC). HPS was thought to be induced by viral infection, even though causative viral infection was not detected. Her general condition worsened with persistent high fever and liver dysfunction. Plasma exchange was carried for two consecutive days, followed by cyclosporine A and lipo-dexamethasone, which improved her fever rapidly. Her general condition gradually improved. Serum levels of ferritin, soluble interleukin 2 receptor (sIL 2-R), interferon-gamma and interleukin 6 decreased associated with improvements of her clinical condition. We thought plasma exchange could be effective to decrease serum levels of cytokine, which was suggested to be the pathogenic to HPS. However serum levels of IFN-gamma and IL 6 after plasma exchange did not change in this case. Further studies are required to confirm the effects of plasma exchange for HPS.

Adult↗