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PubMed1993

Chronic melioidosis: a report of the first case in Japan.

A 41-year-old Japanese male with uncontrolled diabetes mellitus and alcoholic liver dysfunction developed melioidosis after his business trip to Indonesia and Singapore in 1988. His disease started with spiked fever on the following day after extraction of a tooth, and a liver abscess developed, followed by abscesses in the spleen and in the subphrenic space. In spite of splenectomy and intensive antimicrobial treatments for three months, he developed parotitis, prostatitis, and abscess of the right submandibular gland at 5 to 16-month interval. Pseudomonas pseudomallei was isolated from the blood and pus from each abscess. The lung was not involved. At present, he has returned to work, with continued intravenous instillation of imipenem/cilastatin.

Adult↗
PubMed2007

Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Algorithms↗
PubMedDate not supplied

Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.

Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.

Acute Disease↗
PubMedDate not supplied

Lidocaine elimination in patients with liver cirrhosis.

The aim of the study was to evaluate lidocaine elimination in patients with liver cirrhosis. The study was carried out in 30 cirrhotic patients classified according to the Child-Pugh's score to subgroups A (n=11). B (n=12) and C (n=7), and 14 healthy volunteers. Lidocaine was administered intravenously, at a dose of I mg/kg, and blood samples for lidocaine and monoethylglycinexylidide (MEGX) assays were collected for up to 6 h. Decreased elimination half-live for lidocaine as well as reduced formation rate of MEGX was found in cirrhotic patients. Lidocaine metabolising capacity of the liver was irrespective of etiology of cirrhosis. It was also found that evaluation of elimination half-life of lidocaine is more closely related to the Child-Pugh's staging of liver dysfunction than 15-minute MEGX concentration.

Adult↗
PubMedDate not supplied

Hepatitis B virus-related markers in secondary and in essential mixed cryoglobulinemias: a multicentric study of 596 cases. The Italian Group for the Study of Cryoglobulinemias (GISC).

The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p < 0.0001) and in those associated with liver involvement at diagnosis (p < 0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p < 0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC.

Biomarkers↗
PubMed2003

Primary mixed germ cell tumour of the liver--a case report.

Germ cell tumours in liver are uncommon. Fewer than 20 cases have been reported in the literature. Primary mixed malignant germ cell tumours of liver are even rare. Here we describe a case of primary mixed malignant germ cell tumour of left lobe of liver in a two and half year old male boy. This is the first reported case of primary mixed malignant germ cell tumour with components of yolk sac tumour and mature teratoma in an infant. The patient complained of gradual increase in abdominal distension, upper abdominal pain and loss of weight. Ultrasonography and computed tomography of the abdomen revealed a large hepatic mass. Serum alpha-feto protein levels were raised. Left lobectomy of liver was done and chemotherapy was initiated. Histopathology of specimen disclosed yolk sac tumour and mature teratoma. Levels of serum alpha-feto protein declined rapidly. Widespread intrahepatic metastasis developed and patient died due to liver dysfunction after six months of left lobectomy.

Child, Preschool↗
PubMed2004

[Fatal acute visceral disseminated varicella-zoster virus infection in a patient with chronic graft-versus-host disease].

A 34-year-old woman was admitted for chronic graft-versus-host disease ten months after an unrelated bone marrow transplantation. Cytomegalovirus (CMV) antigenemia on day 5 of hospitalization was negative. Thrombocytopenia occurred on day 9. Laboratory findings revealed severe liver dysfunction on day 13. On day 14, the patient developed interstitial pneumonia and disseminated intravascular coagulation, and died from progressive respiratory failure. Multinucleated giant cells were found in the lung, liver, spleen, esophagus, pancreas and intestine obtained at autopsy. Varicella-zoster virus (VZV) was detected in the blood using the polymerase chain reaction (PCR) technique. CMV, herpes virus type 6 and Epstein-Barr virus were detected in the liver and lung with the PCR technique. We concluded visceral VZV infection was the main cause of her death because of her aggressive clinical course and the histology at autopsy. In this case, chronic GVHD and its immunosuppressive treatment resulted in her fatal VZV reactivation.

Adult↗
PubMed2004

[Clinical analysis of liver non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: Incidence of liver non-Hodgkin's lymphoma (NHL) is increasing. This study was to explore clinical features, diagnosis, treatment, and prognosis of liver NHL. METHODS: Records of 45 patients with liver NHL treated in our hospital from Jan. 1998 to May 2002, 9.6% of all NHL patients treated in the same period, were retrospectively analyzed with statistic software package of SPSS10.0. RESULTS: Of 45 patients, 32 were male,and 13 were female, the median age was 50 years. Immunophenotyping revealed that 24 cases were T cell original, 19 were B cell original, and 2 were undefined. According to International Work Formulation (IWF), 92% of 45 patients belonged to intermediate-grade. Clinical features of liver NHL were presented with fever, jaundice, hepatosplenomegalia, and liver dysfunction. Combination treatment based on chemotherapy was the major therapy. Median survival time was 4 months, overall 1-, and 2-year survival rates were 22%, and 18%. CONCLUSION: Early diagnose liver NHL is difficult, its treatment effect and prognosis are poor, combination therapy should be given as early as possible.

Adolescent↗
PubMed1990

Phase I clinical and pharmacological study of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II).

cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP) is a liposome dependent cisplatin analogue since the liposome carrier is required for its i.v. administration and for its biological activity. A Phase I study of liposome entrapped NDDP (L-NDDP) was performed using a single i.v. injection every 4 weeks. L-NDDP was prepared and characterized at M. D. Anderson Cancer Center. The maximum tolerated dose of L-NDDP was 312.5 mg/m2. The dose-limiting toxicity was myelosuppression, affecting all three blood cell lineages. The granulocyte nadir occurred on days 14-18, and the platelet nadir consistently earlier (days 11-12). The median day of recovery of blood cell counts was day 21 (range, 18-32). Other toxicities included grade 2 nausea and vomiting, fever consisting of a single temperature spike in most patients, grade 1 diarrhea after 60% of courses, and grade 1-2 malaise lasting for 5-10 days after the infusion in 73% of courses. Transient alanine aminotransferase elevations without clinical relevance were common. No signs of renal dysfunction or ototoxicity were observed. One patient with a preexisting peripheral neuropathy showed some progression of the neuropathy after a cumulative dose of 1605 mg/m2. Except for fever and transient liver dysfunction, no liposome related side effects were observed in spite of the high doses of lipid administered. The blood clearance of L-NDDP fits a two-compartment model at lower doses and a single-compartment model at the maximum tolerated dose, suggesting that saturation of the reticuloendothelial organs occurs at the maximum tolerated dose. Two minimal responses were observed. L-NDDP has a toxicity profile similar to that of carboplatin. Phase II studies to address the issue of how the therapeutic index of platinum compounds is affected by liposome entrapment are being planned.

Antineoplastic Agents↗
PubMed1983

[Development on segmentectomy and subsegmentectomy of the liver due to introduction of ultrasonography].

Due to introduction of preoperative and intraoperative ultrasound into liver surgery, three dimensional structure of the liver is understood much better than before. Intraoperative sonography demonstrated many daughter nodules and tumor thrombi which were not detected preoperatively. Therefore, a part of noncurative resection of the liver can be avoided. In patients with liver cirrhosis and small hepatoma, 60 per cent of hepatomas could not be visible nor palpable from the surface of the liver. In these patients, if hepatic lobectomy is performed, liver dysfunction will develop after surgery. Therefore, small partial resection is indicated and identification of site of the tumor is indispensable. With intraoperative sonography, all invisible and nonpalpable tumors in the liver were demonstrated. Clinicopathological studies of the hepatocellular carcinoma suggest that the tumor cells spread in the liver through the portal venous branches even in the small hepatocellular carcinoma. Daughter nodules will grow in the distal region of the portal venous branch. Therefore, total resection of the subsegment which contains the tumor is indicated. For this purpose, systematic subsegmentectomy is considered. In this operation, portal area containing tumor is identified by ultrasonically guided puncture of the portal venous branch. By identification of the inferior right hepatic vein, the right postero-inferior area can be preserved, even if right hepatic vein is resected. This type of hepatectomy is called inferior right hepatic vein preserving operation. We already performed this operation in three patients.

Carcinoma, Hepatocellular↗
PubMed1997

Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: a preliminary report.

With the aim of minimizing postoperative liver dysfunction and promoting increased resectability, we employed portal vein embolization (PVE). In this study, the effect of PVE on major hepatic resection for advanced-stage hepatocellular carcinoma (HCC) in injured livers was evaluated. PVE was performed prior to hepatectomy in 13 patients with stage III and IV HCCs. Following PVE, right trisegmentectomy was performed in 3 patients, extended right lobectomy in 3 and right lobectomy in 7. To evaluate the effect of PVE, the changes in liver functional capacity and estimated remnant liver volume (ERLV), determined by computed tomography, were examined before and after PVE. The operative morbility, mortality, and survival rates after hepatectomy were also assessed. By 2 weeks after PVE, ERLV had increased in all patients, by an average of 28%, and the mean resection rates had decreased from 70.0% to 62.2%. Postoperatively, the 30-day mortality rate was 15.3%, and the 1- and 2-year survival rates were 69% and 46%, respectively. The results of this study indicate that resectability can be increased, and major hepatectomy can be made safer by employing PVE preoperatively, in view of the fact that major hepatectomy was not considered feasible without PVE in these patients.

Aged↗
PubMed1997

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with impaired liver function.

OBJECTIVE: The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated. METHODS: Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days. RESULTS: Plasma imidapril concentrations after single and, although less pronounced, after repeated dosing were higher in the liver disease patients, whereas imidaprilat concentrations were lower. This suggests that the conversion of imidapril into imidaprilat in the liver is delayed in patients with impaired liver function. However, the slower biotransformation did not result in statistically significant differences in Cmax and AUC for either imidapril or its active metabolite following repeated administration. Moreover, no relevant accumulation of either imidapril or imidaprilat occurred after repeated dosing. CONCLUSIONS: Imidapril is regarded as an ACE inhibitor of which the pharmacokinetic disposition is only slightly affected in patients with impaired liver function.

Adult↗
PubMed2002

Progressive liver fibrosis in late-onset argininosuccinate lyase deficiency.

A 4-month-old boy, with late-onset argininosuccinate lyase (ASL) deficiency with hepatomegaly, was treated by protein restricted diet and arginine supplementation; he was followed for 3 years. Hepatomegaly and mild liver dysfunction persisted without significant hyperammonemia. He maintained normal psychomotor development to the age of 12 months, but, at 3 years of age, his developmental status is in the borderline normal range. Liver biopsy performed at 12 months of age demonstrated swollen and pale hepatocytes with abnormal glycogen deposition and mild periportal fibrosis. A subsequent liver biopsy at 3 years of age showed progressive liver fibrosis in the periportal and central areas, which extended into the liver lobule. These findings suggest that liver impairment in ASL deficiency may advance without significant hyperammonemia and underline the importance of repeated liver biopsy in this disorder, even when the plasma ammonia level is well controlled.

Arginine↗
PubMed1992

Isocaloric feeding and medium chain triglycerides fail to improve liver function tests in a patient with Crohn's disease and a high output stoma.

A patient with Crohn's disease complicated by multiple fistulae to the skin and bladder and a high-output stoma following previous multiple short bowel resections developed liver dysfunction during total parenteral nutrition. Isocaloric feeding based on calorimetry and changing from a long chain triglyceride emulsion to a mixture of medium and long chain triglyceride emulsion failed to improve liver function. Surgical removal of the affected small bowel resulted in a rapid improvement of the liver function despite continuation of total parenteral nutrition.

Journal Article↗
PubMed1996

Insulin-like growth factor-I serum concentrations and patterns of insulin-like growth factor binding proteins in patients with chronic liver disease.

BACKGROUND/AIMS: Serum concentrations of insulin-like growth factor-I are decreased in liver cirrhosis. However, this growth factor is bound for the most part to specific binding proteins that are known to modulate biological actions. Plasma insulin-like growth factor binding proteins are predominantly synthesized in the liver. METHODS: The effect of liver disease on basal and on growth hormone-stimulated serum concentrations of total and "free" insulin-like growth factor-I and on insulin-like growth factor binding protein patterns is reported. Sera were obtained from 20 patients with non-cirrhotic chronic liver diseases and from 20 patients with cirrhosis before and 24 h after a single subcutaneous dose of growth hormone. Samples were analyzed using radioimmunoassays, gel chromatography, ligand blotting and immunoblotting. RESULTS: In cirrhosis, serum concentrations of total and "free" insulin-like growth factor-I were decreased, the binding protein pattern was changed profoundly showing a reduction in the 150 kD complex and an increase in the 30-40 kD complexes. Concentrations of binding protein-1 and -2 were increased, while that of binding protein-3 was decreased in cirrhosis. The response to growth hormone was blunted. These changes were related to the degree of liver dysfunction as assessed by the Child-Pugh classification. CONCLUSIONS: A pathogenetic link of altered bio-availability of insulin-like growth factor-I to clinical characteristics of advanced liver disease, e.g. insulin resistance or skeletal muscle wasting, may be suggested by the present data.

Adult↗
PubMed1998

Gallstones and isoflurane hepatitis.

This report is of a case of a previously fit 65-year-old woman who developed postoperative liver dysfunction following an anaesthetic involving isoflurane. Biliary ultrasound demonstrated gallstones. However, serum antibodies to trifluoroacetylated proteins were detected, suggesting that immune sensitisation to the anaesthetic could have contributed to the impaired liver function.

Aged↗
PubMed1999

The effect of short stature, portal hypertension, and cholestasis on growth hormone resistance in children with liver disease.

Chronic liver disease is associated with GH resistance, which is characterized by high circulating GH and low insulin-like growth factor I (IGF-I) concentrations. Standard GH replacement has no effect on serum IGF-I in pediatric liver disease. The aims were to examine whether GH resistance can be overcome by supraphysiological GH and to determine whether GH resistance worsens with the progression of liver disease. Thirty children, divided into five groups whose liver disease was at clinically different stages, were studied. They were given 0.2 IU/kg x day GH for 4 days and then 0.4 IU/kg x day for the next 4 days. Serum IGF-I and binding proteins (IGFBPs) were measured by immunoassay. IGF-I was lower in all study groups than in normal controls. IGF-I, IGFBP-3, and acid-labile subunit rose in response to GH. The magnitude of the response reflected nutritional status and liver dysfunction; in particular, portal hypertension was associated with a poor IGF-I response. There was no change in IGFBP-2. GH resistance begins early in the natural history of childhood liver disease and develops with the progression of liver disease, particularly with portal hypertension. It may be partially overcome by supraphysiological GH administration, but the effect becomes smaller with worsening liver disease.

Body Height↗