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PubMed2004

[Analysis of acute liver "graft-versus-host disease" following allogeneic myeloablative stem cell transplant].

The purpose of this study was to evaluate liver graft-versus-host disease (GVHD) after allogeneic myeloablative stem cell transplant (within day 100). We retrospectively reviewed the data on 61 patients with incidence of hepatic GVHD, the clinical course, laboratory data and histologic features of the liver biopsy. Between February 1998 and March 2002, 61 patients received an allogeneic myeloablative stem cell transplant. The diagnosis of liver dysfunction was based on marked (more than 3 times the upper normal limit) elevation of serum aminotransferases or on a level above 2 mg/dl of total bilirubin. We used criteria for grading (GVHD) on consensus conference. The diagnosis of hepatic "GVHD" was based on classical liver GVHD, on histological GVHD without jaundice or on elevation of serum aminotransferases with other GVHD. Liver function abnormality occurred in 50 out of 61 (82%). The main causes of hepatic dysfunction were hepatic "GVHD" (19 out of 50, 38%). Of the 19 hepatic "GVHD" patients, elevation of serum aminotransferases alone was seen in 13 patients (68%), jaundice alone was seen in 1 patient (5%) and both were seen in 5 patients (27%). The treatment with glucocorticoids was successful in those patients with elevation of serum aminotransferases alone.

Acute Disease↗

PubMedDate not supplied

Amelioration of hepatocellular integrity and inhibition of sinusoidal oxidative stress by N-acetylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver.

Further improvements of donor liver preservation are still required in liver transplantation. In the present study, we investigated whether intraportal injection of N-acetylcysteine (NAC) 15 min before flush-out of UW solution (NAC pretreatment) improves liver dysfunction after cold preservation or has a protective effect on sinusoidal oxidative stress. The effect of NAC pretreatment was examined using an isolated perfused rat liver model. The NAC pretreatment significantly reduced sinusoidal oxidative stress relative to a control dextrose 5% injection. Under a glutathione-depleted condition produced by L-buthionine-[S-R]-sulfoximine, the NAC pretreatment also significantly reduced hepatocellular as well as sinusoidal oxidative stress, resulting in improvement of hepatocelllar integrity relative to a control dextrose 5% injection.

Acetylcysteine↗

PubMed1994

Hydrazine production in children receiving isoniazid for the treatment of tuberculous meningitis.

OBJECTIVE: To study the generation of the hepatotoxin hydrazine in 32 malnourished children receiving isoniazid for the treatment of tuberculous meningitis. DESIGN AND SETTING: This observational study was undertaken in the pediatric ward of a teaching hospital admitting children with advanced forms of tuberculous meningitis for treatment and management of complications. METHODS: Thirty-two children (mean age 2.28 years) receiving isoniazid 20 mg/kg/d were studied. Plasma isoniazid, acetylisoniazid, and hydrazine concentrations were determined by an HPLC method. Fourteen children were studied at weekly intervals for the first month of treatment and again after six months of therapy; 18 additional children were studied on one or more occasions during the first month of treatment only. RESULTS: The area under the curve for hydrazine two to five hours after the isoniazid dose correlated with the isoniazid elimination rate and with acetylisoniazid generation. Hydrazine production increased significantly during the first month of treatment, but decreased to approximate initial values at six months. No correlation was found between any clinical or biochemical indicator of liver dysfunction and hydrazine production. CONCLUSIONS: Hydrazine is formed in significant concentrations during the metabolism of isoniazid in young children. However, additional factors such as preexisting liver damage (e.g., from viral hepatitis) may be necessary for it to reach its toxic potential.

Child↗

PubMedDate not supplied

Scalp hypothermia in the prevention of chemotherapy-induced alopecia.

Alopecia is a common side effect of cancer chemotherapy, especially in combination with regimens with doxorubicin (Adriamycin). The effect of scalp hypothermia in connection with chemotherapy was evaluated as hair protection in 61 women with disseminated breast carcinoma, where earlier treatment routines had caused wig-requiring alopecia in nearly all patients. The cooling was performed with a gel-helmet (Hypotherm Gel-Kap). Of the 61 patients, 47 (77%) had no or slight, not wig-demanding hair loss, and 14 (23%) had severe (wig-demanding) hair loss. Seven patients had liver dysfunction; in 5 of these severe hair loss was observed; 2 had slight hair loss. Eighty-three per cent of the patients with normal liver function had no hair loss. Treatment tolerance was found to be good, and side effects were minimal. The method is found to be simple, effective and inexpensive, though still not technically optimal.

Adult↗

PubMed1999

[Non A-G chronic hepatitis in Japan].

It is clear that certain patients with viral hepatitis are also seronegative for types A, B, C, D, and E. Although hepatitis G virus was discovered recently, this virus has been reported to be non-contributing or only slightly conductive to liver dysfunction. In this article, epidemiological studies regarding patients seronegative for types A to G chronic hepatitis in Japan are reported. Among 1089 patients with chronic liver disease, twenty-five patients (1.8%; 14 chronic hepatitis, 4 cirrhosis, 2 hepatocellular carcinoma) were diagnosed as non A-G hepatitis (negative for HbsAg, HCV-Ab, and HGV RNA). Only 3 of 25 these patients had histories of blood transfusion. The levels of transaminase in the patients with chronic non-A to G hepatitis (without hepatocellular carcinoma) was as the same as those in patients with chronic hepatitis type B and C. Our results indicated a low prevalence of non-A to G chronic hepatitis, yet a few cases were progressive to cirrhosis or HCC, and this may be due to another unknown agents for non-A to G hepatitis.

Adult↗

PubMed2001

GB virus-C/hepatitis G virus.

GB virus-C (GBV-C)/hepatitis G virus (HGV) is a positive, single-strand RNA virus that has been classified in the family Flaviviridae. Interestingly, GBV-C/HGV appears to have a truncated or absent core protein at the amino terminus of the polyprotein. GBV-C/HGV is transmitted parenterally and probably sexually. Most GBV-C/HGV infections appear to be asymptomatic, persistent, and no correlation between virus infection and liver dysfunction although the disease-inducing activity of GBV-C/HGV remains to be investigated. Furthermore, there was no evidence of pathogenesis in the liver by experiment with chimpanzees. From these results, GBV-C/HGV might be considered as a kind of "orphan" virus in search of a disease. Epidemiological investigation demonstrated that GBV-C/HGV infection is present in about 1-1.4% of the healthy population in developed countries and in 8-14.6% in developing countries. The genome of GBV-C/HGV exhibits a sequence variation among different isolates. On the basis of this variation, it has been proposed that GBV-C/HGV can be classified into at least four major genotypes, consisting of type 1 (West Africa), type 2 (US/Europe), type 3 (Asia), and type 4 (Southeast Asia).

Africa↗

PubMed1997

[Study on the evaluation of total and regional liver function using 99mTc-GSA dynamic SPECT].

To evaluate regional and total liver function, 99mTc-GSA dynamic SPECT was studied in 58 patients with various liver disease and 5 normal volunteers. Using dual-head gamma camera, 60 projection data (90 seconds/rotation) were acquired to obtain SPECT imaging. Forty continuous SPECT were obtained for 60 minutes. Time activity curve (TAC) of each voxel was created. The TAC was assumed to be equally the function of C(t) = Cmax (l-e-kt). The liver uptake rate (K value) was calculated using the least squares method. The product of K value and functional volume of each voxel was defined as liver functional index and the sum of the indices was defined as total liver functional index. The total liver functional index had good correlation with various liver function test, HH15, LHL15, and the index showed significant difference between each group of Child-Pugh's liver dysfunction stage. Because of unnecessariness of setting up the ROI, this method is simple and the result is no difference among operators. Three-dimensional liver functional index map exactly shows regional liver function. So that, this method seems to be useful for predicting the residual liver function after hepatectomy.

Adult↗

PubMed1983

Manganese absorption through a burn.

A case of manganese absorption occurring in association with a burn is presented. We maintain that acute manganese toxicity was a likely cause of liver dysfunction in our patient.

Adult↗

PubMed1979

Serum triiodothyronine and other clinical and laboratory indices of alcoholic liver disease.

Admission serum triiodothyronine (T3) values in 124 patients hospitalized for alcoholic liver disease were correlated with clinical and laboratory indices of liver function and commonly used determinants of thyroid function. Patients with low admission serum T3 levels had significant alterations in serum albumin, bilirubin, prothrombin time, and alkaline phosphatase associated with clinical signs of portal hypertension and collateral circulation, with little difference in serum glutamic-oxaloacetic transaminase, serum gamma glutamyl transpeptidase, or serum ornithine carbamyl transferase. This group also had a significant decrease in free T3 index despite an increase in T3 uptake; the slight reduction in total thyroxine (T4) was associated with an increase in free T4 index and no change in serum thyrotropin (TSH). For patients with alcoholic liver disease, low admission serum T3 and free T3 index values when accompanied by normal serum T4, free T4 index, and TSH levels appear to be indicative of severe liver dysfunction and increased mortality risk.

Humans↗

PubMed1995

Renal dysfunction associated with liver transplantation.

It has been known for some time that a variety of liver diseases affect kidney function, but renal dysfunction associated with orthotopic liver transplantation has received scant attention. Although the mechanisms mediating these abnormalities are incompletely defined, advances in the understanding of renal pathophysiology after liver transplantation have made it possible to develop new treatment strategies. Aggressive and early intervention to diagnose and treat renal complications associated with liver transplantation should be the goal for transplant centres.

Chronic Disease↗

PubMed1997

Transthoracic transdiaphragmatic approach for hepatectomy of Couinaud's segments VII and VIII.

For hepatectomy of Couinaud's segment VII or VIII, severe compression and mobilization of the liver is required to establish the operative field via the usual transabdominal approach. Compression of the cirrhotic liver impairs hepatic and systemic blood circulation, which may cause liver dysfunction. We adopted a transthoracic transdiaphragmatic approach for hepatectomy of segment VII or VIII in cirrhotic patients to establish a good operative field without compressing the liver. The aim of this study was to evaluate the benefits of this approach. Forty-four patients with hepatocellular carcinoma (HCC) complicating liver cirrhosis who underwent limited hepatectomy of Couinaud's segment VII or VIII were studied. The patients were randomized to two groups preoperatively: group I (n = 22), transabdominal approach; group II (n = 22), transthoracic transdiaphragmatic approach. There were no differences in preoperative liver function tests, hepatic functional reserve, or extent of tumor between the two groups. The operative time in group II was significantly shorter than that in group I (243 +/- 50 versus 313 +/- 80 minutes;p < 0.01). Operative blood loss in group II was also significantly smaller than that in group I (1190 +/- 1098 versus 2679 +/- 2267 g;p < 0.01). Serum lactate dehydrogenase levels on postoperative day 1 in group II were significantly lower than those in group I (587 +/- 154 versus 791 +/- 383 IU/L;p < 0.05). Major postoperative complications were significantly fewer in group II. It was concluded that the transthoracic transdiaphragmatic approach is a useful method for hepatectomy of segments VII and VIII in cirrhotic patients.

Chi-Square Distribution↗

PubMed2001

Reactivation of latently infected hepatitis B virus in a leukemia patient with antibodies to hepatitis B core antigen.

A 66-year-old man with chronic B-cell leukemia who had antibody to hepatitis B core antigen (anti-HBc) but not hepatitis B surface antigen (HBsAg) suffered from lethal hepatitis caused by hepatitis B virus (HBV) reactivation. He initially lacked circulating viral genomes in his sera and did not have a past history of liver dysfunction. In this patient, the immunosuppressive condition introduced by disease progression of leukemia induced reactivation of dormant HBV, and the withdrawal of chemotherapy resulted in fatal liver failure. Mutation-specific assay based on competitive polymerase chain reaction (PCR) and sequencing analyses revealed the predominant reactivation of an HBV strain with missence mutation (point mutation G-to-A at nucleotide 1896) in the precore regions, as well as point mutations in the core promoter regions. Therefore, it is important to note the risk of HBV reactivation, with resulting lethal hepatic failure, in anti-HBc-positive healthy individuals, even when they lack HBsAg. who receive immunomodulating therapy.

Aged↗

PubMed1999

Oral UFT (uracil plus futrafur) for neoadjuvant chemotherapy of gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has become one of the topics of interest in chemotherapy of gastric cancer; the present study assessed the clinical benefits of neoadjuvant chemotherapy with oral uracil and futrafur (UFT) for gastric cancer.METHODS: Between 1991 and 1997, 82 patients with gastric cancer (36 with early and 46 with advanced cancers) received UFT at 300-600 mg/day orally for 1-6 weeks before surgery. Objective responses, histological effects, and postsurgical survival rates were assessed.RESULTS: In 69 of the 82 patients, the objective responses of the primary lesions were assessed by endoscopy or upper gastrointestinal series examination, and 2 complete responses (CR)s, 25 partial responses (PRs), and 42 no changes (NCs) were seen (39.1% response). Histological effects were evaluated in 82 patients, and 2 grade 3, 11 grade 2, 11 grade 1b, 27 grade 1a, and 31 grade 0 effects were seen. A longer period of UFT administration was associated with a CR or PR. However, the objective responses did not correlate with the histological effects. All the patients underwent gastrectomy, and during the median follow-up period of 41 months, 3-year survival rates were 97.1% for pTNM stage 1, 75% for stage 2, 86.7% for stage 3, and 41.6% for stage 4. The survival rates of stage 3 and stage 4 patients were higher than those of the historical controls in our department. However, CR or PR did not correlate with the improvement in survival. Side effects before surgery were not serious; they included slight myelotoxicity, liver dysfunction, and anorexia; however, 3 patients (3.7%) had suture insufficiency, 3 patients (3.7%) had methicillin-resistant Staphylococcus aureus (MRSA) enteritis, and 7 patients (8.5%) had liver dysfunction.CONCLUSIONS: Preoperative chemotherapy for gastric cancer with oral UFT was safe and resulted in a good local response (macro- and microscopically) which may indicate the possibility of improved survival with neoadjuvant chemotherapy with UFT. Furthermore, preoperative chemotherapy with oral UFT is easy and patients can receive this treatment on an outpatient basis.

Journal Article↗

PubMed1996

A new oral formulation of cyclosporine for early oral immunosuppressive therapy in liver transplant recipients.

CsA-ME is a new oral microemulsion formulation of CsA. Studies in stable liver grafted patients with cholestasis and subsequent poor absorption of the conventional cyclosporine formulation showed a substantial increase in CsA absorption after conversion to CsA-ME. To investigate its use in patients during the early course after liver transplantation we recruited 50 liver transplant recipients in two centers. During the first study phase A CsA-ME was administered to 20 patients in incremental doses after a short initial course of intravenous cyclosporine. During the second study phase B (30 patients) CsA-ME was administered from the time of transplantation. One year actual patient and graft survival of patients included in phase A and B of the trial was between 90% and 93.3%; 50% and 60% of the patients enrolled in phase A and phase B of the trial were free from rejection at month 3, respectively. Chronic rejection was diagnosed in one patient. No increase in the incidence of CsA related side effects was observed. The optimum CsA-ME starting dose was found to be 10 mg/kgbw/day for patients without external biliary diversion and 15 mg/kgbw/day for patients with a T tube in situ. Using these starting doses, 26 consecutive patients with external bile diversion via T tube were treated with CsA-ME from the day of transplantation. Intravenous CsA was necessary only in three patients. When CsA-ME absorption in patients with stable liver function was compared with that in patients with early liver dysfunction, no difference in the pharmacokinetic profiles was observed between the groups. Our results indicate that CsA-ME therapy is effective and well tolerated in liver graft recipients, even in patients with external biliary diversion during the early posttransplant phase. Thus, CsA-ME is a useful alternative to intravenous CsA treatment in these patients.

Administration, Oral↗

PubMed1997

Successful emergency transplantation of a liver allograft from a donor maintained on extracorporeal membrane oxygenation.

The critical shortage of cadaveric donors for organ transplantation has led many transplant centers to accept life-saving organs from donors who would have previously been refused for transplantation. We report a novel case of the use of a liver allograft from a donor whose oxygen delivery was maintained by extracorporeal membrane oxygenation (ECMO) for 29 days before suffering an anoxic brain injury from ECMO dysfunction. Liver transplantation was successfully performed in a patient with fulminant hepatic failure. Immediate graft function was obtained in the recipient, with full neurologic recovery and return to gainful employment 4 months after transplantation. ECMO may provide an intriguing option for the maintenance of organ function in the critically unstable brain-dead organ donor to salvage organs for transplantation. Further studies are currently underway.

Adult↗

PubMed2002

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene.

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1988

The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men.

Seventy-three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined before entry and during follow-up. No significant differences were observed before entry or during follow-up between the two treatment groups. T3, T4 and T4/TBG ratio did not change significantly during follow-up, while TBG concentrations decreased (P less than 0.05). Using a multivariate test, it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function of sex hormone receptors in their liver.

Administration, Oral↗

PubMed1988

Disseminated intravascular coagulation and mesenteric venous thrombosis in fatal Amanita poisoning.

1. A case of fatal Amanita phalloides poisoning in a 14-year-old boy is described. 2. The patient presented severe acute liver dysfunction, disseminated intravascular coagulation and refractory hypoxaemia, and died on the 9th day after mushroom ingestion. 3. Post-mortem examination revealed mesenteric venous thrombosis, massive liver necrosis and haemorrhagic pulmonary alveolitis.

Adolescent↗