Home About us Contact
|
Home About us Contact | ||
|
|
||
Hepatic Dysfunction (hepatic + dysfunction)
Selected AbstractsHepatic dysfunction and insulin insensitivity in type 2 diabetes mellitus: a critical target for insulin-sensitizing agentsDIABETES OBESITY & METABOLISM, Issue 9 2008P. D. Home The liver plays an essential role in maintaining glucose homeostasis, which includes insulin-mediated processes such as hepatic glucose output (HGO) and uptake, as well as in clearance of insulin itself. In type 2 diabetes, the onset of hyperglycaemia [itself a potent inhibitor of hepatic glucose output (HGO)], alongside hyperinsulinaemia, indicates the presence of hepatic insulin insensitivity. Increased HGO is central to the onset of hyperglycaemia and highlights the need to target hepatic insulin insensitivity as a central component of glucose-lowering therapy. The mechanisms underlying the development of hepatic insulin insensitivity are not well understood, but may be influenced by factors such as fatty acid oversupply and altered adipocytokine release from dysfunctional adipose tissue and increased liver fat content. Furthermore, although the impact of insulin insensitivity as a marker of cardiovascular disease is well known, the specific role of hepatic insulin insensitivity is less clear. The pharmacological tools available to improve insulin sensitivity include the biguanides (metformin) and thiazolidinediones (rosiglitazone and pioglitazone). Data from a number of sources indicate that thiazolidinediones, in particular, can improve multiple aspects of hepatic dysfunction, including reducing HGO, insulin insensitivity and liver fat content, as well as improving other markers of liver function and the levels of mediators with potential involvement in hepatic function, including fatty acids and adipocytokines. The current review addresses this topic from the perspective of the role of the liver in maintaining glucose homeostasis, its key involvement in the pathogenesis of type 2 diabetes and the tools currently available to reduce hepatic insulin insensitivity. [source] Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009G. T. EVERSON Summary Backgroud, The impact of virologic response on hepatic function has not been previously defined. Aim, To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) ± ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). Methods, Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24- 13C]cholate, galactose and 99mTc-sulfur colloid were administered intravenously; [2,2,4,2- 2H]cholate, [1- 13C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath 13CO2, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Results, Rates of SVR were 18,26% in patients with good function by QLFTs, but ,6% in patients with poor function. Hepatic metabolism, measured by caffeine kelim (P = 0.02), antipyrine kelim (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cloral (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Conclusion, Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM. [source] Hepatic dysfunction and insulin insensitivity in type 2 diabetes mellitus: a critical target for insulin-sensitizing agentsDIABETES OBESITY & METABOLISM, Issue 9 2008P. D. Home The liver plays an essential role in maintaining glucose homeostasis, which includes insulin-mediated processes such as hepatic glucose output (HGO) and uptake, as well as in clearance of insulin itself. In type 2 diabetes, the onset of hyperglycaemia [itself a potent inhibitor of hepatic glucose output (HGO)], alongside hyperinsulinaemia, indicates the presence of hepatic insulin insensitivity. Increased HGO is central to the onset of hyperglycaemia and highlights the need to target hepatic insulin insensitivity as a central component of glucose-lowering therapy. The mechanisms underlying the development of hepatic insulin insensitivity are not well understood, but may be influenced by factors such as fatty acid oversupply and altered adipocytokine release from dysfunctional adipose tissue and increased liver fat content. Furthermore, although the impact of insulin insensitivity as a marker of cardiovascular disease is well known, the specific role of hepatic insulin insensitivity is less clear. The pharmacological tools available to improve insulin sensitivity include the biguanides (metformin) and thiazolidinediones (rosiglitazone and pioglitazone). Data from a number of sources indicate that thiazolidinediones, in particular, can improve multiple aspects of hepatic dysfunction, including reducing HGO, insulin insensitivity and liver fat content, as well as improving other markers of liver function and the levels of mediators with potential involvement in hepatic function, including fatty acids and adipocytokines. The current review addresses this topic from the perspective of the role of the liver in maintaining glucose homeostasis, its key involvement in the pathogenesis of type 2 diabetes and the tools currently available to reduce hepatic insulin insensitivity. [source] Movement-Induced Focal Motor Seizures and Choreoathetosis As- sociated with Nonketotic Hyperglycemia: A Case ReportEPILEPSIA, Issue 2000Hisashi Tanaka Case Report: We report the case of a diabetic woman who developed right-sided reflex seizures and bilateral choreoathetosis during an episode of nonketotic hyperglycemia. The patient was a 67-year-old woman with a 14-year history of HCV-related liver cirrhosis who experienced polydipsia and polyuria in January 1998. She began to have episodes of abnormal hyperkinetic movements of the right upper extremity and tonic-clonic seizures in the right arm triggered by voluntary movements of right or bilateral arms in the beginning of March 1998. The seizures increased in frequency and consequently left her disabled. She was admitted to our hospital with complaints of these abnormal motor phenomena on March 9, 1998. Neurological examinations revealed that she was alert, well-oriented, and that cranial nerve functions were normal. Slight motor weakness of the right upper limb and deep tendon hyporeflexes were observed in all extremities. Sensations and cerebellar functions were intact. Choreic or athetotic involuntary movements were seen in the bilateral upper limbs and neck. These involuntary movements were increased by voluntary movement or posturing of the upper limbs. The focal tonic-clonic seizures were easily triggered by voluntary movements such as knotting a cord. This seizure suddenly began by tonic movements in the right upper limb and gradually progressed to the right hemi-face and neck without loss of consciousness. The average duration of seizures was about one minute. The laboratory data demonstrated mild leukocytopenia, thrombocytopenia, hepatic dysfunction, and hyperglycemia without ketosis. Fasting blood glucose was 41 I mg/dl, and HbAlc was 14.5%. Blood ammonia was within normal levels. Cranial CT revealed no abnormalities. Brain MRI on T I-weighted images demonstrated bilateral high signal intensity in the putamen. An interictal EEG revealed a symmetrical slow background activity of 7,8 Hz. An ictal EEG recording showed a 2.5 4 Hz irregular sharp and slow wave discharge in the bilateral frontal-central regions. Treatment with carbamazepine was ineffective for the seizures. However, the seizures completely disappeared after the administration of insulin on March 17. Under good control of the hyperglycemia, the abnormal involuntary movements decreased gradually and then completely disappeared; the patient became neurologically asymptomatic by March 30. The follow-tip EEG demonstrated 9-Hz alpha background activity without any epileptic discharges. Conclusions: Nonketotic hyperglycemia has been rarely reported to cause stimulus-induced seizures or hyperkinetic involuntary movements such as hemichorea-ballism. To our knowledge, this is the first reported case of both induced seizures and involuntary movements simultaneously caused by hyperglycemia. Movement-induced seizures and choreoathetoid movements in this patient can be considered to result from transiently-increased activity in the basal ganglia and/or cerebral cortex associated with metaholic disorders. [source] Adenosine reverses a preestablished CCl4 -induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in ratsHEPATOLOGY, Issue 4 2001Rolando Hernández-Muñoz Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl4 -induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl4 (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of ,-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl4 discontinuation (5 weeks), increased persitance of ,-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl4 withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl4 -induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery. [source] Screening for hepatitis B in chemotherapy patients: survey of current oncology practicesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010T. T. TRAN Summary Background, Hepatitis B virus (HBV) reactivation occurs in up to 78% of patients receiving cytotoxic chemotherapy for nonhepatic malignancies. Reactivation can lead to hepatic dysfunction, jaundice and fulminant hepatic failure. Current recommendations include screening patients at risk for HBV prior to immunosuppressive therapy and initiating antiviral prophylaxis in patients with chronic HBV. Aim, To investigate current practice among oncologists regarding HBV screening and antiviral prophylaxis in candidates for chemotherapy. Methods, A survey was sent to American Medical Association registered oncologists assessing demographics and HBV screening practices. Statistical analysis was performed using Fisher's exact test. Results, In all, 265 responses were received. Office-based physicians were less likely to screen for HBV prior to chemotherapy (P < 0.001). Years in practice varied: 51% with <5 years, 29% with 5,15 years and 18% with >15 years, with no difference in screening practices between groups (P = N.S.). Responders screen for HBV as follows: never , 20%, only in the presence of abnormal liver biochemistries , 30%, risk factors or history of hepatitis , 38%. In patients with known HBV, 75% of oncologists refer to specialists, 7% initiate therapy, while 15% do not refer or initiate therapy, most of whom are in an office setting (P = 0.02). Conclusions, Twenty per cent of oncologists never screen for HBV prior to initiating chemotherapy. Office-based physicians were less likely to screen, treat or refer to a specialist prior to chemotherapy. Greater education regarding risk of HBV reactivation is needed for clinicians treating patients with immunosuppressive therapies. Aliment Pharmacol Ther,31, 240,246 [source] The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health and diseaseLIVER INTERNATIONAL, Issue 3 2000Lynn Everett Abstract: The liver has long been known to respond to exposure to certain chemicals with hyperplasia and proliferation of the peroxisomal compartment. This response is now known to be mediated by specific receptors. The peroxisome proliferator-activated receptors (PPARs) were cloned 10 years ago, and in that interval, have been found to serve as receptors for a number of endogenous lipid compounds, in addition to the peroxisome proliferators that originally led to their study. Three receptors, designated the ,, ,, and , receptors, have been found in mammals. PPAR, is the most abundant form found in the liver, with smaller amounts of the , and , forms also expressed there. Kupffer cells, like other macrophages, appear to express the , and , isoforms. Hepatic stellate cells are reported to express the , isoform. PPAR, knock-out mice fail to undergo peroxisome proliferation when challenged with the proliferators. Moreover, they have severe derangements of lipid metabolism, particularly during fasting, indicating that normal function of the alpha receptors is needed for lipid homeostasis. This in turn suggests that inadequate PPAR-mediated responses may contribute to abnormal fatty acid metabolism in alcoholic and non-alcoholic steatohepatitis. Recent information suggests that PPAR, receptors may be important in control of the activation state of the stellate cells, and their repression or inactivation may predispose to hepatic fibrosis. The first approved drug that specifically activates PPAR,, troglitazone, has rarely been found to cause serious liver injury. Although this is likely to represent an idiosyncratic reaction, the medical community will need to be alert to the possibility that activation or blockade of these receptors may cause hepatic dysfunction. [source] MELD and prediction of post,liver transplantation survivalLIVER TRANSPLANTATION, Issue 3 2006Shahid Habib The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991,2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (,15), medium risk (16,25), and high risk (>25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5- and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age >65 years, donor age >50 years, male sex, and retransplantation and pretransplant MELD scores >25 were associated with poor patient and graft survival. The impact of MELD score >25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction. Liver Transpl 12:440,447, 2006. © 2006 AASLD. [source] Effects of hyperbaric oxygen exposure on experimental hepatic ischemia reperfusion injury: Relationship between its timing and neutrophil sequestrationLIVER TRANSPLANTATION, Issue 12 2005Kenji Kihara Recent studies have shown that hyperbaric oxygen therapy (HBOT) reduces neutrophil endothelial adherence in venules and also blocks the progressive arteriolar vasoconstriction associated with ischemia-reperfusion (I-R) injury in the extremities and the brain. In order to elucidate the effects of HBOT after I-R in digestive organs, particularly in the liver, we evaluated the following: 1) the relationship between timing of HBOT and tissue damage; and 2) HBOT's effects on neutrophil sequestration. Using a hepatic I-R (45 minute) model in male rats, survival rate, liver tissue damage, and neutrophil accumulation within the sinusoids in the HBOT-treated group (Group H) were compared to those in the nontreated group (Group C). For the HBOT-treated group, HBOT was administered as 100% oxygen, at 2.5 atm absolute, for 60 minutes. When HBOT was given 30 minute after I-R, the survival rate was much better in Group H than in Group C. HBOT performed within 3 hours of I-R markedly suppressed increases in the malondialdehyde level in tissues of the liver and lessened the congestion in the sinusoids. In addition, HBOT just after I-R caused decreased number of cells stained by the naphthol AS-D chloroacetate esterase infiltrating into the sinusoids. HBOT 3 hours after reperfusion, however, showed no clear effects upon neutrophil sequestration compared to Group C. These results indicate that HBOT performed within 3 hours of I-R alleviates hepatic dysfunction and improves the survival rate after I-R. Herein, we propose 1 possible mechanism for these beneficial effects: early HBOT given before neutrophil-mediated injury phase may suppress the accumulation of neutrophils after I-R. In conclusion, we believe that the present study should lead to an improved understanding of HBOT's potential role in hepatic surgery. (Liver Transpl 2005;11:1574,1580.) [source] Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patientsLIVER TRANSPLANTATION, Issue 9 2003Ashokkumar B. Jain With the advent of highly active antiretroviral therapy (HAART), HIV positivity is no longer a contraindication for liver transplantation. Some of the antiretroviral agents, particularly protease inhibitors (e.g., ritonavir, indinavir, and nelfinavir) have been described as potent inhibitors of the metabolism of certain immunosuppressive drugs. In this article we describe a profound interaction between tacrolimus and Kaletra (Abbott Laboratories, Chicago, IL) (a combination of lopinavir and ritonavir) in 3 liver transplantation patients. Patient 1, who was maintained on a 5 mg twice daily dose of tacrolimus with a trough blood concentration around 10.6 ng/mL, required only 0.5 mg of tacrolimus per week after addition of Kaletra to achieve similar tacrolimus blood concentrations, with a half-life of 10.6 days. In patient 2, the area under the blood concentration versus time curve for tacrolimus increased from 31 ng/mL/h to 301 ng/mL/h after addition of Kaletra, with a corresponding half-life of 20 days. When the patient was subsequently switched to nelfinavir, the half-life decreased to 10.3 days. Patient 3, who was maintained with 4 to 8 mg/d of tacrolimus and a corresponding blood concentration of 10 ng/mL before Kaletra, required a tacrolimus dose of 1 mg/wk and tacrolimus concentrations of 5 ng/mL with Kaletra. In conclusion, a combination of lopinavir and ritonavir led to a much more profound increase in tacrolimus blood concentrations than use of single protease inhibitor, nelfinavir. A tacrolimus dose of less than 1 mg/wk may be sufficient to maintain adequate blood tacrolimus concentrations in patients on Kaletra. Patients may not need a further dose of tacrolimus for 3 to 5 weeks depending on liver function when therapy with Kaletra is initiated. Great caution is required in the management of tacrolimus dosage when Kaletra is introduced or withdrawn in HIV-positive patients after liver transplantation, particularly in the presence of hepatic dysfunction. [source] Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2000T. Azuma Summary Background: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication. However, the efficacy and the safety of this therapy in patients with liver cirrhosis have not been established. Aim: To evaluate the effect of hepatic dysfunction on metabolism of clarithromycin as it is used for H. pylori eradication therapy in patients with liver cirrhosis, and the efficacy of eradication therapy in those patients. Methods: Serum levels of clarithromycin and its meta-bolite, 14-(R)-hydroxyclarithromycin, were examined in 18 subjects (five normal controls and 13 hospitalized patients with liver cirrhosis) on a selected day between days 7 and 10 of a 2-week course of eradication therapy. This therapy consisted of lansoprazole (30 mg, once a day) together with clarithromycin (200 mg, twice a day) and metronidazole (250 mg, twice a day). In addition, 118 H. pylori -positive out-patients, 88 with peptic ulcer and 30 with liver cirrhosis, underwent the same eradication therapy. Results: Values for the area under the 0,6 h concentration,time curve (AUC) for clarithromycin were not significantly different among the groups. However, the AUC (0,6 h) values of 14-(R)-hydroxyclarithromycin were significantly lower in the Child-Pugh C group than in either the normal controls or the Child-Pugh A/B group. The cure rate for the peptic ulcer patients was 84% on a per protocol analysis (95% CI: 80%,88%) and 81% on an intention-to-treat analysis (95% CI: 77%,85%), while in the liver cirrhosis patients it was 89% in a per protocol analysis (95% CI: 78%,99%) and 83% in an intention-to-treat analysis (95% CI: 70%,97%). Mild adverse effects were observed in 10% of the peptic ulcer patients and 13% of the liver cirrhosis patients, with none leading to premature withdrawal from the study. Conclusion: The 2-week low-dose lansoprazole-based triple therapy tested is a simple, effective and well-tolerated regimen for H. pylori eradication in patients with liver cirrhosis. [source] Rare case of Alstrom syndrome without obesity and with short stature, diagnosed in adulthood (Case Report)NEPHROLOGY, Issue 2 2006EYUP KOÇ SUMMARY: Alstrom syndrome is a rare autosomal recessive disorder characterized by retinal degeneration, sensorineural hearing loss, obesity, type 2 diabetes mellitus and chronic nephropathy. It may be associated with acanthosis nigricans, hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis, hyperlipidaemia, dilated cardiomyopathy and short stature. We report a patient with Alstrom syndrome who had hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis and short stature with normal body weight, all of which are seen infrequently with this syndrome. [source] Amphotericin B-induced hepatorenal failure in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 6 2002MRCPCH, Uthara R. Mohan MB Abstract Although nephrotoxicity is a common and well-recognized side effect of amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with cystic fibrosis who developed fulminant renal and hepatic dysfunction following a short course of intravenous amphotericin B for a suspected aspergillus infection, although she did not have clinical evidence of invasive aspergillosis. The toxicity became apparent after changing to liposomal amphotericin. This association of renal and hepatotoxicity with liposomal amphotericin B has not previously been reported in children. Pediatr Pulmonol. 2002; 33:497,500. © 2002 Wiley-Liss, Inc. [source] The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2006Andrew T. McAfee MD Abstract Purpose The purpose of this study was to compare incidence rates of hospitalization associated with rhabdomyolysis, myopathy, renal, or hepatic dysfunction, and of in-hospital death, between initiators of rosuvastatin and other statins. Methods This was a matched cohort study of statin initiators from the administrative database of a large health insurer in the US, during the first 6 months of rosuvastatin availability with up to 18 months of follow-up. All outcome events were verified by medical record review. Incidence rates, risk ratios, and associated 95% confidence intervals were estimated. Results From an initial pool of 12,217, 11,249 eligible rosuvastatin initiators were matched to 37,282 initiators of other statins. The incidence rate (IR) per 1000 person-years for rhabdomyolysis was 0.10 [0.00, 0.55] for rosuvastatin initiators (n,=,1) and 0.06 [0.01, 0.22] for other statin initiators (n,=,2), for a hazard ratio (HR) of 1.98 [0.18, 21.90]. The IR for myopathy was 0.20 [0.02, 0.71] for rosuvastatin initiators (n,=,2) and 0.00 [0.00, 0.09] for other statin initiators (n,=,0). The IR for renal dysfunction was 1.18 [0.61, 2.06] for rosuvastatin initiators (n,=,12) and 1.26 [0.91, 1.71] for other statin initiators (n,=,42), for a HR of 0.90 [0.47, 1.73]. The IR for hepatic dysfunction was 0.20 (0.02, 0.71) for rosuvastatin initiators (n,=,2) and 0.24 (0.10, 0.47) for other statin initiators (n,=,8), for a HR of 0.87 (0.18, 4.14). Conclusions This study found no difference between rosuvastatin and the other statins in the incidence of hospitalizations associated with renal or hepatic events, or death. The absolute incidence rates of rhabdomyolysis and myopathy were reassuringly low among all statin initiators but remain too small for firm conclusions to be drawn on any difference between the statins. Copyright © 2006 John Wiley & Sons, Ltd. [source] Antituberculosis drugs and hepatotoxicityRESPIROLOGY, Issue 6 2006Wing Wai YEW Abstract: Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity. [source] Effect of perioperative steroids on renal function after liver transplantation,ANAESTHESIA, Issue 3 2006S. Turner Summary Subclinical renal dysfunction is thought to occur as a systemic manifestation of ischaemia-reperfusion injury of other organs. Liver transplantation is associated with major ischaemia-reperfusion injury. Thirty-four patients undergoing elective liver transplantation were randomly allocated to receive either saline or 10 mg.kg,1 methylprednisolone on induction of anaesthesia. Urine was taken for N-acetyl-,-D-glucosaminidase, creatinine and other markers of tubular function. Serum chemistry was measured for 7 days. Creatinine concentration increased in the saline group but not in the methylprednisolone group (p < 0.0001), with the greatest difference on the third postoperative day (mean (SD) 164.8 (135.8) ,mol.l,1vs 88.5 (39.4) ,mol.l,1, respectively). Similar changes were seen in postoperative alanine transferase (865 (739) U.l,1vs 517 (608) U.l,1, respectively; p <,0.0001) on the second postoperative day. Both groups exhibited increases in markers of renal tubular dysfunction and of glomerular permeability. Patients in the saline group sustained more adverse events (8/17 (47%) vs 2/17 (12%); p = 0.02). The data confirm increased proximal tubular lysosomal turnover, consistent with an increased tubular protein load, following liver transplantation, and suggest that methylprednisolone protects against renal and hepatic dysfunction. [source] Pharmacokinetics of sabeluzole and dextromethorphan oxidation capacity in patients with severe hepatic dysfunction and healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2001G. P. Pageaux Aims, The primary objective of this study was to determine how the pharmacokinetics of sabeluzole, an investigational drug with specific effects on memory and learning abilities, are affected by chronic liver disease. Since sabeluzole is metabolised by CYP2D6, a secondary objective was to study the correlation between CYP2D6 activity (as assessed by the dextromethorphan dextrorphan metabolic ratio) and hepatic dysfunction. Methods, The single-dose pharmacokinetics of sabeluzole (10 mg) was compared in 10 healthy Caucasian subjects and 10 patients with severe hepatic dysfunction. The urinary dextromethorphan/dextrorphan (DMP/DRP) metabolic ratio was determined after intake of 20 mg dextromethorphan (NODEX® capsules). Results, The terminal half-life of sabeluzole was significantly prolonged in subjects with severe hepatic dysfunction vs healthy subjects (respectively 39.3 ± 11.5 h; 17.5 ± 10.2 h (mean ±,s.d.)). The areas under the curve (AUC) were significantly higher in subjects with severe hepatic dysfunction than in healthy volunteers (681 ± 200 ng ml ,1h vs 331 ± 282 ng ml ,1h). There was a significant correlation between the AUC(0,,) and the DMP/DRP metabolic ratio in healthy volunteers and subjects with severe hepatic dysfunction. AUC was greater and elimination of sabeluzole slower in poor metabolizers compared with extensive metabolizers. Conclusions, These results suggest that a) sabeluzole dose should be reduced in patients with severe hepatic dysfunction and b) the AUC of sabeluzole is linked to individual CYP2D6 activity. [source] Prediction of posthepatectomy hepatic functional reserve by serum hyaluronateBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2009S. Yachida Background: Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function and hepatic fibrosis. This study was designed to clarify the clinical significance of the serum hyaluronate level as a parameter of functional reserve. Methods: The study included 283 patients undergoing hepatectomy. Liver function parameters were examined before surgery and compared with outcomes. Patients were retrospectively grouped according to the presence or absence of postoperative hepatic dysfunction. Results: Preoperative serum hyaluronate levels were significantly raised in parallel with the degree of severity of the underlying chronic liver disease. Regression analysis revealed serum hyaluronate level to be an independent predictor of portal hypertension. In 131 patients undergoing major hepatectomy, preoperative hyaluronate levels were significantly higher in patients with poor outcome. Multivariable logistic regression analysis demonstrated serum hyaluronate and total bilirubin levels to be independent variables associated with postoperative hepatic dysfunction. Patients with high indocyanine green retention rate at 15 min (over 15 per cent) showed significantly higher morbidity and mortality rates when their serum hyaluronate levels were over 180 ng/ml. Conclusion: Serum hyaluronate is a simple clinical marker for portal venous pressure and a reliable auxiliary parameter of hepatic functional reserve in combination with other liver function tests. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] The protective mechanisms of defibrotide on liver ischaemia,reperfusion injuryCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2003E. O. Aydemir Abstract During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia,reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45,min of portal occlusion. DEF 175,mg/kg,1 was infused before ischaemia in 10,ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p,<,0.01 and p,<,0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p,<,0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p,<,0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels. Copyright © 2003 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||